medication_name stringlengths 6 170 | section_title stringclasses 42 values | text stringlengths 0 47.1k |
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Gabapentin Amarox 300 mg hard capsules | Name of the medicinal product | Gabapentin Amarox 300 mg hard capsules
2. |
Gabapentin Amarox 300 mg hard capsules | Qualitative and quantitative composition | Each hard capsule contains 300 mg of gabapentin.
3. |
Gabapentin Amarox 300 mg hard capsules | Pharmaceutical form | Hard capsule
White to off white granular powder filled in size “1” hard gelatin capsules with white opaque cap imprinted with “H” in blue colour and white opaque body imprinted with “G2” in blue colour.
4. |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Therapeutic indications | Therapeutic indications
Epilepsy
Gabapentin Amarox is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults and children aged 6 years and above (see section 5.1).
Gabapentin Amarox is indicated as monotherapy in the treatment of partial seizures with and without secondary generalization in adults and adolescents aged 12 years and above.
Treatment of peripheral neuropathic pain
Gabapentin Amarox is indicated for the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post- herpetic neuralgia in adults.
4.2 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Posology and method of administration | Posology and method of administration
Posology
For all indications a titration scheme for the initiation of therapy is described in Table 1, which is recommended for adults and adolescents aged 12 years and above. Dosing instructions for children under 12 years of age are provided under a separate sub-heading later in this section.
Table 1
DOSING CHART – INITIAL TITRATION
Day 1
Day 2
Day 3
300 mg once a day
300 mg two times a day
300 mg three times a day
Discontinuation of gabapentin
In accordance with current clinical practice, if gabapentin has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication.
Epilepsy
Epilepsy typically requires long-term therapy. Dosage is determined by the treating physician according to individual tolerance and efficacy.
Adults and adolescents
In clinical trials, the effective dosing range was 900 to 3600 mg/day. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300 mg three times a day (TID) on Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks. Dosages up to 4800 mg/day have been well tolerated in long-term open-label clinical studies. The total daily dose should be divided in three single doses, the maximum time interval between the doses should not exceed 12 hours to prevent breakthrough convulsions.
Children aged 6 years and above
The starting dose should range from 10 to 15 mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of gabapentin in children aged 6 years and older is 25 to 35 mg/kg/day. Dosages up to 50 mg/kg/day have been well tolerated in a long- term clinical study. The total daily dose should be divided in three single doses, the maximum time interval between doses should not exceed 12 hours.
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, gabapentin may be used in combination with other antiepileptic medicinal products without concern for alteration of the plasma concentrations of gabapentin or serum concentrations of other antiepileptic medicinal products.
Peripheral neuropathic pain
Adults
The therapy may be initiated by titrating the dose as described in Table 1. Alternatively, the starting dose is 900 mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.
In the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been examined in clinical studies for treatment periods longer than 5 months. If a patient requires dosing longer than 5 months for the treatment of peripheral neuropathic pain, the treating physician should assess the patient's clinical status and determine the need for additional therapy.
Instruction for all areas of indication
In patients with poor general health, i.e., low body weight, after organ transplantation etc., the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases.
Elderly (over 65 years of age)
Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.
Renal impairment
Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis. Gabapentin 100 mg hard capsules can be used to follow dosing recommendations for patients with renal insufficiency.
Table 2
DOSAGE OF GABAPENTIN IN ADULTS BASED ON RENAL FUNCTION
Creatinine Clearance (mL/min)
Total Daily Dosea (mg/day)
≥80
900-3600
50-79
600-1800
30-49
300-900
15-29
150b-600
<15c
150b-300
a Total daily dose should be administered as three divided doses. Reduced dosages are for patients with renal impairment (creatinine clearance <79 mL/min).
b The 150 mg daily dose to be administered as 300 mg every other day.
c For patients with creatinine clearance <15 mL/min, the daily dose should be reduced in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).
Use in patients undergoing haemodialysis
For anuric patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg, then 200 to 300 mg of gabapentin following each 4 hours of haemodialysis, is recommended. On dialysis-free days there should be no treatment with gabapentin.
For renally impaired patients undergoing haemodialysis, the maintenance dose of gabapentin should be based on the dosing recommendations found in Table 2. In addition to the maintenance dose, an additional 200 to 300 mg dose following each 4-hour haemodialysis treatment is recommended.
Method of administration
For oral use.
Gabapentin can be given with or without food and should be swallowed whole with sufficient fluid-intake (e.g. a glass of water).
4.3 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Contraindications | Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug rash with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in association with gabapentin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, gabapentin should be withdrawn immediately and an alternative treatment considered (as appropriate).
If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of gabapentin, treatment with gabapentin must not be restarted in this patient at any time.
Anaphylaxis
Gabapentin can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis (see section 4.8).
Suicidal ideation and behaviour
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known. Cases of suicidal ideation and behaviour have been observed in patients treated with gabapentin in the post-marketing experience (see section 4.8).
Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Discontinuation of gabapentin treatment should be considered in case of suicidal ideation and behaviour.
Acute pancreatitis
If a patient develops acute pancreatitis under treatment with gabapentin, discontinuation of gabapentin should be considered (see section 4.8).
Seizures
Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus (see section 4.2).
As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with gabapentin.
As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in treatment refractive patients on more than one anti-epileptic, in order to reach gabapentin monotherapy have a low success rate.
Gabapentin is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients.
Therefore, gabapentin should be used with caution in patients with mixed seizures including absences.
Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been post-marketing reports of confusion, loss of consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Concomitant use with opioids
Patients who require concomitant treatment with opioids should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression. Patients who use gabapentin and morphine concomitantly may experience increases in gabapentin concentrations. The dose of gabapentin or opioids should be reduced appropriately (see section 4.5).
Respiratory depression
Gabapentin has been associated with severe respiratory depression. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly might be at higher risk of experiencing this severe adverse reaction. Dose adjustments might be necessary in these patients.
Elderly (over 65 years of age)
No systematic studies in patients 65 years or older have been conducted with gabapentin. In one double blind study in patients with neuropathic pain, somnolence, peripheral oedema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.
Paediatric population
The effects of long-term (greater than 36 weeks) gabapentin therapy on learning, intelligence, and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.
Misuse, abuse potential and dependence
Gabapentin can cause drug dependence, which may occur at therapeutic doses. Cases of abuse and misuse have been reported. Patients with a history of substance abuse may be at higher risk for gabapentin misuse, abuse and dependence, and gabapentin should be used with caution in such patients. Before prescribing gabapentin, the patient's risk of misuse, abuse or dependence should be carefully evaluated.
Patients treated with gabapentin should be monitored for symptoms of gabapentin misuse, abuse or dependence, such as development of tolerance, dose escalation and drug-seeking behaviour.
Withdrawal symptoms
After discontinuation of short-term and long-term treatment with gabapentin, withdrawal symptoms have been observed. Withdrawal symptoms may occur shortly after discontinuation, usually within 48 hours. Most frequently reported symptoms include anxiety, insomnia, nausea, pains, sweating, tremor, headache, depression, feeling abnormal, dizziness, and malaise. The occurrence of withdrawal symptoms following discontinuation of gabapentin may indicate drug dependence (see section 4.8). The patient should be informed about this at the start of the treatment. If gabapentin should be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication (see section 4.2).
Laboratory tests
False positive readings may be obtained in the semi-quantitative determination of total urine protein by dipstick tests. It is therefore recommended to verify such a positive dipstick test result by methods based on a different analytical principle such as the Biuret method, turbidimetric or dye-binding methods, or to use these alternative methods from the beginning.
Gabapentin Amarox contains sodium
This medicines contains less than 1 mmol sodium (23mg) per hard capsule, that is to say essentially 'sodium-free'.
4.5 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
There are spontaneous and literature case reports of respiratory depression and/or sedation associated with gabapentin and opioid use. In some of these reports, the authors considered this a particular concern with the combination of gabapentin and opioids, especially in elderly patients.
In a study involving healthy volunteers (N=12), when a 60 mg controlled- release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule, mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Therefore, patients who require concomitant treatment with opioids should be carefully observed for signs of CNS depression, such as somnolence, sedation and respiratory depression and the dose of gabapentin or opioid should be reduced appropriately.
No interaction between gabapentin and phenobarbital, phenytoin, valproic acid or carbamazepine has been observed.
Gabapentin steady-state pharmacokinetics are similar for healthy subjects and patients with epilepsy receiving these antiepileptic agents.
Co-administration of gabapentin with oral contraceptives containing norethindrone and/or ethinyl estradiol, does not influence the steady-state pharmacokinetics of either component.
Co-administration of gabapentin with antacids containing aluminium and magnesium, reduces gabapentin bioavailability up to 24%. It is recommended that gabapentin be taken at the earliest two hours following antacid administration.
Renal excretion of gabapentin is unaltered by probenecid.
A slight decrease in renal excretion of gabapentin that is observed when it is co-administered with cimetidine is not expected to be of clinical importance.
4.6 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Fertility, pregnancy and lactation | Fertility, pregnancy and lactation
Pregnancy
Risk related to epilepsy and antiepileptic medicinal products in general
The risk of birth defects is increased by a factor of 2 – 3 in the offspring of mothers treated with an antiepileptic medicinal product. Most frequently reported are cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic drug therapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is important that monotherapy is practised whenever possible. Specialist advice should be given to women who are likely to become pregnant or who are of childbearing potential and the need for antiepileptic treatment should be reviewed when a woman is planning to become pregnant. No sudden discontinuation of antiepileptic therapy should be undertaken as this may lead to breakthrough seizures, which could have serious consequences for both mother and child.
Developmental delay in children of mothers with epilepsy has been observed rarely. It is not possible to differentiate if the developmental delay is caused by genetic, social factors, maternal epilepsy or the antiepileptic therapy.
Neonatal withdrawal syndrome has been reported in newborns exposed in utero to gabapentin.
Co-exposure to gabapentin and opioids during pregnancy may increase the risk of neonatal withdrawal syndrome. Newborns should be monitored carefully.
Risk related to gabapentin
Gabapentin crosses the human placenta.
