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Depo-Medrone with Lidocaine Suspension for Injection | Clinical particulars - Undesirable effects | Undesirable effects, such as dizziness, vertigo, visual disturbances, and fatigue are possible after treatment with corticosteroids. If affected, patients should not drive or operate machinery.
4.8 |
Depo-Medrone with Lidocaine Suspension for Injection | Clinical particulars - Overdose | Undesirable effects
The incidence of predictable undesirable side effects associated with the use of corticosteroids, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and duration of treatment (see section 4.4).
MedDRA
System Organ Class
Frequency
Undesirable Effects
Infections and infestations
Not Known
Opportunistic infectione; Infectione (including increased susceptibility and severity of infections with suppression of clinical symptoms and signs); Injection site infection; Peritonitisc,e; Recurrence of dormant tuberculosis
Blood and lymphatic system disorders
Not Known
Leukocytosise
Immune system disorders
Not Known
Drug hypersensitivitye; Anaphylactic reaction; Anaphylactoid reactione
Endocrine disorders
Not Known
Cushingoide; Hypopituitarisme; Withdrawal symptoms - too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death. However, this is more applicable to corticosteroids with an indication where continuous therapy is given (see section 4.4).
A 'withdrawal syndromee' may also occur including, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.
Metabolism and nutrition disorders
Not Known
Metabolic acidosise; Sodium retentione; Fluid retentione; Alkalosis hypokalaemice; Dyslipidaemiae; Glucose tolerance impairede; Increased requirements for insulin (or oral hypoglycemic agents in diabetics)a,e; Lipomatosise; Increased appetite (which may result in Weight increased)e
Psychiatric disorders
Not Known
Affective disordere (including Depressed moode, Euphoric mood, Affect labilitye, psychological dependencea,e, Suicidal ideatione), Psychotic disordere (including Maniae, Delusione, Hallucinatione, and Schizophreniae [aggravation of]); Confusional state; Mental disordere; Anxiety; Personality changee; Mood swingse; Abnormal behavioure; Insomniae; Irritabilitye; Nervousnessd
Nervous system disorders
Not Known
Epidural lipomatosise, Intracranial pressure increased (with Papilloedema [Benign intracranial hypertension]e); Loss of consciousnessd; Seizure; Amnesiae; Cognitive disordere; Tremord; Somnolenced; Hypoaesthesiad; Dizziness; Headachee
Eye disorders
Not Known
Exophthalmose; Vision blurredd (see also section 4.4); Chorioretinopathye; Cataracte; Glaucomae; Diplopiad; Rare instances of blindness associated with intralesional therapy around the face and heada; Corneal or scleral thinning; Exacerbation of ophthalmic viral or fungal disease
Ear and labyrinth disorders
Not Known
Vertigoe; Tinnitusd
Cardiac disorders
Not Known
Cardiac arrestd; Cardiac failure congestive (in susceptible patients)e; Bradycardiad
Vascular disorders
Not Known
Circulatory collapsed; Hypertensione; Hypotension; Embolism arterial; Thrombotic eventse; Flushing
Respiratory, thoracic and mediastinal disorders
Not Known
Respiratory arrestd; Respiratory depressiond; Pulmonary embolisme; Hiccupse
Gastrointestinal disorders
Not Known
Peptic ulcerb,e (with possible Peptic ulcer perforation and Peptic ulcer haemorrhage); Gastric haemorrhagee; Intestinal perforatione; Pancreatitise; Oesophagitis ulcerativee; Oesophagitis; Oesophageal candidiasis; Abdominal paine; Abdominal distensione; Diarrhoeae; Dyspepsiae; Nauseae; Vomitingd
Hepatobiliary disorders
Not Known
Hepatitis, Increase of liver enzymes
Skin and subcutaneous tissue disorders
Not Known
Angioedemae; Petechiaee; Ecchymosise; Skin atrophye; Skin striaee; Skin hyperpigmentatione; Skin hypopigmentatione; Hirsutisme; Rashe; Erythemae; Prurituse; Urticaria; Acnee; Hyperhidrosise; Skin lesiond
Musculoskeletal and connective tissue disorders
Not Known
Muscular weaknesse, Osteonecrosise; Osteoporosise; Pathological fracturee; Muscle atrophye; Myopathye; Neuropathic arthropathye; Growth retardatione; Arthralgia; Myalgiae; Muscle twitchingd
Reproductive system and breast disorders
Not Known
Menstruation irregulare
General disorders and administration site conditions
Not Known
Impaired healinge; Oedema peripherale; Injection site reactione; Abscess sterilee; Fatiguee; Malaisee; Feeling coldd; Feeling hotd
Investigations
Not Known
Intraocular pressure increasede; Alanine aminotransferase increasede; Aspartate aminotransferase increased; Blood alkaline phosphatase increasede; Blood potassium decreasede; Carbohydrate tolerance decreasede; Urine calcium increasede; Blood urea increasede; Nitrogen balance negative (due to protein catabolism); Suppression of reactions to skin testsa,e
Injury, poisoning and procedural complications
Not Known
Tendon rupturee (particularly of the Achilles tendon); Spinal compression fracturee.
Systemic corticosteroids are not indicated for, and therefore should not be used to treat, traumatic brain injury.
a Not a MedDRA Preferred term.
b Peptic ulcer perforation and Peptic ulcer haemorrhage.
c Peritonitis may be the primary presenting sign or symptom of a gastrointestinal disorder such as perforation, obstruction or pancreatitis (see section 4.4).
d Reported for lidocaine only.
e Reported for methylprednisolone acetate only.
CERTAIN SIDE EFFECTS REPORTED WITH SOME NON-RECOMMENDED ROUTES OF ADMINISTRATION:
Intrathecal/Epidural: Usual systemic corticoid adverse reactions, headache, meningismus, meningitis, paraparesis/paraplegia, spinal fluid abnormalities, nausea, vomiting, sweating, arachnoiditis, functional gastrointestinal disorder/bladder dysfunction, seizure, sensory disturbance.
Extradural: Wound dehiscence, loss of sphincter control.
Intranasal: Permanent/temporary blindness, allergic reactions, rhinitis.
Ophthalmic (Subconjunctival): Redness and itching, abscess, slough at injection site, residue at injection site, increased intra-ocular pressure, decreased vision - blindness, infection.
Miscellaneous: Scalp, tonsillar fauces, sphenopalatine ganglion: blindness.
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 |
Depo-Medrone with Lidocaine Suspension for Injection | Clinical particulars - Subsection 10 | Overdose
Methylprednisolone
Following overdosage the possibility of adrenal suppression should be guarded against by gradual diminution of dose levels over a period of time. In such event the patient may require to be supported during any further traumatic episode.
Reports of acute toxicity and/or death following overdosage of corticosteroids are rare. In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic.
Methylprednisolone is dialysable.
Lidocaine |
Depo-Medrone with Lidocaine Suspension for Injection | Clinical particulars - Subsection 11 | Overdose with lidocaine can manifest itself in a transient stimulation of the central nervous system with early symptoms: yawning, restlessness, dizziness, nausea, vomiting, dysarthria, ataxia, hearing and visual disturbances. With moderate intoxication also twitching and convulsions can occur. This can be followed by unconsciousness, respiratory depression and coma. In very severe intoxication due to decreased myocardial contractility and delayed impulse conduction, hypotension and cardiovascular collapse can be expected to be followed by a complete heart block and cardiac arrest. Convulsions, hypotension and respiratory depression and cardiac events should be treated as necessary. Continual optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance.
5. Pharmacological properties
5.1 |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
No pharmacokinetic studies have been performed with the combination product of methylprednisolone and lidocaine, however, data are provided from pharmacokinetic studies performed with the individual product components methylprednisolone and lidocaine.
Absorption:
Methylprednisolone:
One in-house study of eight volunteers determined the pharmacokinetics of a single 40 mg intramuscular dose of Depo-Medrone. The average of the individual peak plasma concentrations was 14.8 ± 8.6 ng/ml, the average of the individual peak times (tmax) was 7.25 ± 1.04 hours, and the average area under the curve (AUC) was 1354.2 ± 424.1 ng/ml x hrs (Day 1-21).
Lidocaine:
Pharmacokinetics of lidocaine after synovial absorption following intra-articular bolus injection in patients with knee joint arthroscopy was studied with different maximum concentration (Cmax) values reported. The Cmax values are 2.18 µg/ml at 1 hour (serum) and 0.63 µg/ml at 0.5 hour (plasma) following administration of lidocaine doses of 7 mg/kg and 400 mg, respectively. Other reported serum Cmax values are 0.69 µg/ml at 5 minutes and 0.278 µg/ml at 2 hours following administration of lidocaine doses of 25 ml of 1% and 20 ml of 1.5%, respectively.
Pharmacokinetic data of lidocaine after intra-bursa and intra-cyst administrations for local effect are not available.
Distribution:
Methylprednisolone:
Methylprednisolone is widely distributed into the tissues, crosses the blood-brain barrier, and is secreted in breast milk. Its apparent volume of distribution is approximately 1.4 l/kg. The plasma protein binding of methylprednisolone in humans is approximately 77%.
Lidocaine:
The plasma protein binding of lidocaine is concentration-dependent, and binding decreases as concentration increases. At concentrations of 1 to 5 µg/ml, 60%-80% lidocaine is protein bound. Binding is also dependent on the plasma concentration of the α1-acid glycoprotein.
Lidocaine has a volume of distribution at steady state of 91 l.
Lidocaine readily crosses the placenta, and equilibrium of unbound drug concentration is rapidly reached. The degree of plasma protein binding in the foetus is less than in the mother, which results in lower total plasma concentrations in the foetus.
Metabolism:
Methylprednisolone:
In humans, methylprednisolone is metabolized in the liver to inactive metabolites; the major ones are 20α-hydroxymethylprednisolone and 20β-hydroxymethylprednisolone. Metabolism in the liver occurs primarily via the CYP3A4. (For a list of drug interactions based on CYP3A4-mediated metabolism, see section 4.5.)
Methylprednisolone, like many CYP3A4 substrates, may also be a substrate for the ATP-binding cassette (ABC) transport protein p-glycoprotein, influencing tissue distribution and interactions with other medicines modulated by P-gp.
Lidocaine:
Lidocaine is mainly metabolized by the liver. The main metabolites of lidocaine are monoethylglycine xylidide, glycinexylidide, 2,6-dimethylaniline, and 4-hydroxy-2,6-dimethylaniline. The lidocaine N-dealkylation to monoethylglycine xylidide is considered to be mediated by both CYP1A2 and CYP3A4. The metabolite 2,6-dimethylaniline is converted to 4-hydroxy-2,6-dimethylaniline by CYP2A6 and CYP2E1.
Elimination:
Methylprednisolone:
The mean elimination half-life for total methylprednisolone is in the range of 1.8 to 5.2 hours. Total clearance is approximately 5 to 6 ml/min/kg.
Lidocaine:
The clearance of lidocaine in plasma following intravenous bolus administration is 9 to 10 ml/min/kg.
The elimination half-life of lidocaine following intravenous bolus injection is typically 1.5 to 2 hours.
The pharmacological actions of monoethylglycine xylidide and glycinexylidide are similar to but less potent than those of lidocaine. Monoethylglycine xylidide has a half-life of approximately 2.3 hours and glycinexylidide has a half-life of about 10 hours and may accumulate after long-term administration.
Only 3% of lidocaine is excreted unchanged by the kidneys. About 73% of lidocaine appears in the urine as 4-hydroxy-2,6-dimethylaniline metabolite.
Special Population
Methylprednisolone:
No pharmacokinetic studies have been performed for methylprednisolone in special populations.
Special Population
Lidocaine:
Hepatic impairment
Following intravenous administration, the half-life of lidocaine has approximately 3-fold increase in patients with liver impairment. Pharmacokinetic data of lidocaine after intra-articular, intra-bursa and intra-cyst administrations for local effect are not available in hepatic impairment.
Renal impairment
Mild to moderate renal impairment (CLcr 30-60 ml/min) does not affect lidocaine pharmacokinetics but may increase the accumulation of glycinexylidide metabolite following intravenous administration. However, lidocaine clearance decreases about half and its half-life is approximately doubled with increased accumulation of glycinexylidide metabolite in patients with severe renal impairment (Clcr < 30 ml/min).
The pharmacokinetics of lidocaine and its main metabolite of monoethylglycine xylidide are not altered significantly in haemodialysis patients who receive an intravenous dose of lidocaine.
Pharmacokinetic data of lidocaine after intra-articular, intra-bursa and intra-cyst administrations for local effect are not available in renal impairment.
No dosing adjustments are necessary in renal failure. Methylprednisolone is haemodialysable.
5.3 |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
Methylprednisolone
Based on conventional studies of safety pharmacology and repeated dose toxicity, no unexpected hazards were identified. The toxicities seen in the repeated-dose studies were those expected to occur with continued exposure to exogenous adrenocortical steroids.
Mutagenesis:
Methylprednisolone has not been formally evaluated for genotoxicity. Studies using structurally related analogues of methylprednisolone showed no evidence of a potential for genetic and chromosome mutations in limited studies in bacteria and mammalian cells.
Carcinogenesis:
Methylprednisolone has not been formally evaluated in rodent carcinogenicity studies. Variable results have been obtained with other glucocorticoids tested for carcinogenicity in mice and rats. However, published data indicate that several related glucocorticoids including budesonide, prednisolone, and triamcinolone acetonide can increase the incidence of hepatocellular adenomas and carcinomas after oral administration in drinking water to male rats. These tumorigenic effects occurred at doses which were less than the typical clinical doses on a mg/m2 basis. The clinical relevance of these findings is unknown.
Reproductive toxicity:
Methylprednisolone has not been evaluated in animal fertility studies. Corticosteroids have been shown to reduce fertility when administered to rats. Adverse effects on fertility in male rats administered corticosterone were observed and were reversible. Decreased weights and microscopic changes in prostate and seminal vesicles were observed. The numbers of implantations and live foetuses were reduced and these effects were not present following mating at the end of the recovery period.
An increased frequency of cleft palate was observed among the offspring of mice treated during pregnancy with methylprednisolone in doses similar to those typically used for oral therapy in humans.
An increased frequency of cardiovascular defects and decreased body weight were observed among the offspring of pregnant rats treated with methylprednisolone in a dose that was similar to that used for oral therapy in humans but was toxic to the mothers. In contrast, no teratogenic effect was noted in rats with doses < 1-18 times those typically used for oral therapy in humans in another study. High frequencies of foetal death and a variety of central nervous system and skeletal anomalies were reported in the offspring of pregnant rabbits treated with methylprednisolone in doses less than those used in humans. The relevance of these findings to the risk of malformations in human infants born to mothers treated with methylprednisolone in pregnancy is unknown. Safety margins for the reported teratogenic effects are unknown.
Lidocaine
Carcinogenesis:
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of lidocaine.
A metabolite of lidocaine, 2,6-xylidine, has been shown to be carcinogenic in rats with unknown clinical relevance in relation to short-term/intermittent use of lidocaine as a local anaesthetic.