There are no or limited amount of data from the use of gabapentin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the foetus.
No definite conclusion can be made as to whether gabapentin is causally associated with an increased risk of congenital malformations when taken during pregnancy, because of epilepsy itself and the presence of concomitant antiepileptic medicinal products during each reported pregnancy.
Breast-feeding
Gabapentin is excreted in human milk. Because the effect on the breast-fed infant is unknown, caution should be exercised when gabapentin is administered to a breast-feeding mother. Gabapentin should be used in breast- feeding mothers only if the benefits clearly outweigh the risks.
Fertility
There is no effect on fertility in animal studies (see section 5.3).
4.7 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Effects on ability to drive and use machines | Effects on ability to drive and use machines
Gabapentin may have minor or moderate influence on the ability to drive and use machines. Gabapentin acts on the central nervous system and may cause drowsiness, dizziness or other related symptoms. Even, if they were only of mild or moderate degree, these undesirable effects could be potentially dangerous in patients driving or operating machinery. This is especially true at the beginning of the treatment and after increase in dose.
4.8 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Undesirable effects | Undesirable effects
The adverse reactions observed during clinical studies conducted in epilepsy (adjunctive and monotherapy) and neuropathic pain have been provided in a single list below by class and frequency: very common (≥ 1/10); common (≥ 1/100 to< 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000). Where an adverse reaction was seen at different frequencies in clinical studies, it was assigned to the highest frequency reported.
Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in italics in the list below.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
System organ class
Adverse drug reactions
Infections and infestations
Very Common
viral infection
Common
pneumonia, respiratory infection, urinary tract infection, infection, otitis media
Blood and the lymphatic system disorders
Common
leucopenia
Not known
Thrombocytopenia
Immune system disorders
Uncommon
allergic reactions (e.g. urticaria)
Not known
hypersensitivity syndrome (a systemic reaction with a variable presentation that can include fever, rash, hepatitis, lymphadenopathy, eosinophilia, and sometimes other signs and symptoms), anaphylaxis (see section 4.4)
Metabolism and nutrition disorders
Common
anorexia, increased appetite
Uncommon
hyperglycaemia (most often observed in patients with diabetes)
Rare
hypoglycaemia (most often observed in patients with diabetes)
Not known
hyponatraemia
Psychiatric disorders
Common
hostility, confusion and emotional lability, depression, anxiety, nervousness, thinking abnormal
Uncommon
agitation
Not known
hallucinations, suicidal ideation, drug dependence
Nervous system disorders
Very Common
somnolence, dizziness, ataxia
Common
convulsions,hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesia, coordination abnormal, nystagmus, increased, decreased, or absent reflexes
Uncommon
hypokinesia, mental impairment
Rare
loss of consciousness
Not known
other movement disorders (e.g. choreoathetosis, dyskinesia, dystonia)
Eye disorders
Common
visual disturbances such as amblyopia, diplopia
Ear and labyrinth disorders
Common
vertigo
Not known
tinnitus
Cardiac disorders
Uncommon
palpitations
Vascular disorders
Common
hypertension, vasodilatation
Respiratory, thoracic and mediastinal disorders
Common
dyspnoea, bronchitis, pharyngitis, cough, rhinitis
Rare
respiratory depression
Gastrointestinal disorders
Common
vomiting, nausea, dental abnormalities, gingivitis, diarrhoea, abdominal pain, dyspepsia, constipation, dry mouth or throat, flatulence
Uncommon
dysphagia
Not known
pancreatitis
Hepatobiliary disorders
Not known
hepatitis, jaundice
Skin and subcutaneous tissue disorders
Common
facial oedema, purpura most often described as bruises resulting from physical trauma, rash, pruritus, acne
Not known
Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, erythema multiforme, alopecia, drug rash with eosinophilia and systemic symptoms (see section 4.4)
Musculoskeletal and connective tissue disorders
Common
arthralgia, myalgia, back pain, twitching
Not known
rhabdomyolysis, myoclonus
Renal and urinary disorder
Not known
acute renal failure, incontinence
Reproductive system and breast disorders
Common
impotence
Not known
breast hypertrophy, gynaecomastia, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia)
General disorders and administration site conditions
Very Common
fatigue, fever
Common
peripheral oedema, abnormal gait, asthenia, pain, malaise, flu syndrome
Uncommon
generalized oedema
Not known
withdrawal reactions*, chest pain. Sudden unexplained deaths have been reported where a causal relationship to treatment with gabapentin has not been established.
Investigations
Common
WBC (white blood cell count) decreased, weight gain
Uncommon
elevated liver function tests SGOT (AST), SGPT (ALT) and bilirubin
Not known
blood creatine phosphokinase increased
Injury, poisoning and procedural complications
Common
accidental injury, fracture, abrasion
Uncommon
fall
*After discontinuation of short-term and long-term treatment with gabapentin, withdrawal symptoms have been observed. Withdrawal symptoms may occur shortly after discontinuation, usually within 48 hours. Most frequently reported symptoms include anxiety, insomnia, nausea, pains, sweating, tremor, headache, depression, feeling abnormal, dizziness, and malaise (see section 4.4). The occurrence of withdrawal symptoms following discontinuation of gabapentin may indicate drug dependence (see section 4.8). The patient should be informed about this at the start of the treatment. If gabapentin should be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication (see section 4.2).
Under treatment with gabapentin cases of acute pancreatitis were reported. Causality with gabapentin is unclear (see section 4.4).
In patients on haemodialysis due to end-stage renal failure, myopathy with elevated creatine kinase levels has been reported.
Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children.
Additionally, in clinical studies in children, aggressive behaviour and hyperkinesias were reported commonly.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 |
Gabapentin Amarox 300 mg hard capsules | Clinical particulars - Overdose | Overdose
Acute, life-threatening toxicity has not been observed with gabapentin overdoses of up to 49 g. Symptoms of the overdoses included dizziness, double vision, slurred speech, drowsiness, loss of consciousness, lethargy and mild diarrhoea. All patients recovered fully with supportive care. Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, minimize toxicity from overdoses.
Overdoses of gabapentin, particularly in combination with other CNS depressant medications, may result in coma.
Although gabapentin can be removed by haemodialysis, based on prior experience it is usually not required. However, in patients with severe renal impairment, haemodialysis may be indicated.
An oral lethal dose of gabapentin was not identified in mice and rats given doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis, hypoactivity, or excitation.
5. Pharmacological properties
5.1 |
Gabapentin Amarox 300 mg hard capsules | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
Absorption
Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours. Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on gabapentin pharmacokinetics.
Gabapentin pharmacokinetics are not affected by repeated administration. Although plasma gabapentin concentrations were generally between 2 μg/mL and 20 μg/mL in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 3.
Table 3
SUMMARY OF GABAPENTIN MEAN (%CV) STEADY-STATE PHARMACOKINETIC PARAMETERS FOLLOWING EVERY EIGHT HOURS ADMINISTRATION
Pharmacokinetic parameter
300 mg
(N=7)
400 mg
(N=14)
800 mg
(N=14)
Mean
%CV
Mean
%CV
Mean
%CV
Cmax (μg/mL)
4.02
(24)
5.74
(38)
8.71
(29)
tmax (hr)
2.7
(18)
2.1
(54)
1.6
(76)
T1/2 (hr)
5.2
(12)
10.8
(89)
10.6
(41)
AUC (0-8)
μg•hr/mL)
24.8
(24)
34.5
(34)
51.4
(27)
Ae% (%)
NA
NA
47.2
(25)
34.4
(37)
Cmax = Maximum steady state plasma concentration
tmax = Time for Cmax
T1/2 = Elimination half-life
AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours postdose
Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours postdose
NA = Not available
Distribution
Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady- state trough plasma concentrations. Gabapentin is present in the breast milk of breast-feeding women.
Biotransformation
There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.
Elimination
Gabapentin is eliminated unchanged solely by renal excretion. The elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.
In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.
Gabapentin is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended (see section 4.2).
Gabapentin pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma gabapentin concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.
In a pharmacokinetic study in 24 healthy paediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower Cmax and higher clearance per body weight have been observed in comparison to available reported data in children older than 5 years.
Linearity/non-linearity
Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma gabapentin concentrations are predictable from single-dose data.
5.3 |
Gabapentin Amarox 300 mg hard capsules | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
Carcinogenesis
Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000, and 2000 mg/kg/day for two years. A statistically significant increase in the incidence of pancreatic acinar cell tumors was found only in male rats at the highest dose. Peak plasma drug concentrations in rats at 2000 mg/kg/day are 10 times higher than plasma concentrations in humans given 3600 mg/day. The pancreatic acinar cell tumors in male rats are low- grade malignancies, did not affect survival, did not metastasize or invade surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic acinar cell tumors in male rats to carcinogenic risk in humans is unclear.
Mutagenesis
Gabapentin demonstrated no genotoxic potential. It was not mutagenic in vitro in standard assays using bacterial or mammalian cells. Gabapentin did not induce structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not induce micronucleus formation in the bone marrow of hamsters.
Impairment of fertility
No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg (approximately five times the maximum daily human dose on a mg/m2 of body surface area basis).
Teratogenesis
Gabapentin did not increase the incidence of malformations, compared to controls, in the offspring of mice, rats, or rabbits at doses up to 50, 30 and 25 times respectively, the daily human dose of 3600 mg, (four, five or eight times, respectively, the human daily dose on a mg/m2 basis).
Gabapentin induced delayed ossification in the skull, vertebrae, forelimbs, and hindlimbs in rodents, indicative of fetal growth retardation. These effects occurred when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during organogenesis and in rats given 2000 mg/kg prior to and during mating and throughout gestation. These doses are approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.
No effects were observed in pregnant mice given 500 mg/kg/day (approximately 1/2 of the daily human dose on a mg/m2 basis).
An increased incidence of hydroureter and/or hydronephrosis was observed in rats given 2000 mg/kg/day in a fertility and general reproduction study, 1500 mg/kg/day in a teratology study, and 500, 1000, and 2000 mg/kg/day in a perinatal and postnatal study. The significance of these findings is unknown, but they have been associated with delayed development. These doses are also approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.