Mutagenesis:
Genotoxicity tests with lidocaine showed no evidence of mutagenic potential. A metabolite of lidocaine, 2,6-xylidine, showed weak genotoxic potential in vitro and in vivo.
Reproductive toxicity:
A study was conducted on male and female rats administered orally 30 mg/kg bw of lidocaine daily for 8 months. During that period, 3 matings were conducted and reproductive parameters were analysed for each gestation, as well as offspring development up to weaning. No effects could be detected.
Methylprednisolone plus Lidocaine
Carcinogenesis:
Long-term studies in animals have not been performed to evaluate carcinogenic potential.
The toxicity of lidocaine was not significantly altered in rats that were treated with the combination of lidocaine and methylprednisolone.
Mutagenesis:
Genotoxicity studies have not been conducted with the combination of methylprednisolone and lidocaine (see above for genotoxicity as it pertains to the individual drugs).
Reproductive toxicity:
Reproductive toxicity studies have not been conducted with the combination of methylprednisolone and lidocaine (see above for reproductive toxicity as it pertains to the individual drugs).
6. |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmaceutical particulars - List of excipients | List of excipients
Sodium chloride
Myristyl-gamma-picolinium chloride
Benzyl alcohol (E1519)
Macrogol
Sodium hydroxide
Hydrochloric acid
Water for injections.
6.2 |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmaceutical particulars - Incompatibilities | Incompatibilities
Not applicable.
6.3 |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmaceutical particulars - Shelf life | Shelf life
2 years.
6.4 |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmaceutical particulars - Special precautions for storage | Special precautions for storage
Do not store above 25°C.
Do not freeze.
6.5 |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmaceutical particulars - Nature and contents of container | Nature and contents of container
Glass vials with rubber cap containing 1 or 2 ml of suspension.
Not all pack sizes may be marketed.
6.6 |
Depo-Medrone with Lidocaine Suspension for Injection | Pharmaceutical particulars - Special precautions for disposal and other handling | Special precautions for disposal and other handling
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. |
Depo-Medrone with Lidocaine Suspension for Injection | Marketing authorisation holder | Pfizer Limited
Ramsgate Road
Sandwich
Kent CT13 9NJ
UK
8. Marketing authorisation number(s)
PL 00057/0964
9. |
Depo-Medrone with Lidocaine Suspension for Injection | Date of first authorisation/renewal of the authorisation | MA granted: 03 March 1981
MA renewed: 25 November 1991
10. |
Depo-Medrone with Lidocaine Suspension for Injection | Date of revision of the text | 06/2023
Ref: DML 31_0 UK |
Deponit 10 mg/24 h transdermal patch | Name of the medicinal product | Deponit 10 mg/24 h transdermal patch
2. |
Deponit 10 mg/24 h transdermal patch | Qualitative and quantitative composition | One patch contains glyceryl trinitrate 37.4 mg
The average amount of glyceryl trinitrate absorbed from each patch in 24 hours is 10 mg.
For the full list of excipients, see section 6.1.
3. |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical form | Transdermal patch
White, translucent square patch with convex round corners with “Deponit 10” marked on the outer face.
4. |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Therapeutic indications | Therapeutic indications
Prophylaxis of angina pectoris alone or in combination with other anti-anginal therapy.
4.2 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Posology and method of administration | Posology and method of administration
Posology
Adults
Treatment should be initiated with one patch daily. If necessary, the dosage may be increased to two patches. The maximum daily dose is 20 mg, any increases or decreases in dose should be made gradually.
Elderly population
No specific information on use in the elderly is available, however there is no evidence to suggest that an alteration in dose is required.
Paediatric population
The safety and efficacy of this Deponit patch in children has not yet been established.
Method of administration
Dermal
It is recommended that the patch is applied to healthy, undamaged, relatively crease free and hairless skin. The best places to apply Deponit patches are the easily reached, fairly static areas at the front or side of the chest. However, Deponit patches may also be applied to the upper arm, thigh, abdomen or shoulder. Skin care products should not be used before applying the patch. The replacement patch should be applied to a new area of skin. Allow several days to elapse before applying a fresh patch to the same area of skin.
Tolerance may occur during chronic nitrate therapy. To avoid development of tolerance, the GTN patch should remain on the skin only for about 12-14 hours, to ensure a nitrate free interval of 10-12 hours. Additional anti-anginal therapy with drugs not containing nitro compounds should be considered for the nitrate-free interval if required.
As with any nitrate therapy, treatment with these patches should not be stopped abruptly. If the patient is being changed to another type of treatment, the two should overlap.
4.3 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Contraindications | Contraindications
• Hypersensitivity to the active substance, to other nitro compounds or to any of the excipients listed in section 6.1
• Raised intracranial pressure including that caused by head trauma or cerebral haemorrhage
• Acute circulatory failure associated with marked hypotension (shock).
• Myocardial insufficiency due to obstruction, as in aortic or mitral stenosis or constrictive pericarditis.
• Marked anaemia
• Closed angle glaucoma
• Severe Hypotensive conditions (systolic blood pressure less than 90mmHg)
• Severe hypovolaemia
• Hypertrophic obstructive cardiomyopathy
• Aortic stenosis and mitral stenosis
• Constrictive pericarditis
• Cardiac tamponade
• Concomitant use of phosphodiesterase type-5 inhibitors. Phosphodiesterase type-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contra-indicated.
• During nitrate therapy, the soluble guanylate cyclase stimulator riociguat must not be used (see section 4.5).
4.4 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
Warnings:
In cases of recent myocardial infarction or acute heart failure, treatment with the preparation should be carried out cautiously under strict medical surveillance and/or haemodynamic monitoring.
Removal of the patch should be considered as part of the management of patients who develop significant hypotension.
Precautions:
This patch should be used with caution in patients with
• Severe hepatic or renal impairment
• Hypothyroidism
• Hypothermia
• Malnutrition
• A recent history of myocardial infarction
• Hypoxaemia or a ventilation/perfusion imbalance due to lung disease or ischaemic heart failure.
• Arterial Hypoxaemia due to severe anaemia (including G6PD deficiency induced forms), because in such patients the biotransformation of nitroglycerin is reduced.
• Alveolar hypoventilation a vasoconstriction occurs within the lung to shift perfusion from areas of alveolar hypoxia to better ventilated regions of the lung (Euler–Liljestrand mechanism).
• Angina pectoris, myocardial infarction, or cerebral ischaemia frequently suffer from abnormalities of the small airways (especially alveolar hypoxia).Under these circumstances vasoconstriction occurs within the lung to shift perfusion from areas of alveolar hypoxia to better ventilated regions of the lung. As a potent vasodilator, nitroglycerin could reverse this protective vasoconstriction and thus result in increased perfusion of poorly ventilated areas, worsening of the ventilation/perfusion imbalance, and a further decrease in the arterial partial pressure of oxygen.
• Methemoglobinemia
Following treatment with GTN, methemoglobinemia has been reported. Treatment of methaemoglobinemia with methylene blue is contraindicated in patients with glucose-6-phosphate deficiency or methemoglobin-reductase deficiency (see also section 4.9).
The patch is not indicated for use in acute angina attacks. In the event of an acute angina attack, sublingual treatment such as a spray or tablet should be used.
As with all nitrate preparations withdrawal of long-term treatment should be gradual by replacement with decreasing doses of long acting oral nitrates.
Also when transferring the patient on long-term therapy to another form of medication, nitroglycerin should be gradually withdrawn and overlapping treatment started.
If the patches are not used as indicated (see Section 4.2) tolerance to the medication could develop.
Patients should be warned not to discontinue or interrupt GTN patch therapy in order to use phosphodiesterase inhibitor-containing products (e. g. sildenafil, vardenafil, tadalafil).
During treatment with GTN alcohol should be avoided as it may potentiate the hypotensive and vasodilating effect of GTN (see section 4.5).
4.5 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
Concomitant treatment with other vasodilators (e.g. phosphodiesterase inhibitors such as sildenafil, vardenafil, tadalafil), calcium channel antagonists, ACE-inhibitors, monoamine oxidase inhibitors, beta-blockers, diuretics, antihypertensives, tricyclic antidepressants and major tranquillisers, as well as the consumption of alcohol, may potentiate the hypotensive effect of the preparation.
The blood pressure lowering effect of these patches will be increased if used together with phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, tadalafil) which are used for erectile dysfunction (see Section 4.3). This might lead to life threatening cardiovascular complications. Patients who have recently taken phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, tadalafil) therefore must not be treated with GTN. Patients who are on nitrate patch therapy therefore must not use phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, tadalafil).
The use of GTN with riociguat, a soluble guanylate cyclase stimulator, is contraindicated (see section 4.3) since concomitant use can cause hypotension.
If administered concurrently, these patches may increase the blood level of dihydroergotamine and lead to coronary vasoconstriction.
The possibility that ingestion of non-steroidal anti-inflammatory drugs except Acetyl Salicylic acid might diminish the therapeutic response to the patch cannot be excluded.
Concurrent administration with Amifostine and acetyl salicylic acid may potentiate the hypotensive effect of the preparation.
Sapropterine (Tetrahydrobiopterine, BH4) is a cofactor for nitric oxide synthetase. Caution is recommended during concomitant use of sapropterine-containing medicine with all agents that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors (e.g. glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide 5-mononitrate (5-ISMN) and others).
4.6 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Fertility, pregnancy and lactation | Fertility, pregnancy and lactation
Pregnancy and breast-feeding
Like any drug, Deponit 10 should be employed with caution during pregnancy, especially in the first 3 months.
These patches should not be used during pregnancy or lactation unless considered absolutely essential by the physician.
It is not known whether the active substance passes into the breast milk. Benefits to the mother must be weighed against risk to the child.
Fertility
Reproduction toxicity studies performed in rats and rabbits using various routes of administration did not reveal any effect on mating, fertility and general reproductive parameters. There is no data available on the effect of Deponit 10 on fertility in humans.
4.7 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Effects on ability to drive and use machines | Effects on ability to drive and use machines
Glyceryl trinitrate can cause postural hypotension and dizziness. Patients should not drive or operate machinery if they feel affected.
4.8 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Undesirable effects | Undesirable effects |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Overdose | Undesirable effects frequencies are defined as: very common (≥1/10), common (≥1/100,<1/10), uncommon (≥1/1,000,<1/100), rare ≥1/10,000,<1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
During administration of Deponit 10 the following undesirable effects may be observed:
SOC
Very common (≥1/10)
Common (≥1/100,<1/10)
Uncommon (≥1/1,000,<1/100)
Rare ≥1/10,000,<1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from the available data)
Nervous system disorders
Headache
Dizziness (including dizziness postural), somnolence
Cardiac disorders
Tachycardia
Enhanced angina pectoris symptoms
Palpitations
Vascular disorders
Orthostatic hypotension
Circulatory collapse (sometimes accompanied by bradyarrythmia and syncope)
Flushing, hypotension
Gastrointestinal disorders
Nausea, vomiting
Heartburn
Skin and subcutaneous tissue disorders
Allergic skin reactions (e.g. rash), allergic contact dermatitis
Dermatitis exfoliative, rash generalized
General disorders and administration site conditions
Asthenia
Pruritus, pruritus at patch application site, burning, erythema, irritation
rash
Investigations
Heart rate increase
Severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness, pallor and excessive perspiration.
During the treatment with these patches, a temporary hypoxaemia may occur due to a relative redistribution of the blood flow in hypoventilated alveolar areas. Particularly in patients with coronary artery disease this may lead to a myocardial hypoxia.
Like other nitrate preparations, GTN commonly causes dose-dependent headaches due to cerebral vasodilation. These often regress after a few days despite the maintenance of therapy. If headaches persist during intermittent therapy, they should be treated with mild analgesics. Unresponsive headaches are an indication for reducing the dosage of GTN or discontinuing treatment.
A slight reflex-induced increase in heart rate can be avoided by resorting, if necessary, to combined treatment with a beta-blocker.
Upon removal of the patch, any slight reddening of the skin will usually disappear within a few hours. The application site should be changed regularly to prevent local irritation.
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.
By reporting side effects, you can help provide more information on the safety of this medicine.
4.9 |
Deponit 10 mg/24 h transdermal patch | Clinical particulars - Subsection 10 | Overdose
In view of the transdermal mode of delivery, an overdose of glyceryl trinitrate is unlikely to occur. However, in the unlikely event of an overdose, the symptoms could include the following:
• Fall in blood pressure ≤ 90 mmHg
• Collapse or syncope
• Paleness
• Sweating
• Weak pulse
• Reflex tachycardia
• Flushing
• Light-headedness on standing
• Headache
• Weakness
• Dizziness
• Nausea
• Vomiting
• Methaemoglobinaemia has been reported in patients receiving other organic nitrates. During glyceryl trinitrate biotransformation nitrite ions are released, which may induce methaemoglobinaemia and cyanosis with subsequent tachypnoea, anxiety, loss of consciousness and cardiac arrest. It can not be excluded that an overdose of glyceryl trinitrate may cause this adverse reaction
• In very high doses the intracranial pressure may be increased. This might lead to cerebral symptoms
General procedure:
• Since these patches are applied to the skin, removing the patch immediately stops delivery of the drug.
• General procedures in the event of nitrate-related hypotension
- Patient should be kept horizontal with the head lowered and legs raised or, if necessary, compression bandaging of the patient's legs.
- Supply oxygen
- Expand plasma volume
- For specific shock treatment admit patient to intensive care unit
Special procedure:
• Raising the blood pressure if the blood pressure is very low
• Treatment of methaemoglobinaemia
Treatment with intravenous methylene blue
- Initially 1 to 2 mg/kg, not exceeding 4 mg/kg of a 1% solution over 5 minutes.
- Repeat dose in 60 minutes if there is no response.
- Administer oxygen (if necessary)
- Initiate artificial ventilation
Treatment with methylene blue is contraindicated in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or methaemoglobin reductase deficiency. (see also section 4.4).
Where treatment with methylene blue is contraindicated or is not effective, exchange transfusion and / or transfusion of packed red blood cells is recommended.
Resuscitation measures:
In case of signs of respiratory and circulatory arrest, initiate resuscitation measures immediately.
5. Pharmacological properties
5.1 |
Deponit 10 mg/24 h transdermal patch | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
Absorption:
The transdermal absorption of glyceryl trinitrate circumvents the extensive hepatic first pass metabolism so the bioavailability is about 70% of that achieved after i.v. administration.
Distribution
The steady-state concentration in the plasma depends on the patch dosage and the corresponding rate of absorption. At a rate of absorption of 0.4 mg/h, the steady-state concentration is about 0.2 µg/l on average. Plasma protein binding is about 60%.
Metabolism
Glyceryl trinitrate is metabolized to 1,2- and 1,3-dinitroglycerols. The dinitrates exert less vasodilatory activity than glyceryl trinitrate. The contribution to the overall effect is not known. The dinitrates are further metabolized to inactive mononitrates, glyceryl and carbon dioxide. The metabolism of glyceryl trinitrate, which is effected in the liver, but also in many other cells, e.g. the red blood cells, includes the separation of one or more nitrate groups.
Elimination
The elimination half-life of glyceryl trinitrate is 2-4 min. In addition to the metabolism of glyceryl trinitrate, there is a renal excretion of the catabolites.