In a teratology study in rabbits, an increased incidence of post-implantation foetal loss, occurred in pregnant rabbits given 60, 300, and 1500 mg/kg/day during organogenesis. These doses are approximately 0.3 to 8 times the daily human dose of 3600 mg on a mg/m2 basis. The margins of safety are insufficient to rule out the risk of these effects in humans.
6. |
Gabapentin Amarox 300 mg hard capsules | Pharmaceutical particulars - List of excipients | List of excipients
Capsule content
Mannitol
Starch, Pregelatinised
Talc
CAP & Body
Titanium Dioxide (E171)
Gelatin
Sodium lauryl sulphate
Printing Ink
Shellac (E904)
Dehydrated Alcohol (E1510)
Isopropyl Alcohol
Butyl Alcohol
Propylene Glycol (E1520)
Strong Ammonia Solution (E527)
FD & C Blue # 2 Aluminum Lake (El32)
6.2 |
Gabapentin Amarox 300 mg hard capsules | Pharmaceutical particulars - Incompatibilities | Incompatibilities
Not applicable.
6.3 |
Gabapentin Amarox 300 mg hard capsules | Pharmaceutical particulars - Shelf life | Shelf life
2 years.
6.4 |
Gabapentin Amarox 300 mg hard capsules | Pharmaceutical particulars - Special precautions for storage | Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 |
Gabapentin Amarox 300 mg hard capsules | Pharmaceutical particulars - Nature and contents of container | Nature and contents of container
Clear PVC/PVDC-aluminium foil blister pack containing 100 hard capsules
6.6 |
Gabapentin Amarox 300 mg hard capsules | Pharmaceutical particulars - Special precautions for disposal and other handling | Special precautions for disposal and other handling
No special requirements
7. |
Gabapentin Amarox 300 mg hard capsules | Marketing authorisation holder | Amarox Limited
Congress House,
14 Lyon Road,
Harrow, Middlesex HA1 2EN,
United Kingdom
8. Marketing authorisation number(s)
PL 49445/0110
9. |
Gabapentin Amarox 300 mg hard capsules | Date of first authorisation/renewal of the authorisation | 06/10/2021
10. |
Gabapentin Amarox 300 mg hard capsules | Date of revision of the text | 15/03/2023 |
Gabapentin Amarox 400 mg hard capsules | Name of the medicinal product | Gabapentin Amarox 400 mg hard capsules
2. |
Gabapentin Amarox 400 mg hard capsules | Qualitative and quantitative composition | Each hard capsule contains 400 mg of gabapentin.
3. |
Gabapentin Amarox 400 mg hard capsules | Pharmaceutical form | Hard capsule
White to off white granular powder filled in size “0” hard gelatin capsules with white opaque cap imprinted with “H” in blue colour and white opaque body imprinted with “G3” in blue colour.
4. |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Therapeutic indications | Therapeutic indications
Epilepsy
Gabapentin Amarox is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults and children aged 6 years and above (see section 5.1).
Gabapentin Amarox is indicated as monotherapy in the treatment of partial seizures with and without secondary generalization in adults and adolescents aged 12 years and above.
Treatment of peripheral neuropathic pain
Gabapentin Amarox is indicated for the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post- herpetic neuralgia in adults.
4.2 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Posology and method of administration | Posology and method of administration
Posology
For all indications a titration scheme for the initiation of therapy is described in Table 1, which is recommended for adults and adolescents aged 12 years and above. Dosing instructions for children under 12 years of age are provided under a separate sub-heading later in this section.
Table 1
DOSING CHART – INITIAL TITRATION
Day 1
Day 2
Day 3
300 mg once a day
300 mg two times a day
300 mg three times a day
Discontinuation of gabapentin
In accordance with current clinical practice, if gabapentin has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication.
Epilepsy
Epilepsy typically requires long-term therapy. Dosage is determined by the treating physician according to individual tolerance and efficacy.
Adults and adolescents
In clinical trials, the effective dosing range was 900 to 3600 mg/day. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300 mg three times a day (TID) on Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks. Dosages up to 4800 mg/day have been well tolerated in long-term open-label clinical studies. The total daily dose should be divided in three single doses, the maximum time interval between the doses should not exceed 12 hours to prevent breakthrough convulsions.
Children aged 6 years and above
The starting dose should range from 10 to 15 mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of gabapentin in children aged 6 years and older is 25 to 35 mg/kg/day. Dosages up to 50 mg/kg/day have been well tolerated in a long- term clinical study. The total daily dose should be divided in three single doses, the maximum time interval between doses should not exceed 12 hours.
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, gabapentin may be used in combination with other antiepileptic medicinal products without concern for alteration of the plasma concentrations of gabapentin or serum concentrations of other antiepileptic medicinal products.
Peripheral neuropathic pain
Adults
The therapy may be initiated by titrating the dose as described in Table 1. Alternatively, the starting dose is 900 mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.
In the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been examined in clinical studies for treatment periods longer than 5 months. If a patient requires dosing longer than 5 months for the treatment of peripheral neuropathic pain, the treating physician should assess the patient's clinical status and determine the need for additional therapy.
Instruction for all areas of indication
In patients with poor general health, i.e., low body weight, after organ transplantation etc., the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases.
Elderly (over 65 years of age)
Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.
Renal impairment
Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis. Gabapentin 100 mg hard capsules can be used to follow dosing recommendations for patients with renal insufficiency.
Table 2
DOSAGE OF GABAPENTIN IN ADULTS BASED ON RENAL FUNCTION
Creatinine Clearance (mL/min)
Total Daily Dosea (mg/day)
≥80
900-3600
50-79
600-1800
30-49
300-900
15-29
150b-600
<15c
150b-300
a Total daily dose should be administered as three divided doses. Reduced dosages are for patients with renal impairment (creatinine clearance <79 mL/min).
b The 150 mg daily dose to be administered as 300 mg every other day.
c For patients with creatinine clearance <15 mL/min, the daily dose should be reduced in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).
Use in patients undergoing haemodialysis
For anuric patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg, then 200 to 300 mg of gabapentin following each 4 hours of haemodialysis, is recommended. On dialysis-free days there should be no treatment with gabapentin.
For renally impaired patients undergoing haemodialysis, the maintenance dose of gabapentin should be based on the dosing recommendations found in Table 2. In addition to the maintenance dose, an additional 200 to 300 mg dose following each 4-hour haemodialysis treatment is recommended.
Method of administration
For oral use.
Gabapentin can be given with or without food and should be swallowed whole with sufficient fluid-intake (e.g. a glass of water).
4.3 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Contraindications | Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug rash with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in association with gabapentin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, gabapentin should be withdrawn immediately and an alternative treatment considered (as appropriate).
If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of gabapentin, treatment with gabapentin must not be restarted in this patient at any time.
Anaphylaxis
Gabapentin can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis (see section 4.8).
Suicidal ideation and behaviour
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known. Cases of suicidal ideation and behaviour have been observed in patients treated with gabapentin in the post-marketing experience (see section 4.8).
Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Discontinuation of gabapentin treatment should be considered in case of suicidal ideation and behaviour.
Acute pancreatitis
If a patient develops acute pancreatitis under treatment with gabapentin, discontinuation of gabapentin should be considered (see section 4.8).
Seizures
Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus (see section 4.2).
As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with gabapentin.
As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in treatment refractive patients on more than one anti-epileptic, in order to reach gabapentin monotherapy have a low success rate.
Gabapentin is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients.
Therefore, gabapentin should be used with caution in patients with mixed seizures including absences.
Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been post-marketing reports of confusion, loss of consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Concomitant use with opioids
Patients who require concomitant treatment with opioids should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression. Patients who use gabapentin and morphine concomitantly may experience increases in gabapentin concentrations. The dose of gabapentin or opioids should be reduced appropriately (see section 4.5).
Respiratory depression
Gabapentin has been associated with severe respiratory depression. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly might be at higher risk of experiencing this severe adverse reaction. Dose adjustments might be necessary in these patients.
Elderly (over 65 years of age)
No systematic studies in patients 65 years or older have been conducted with gabapentin. In one double blind study in patients with neuropathic pain, somnolence, peripheral oedema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.
Paediatric population
The effects of long-term (greater than 36 weeks) gabapentin therapy on learning, intelligence, and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.
Misuse, abuse potential and dependence
Gabapentin can cause drug dependence, which may occur at therapeutic doses. Cases of abuse and misuse have been reported. Patients with a history of substance abuse may be at higher risk for gabapentin misuse, abuse and dependence, and gabapentin should be used with caution in such patients. Before prescribing gabapentin, the patient's risk of misuse, abuse or dependence should be carefully evaluated.
Patients treated with gabapentin should be monitored for symptoms of gabapentin misuse, abuse or dependence, such as development of tolerance, dose escalation and drug-seeking behaviour.
Withdrawal symptoms
After discontinuation of short-term and long-term treatment with gabapentin, withdrawal symptoms have been observed. Withdrawal symptoms may occur shortly after discontinuation, usually within 48 hours. Most frequently reported symptoms include anxiety, insomnia, nausea, pains, sweating, tremor, headache, depression, feeling abnormal, dizziness, and malaise. The occurrence of withdrawal symptoms following discontinuation of gabapentin may indicate drug dependence (see section 4.8). The patient should be informed about this at the start of the treatment. If gabapentin should be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication (see section 4.2).
Laboratory tests
False positive readings may be obtained in the semi-quantitative determination of total urine protein by dipstick tests. It is therefore recommended to verify such a positive dipstick test result by methods based on a different analytical principle such as the Biuret method, turbidimetric or dye-binding methods, or to use these alternative methods from the beginning.
Gabapentin Amarox contains sodium
This medicines contains less than 1 mmol sodium (23mg) per hard capsule, that is to say essentially 'sodium-free'.
4.5 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
There are spontaneous and literature case reports of respiratory depression and/or sedation associated with gabapentin and opioid use. In some of these reports, the authors considered this a particular concern with the combination of gabapentin and opioids, especially in elderly patients.