5.3 |
Deponit 10 mg/24 h transdermal patch | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
Glyceryl trinitrate is a well-known active substance, established for more than a hundred years. Thus new preclinical studies have not been carried out with Deponit 10.
6. |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical particulars - List of excipients | List of excipients
Acrylate/vinyl acetate copolymer (adhesive matrix)
Polypropylene (backing foil)
Polyethylene (siliconised release liner)
6.2 |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical particulars - Incompatibilities | Incompatibilities
Not applicable.
6.3 |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical particulars - Shelf life | Shelf life |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical particulars - Special precautions for storage | Shelf life of the product as packaged for sale: 48 months.
6.4 |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical particulars - Nature and contents of container | Special precautions for storage
Do not store above 25°C.
6.5 |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical particulars - Special precautions for disposal and other handling | Nature and contents of container
Multilaminate film/foil pouch with heat-sealed edges.
28 patches per carton.
6.6 |
Deponit 10 mg/24 h transdermal patch | Pharmaceutical particulars - Subsection 7 | Special precautions for disposal and other handling
The patch should be removed from the package just before application. After removal of the protective foil, the patch should be applied to unbroken, clean and dry skin that is smooth and with few hairs. The same area of skin should not be used again for some days.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. |
Deponit 10 mg/24 h transdermal patch | Marketing authorisation holder | Norgine Pharmaceuticals Limited
Norgine House, Widewater place,
Moorhall Road, Harefield,
Middlesex, U89 6NS, UK
8. Marketing authorisation number(s)
PL 20011/0045
9. |
Deponit 10 mg/24 h transdermal patch | Date of first authorisation/renewal of the authorisation | Date of latest renewal: 28 February 2008
10. |
Deponit 10 mg/24 h transdermal patch | Date of revision of the text | 03/2019 |
Deponit 5 mg/24 h transdermal patch | Name of the medicinal product | Deponit 5 mg/24 h transdermal patch
2. |
Deponit 5 mg/24 h transdermal patch | Qualitative and quantitative composition | One patch contains glyceryl trinitrate 18.7 mg
The average amount of glyceryl trinitrate absorbed from each patch in 24 hours is 5 mg.
For the full list of excipients, see section 6.1.
3. |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical form | Transdermal patch
White, translucent square patch with convex round corners with “Deponit 5” marked on the outer face.
4. |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Therapeutic indications | Therapeutic indications
Prophylaxis of angina pectoris alone or in combination with other anti-anginal therapy.
4.2 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Posology and method of administration | Posology and method of administration
Posology
Adults
Treatment should be initiated with one patch daily. If necessary, the dosage may be increased to two patches. The maximum daily dose is 20 mg, any increases or decreases in dose should be made gradually.
Elderly population
No specific information on use in the elderly is available, however there is no evidence to suggest that an alteration in dose is required.
Paediatric population
The safety and efficacy of Deponit patch in children has not yet been established
Method of administration
Dermal
It is recommended that the patch is applied to healthy, undamaged, relatively crease free and hairless skin. The best places to apply Deponit patches are the easily reached, fairly static areas at the front or side of the chest. However, Deponit patches may also be applied to the upper arm, thigh, abdomen or shoulder. Skin care products should not be used before applying the patch. The replacement patch should be applied to a new area of skin. Allow several days to elapse before applying a fresh patch to the same area of skin.
Tolerance may occur during chronic nitrate therapy. To avoid development of tolerance, the GTN patch should remain on the skin only for about 12-14 hours, to ensure a nitrate free interval of 10-12 hours. Additional anti-anginal therapy with drugs not containing nitro compounds should be considered for the nitrate-free interval if required.
As with any nitrate therapy, treatment with these patches should not be stopped abruptly. If the patient is being changed to another type of treatment, the two should overlap.
4.3 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Contraindications | Contraindications
• Hypersensitivity to the active substance, to other nitro compounds or to any of the excipients listed in section 6.1
• Raised intracranial pressure including that caused by head trauma or cerebral haemorrhage
• Acute circulatory failure associated with marked hypotension (shock).
• Myocardial insufficiency due to obstruction, as in aortic or mitral stenosis or constrictive pericarditis.
• Marked anaemia
• Closed angle glaucoma
• Severe Hypotensive conditions (systolic blood pressure less than 90mmHg)
• Severe hypovolaemia
• Hypertrophic obstructive cardiomyopathy
• Aortic stenosis and mitral stenosis
• Constrictive pericarditis
• Cardiac tamponade
• Concomitant use of phosphodiesterase type-5 inhibitors. Phosphodiesterase type-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contra-indicated.
• During nitrate therapy, the soluble guanylate cyclase stimulator riociguat must not be used (see section 4.5).
4.4 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
Warnings:
In cases of recent myocardial infarction or acute heart failure, treatment with the preparation should be carried out cautiously under strict medical surveillance and/or haemodynamic monitoring.
Removal of the patch should be considered as part of the management of patients who develop significant hypotension.
Precautions:
This patch should be used with caution in patients with
• Severe hepatic or renal impairment
• Hypothyroidism
• Hypothermia
• Malnutrition
• A recent history of myocardial infarction
• Hypoxaemia or a ventilation/perfusion imbalance due to lung disease or ischaemic heart failure.
• Arterial Hypoxaemia due to severe anaemia (including G6PD deficiency induced forms), because in such patients the biotransformation of nitroglycerin is reduced.
• Alveolar hypoventilation a vasoconstriction occurs within the lung to shift perfusion from areas of alveolar hypoxia to better ventilated regions of the lung (Von Euler–Liljestrand mechanism).
• Angina pectoris, myocardial infarction, or cerebral ischaemia frequently suffer from abnormalities of the small airways (especially alveolar hypoxia).Under these circumstances vasoconstriction occurs within the lung to shift perfusion from areas of alveolar hypoxia to better ventilated regions of the lung. As a potent vasodilator, nitroglycerin could reverse this protective vasoconstriction and thus result in increased perfusion of poorly ventilated areas, worsening of the ventilation/perfusion imbalance, and a further decrease in the arterial partial pressure of oxygen.
• Methemoglobinemia
Following treatment with GTN, methemoglobinemia has been reported. Treatment of methaemoglobinemia with methylene blue is contraindicated in patients with glucose-6-phosphate deficiency or methemoglobin-reductase deficiency (see also section 4.9).
The patch is not indicated for use in acute angina attacks. In the event of an acute angina attack, sublingual treatment such as a spray or tablet should be used.
As with all nitrate preparations withdrawal of long-term treatment should be gradual by replacement with decreasing doses of long acting oral nitrates.
Also when transferring the patient on long-term therapy to another form of medication, nitroglycerin should be gradually withdrawn and overlapping treatment started.
If the patches are not used as indicated (see Section 4.2) tolerance to the medication could develop.
Patients should be warned not to discontinue or interrupt GTN patch therapy in order to use phosphodiesterase inhibitor-containing products (e. g. sildenafil, vardenafil, tadalafil).
During treatment with GTN alcohol should be avoided as it may potentiate the hypotensive and vasodilating effect of GTN (see section 4.5).
4.5 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
Concomitant treatment with other vasodilators (e.g. phosphodiesterase inhibitors such as sildenafil, vardenafil, tadalafil), calcium channel antagonists, ACE-inhibitors, monoamine oxidase inhibitors, beta-blockers, diuretics, antihypertensives, tricyclic antidepressants and major tranquillisers, as well as the consumption of alcohol, may potentiate the hypotensive effect of the preparation.
The blood pressure lowering effect of these patches will be increased if used together with phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, tadalafil) which are used for erectile dysfunction (see Section 4.3). This might lead to life threatening cardiovascular complications. Patients who have recently taken phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, tadalafil) therefore must not be treated with GTN. Patients who are on nitrate patch therapy therefore must not use phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, tadalafil).
The use of GTN with riociguat, a soluble guanylate cyclase stimulator, is contraindicated (see section 4.3) since concomitant use can cause hypotension.
If administered concurrently, these patches may increase the blood level of dihydroergotamine and lead to coronary vasoconstriction.
The possibility that ingestion of non-steroidal anti-inflammatory drugs except Acetyl Salicylic acid might diminish the therapeutic response to the patch cannot be excluded.
Concurrent administration with Amifostine and acetyl salicylic acid may potentiate the hypotensive effect of the preparation.
Sapropterine (Tetrahydrobiopterine, BH4) is a cofactor for nitric oxide synthetase. Caution is recommended during concomitant use of sapropterine-containing medicine with all agents that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors (e.g. glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide 5-mononitrate (5-ISMN) and others).
4.6 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Fertility, pregnancy and lactation | Fertility, pregnancy and lactation
Pregnancy and breast-feeding
Like any drug, Deponit 5 should be employed with caution during pregnancy, especially in the first 3 months.
These patches should not be used during pregnancy or lactation unless considered absolutely essential by the physician.
It is not known whether the active substance passes into the breast milk. Benefits to the mother must be weighed against risk to the child.
Fertility
Reproduction toxicity studies performed in rats and rabbits using various routes of administration did not reveal any effect on mating, fertility and general reproductive parameters. There is no data available on the effect of Deponit 5 on fertility in humans.
4.7 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Effects on ability to drive and use machines | Effects on ability to drive and use machines
Glyceryl trinitrate can cause postural hypotension and dizziness. Patients should not drive or operate machinery if they feel affected.
4.8 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Undesirable effects | Undesirable effects |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Overdose | Undesirable effects frequencies are defined as: very common (≥1/10), common (≥1/100,<1/10), uncommon (≥1/1,000,<1/100), rare ≥1/10,000,<1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
During administration of Deponit 5 the following undesirable effects may be observed:
SOC
Very common (≥1/10)
Common (≥1/100,<1/10)
Uncommon (≥1/1,000,<1/100)
Rare (≥1/10,000,<1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from the available data)
Nervous system disorders
Headache
Dizziness (including dizziness postural), somnolence
Cardiac disorders
Tachycardia
Enhanced angina pectoris symptoms
Palpitations
Vascular disorders
Orthostatic hypotension
Circulatory collapse (sometimes accompanied by bradyarrythmia and syncope)
Flushing, hypotension
Gastrointestinal disorders
Nausea, vomiting
Heartburn
Skin and subcutaneous tissue disorders
Allergic skin reactions (e.g. rash), allergic contact dermatitis
Dermatitis exfoliative, rash generalized
General disorders and administration site conditions
Asthenia
Pruritus, pruritus at patch application site, burning, erythema, irritation
Rash
Investigations
Heart rate increase
Severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness, pallor and excessive perspiration.
During the treatment with these patches, a temporary hypoxaemia may occur due to a relative redistribution of the blood flow in hypoventilated alveolar areas. Particularly in patients with coronary artery disease this may lead to a myocardial hypoxia.
Like other nitrate preparations, GTN commonly causes dose-dependent headaches due to cerebral vasodilation. These often regress after a few days despite the maintenance of therapy. If headaches persist during intermittent therapy, they should be treated with mild analgesics. Unresponsive headaches are an indication for reducing the dosage of GTN or discontinuing treatment.
A slight reflex-induced increase in heart rate can be avoided by resorting, if necessary, to combined treatment with a beta-blocker.
Upon removal of the patch, any slight reddening of the skin will usually disappear within a few hours. The application site should be changed regularly to prevent local irritation.
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.
By reporting side effects, you can help provide more information on the safety of this medicine.
4.9 |
Deponit 5 mg/24 h transdermal patch | Clinical particulars - Subsection 10 | Overdose
In view of the transdermal mode of delivery, an overdose of glyceryl trinitrate is unlikely to occur. However, in the unlikely event of an overdose, the symptoms could include the following:
• Fall in blood pressure ≤ 90 mmHg
• Collapse or syncope
• Paleness
• Sweating
• Weak pulse
• Reflex tachycardia
• Flushing
• Light-headedness on standing
• Headache
• Weakness
• Dizziness
• Nausea
• Vomiting
• Methaemoglobinaemia has been reported in patients receiving other organic nitrates. During glyceryl trinitrate biotransformation nitrite ions are released, which may induce methaemoglobinaemia and cyanosis with subsequent tachypnoea, anxiety, loss of consciousness and cardiac arrest. It can not be excluded that an overdose of glyceryl trinitrate may cause this adverse reaction
• In very high doses the intracranial pressure may be increased. This might lead to cerebral symptoms
General procedure:
• Since these patches are applied to the skin, removing the patch immediately stops delivery of the drug.
• General procedures in the event of nitrate-related hypotension
- Patient should be kept horizontal with the head lowered and legs raised or, if necessary, compression bandaging of the patient's legs.
- Supply oxygen
- Expand plasma volume
- For specific shock treatment admit patient to intensive care unit
Special procedure:
• Raising the blood pressure if the blood pressure is very low
• Treatment of methaemoglobinaemia
Treatment with intravenous methylene blue
- Initially 1 to 2 mg/kg, not exceeding 4 mg/kg of a 1% solution over 5 minutes.
- Repeat dose in 60 minutes if there is no response.
- Administer oxygen (if necessary)
- Initiate artificial ventilation
Treatment with methylene blue is contraindicated in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or methaemoglobin reductase deficiency (see also section 4.4).
Where treatment with methylene blue is contraindicated or is not effective, exchange transfusion and / or transfusion of packed red blood cells is recommended.
Resuscitation measures:
In case of signs of respiratory and circulatory arrest, initiate resuscitation measures immediately.
5. Pharmacological properties
5.1 |
Deponit 5 mg/24 h transdermal patch | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
Absorption
The transdermal absorption of glyceryl trinitrate circumvents the extensive hepatic first pass metabolism so the bioavailability is about 70% of that achieved after i.v. administration.
Distribution
The steady-state concentration in the plasma depends on the patch dosage and the corresponding rate of absorption. At a rate of absorption of 0.4 mg/h, the steady-state concentration is about 0.2 µg/l on average. Plasma protein binding is about 60%.
Metabolism
Glyceryl trinitrate is metabolized to 1,2- and 1,3-dinitroglycerols. The dinitrates exert less vasodilatory activity than glyceryl trinitrate. The contribution to the overall effect is not known. The dinitrates are further metabolized to inactive mononitrates, glyceryl and carbon dioxide. The metabolism of glyceryl trinitrate, which is effected in the liver, but also in many other cells, e.g. the red blood cells, includes the separation of one or more nitrate groups.
Elimination
The elimination half-life of glyceryl trinitrate is 2-4 min. In addition to the metabolism of glyceryl trinitrate, there is a renal excretion of the catabolites.
5.3 |
Deponit 5 mg/24 h transdermal patch | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
Glyceryl trinitrate is a well-known active substance, established for more than a hundred years. Thus new preclinical studies have not been carried out with Deponit 5.
6. |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical particulars - List of excipients | List of excipients
Acrylate/vinyl acetate copolymer (adhesive matrix)
Polypropylene (backing foil)
Polyethylene (siliconised release liner)
6.2 |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical particulars - Incompatibilities | Incompatibilities
Not applicable.