In a study involving healthy volunteers (N=12), when a 60 mg controlled- release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule, mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Therefore, patients who require concomitant treatment with opioids should be carefully observed for signs of CNS depression, such as somnolence, sedation and respiratory depression and the dose of gabapentin or opioid should be reduced appropriately.
No interaction between gabapentin and phenobarbital, phenytoin, valproic acid or carbamazepine has been observed.
Gabapentin steady-state pharmacokinetics are similar for healthy subjects and patients with epilepsy receiving these antiepileptic agents.
Co-administration of gabapentin with oral contraceptives containing norethindrone and/or ethinyl estradiol, does not influence the steady-state pharmacokinetics of either component.
Co-administration of gabapentin with antacids containing aluminium and magnesium, reduces gabapentin bioavailability up to 24%. It is recommended that gabapentin be taken at the earliest two hours following antacid administration.
Renal excretion of gabapentin is unaltered by probenecid.
A slight decrease in renal excretion of gabapentin that is observed when it is co-administered with cimetidine is not expected to be of clinical importance.
4.6 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Fertility, pregnancy and lactation | Fertility, pregnancy and lactation
Pregnancy
Risk related to epilepsy and antiepileptic medicinal products in general
The risk of birth defects is increased by a factor of 2 – 3 in the offspring of mothers treated with an antiepileptic medicinal product. Most frequently reported are cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic drug therapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is important that monotherapy is practised whenever possible. Specialist advice should be given to women who are likely to become pregnant or who are of childbearing potential and the need for antiepileptic treatment should be reviewed when a woman is planning to become pregnant. No sudden discontinuation of antiepileptic therapy should be undertaken as this may lead to breakthrough seizures, which could have serious consequences for both mother and child.
Developmental delay in children of mothers with epilepsy has been observed rarely. It is not possible to differentiate if the developmental delay is caused by genetic, social factors, maternal epilepsy or the antiepileptic therapy.
Neonatal withdrawal syndrome has been reported in newborns exposed in utero to gabapentin.
Co-exposure to gabapentin and opioids during pregnancy may increase the risk of neonatal withdrawal syndrome. Newborns should be monitored carefully.
Risk related to gabapentin
Gabapentin crosses the human placenta.
There are no or limited amount of data from the use of gabapentin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the foetus.
No definite conclusion can be made as to whether gabapentin is causally associated with an increased risk of congenital malformations when taken during pregnancy, because of epilepsy itself and the presence of concomitant antiepileptic medicinal products during each reported pregnancy.
Breast-feeding
Gabapentin is excreted in human milk. Because the effect on the breast-fed infant is unknown, caution should be exercised when gabapentin is administered to a breast-feeding mother. Gabapentin should be used in breast- feeding mothers only if the benefits clearly outweigh the risks.
Fertility
There is no effect on fertility in animal studies (see section 5.3).
4.7 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Effects on ability to drive and use machines | Effects on ability to drive and use machines
Gabapentin may have minor or moderate influence on the ability to drive and use machines. Gabapentin acts on the central nervous system and may cause drowsiness, dizziness or other related symptoms. Even, if they were only of mild or moderate degree, these undesirable effects could be potentially dangerous in patients driving or operating machinery. This is especially true at the beginning of the treatment and after increase in dose.
4.8 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Undesirable effects | Undesirable effects
The adverse reactions observed during clinical studies conducted in epilepsy (adjunctive and monotherapy) and neuropathic pain have been provided in a single list below by class and frequency: very common (≥ 1/10); common (≥ 1/100 to< 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000). Where an adverse reaction was seen at different frequencies in clinical studies, it was assigned to the highest frequency reported.
Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in italics in the list below.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
System organ class
Adverse drug reactions
Infections and infestations
Very Common
viral infection
Common
pneumonia, respiratory infection, urinary tract infection, infection, otitis media
Blood and the lymphatic system disorders
Common
leucopenia
Not known
Thrombocytopenia
Immune system disorders
Uncommon
allergic reactions (e.g. urticaria)
Not known
hypersensitivity syndrome (a systemic reaction with a variable presentation that can include fever, rash, hepatitis, lymphadenopathy, eosinophilia, and sometimes other signs and symptoms), anaphylaxis (see section 4.4)
Metabolism and nutrition disorders
Common
anorexia, increased appetite
Uncommon
hyperglycaemia (most often observed in patients with diabetes)
Rare
hypoglycaemia (most often observed in patients with diabetes)
Not known
hyponatraemia
Psychiatric disorders
Common
hostility, confusion and emotional lability, depression, anxiety, nervousness, thinking abnormal
Uncommon
agitation
Not known
hallucinations, suicidal ideation, drug dependence
Nervous system disorders
Very Common
somnolence, dizziness, ataxia
Common
convulsions,hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesia, coordination abnormal, nystagmus, increased, decreased, or absent reflexes
Uncommon
hypokinesia, mental impairment
Rare
loss of consciousness
Not known
other movement disorders (e.g. choreoathetosis, dyskinesia, dystonia)
Eye disorders
Common
visual disturbances such as amblyopia, diplopia
Ear and labyrinth disorders
Common
vertigo
Not known
tinnitus
Cardiac disorders
Uncommon
palpitations
Vascular disorders
Common
hypertension, vasodilatation
Respiratory, thoracic and mediastinal disorders
Common
dyspnoea, bronchitis, pharyngitis, cough, rhinitis
Rare
respiratory depression
Gastrointestinal disorders
Common
vomiting, nausea, dental abnormalities, gingivitis, diarrhoea, abdominal pain, dyspepsia, constipation, dry mouth or throat, flatulence
Uncommon
dysphagia
Not known
pancreatitis
Hepatobiliary disorders
Not known
hepatitis, jaundice
Skin and subcutaneous tissue disorders
Common
facial oedema, purpura most often described as bruises resulting from physical trauma, rash, pruritus, acne
Not known
Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, erythema multiforme, alopecia, drug rash with eosinophilia and systemic symptoms (see section 4.4)
Musculoskeletal and connective tissue disorders
Common
arthralgia, myalgia, back pain, twitching
Not known
rhabdomyolysis, myoclonus
Renal and urinary disorder
Not known
acute renal failure, incontinence
Reproductive system and breast disorders
Common
impotence
Not known
breast hypertrophy, gynaecomastia, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia)
General disorders and administration site conditions
Very Common
fatigue, fever
Common
peripheral oedema, abnormal gait, asthenia, pain, malaise, flu syndrome
Uncommon
generalized oedema
Not known
withdrawal reactions*, chest pain.Sudden unexplained deaths have been reported where a causal relationship to treatment with gabapentin has not been established.
Investigations
Common
WBC (white blood cell count) decreased, weight gain
Uncommon
elevated liver function tests SGOT (AST), SGPT (ALT) and bilirubin
Not known
blood creatine phosphokinase increased
Injury, poisoning and procedural complications
Common
accidental injury, fracture, abrasion
Uncommon
fall
*After discontinuation of short-term and long-term treatment with gabapentin, withdrawal symptoms have been observed. Withdrawal symptoms may occur shortly after discontinuation, usually within 48 hours. Most frequently reported symptoms include anxiety, insomnia, nausea, pains, sweating, tremor, headache, depression, feeling abnormal, dizziness, and malaise (see section 4.4). The occurrence of withdrawal symptoms following discontinuation of gabapentin may indicate drug dependence (see section 4.8). The patient should be informed about this at the start of the treatment. If gabapentin should be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication (see section 4.2).
Under treatment with gabapentin cases of acute pancreatitis were reported. Causality with gabapentin is unclear (see section 4.4).
In patients on haemodialysis due to end-stage renal failure, myopathy with elevated creatine kinase levels has been reported.
Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children.
Additionally, in clinical studies in children, aggressive behaviour and hyperkinesias were reported commonly.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 |
Gabapentin Amarox 400 mg hard capsules | Clinical particulars - Overdose | Overdose
Acute, life-threatening toxicity has not been observed with gabapentin overdoses of up to 49 g. Symptoms of the overdoses included dizziness, double vision, slurred speech, drowsiness, loss of consciousness, lethargy and mild diarrhoea. All patients recovered fully with supportive care. Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, minimize toxicity from overdoses.
Overdoses of gabapentin, particularly in combination with other CNS depressant medications, may result in coma.
Although gabapentin can be removed by haemodialysis, based on prior experience it is usually not required. However, in patients with severe renal impairment, haemodialysis may be indicated.
An oral lethal dose of gabapentin was not identified in mice and rats given doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis, hypoactivity, or excitation.
5. Pharmacological properties
5.1 |
Gabapentin Amarox 400 mg hard capsules | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
Absorption
Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours. Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on gabapentin pharmacokinetics.
Gabapentin pharmacokinetics are not affected by repeated administration. Although plasma gabapentin concentrations were generally between 2 μg/mL and 20 μg/mL in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 3.
Table 3
SUMMARY OF GABAPENTIN MEAN (%CV) STEADY-STATE PHARMACOKINETIC PARAMETERS FOLLOWING EVERY EIGHT HOURS ADMINISTRATION
Pharmacokinetic parameter
300 mg
(N=7)
400 mg
(N=14)
800 mg
(N=14)
Mean
%CV
Mean
%CV
Mean
%CV
Cmax (μg/mL)
4.02
(24)
5.74
(38)
8.71
(29)
tmax (hr)
2.7
(18)
2.1
(54)
1.6
(76)
T1/2 (hr)
5.2
(12)
10.8
(89)
10.6
(41)
AUC (0-8)
μg•hr/mL)
24.8
(24)
34.5
(34)
51.4
(27)
Ae% (%)
NA
NA
47.2
(25)
34.4
(37)
Cmax = Maximum steady state plasma concentration
tmax = Time for Cmax
T1/2 = Elimination half-life
AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours postdose
Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours postdose
NA = Not available
Distribution
Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady- state trough plasma concentrations. Gabapentin is present in the breast milk of breast-feeding women.
Biotransformation
There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.
Elimination
Gabapentin is eliminated unchanged solely by renal excretion. The elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.
In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.
Gabapentin is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended (see section 4.2).
Gabapentin pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma gabapentin concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.