6.3 |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical particulars - Shelf life | Shelf life |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical particulars - Special precautions for storage | Shelf life of the product as packaged for sale: 48 months.
6.4 |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical particulars - Nature and contents of container | Special precautions for storage
Do not store above 25°C.
6.5 |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical particulars - Special precautions for disposal and other handling | Nature and contents of container
Multilaminate film/foil pouch with heat-sealed edges.
28 patches per carton.
6.6 |
Deponit 5 mg/24 h transdermal patch | Pharmaceutical particulars - Subsection 7 | Special precautions for disposal and other handling
The patch should be removed from the package just before application. After removal of the protective foil, the patch should be applied to unbroken, clean and dry skin that is smooth and with few hairs. The same area of skin should not be used again for some days.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. |
Deponit 5 mg/24 h transdermal patch | Marketing authorisation holder | Norgine Pharmaceuticals Limited
Norgine House, Widewater place,
Moorhall Road, Harefield,
Middlesex, U89 6NS, UK
8. Marketing authorisation number(s)
PL 20011/0044
9. |
Deponit 5 mg/24 h transdermal patch | Date of first authorisation/renewal of the authorisation | Date of latest renewal: 28 February 2008
10. |
Deponit 5 mg/24 h transdermal patch | Date of revision of the text | 03/2019 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Name of the medicinal product | Depo-Provera 150 mg/ml
2. |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Qualitative and quantitative composition | Each ml of suspension contains 150 mg medroxyprogesterone acetate
Excipients with known effect:
Methyl parahydroxybenzoate (E218) - 1.35mg
Propyl parahydroxybenzoate (E216) - 0.15mg
For the full list of excipients, see section 6.1
3. |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmaceutical form | Sterile suspension for injection.
4. |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Clinical particulars - Therapeutic indications | Therapeutic indications
Progestogen: for contraception.
Depo-Provera is indicated for long-term female contraception. Each injection prevents ovulation and provides contraception for at least 12 weeks (+/- 5 days). However, it should be taken into consideration that the return to fertility (ovulation) may be delayed for up to one year (see section 4.4).
Depo-Provera is suitable for use in women who have been appropriately counselled concerning the likelihood of menstrual disturbance and the potential for a delay in return to full fertility.
Depo-Provera may also be used for short-term contraception in the following circumstances:
1) For partners of men undergoing vasectomy, for protection until the vasectomy becomes effective.
2) In women who are being immunised against rubella, to prevent pregnancy during the period of activity of the virus.
3) In women awaiting sterilisation.
Since loss of bone mineral density (BMD) may occur in females of all ages who use Depo-Provera injection long-term (see section 4.4), a risk/benefit assessment, which also takes into consideration the decrease in BMD that occurs during pregnancy and/or lactation, should be considered before giving the injection of Depo-Provera.
Paediatric population (12-18 years)
In adolescents, Depo-Provera may be used, but only after other methods of contraception have been discussed with the patient and considered unsuitable or unacceptable.
It is of the greatest importance that adequate explanations of the long-term nature of the product, of its possible side-effects and of the impossibility of immediately reversing the effects of each injection are given to potential users and that every effort is made to ensure that each patient receives such counselling as to enable her to fully understand these explanations. Patient information leaflets are supplied by the manufacturer. It is recommended that the doctor uses these leaflets to aid counselling of the patient before giving the injection of Depo-Provera.
4.2 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Clinical particulars - Posology and method of administration | Posology and method of administration
Posology
Adults:
First injection: To provide contraceptive cover in the first cycle of use, an injection of 150 mg i.m. should be given during the first five days of a normal menstrual cycle. If the injection is carried out according to these instructions, no additional contraceptive cover is required.
Post Partum: To increase assurance that the patient is not pregnant at the time of first administration, this injection should be given within 5 days post partum if not breast-feeding.
There is evidence that women prescribed Depo-Provera in the immediate puerperium can experience prolonged and heavy bleeding. Because of this, the drug should be used with caution in the puerperium. Women who are considering use of the product immediately following delivery or termination should be advised that the risk of heavy or prolonged bleeding may be increased. Doctors are reminded that in the non breast-feeding, post partum patient, ovulation may occur as early as week 4.
If the puerperal woman will be breast-feeding, the initial injection should be given no sooner than six weeks post partum, when the infant's enzyme system is more fully developed. Further injections should be given at 12 week intervals.
Further doses: These should be given at 12 week intervals, however, as long as the injection is given no later than five days after this time, no additional contraceptive measures (e.g. barrier) are required. (N.B. For partners of men undergoing vasectomy, a second injection of 150 mg I.M. 12 weeks after the first may be necessary in a small proportion of patients where the partner's sperm count has not fallen to zero.) If the interval from the preceding injection is greater than 89 days (12 weeks and five days) for any reason, then pregnancy should be excluded before the next injection is given and the patient should use additional contraceptive measures (e.g. barrier) for fourteen days after this subsequent injection.
Elderly: Not appropriate.
Paediatric population:
Depo-Provera is not indicated before menarche (see section 4.1 Therapeutic Indications)
Data in adolescent females (12-18 years) is available for IM administration of medroxyprogesterone acetate (MPA) (see Section 4.4 Special Warnings and Precautions for Use and section 5.1 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmacodynamic properties). Other than concerns about loss of BMD, the safety and effectiveness of Depo-Provera is expected to be the same for adolescents after menarche and adult females. | Switching from other Methods of Contraception
Depo-Provera should be given in a manner that ensures continuous contraceptive coverage. This should be based upon the mechanism of action of other methods, (e.g. patients switching from oral contraceptives should have their first injection of Depo-provera within 7 days of taking their last active pill)
Hepatic Insufficiency
The effect of hepatic disease on the pharmacokinetics of Depo-Provera is unknown. As Depo-Provera largely undergoes hepatic elimination it may be poorly metabolised in patients with severe liver insufficiency (see section 4.3).
Renal Insufficiency
The effect of renal disease on the pharmacokinetics of Depo-Provera is unknown. No dosage adjustment should be necessary in women with renal insufficiency, since Depo-Provera is almost exclusively eliminated by hepatic metabolism.
Method of Administration
The sterile aqueous suspension of Depo-Provera should be vigorously shaken just before use to ensure that the dose being given represents a uniform suspension of Depo-Provera.
Doses should be given by deep intramuscular injection. Care should be taken to ensure that the depot injection is given into the muscle tissue, preferably the gluteus maximus, but other muscle tissue such as the deltoid may be used.
The site of injection should be cleansed using standard methods prior to administration of the injection.
4.3 Contraindications
Hypersensitivity to medroxyprogesterone acetate or to any of excipients listed in section 6.1.
Depo-Provera should not be used during pregnancy, either for diagnosis or therapy.
Depo-Provera is contraindicated as a contraceptive at the above dosage in known or suspected hormone-dependent malignancy of breast or genital organs.
Depo-Provera is contraindicated in patients with the presence or history of severe hepatic disease whose liver function tests have not returned to normal.
Whether administered alone or in combination with oestrogen, Depo-Provera should not be employed in patients with abnormal uterine bleeding until a definite diagnosis has been established and the possibility of genital tract malignancy eliminated.
4.4 Special warnings and precautions for use
Assessment of women prior to starting hormonal contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindications (section 4.3) and warnings (section 4.4) for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.
Loss of Bone Mineral Density:
Use of depot medroxyprogesterone acetate intramuscular (DMPA-IM) reduces serum oestrogen levels and is associated with significant loss of BMD due to the known effect of oestrogen deficiency on the bone remodelling system. Bone loss is greater with increasing duration of use; however BMD appears to increase after DMPA-IM is discontinued and ovarian oestrogen production increases.