In a pharmacokinetic study in 24 healthy paediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower Cmax and higher clearance per body weight have been observed in comparison to available reported data in children older than 5 years.
Linearity/non-linearity
Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma gabapentin concentrations are predictable from single-dose data.
5.3 |
Gabapentin Amarox 400 mg hard capsules | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
Carcinogenesis
Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000, and 2000 mg/kg/day for two years. A statistically significant increase in the incidence of pancreatic acinar cell tumors was found only in male rats at the highest dose. Peak plasma drug concentrations in rats at 2000 mg/kg/day are 10 times higher than plasma concentrations in humans given 3600 mg/day. The pancreatic acinar cell tumors in male rats are low- grade malignancies, did not affect survival, did not metastasize or invade surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic acinar cell tumors in male rats to carcinogenic risk in humans is unclear.
Mutagenesis
Gabapentin demonstrated no genotoxic potential. It was not mutagenic in vitro in standard assays using bacterial or mammalian cells. Gabapentin did not induce structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not induce micronucleus formation in the bone marrow of hamsters.
Impairment of fertility
No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg (approximately five times the maximum daily human dose on a mg/m2 of body surface area basis).
Teratogenesis
Gabapentin did not increase the incidence of malformations, compared to controls, in the offspring of mice, rats, or rabbits at doses up to 50, 30 and 25 times respectively, the daily human dose of 3600 mg, (four, five or eight times, respectively, the human daily dose on a mg/m2 basis).
Gabapentin induced delayed ossification in the skull, vertebrae, forelimbs, and hindlimbs in rodents, indicative of fetal growth retardation. These effects occurred when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during organogenesis and in rats given 2000 mg/kg prior to and during mating and throughout gestation. These doses are approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.
No effects were observed in pregnant mice given 500 mg/kg/day (approximately 1/2 of the daily human dose on a mg/m2 basis).
An increased incidence of hydroureter and/or hydronephrosis was observed in rats given 2000 mg/kg/day in a fertility and general reproduction study, 1500 mg/kg/day in a teratology study, and 500, 1000, and 2000 mg/kg/day in a perinatal and postnatal study. The significance of these findings is unknown, but they have been associated with delayed development. These doses are also approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.
In a teratology study in rabbits, an increased incidence of post-implantation foetal loss, occurred in pregnant rabbits given 60, 300, and 1500 mg/kg/day during organogenesis. These doses are approximately 0.3 to 8 times the daily human dose of 3600 mg on a mg/m2 basis. The margins of safety are insufficient to rule out the risk of these effects in humans.
6. |
Gabapentin Amarox 400 mg hard capsules | Pharmaceutical particulars - List of excipients | List of excipients
Capsule content
Mannitol
Starch, Pregelatinised
Talc
CAP & Body
Titanium Dioxide (E171)
Gelatin
Sodium lauryl sulphate
Printing Ink
Shellac (E904)
Dehydrated Alcohol (E1510)
Isopropyl Alcohol
Butyl Alcohol
Propylene Glycol (E1520)
Strong Ammonia Solution (E527)
FD & C Blue # 2 Aluminum Lake (El32)
6.2 |
Gabapentin Amarox 400 mg hard capsules | Pharmaceutical particulars - Incompatibilities | Incompatibilities
Not applicable.
6.3 |
Gabapentin Amarox 400 mg hard capsules | Pharmaceutical particulars - Shelf life | Shelf life
2 years.
6.4 |
Gabapentin Amarox 400 mg hard capsules | Pharmaceutical particulars - Special precautions for storage | Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 |
Gabapentin Amarox 400 mg hard capsules | Pharmaceutical particulars - Nature and contents of container | Nature and contents of container
Clear PVC/PVDC-aluminium foil blister pack containing 100 hard capsules
6.6 |
Gabapentin Amarox 400 mg hard capsules | Pharmaceutical particulars - Special precautions for disposal and other handling | Special precautions for disposal and other handling
No special requirements
7. |
Gabapentin Amarox 400 mg hard capsules | Marketing authorisation holder | Amarox Limited
Congress House,
14 Lyon Road,
Harrow, Middlesex HA1 2EN,
United Kingdom
8. Marketing authorisation number(s)
PL 49445/0111
9. |
Gabapentin Amarox 400 mg hard capsules | Date of first authorisation/renewal of the authorisation | 06/10/2021
10. |
Gabapentin Amarox 400 mg hard capsules | Date of revision of the text | 15/03/2023 |
Gatalin XL 8mg prolonged release capsules, hard | Name of the medicinal product | Gatalin XL 8 mg prolonged-release capsules, hard
2. |
Gatalin XL 8mg prolonged release capsules, hard | Qualitative and quantitative composition | Each 8 mg prolonged-release capsule contains 8 mg galantamine (as hydrobromide).
For the full list of excipients, see section 6.1.
3. |
Gatalin XL 8mg prolonged release capsules, hard | Pharmaceutical form | Prolonged-release capsule, hard (prolonged-release capsule)
8mg: Opaque white size 2 hard gelatin capsules containing one round biconvex tablet
4. |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Therapeutic indications | Therapeutic indications
Gatalin XL is indicated for the symptomatic treatment of mild to moderately severe dementia of the Alzheimer type.
4.2 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Posology and method of administration | Posology and method of administration
Posology
Adults/Elderly
Before start of treatment
The diagnosis of probable Alzheimer type of dementia should be adequately confirmed according to current clinical guidelines (see section 4.4).
Starting dose
The recommended starting dose is 8 mg galantamine/day for 4 weeks.
Maintenance dose
• The tolerance and dosing of galantamine should be reassessed on a regular basis, preferably within three months after start of treatment. Thereafter, the clinical benefit of galantamine and the patient's tolerance of treatment should be reassessed on a regular basis according to current clinical guidelines. Maintenance treatment can be continued for as long as therapeutic benefit is favourable and the patient tolerates treatment with galantamine. Discontinuation of galantamine should be considered when evidence of a therapeutic effect is no longer present or if the patient does not tolerate treatment.
• The initial maintenance dose is 16 mg galantamine/day and patients should be maintained on 16 mg/day for at least 4 weeks.
• An increase to the maintenance dose of 24 mg galantamine/day should be considered on an individual basis after appropriate assessment including evaluation of clinical benefit and tolerability.
• In individual patients not showing an increased response or not tolerating 24 mg/day, a dose reduction to 16 mg/day should be considered.
Treatment withdrawal
• There is no rebound effect after abrupt discontinuation of treatment (e.g. in preparation for surgery).
Switching to Gatalin XL prolonged-release capsules from galantamine tablets or galantamine oral solution
It is recommended that the same total daily dose of galantamine is administered to patients. Patients switching to the once-daily regimen should take their last dose of galantamine tablets or oral solution in the evening and start Gatalin XL prolonged release capsules once daily the following morning.
Special populations
Concomitant treatment
In patients treated with potent CYP2D6 or CYP3A4 inhibitors, dose reductions can be considered (see section 4.5).
Renal impairment
Galantamine plasma concentrations may be increased in patients with moderate to severe renal impairment (see section 5.2).
For patients with a creatinine clearance ≥ 9 mL/min, no dose adjustment is required. The use of galantamine is contraindicated in patients with creatinine clearance less than 9 mL/min (see section 4.3).
Hepatic impairment
Galantamine plasma concentrations may be increased in patients with moderate to severe hepatic impairment (see section 5.2). In patients with moderately impaired hepatic function (Child-Pugh score 7-9), based on pharmacokinetic modelling, it is recommended that dosing should begin with 8 mg prolonged-release capsule once every other day, preferably taken in the morning, for 1 week. Thereafter, patients should proceed with 8 mg once daily for 4 weeks. In these patients, daily doses should not exceed 16 mg.
In patients with severe hepatic impairment (Child-Pugh score greater than 9), the use of galantamine is contraindicated (see section 4.3).
No dose adjustment is required for patients with mild hepatic impairment.
Paediatric population
There is no relevant use of galantamine in the paediatric population.
Method of administration
Gatalin XL is for oral use and should be administered once daily in the morning, preferably with food. The capsules should be swallowed whole together with some liquid. The capsules must not be chewed or crushed.
Adequate fluid intake during treatment should be ensured (see section 4.8).
4.3 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Contraindications | Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Since no data are available on the use of galantamine in patients with severe hepatic impairment (Child-Pugh score greater than 9) and in patients with creatinine clearance less than 9 mL/min, galantamine is contraindicated in these populations. Galantamine is contraindicated in patients who have both significant renal and hepatic dysfunction.
4.4 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
Types of dementia
Gatalin XL is indicated for a patient with mild to moderately severe dementia of the Alzheimer type. The benefit of galantamine in patients with other types of dementia or other types of memory impairment has not been demonstrated. In 2 clinical trials of two years duration in individuals with so called mild cognitive impairment (milder types of memory impairment not fulfilling the criteria of Alzheimer's dementia), galantamine therapy failed to demonstrate any benefit either in slowing cognitive decline or reducing the clinical conversion to dementia. The mortality rate in the galantamine group was significantly higher than in the placebo group, 14/1,026 (1.4%) patients on galantamine and 3/1,022 (0.3%) patients on placebo. The deaths were due to various causes. About half of the galantamine deaths appeared to result from various vascular causes (myocardial infarction, stroke and sudden death). The relevance of this finding for the treatment of patients with Alzheimer's dementia is unknown.
No increased mortality in the galantamine group was observed in a long-term, randomized, placebo-controlled study in 2,045 patients with mild to moderate Alzheimer´s disease. The mortality rate in the placebo group was significantly higher than in the galantamine group. There were 56/1,021 (5.5%) deaths in patients on placebo and 33/1,024 (3.2%) deaths in patients on galantamine (hazard ratio and 95% confidence intervals of 0.58 [0.37-0.89]; p=0.011).
A diagnosis of Alzheimer's dementia should be made according to current guidelines by an experienced physician. Therapy with galantamine should occur under the supervision of a physician and should only be initiated if a caregiver is available who will regularly monitor medicinal product intake by the patient.
Serious skin reactions
Serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) have been reported in patients receiving galantamine (see section 4.8). It is recommended that patients be informed about the signs of serious skin reactions and that use of galantamine be discontinued at the first appearance of skin rash.
Weight monitoring
Patients with Alzheimer's disease lose weight. Treatment with cholinesterase inhibitors, including galantamine, has been associated with weight loss in these patients. During therapy, patient's weight should be monitored.
Conditions requiring caution
As with other cholinomimetics galantamine should be given with caution in the following conditions:
Cardiac disorders
Because of their pharmacological action, cholinomimetics may have vagotonic effects on heart rate, including bradycardia and all types of atrioventricular node block (see section 4.8). The potential for this action may be particularly important to patients with 'sick sinus syndrome' or other supraventricular cardiac conduction disturbances or in those who use medicinal products that significantly reduce heart rate concomitantly, such as digoxin and beta-blockers or for patients with an uncorrected electrolyte disturbance (e.g. hyperkalaemia, hypokalaemia).
Caution should therefore be exercised when administering galantamine to patients with cardiovascular diseases, e.g. immediate post-myocardial infarction period, new-onset atrial fibrillation, second degree heart block or greater, unstable angina pectoris or congestive heart failure, especially NYHA group III – IV.
There have been reports of QTc prolongation in patients using therapeutic doses of galantamine and of torsade de pointes in association with overdoses (see section 4.9). Galantamine should therefore be used with caution in patients with prolongation of the QTc interval, in patients treated with drugs affecting the QTc interval, or in patients with relevant pre-existing cardiac disease or electrolyte disturbances.
In a pooled analysis of placebo-controlled studies in patients with Alzheimer's dementia treated with galantamine an increased incidence of certain cardiovascular adverse events were observed (see section 4.8).
Gastrointestinal disorders
Patients at increased risk of developing peptic ulcers, e.g. those with a history of ulcer disease or those predisposed to these conditions, including those receiving concurrent non-steroidal anti-inflammatory drugs (NSAIDs), should be monitored for symptoms. The use of galantamine is not recommended in patients with gastrointestinal obstruction or recovering from gastrointestinal surgery.
Nervous system disorders
Seizures have been reported with galantamine (see section 4.8).
Seizure activity may also be a manifestation of Alzheimer's disease. An increase in cholinergic tone may worsen symptoms related to extrapyramidal disorders (see section 4.8).
In a pooled analysis of placebo-controlled studies in patients with Alzheimer's dementia treated with galantamine cerebrovascular events were uncommonly observed (see section 4.8). This should be considered when administering galantamine to patients with cerebrovascular disease.
Respiratory, thoracic and mediastinal disorders
Cholinomimetics should be prescribed with care for patients with a history of severe asthma or obstructive pulmonary disease or active pulmonary infections (e.g. pneumonia).
Renal and urinary disorders
The use of galantamine is not recommended in patients with urinary outflow obstruction or recovering from bladder surgery.
Surgical and medical procedures
Galantamine, as a cholinomimetic, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia, especially in cases of pseudocholinesterase deficiency.
4.5 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
Pharmacodynamic interactions
Because of its mechanism of action, galantamine should not be given concomitantly with other cholinomimetics (such as ambenonium, donepezil, neostigmine, pyridostigmine, rivastigmine or systemically administered pilocarpine). Galantamine has the potential to antagonise the effect of anticholinergic medicinal products. Should anticholinergic medicinal products such as atropine be abruptly stopped, there is a potential risk that galantamine's effects could be exacerbated. As expected with cholinomimetics, a pharmacodynamic interaction is possible with medicinal products that significantly reduce the heart rate such as digoxin, beta-blockers, certain calcium-channel blocking agents and amiodarone. Caution should be taken with medicinal products that have potential to cause torsades de pointes. In such cases an ECG should be considered.
Galantamine, as a cholinomimetic, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia, especially in cases of pseudocholinesterase deficiency.
Pharmacokinetic interactions
Multiple metabolic pathways and renal excretion are involved in the elimination of galantamine. The possibility of clinically relevant interactions is low. However, the occurrence of significant interactions may be clinically relevant in individual cases.
Concomitant administration with food slows the absorption rate of galantamine but does not affect the extent of absorption. It is recommended that Gatalin XL be taken with food in order to minimise cholinergic adverse reactions.
Other medicinal products affecting the metabolism of galantamine
Formal interaction studies with other medicinal products showed an increase in galantamine bioavailability of about 40% during co-administration of paroxetine (a potent CYP2D6 inhibitor) and of 30% and 12% during co-treatment with ketoconazole and erythromycin (both CYP3A4 inhibitors). Therefore, during initiation of treatment with potent inhibitors of CYP2D6 (e.g. quinidine, paroxetine or fluoxetine) or CYP3A4 (e.g. ketoconazole or ritonavir) patients may experience an increased incidence of cholinergic adverse reactions, predominantly nausea and vomiting. Under these circumstances, based on tolerability, a reduction of the galantamine maintenance dose can be considered (see section 4.2).
Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, at a dose of 10 mg once a day for 2 days followed by 10 mg twice a day for 12 days, had no effect on the pharmacokinetics of galantamine (as galantamine prolonged-release capsules 16 mg once a day) at steady state.
Effect of galantamine on the metabolism of other medicinal products
Therapeutic doses of galantamine 24 mg/day had no effect on the kinetics of digoxin, although pharmacodynamic interactions may occur (see also pharmacodynamic interactions).
Therapeutic doses of galantamine 24 mg/day had no effect on the kinetics and prothrombin time of warfarin.
4.6 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Fertility, pregnancy and lactation | Fertility, pregnancy and lactation
Pregnancy
For galantamine no clinical data on exposed pregnancies are available. Studies in animals have shown reproductive toxicity (see section 5.3). Caution should be exercised when prescribing to pregnant women.
Breast-feeding
It is not known whether galantamine is excreted in human breast milk and there are no studies in lactating women. Therefore, women on galantamine must not breast-feed.
Fertility
The effect of galantamine on human fertility has not been evaluated.
4.7 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Effects on ability to drive and use machines | Effects on ability to drive and use machines
Galantamine has minor or moderate influence on the ability to drive and use machines. Symptoms include dizziness and somnolence, especially during the first weeks after initiation of treatment.
4.8 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Undesirable effects | Undesirable effects
The table below reflects data obtained with galantamine in eight placebo-controlled, double-blind clinical trials (N=6,502), five open-label clinical trials (N=1,454) and from post-marketing spontaneous reports. The most commonly reported adverse drug reactions were nausea (21%) and vomiting (11%). They occurred mainly during titration periods, lasted less than a week in most cases and the majority of patients had one episode. Prescription of anti-emetics and ensuring adequate fluid intake may be useful in these instances.
In a randomised, double-blind, placebo-controlled clinical trial, the safety profile of once-daily treatment with galantamine prolonged-release capsules was similar in frequency and nature to that seen with galantamine tablets.
Frequency estimate: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <1/1,000).
System Organ Class
Adverse Drug Reaction
Frequency
Very common
Common
Uncommon
Rare
Immune system disorders
Hypersensitivity
Metabolism and nutrition disorders
Decreased appetite
Dehydration
Psychiatric disorders
Hallucination; Depression
Hallucination visual; Hallucination auditory
Nervous system disorders
Syncope; Dizziness; Tremor; Headache; Somnolence; Lethargy
Paraesthesia; Dysgeusia; Hypersomnia
Seizures*, Extrapyramidal disorder
Eye disorders
Vision blurred
Ear and labyrinth disorders
Tinnitus
Cardiac disorders
Bradycardia
Supraventricular extrasystoles; Atrioventricular block first degree; Sinus bradycardia; Palpitations
Atrioventricular block complete
Vascular disorders
Hypertension
Hypotension; Flushing
Gastrointestinal disorders
Vomiting; Nausea
Abdominal pain; Abdominal pain upper; Diarrhoea; Dyspepsia; Abdominal discomfort
Retching
Hepatobiliary disorders
Hepatitis
Skin and subcutaneous tissue disorders
Hyperhidrosis
Stevens-Johnson Syndrome; Acute generalized exanthematous pustulosis; Erythema multiforme
Musculoskeletal and connective tissue disorders
Muscle spasms
Muscular weakness
General disorders and administration site conditions
Fatigue; Asthenia; Malaise
Investigations
Weight decreased
Hepatic enzyme increased
Injury, poisoning and procedural complications
Fall; Laceration
* Class-related effects reported with acetylcholinesterase-inhibitor antidementia medicinal products include convulsions/seizures (see section 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store).
4.9 |
Gatalin XL 8mg prolonged release capsules, hard | Clinical particulars - Overdose | Overdose
Symptoms
Signs and symptoms of significant overdosing of galantamine are predicted to be similar to those of overdosing of other cholinomimetics. These effects generally involve the central nervous system, the parasympathetic nervous system and the neuromuscular junction. In addition to muscle weakness or fasciculations, some or all the signs of a cholinergic crisis may develop: severe nausea, vomiting, gastrointestinal cramping, salivation, lacrimation, urination, defecation, sweating, bradycardia, hypotension, collapse and convulsions. Increasing muscle weakness together with tracheal hypersecretions and bronchospasm, may lead to vital airway compromise.
There have been post-marketing reports of torsade de pointes, QT prolongation, bradycardia, ventricular tachycardia and brief loss of consciousness in association with inadvertent overdoses of galantamine. In one case where the dose was known, eight galantamine 4 mg tablets (32 mg total) were ingested on a single day.
Two additional cases of accidental ingestion of 32 mg (nausea, vomiting and dry mouth; nausea, vomiting and substernal chest pain) and one of 40 mg (vomiting) resulted in brief hospitalisations for observation with full recovery. One patient, who was prescribed 24 mg/day and had a history of hallucinations over the previous two years, mistakenly received 24 mg twice daily for 34 days and developed hallucinations requiring hospitalisation. Another patient, who was prescribed 16 mg/day of oral solution, inadvertently ingested 160 mg (40 mL) and experienced sweating, vomiting, bradycardia and near-syncope one hour later, which necessitated hospital treatment. His symptoms resolved within 24 hours.
Treatment
As in any case of overdose, general supportive measures should be used. In severe cases, anticholinergics such as atropine can be used as a general antidote for cholinomimetics. An initial dose of 0.5 to 1.0 mg intravenously is recommended, with subsequent doses based on the clinical response.
Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control centre to determine the latest recommendations for the management of an overdose.
5. Pharmacological properties
5.1 |
Gatalin XL 8mg prolonged release capsules, hard | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
Galantamine is an alkalinic compound with one ionisation constant (pKa 8.2). It is slightly lipophilic and has a partition coefficient (Log P) between n-octanol/buffer solution (pH 12) of 1.09. The solubility in water (pH 6) is 31 mg/mL. Galantamine has three chiral centres. The S, R, S-form is the naturally occurring form. Galantamine is partially metabolised by various cytochromes, mainly CYP2D6 and CYP3A4. Some of the metabolites formed during the degradation of galantamine have been shown to be active in vitro but are of no importance in vivo.
Absorption
The absolute bioavailability of galantamine is high, 88.5 ± 5.4%. Galantamine prolonged-release capsules are bioequivalent to the twice-daily immediate-release tablets with respect to AUC24h and Cmin. The Cmax value is reached after 4.4 hours and is about 24% lower than that of the tablet. Food has no significant effect on AUC of the prolonged-release capsules. Cmax was increased by about 12% and Tmax increased by about 30 minutes when the capsule was given after food. However, these changes are unlikely to be clinically significant.
Distribution
The mean volume of distribution is 175 L. Plasma protein binding is low, 18%.
Biotransformation
Up to 75% of galantamine dosed is eliminated via metabolism. In vitro studies indicate that CYP2D6 is involved in the formation of O-desmethyl-galantamine and CYP3A4 is involved in the formation of N-oxide-galantamine. The levels of excretion of total radioactivity in urine and faeces were not different between poor and extensive CYP2D6 metabolisers. In plasma from poor and extensive metabolisers, unchanged galantamine and its glucuronide accounted for most of the sample radioactivity. None of the active metabolites of galantamine (norgalantamine, O-desmethyl-galantamine and O-desmethyl-norgalantamine) could be detected in their unconjugated form in plasma from poor and extensive metabolisers after single dosing. Norgalantamine was detectable in plasma from patients after multiple dosing, but did not represent more than 10% of the galantamine levels. In vitro studies indicated that the inhibition potential of galantamine with respect to the major forms of human cytochrome P450 is very low.
Elimination
Galantamine plasma concentration declines bi-exponentially, with a terminal half-life around 8-10 hours in healthy subjects. Typical oral clearance in the target population is about 200 mL/min with intersubject variability of 30% as derived from the population analysis of immediate-release tablets. Seven days after a single oral dose of 4 mg ³H-galantamine, 90-97% of the radioactivity is recovered in urine and 2.2-6.3% in faeces. After intravenous infusion and oral administration, 18-22% of the dose was excreted as unchanged galantamine in the urine in 24 hours, with a renal clearance of 68.4 ± 22.0 mL/min, which represents 20-25% of the total plasma clearance.
Dose-linearity
Galantamine pharmacokinetics of galantamine prolonged-release capsules are dose proportional within the studied dose range of 8 mg to 24 mg once-daily in elderly and young age groups.
Characteristics in patients with Alzheimer's disease
Data from clinical trials in patients indicate that the plasma concentrations of galantamine in patients with Alzheimer's disease are 30% to 40% higher than in healthy young subjects primarily due to the advanced age and reduced kidney function. Based upon the population pharmacokinetic analysis, clearance in female subjects is 20% lower as compared to males. The galantamine clearance in poor metabolisers of CYP2D6 is about 25% lower than in extensive metabolisers, but no bimodality in the population is observed. Therefore, the metabolic status of the patient is not considered to be of clinical relevance in the overall population.
Special populations
Renal impairment
Elimination of galantamine decreases with decreasing creatinine clearance as observed in a study with renally impaired subjects. Compared to Alzheimer patients, peak and trough plasma concentrations are not increased in patients with a creatinine clearance of ≥ 9 mL/min. Therefore, no increase in adverse events is expected and no dose adjustments are needed (see section 4.2).
Hepatic impairment
The pharmacokinetics of galantamine in subjects with mild hepatic impairment (Child-Pugh score of 5 to 6) were comparable to those in healthy subjects. In patients with moderate hepatic impairment (Child-Pugh score of 7 to 9), AUC and half-life of galantamine were increased by about 30% (see section 4.2).
Pharmacokinetic/pharmacodynamic relationship
No apparent correlation between average plasma concentrations and efficacy parameters (i.e. change in ADAS-cog/11 and CIBIC-plus at month 6) were observed in the large Phase III trials with a dose-regimen of 12 and 16 mg twice-daily.
Plasma concentrations in patients experiencing syncope were within the same range as in the other patients at the same dose.
The occurrence of nausea is shown to correlate with higher peak plasma concentrations (see section 4.5).
5.3 |
Gatalin XL 8mg prolonged release capsules, hard | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
Non-clinical data suggest no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
Reproduction toxicity studies showed a slight delay in development in rats and rabbits, at doses that are below the threshold of toxicity in the pregnant females.
6. |
Gatalin XL 8mg prolonged release capsules, hard | Pharmaceutical particulars - List of excipients | List of excipients
Capsule content
Cellulose microcrystalline
Hypromellose
Ethylcellulose
Magnesium stearate
Capsule shell
8 mg:
Gelatin
Titanium dioxide (E171)
6.2 |
Gatalin XL 8mg prolonged release capsules, hard | Pharmaceutical particulars - Incompatibilities | Incompatibilities
Not applicable.
6.3 |
Gatalin XL 8mg prolonged release capsules, hard | Pharmaceutical particulars - Shelf life | Shelf life
2 years
6.4 |
Gatalin XL 8mg prolonged release capsules, hard | Pharmaceutical particulars - Special precautions for storage | Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 |
Gatalin XL 8mg prolonged release capsules, hard | Pharmaceutical particulars - Nature and contents of container | Nature and contents of container
Transparent PVC/PE/PVDC - Aluminum blister
Pack sizes: 1, 7, 14, 28, 30, 56, 60, 84, 90, 300 prolonged-release capsules, hard.
Not all pack sizes may be marketed
6.6 |
Gatalin XL 8mg prolonged release capsules, hard | Pharmaceutical particulars - Special precautions for disposal and other handling | Special precautions for disposal and other handling
No special requirements.
7. |
Gatalin XL 8mg prolonged release capsules, hard | Marketing authorisation holder | Aspire Pharma Limited
Unit 4, Rotherbrook Court
Bedford Road
Petersfield
Hampshire
GU32 3QG
8. Marketing authorisation number(s)
PL 35533/0015
9. |
Gatalin XL 8mg prolonged release capsules, hard | Date of first authorisation/renewal of the authorisation | 30/06/2015
10. |
Gatalin XL 8mg prolonged release capsules, hard | Date of revision of the text | 11/01/2023 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Name of the medicinal product | Ranitidine 75 mg film-coated tablets
Gavilast Heartburn and Indigestion 75mg Film-coated tablets
2. |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Qualitative and quantitative composition | Each tablet contains ranitidine 75 mg (as the hydrochloride).
For excipients, see 6.1.
3. |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmaceutical form | Film-coated tablets.
White coloured, round, biconvex film coated tablets with k logo on one face and 75 on the other.
4. |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Therapeutic indications | Therapeutic indications
Symptomatic relief of heartburn, indigestion, acid indigestion and hyperacidity.
4.2 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Posology and method of administration | Posology and method of administration
Route of Administration
Oral
Dosage
Adults (Including the Elderly) and children 16 years of age and older:
Swallow one Ranitidine 75 mg film-coated tablet whole, with a drink of water, as soon as you have symptoms. If symptoms persist for more than one hour or return, take another tablet.
Do not take more than two tablets in 24 hours.
Do not take the tablets for more than 6 days without the advice of a pharmacist or doctor.
Children under 16 years
Not recommended for children under 16 years of age
4.3 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Contraindications | Contraindications
Ranitidine is contraindicated for people known to be hypersensitive to the drug or any ingredients of Ranitidine 75mg Film-coated tablets.
4.4 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
Treatment with a histamine H2-antagonist such as ranitidine may mask symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition.
Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with severe renal impairment. Ranitidine 75 mg film-coated tablet is not suitable for these patients without medical supervision
People taking non-steroidal anti-inflammatory drugs, especially those with a history of peptic ulcer and the elderly should not self-medicate with Ranitidine 75 mg film-coated tablet but seek their doctor's advice before use.
People with a history of porphyria should avoid use of the product.
Consumers will be advised not to purchase a second pack of tablets without the advice of a pharmacist of doctor.
The product is not indicated in the following people without seeking their doctor's advice:
• Patients with severe renal and/or hepatic impairment.
• Patients under regular medical supervision for other reasons.
• Patients taking medications either physician prescribed or self prescribed.
• Those with difficulty swallowing, persistent stomach pain or unintended weight loss in association with symptoms of indigestion.
• Those who are middle-aged or elderly with new or recently changed symptoms of indigestion.
In patients such as the elderly, persons with chronic lung disease, diabetes or the immunocompromised, there may be an increased risk of developing community acquired pneumonia.
A large epidemiological study showed an increased risk of developing community acquired pneumonia in current users of H2 receptor antagonists versus those who had stopped treatment, with an observed adjusted relative risk increase of 1.82 (95% CI, 1.26–2.64).
4.5 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
Ranitidine has the potential to affect the absorption, metabolism or renal excretion of other drugs. The altered pharmacokinetics may necessitate dosage adjustment of the affected drug or discontinuation of treatment.
Interactions occur by several mechanisms including:
1) Inhibition of cytochrome P450-linked mixed function oxygenase system:
Ranitidine at usual therapeutics doses does not potentiate the actions of drugs which are inactivated by this enzyme systems such as diazepam, lidocaine, phenytoin, propranol and theophylline.
There have been reports of altered prothrombin time with coumarin anticoagulants (e.g. warfarin). Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.
2) Alteration of gastric pH:
The bioavailability of certain drugs may be affected. This can result in either an increase in absorption or a decrease in absorption.
4.6 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Fertility, pregnancy and lactation | Fertility, pregnancy and lactation
Ranitidine crosses the placenta but therapeutic doses administered to obstetric patients in labour or undergoing caesarean section have been without any adverse effect on labour, delivery or subsequent neonatal progress.
Like other over the counter drugs it should not be taken during pregnancy without consulting a doctor or pharmacist. It is also excreted in human breast milk and women who are breast-feeding will be advised to speak to their doctor before taking Ranitidine tablets.
4.7 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Effects on ability to drive and use machines | Effects on ability to drive and use machines
No known effect. However, when driving vehicles or operating machinery it must be borne in mind that dizziness or drowsiness, confusion and a blurred vision may occasionally occur when taking Ranitidine Tablets
4.8 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Undesirable effects | Undesirable effects
The following convention has been utilised for the classification of undesirable effects: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), very rare (1/10,000).
Adverse event frequencies have been estimated from spontaneous reports from post-marketing data.
Hepatobiliary Disorders
Rare: Transient and reversible changes in liver function tests.
Very Rare: Hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice. These were usually reversible.
Gastrointestinal Disorders
Very Rare: Acute pancreatitis and diarrhoea.
Uncommon: Abdominal pain, constipation, nausea. (these symptoms mostly improved during continued treatment).
Blood & Lymphatic System Disorders
Very rare: Blood count changes (Leucopenia and thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or aplasia.
Immune System Disorders
Rare: Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension, chest pain)
Very rare: Anaphylactic shock.
These reactions have occasionally occurred after a single dose.
Cardiac Disorders
Very Rare: As with other H2 receptor antagonists bradycardia and A-V block.
Nervous System Disorders
Very rare: Headache (sometimes severe), dizziness and reversible involuntary movement disorders.
Psychiatric Disorders
Very rare: reversible mental confusion, depression and hallucinations
These have been reported, predominantly in severely ill and elderly patients.
Skin and Subcutaneous Tissue Disorders
Rare: Skin rash
Very rare: erythema multiforme and alopecia.
Musculoskeletal and Connective Tissue Disorders
Very rare: Musculoskeletal symptoms such as arthralgia and myalgia
Eye Disorders
Very Rare: Reversible blurred vision.
There have been reports of blurred vision, which is suggestive of a change of accommodation.
Vascular Disorders
Very Rare: Vasculitis
Renal and Urinary Disorders
Very Rare: Acute interstitial nephritis
Rare: Elevation of plasma creatinine (usually slight; normalised during continued treatment)
Reproductive System and Breast Disorders
Very Rare: Reversible impotence. Breast symptoms and conditions (such as gynaecomastia and galactorrhea)
Discontinuation of therapy may be necessary in order to establish the underlying cause.
No clinically significant interference with endocrine or gonadal function has been reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Clinical particulars - Overdose | Overdose
Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage with the drug. Symptomatic and supportive therapy should be given as appropriate. If need be, the drug may be removed from the plasma by haemodialysis.
5. Pharmacological properties
5.1 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
Absorption
Following oral administration of 150 mg ranitidine, maximum plasma concentrations (300 to 550 ng/mL) occurred after 1-3 hours. Two distinct peaks or a plateau in the absorption phase result from reabsorption of drug excreted into the intestine. The absolute bioavailability of ranitidine is 50-60%, and plasma concentrations increase proportionally with increasing dose up to 300 mg.
Absorption is not significantly impaired by food or antacids.
Distribution
Ranitidine is not extensively bound to plasma proteins (15%), but exhibits a large volume of distribution ranging from 96 to 142 L.
Metabolism
Ranitidine is not extensively metabolised. The fraction of the dose recovered as metabolites includes 6% of the dose in urine as the N-Oxide, 2% as the S-Oxide, 2% as desmethyl ranitidine and 1-2% as the furoic acid analogue.
Elimination
Plasma concentrations decline bi-exponentially, with a terminal half-life of 2-3 hours. The major route of elimination is renal. After IV administration of 150 mg 3H-ranitidine, 98% of the dose was recovered, including 5% in the faeces and 93% in the urine, of which 70% was unchanged parent drug. After oral administration of 150 mg 3H-ranitidine, 96% of the dose was recovered, 26% in the faeces and 70% in urine of which 35% was unchanged parent drug. Less than 3% of the dose is excreted in bile. Renal clearance is approximately 500mL/min, which exceeds glomerular filtration indicating net renal tubular secretion.
Special Patient Populations
• Patients over 50 years of age
In patients over 50 years of age, half-life is prolonged (3-4 h) and clearance is reduced, consistent with the age-related decline of renal function. However, systemic exposure and accumulation are 50% higher. This difference exceeds the effect of declining renal function, and indicates increased bioavailability in older patients.
5.3 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
Extensive studies have been carried out in animals. The pharmacology of ranitidine hydrochloride shows it to be a surmountable H2 receptor antagonist which produces an inhibition of gastro acid secretion. Extensive toxicological investigators have been conducted which predicted a very safe profile for clinical use. This safety has been confirmed by extensive use in patients for many years.
6. |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmaceutical particulars - List of excipients | List of excipients
Microcrystalline cellulose,
Magnesium stearate,
Hypromellose,
Titanium dioxide.
6.2 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmaceutical particulars - Incompatibilities | Incompatibilities
None known
6.3 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmaceutical particulars - Shelf life | Shelf life
36 months.
6.4 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmaceutical particulars - Special precautions for storage | Special precautions for storage
Do not store above 25°C.
Store in the original package in order to protect from light.
6.5 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmaceutical particulars - Nature and contents of container | Nature and contents of container
Blister of 6 and 12 tablets.
The blisters are made from:
a) Polyamide/Aluminium/PVC lidded with Aluminium
b) PVC/PVDC lidded with Aluminium
6.6 |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Pharmaceutical particulars - Special precautions for disposal and other handling | Special precautions for disposal and other handling
Not applicable.
7. |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Marketing authorisation holder | Noumed Life Sciences Limited
Noumed House
Shoppenhangers Road
Maidenhead
Berkshire
SL6 2RB
United Kingdom
8. Marketing authorisation number(s)
PL 44041/0028
9. |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Date of first authorisation/renewal of the authorisation | 29/09/2016
10. |
Gavilast Heartburn and Indigestion 75mg Film-coated tablets | Date of revision of the text | 18/05/2017 |
Gaviscon Advance Aniseed flavour Oral Suspension | Name of the medicinal product | Gaviscon Advance Aniseed flavour Oral Suspension
2. |
Gaviscon Advance Aniseed flavour Oral Suspension | Qualitative and quantitative composition | Active Substances
mg/10ml
Sodium alginate
1000.0
Potassium hydrogen carbonate
200.0
Excipient(s) with known effect:
Methyl parahydroxybenzoate E218 (20 mg/ 5 ml)
Propyl parahydroxybenzoate E216 (3 mg/ 5 ml).
Sodium (57.85 mg/ 5 ml)
Potassium (39.06 mg/ 5 ml)
Benzyl alcohol* (0.525 mg/ 5 ml)
*present in the fennel flavour
For full list of excipients, see section 6.1.
3. |
Gaviscon Advance Aniseed flavour Oral Suspension | Pharmaceutical form | Oral suspension.
An off-white, viscous suspension.
4. |
Gaviscon Advance Aniseed flavour Oral Suspension | Clinical particulars - Therapeutic indications | Therapeutic indications
Treatment of symptoms resulting from the reflux of acid, bile and pepsin into the oesophagus such as acid regurgitation, heartburn, indigestion (occurring due to the reflux of stomach contents), for instance, after gastric surgery, as a result of hiatus hernia, during pregnancy, accompanying reflux oesophagitis, including symptoms of laryngopharyngeal reflux such as hoarseness and other voice disorders, sore throats and cough. Can also be used to treat the symptoms of gastro-oesophageal reflux during concomitant treatment with or following withdrawal of acid suppressing therapy.
4.2 |
Gaviscon Advance Aniseed flavour Oral Suspension | Clinical particulars - Posology and method of administration | Posology and method of administration
Adults and children 12 years and over: 5-10ml after meals and at bedtime
Children under 12 years: Should be given only on medical advice
Elderly: No dose modification is required for this age group.
Hepatic Impairment: No dose modification necessary.
Renal Insufficiency: Caution if highly restricted salt diet is necessary (see section 4.4).
4.3 |
Gaviscon Advance Aniseed flavour Oral Suspension | Clinical particulars - Contraindications | Contraindications
This medicinal product is contraindicated in patients with known or suspected hypersensitivity to any of the ingredients, or any of the excipients listed in section 6.1, including methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) (see section 4.4).
4.4 |
Gaviscon Advance Aniseed flavour Oral Suspension | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
If symptoms do not improve after 7 days, the clinical situation should be reviewed.
This medicinal product contains 57.85 mg sodium per 5 ml, equivalent to 2.9 % of the WHO recommended maximum daily intake for sodium. The maximum daily dose of this product is equivalent to 23.14 % of the WHO recommended maximum daily intake for sodium.
This product is considered high in sodium. This should be particularly taken into account for those on a low salt diet
Potassium: This medicine contains 1.0 mmol (39.06 mg) potassium per 5 ml . To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.
Each 10 ml contains 200 mg (2.0 mmol) of calcium carbonate. Care needs to be taken in treating patients with hypercalcaemia, nephrocalcinosis and recurrent calcium containing renal calculi.
Contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216): May cause allergic reactions (possibly delayed).
This medicine contains 0.525 mg benzyl alcohol in each 5 ml.
Ask your doctor or pharmacist for advice if you are pregnant or breast-feeding. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”).
Ask your doctor or pharmacist for advice if you have liver or kidney disease. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”).
4.5 |
Gaviscon Advance Aniseed flavour Oral Suspension | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
A time-interval of 2 hours should be considered between Gaviscon intake and the administration of other medicinal products, especially tetracyclines, fluoroquinolones, iron salts, thyroid hormones, chloroquine, bisphosphonates, and estramustine.
4.6 |
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