This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. It is unknown if use of DMPA-IM by younger women will reduce peak bone mass and increase the risk for fracture in later life i.e. after menopause.
A study to assess the BMD effects of DMPA-IM (Depo-Provera) in adolescent females showed that its use was associated with a statistically significant decline in BMD from baseline. After discontinuing DMPA-IM in adolescents, return of mean BMD to baseline values required 1.2 years at the lumbar spine, 4.6 years at the total hip and 4.6 years at the femoral neck (see section 5.1). However in some participants, BMD did not fully return to baseline during follow-up and the long-term outcome is not known in this group. In adolescents, Depo-Provera may be used, but only after other methods of contraception have been discussed with the patients and considered to be unsuitable or unacceptable.
A large observational study of predominantly adult female contraceptive users showed that use of DMPA-IM did not increase risk for bone fractures. Importantly, this study could not determine whether use of DMPA has an effect on fracture rate later in life (see section 5.1 – Relationship of fracture incidence to use of DMPA-IM by women of reproductive age).
In women of all ages, careful re-evaluation of the risks and benefits of treatment should be carried out in those who wish to continue use for more than 2 years. In particular, in women with significant lifestyle and/or medical risk factors for osteoporosis, other methods of contraception should be considered prior to use of Depo-Provera.
Significant risk factors for osteoporosis include:
• Alcohol abuse and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g. anticonvulsants or corticosteroids
• Low body mass index or eating disorder, e.g. anorexia nervosa or bulimia
• Previous low trauma fracture
• Family history of osteoporosis
For further information on BMD changes in both adult and adolescent females, refer to section 5.1.
Adequate intake of calcium and Vitamin D, whether from the diet or from supplements, is important for bone health in women of all ages.
Menstrual Irregularity: The administration of Depo-Provera usually causes disruption of the normal menstrual cycle. Bleeding patterns include amenorrhoea (present in up to 30% of women during the first 3 months and increasing to 55% by month 12 and 68% by month 24); irregular bleeding and spotting; prolonged (>10 days) episodes of bleeding (up to 33% of women in the first 3 months of use decreasing to 12% by month 12). Rarely, heavy prolonged bleeding may occur. Evidence suggests that prolonged or heavy bleeding requiring treatment may occur in 0.5-4 occasions per 100 women years of use. If abnormal bleeding persists or is severe, appropriate investigation should take place to rule out the possibility of organic pathology and appropriate treatment should be instituted when necessary. Excessive or prolonged bleeding can be controlled by the co-administration of oestrogen. This may be delivered either in the form of a low dose (30 micrograms oestrogen) combined oral contraceptive pill or in the form of oestrogen replacement therapy such as conjugated equine oestrogen (0.625-1.25 mg daily). Oestrogen therapy may need to be repeated for 1-2 cycles. Long-term co-administration of oestrogen is not recommended.
Return to Fertility: There is no evidence that Depo-Provera causes permanent infertility. Pregnancies have occurred as early as 14 weeks after a preceding injection, however, in clinical trials, the mean time to return of ovulation was 5.3 months following the preceding injection. Women should be counselled that there is a potential for delay in return to full fertility following use of the method, regardless of the duration of use, however, 83% of women may be expected to conceive within 12 months of the first "missed" injection (i.e. 15 months after the last injection administered). The median time to conception was 10 months (range 4-31) after the last injection.
Cancer Risks: Long-term case-controlled surveillance of Depo-Provera users found no overall increased risk of ovarian, liver, or cervical cancer and a prolonged, protective effect of reducing the risk of endometrial cancer in the population of users.
Breast cancer is rare among women under 40 years of age whether or not they use hormonal contraceptives.
Results from some epidemiological studies suggest a small difference in risk of the disease in current and recent users compared with never-users. Any excess risk in current or recent DMPA users is small in relation to the overall risk of breast cancer, particularly in young women (see below), and is not apparent after 10 years since last use. Duration of use does not seem to be important.
Possible number of additional cases of breast cancer diagnosed up to 10 years after stopping injectable progestogens*
Age at last use of DMPA
No of cases per 10,000 women who are never-users
Possible additional cases per 10,000 DMPA users
20
Less than 1
Much less than 1
30
44
2-3
40
160
10
*based on use for 5 years”
Weight Gain: There is a tendency for women to gain weight while on Depo-Provera therapy. Studies indicate that over the first 1-2 years of use, average weight gain was 5-8 lbs. Women completing 4-6 years of therapy gained an average of 14-16.5 lbs. There is evidence that weight is gained as a result of increased fat and is not secondary to an anabolic effect or fluid retention.
Anaphylaxis: Reports of anaphylactic responses (anaphylactic reactions, anaphylactic shock, anaphylactoid reactions) have been received.
Thrombo-embolic Disorders: Should the patient experience pulmonary embolism, cerebrovascular disease or retinal thrombosis while receiving Depo-Provera, the drug should not be re-administered.
Psychiatric Disorders: Patients with a history of endogenous depression should be carefully monitored. Some patients may complain of premenstrual-type depression while on Depo-Provera therapy.
Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use (see section 4.8). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.
Abscess formation: As with any intramuscular injection, especially if not administered correctly, there is a risk of abscess formation at the site of injection, which may require medical and/or surgical intervention.
Precautions:
History or emergence of the following conditions require careful consideration and appropriate investigation: migraine or unusually severe headaches, acute visual disturbances of any kind, pathological changes in liver function and hormone levels.
Patients with thromboembolic or coronary vascular disease should be carefully evaluated before using Depo-Provera.
A decrease in glucose tolerance has been observed in some patients treated with progestogens. The mechanism for this decrease is obscure. For this reason, diabetic patients should be carefully monitored while receiving progestogen therapy.
Rare cases of thrombo-embolism have been reported with use of Depo-Provera, but causality has not been established.
The effects of medroxyprogesterone acetate on lipid metabolism have been studied with no clear impact demonstrated. Both increases and decreases in total cholesterol, triglycerides and low-density lipoprotein (LDL) cholesterol have been observed in studies.
The use of Depo-Provera appears to be associated with a 15-20% reduction in serum high density lipoprotein (HDL) cholesterol levels which may protect women from cardiovascular disease. The clinical consequences of this observation are unknown. The potential for an increased risk of coronary disease should be considered prior to use.
Doctors should carefully consider the use of Depo-Provera in patients with recent trophoblastic disease before levels of human chorionic gonadotrophin have returned to normal.
Physicians should be aware that pathologists should be informed of the patient's use of Depo-Provera if endometrial or endocervical tissue is submitted for examination.
The results of certain laboratory tests may be affected by the use of Depo-Provera. These include gonadotrophin levels (decreased), plasma progesterone levels (decreased), urinary pregnanediol levels (decreased), plasma oestrogen levels (decreased), plasma cortisol levels (decreased), glucose tolerance test, metyrapone test, liver function tests (may increase), thyroid function tests (protein bound iodine levels may increase and T3 uptake levels may decrease). Coagulation test values for prothrombin (Factor II), and Factors VII, VIII, IX and X may increase.
Women should be counselled that Depo-Provera does not protect against sexually transmitted infections (STIs) including HIV infection (AIDS). Safer sex practices including correct and consistent use of condoms reduce the transmission of STIs through sexual contact, including HIV.
The benefits of contraceptive options and their risks must be evaluated individually for each woman.If any of the conditions/risk factors mentioned is present, the benefits of Depo-Provera use should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether Depo-Provera use should be discontinued.
Excipient information:
As this product contains methylparahydroxybenzoate and propylparahydroxybenzoate, it may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.
Depo-provera contains less than 1 mmol sodium (23 mg) per pre-filled syringe or vial, that is to say essentially 'sodium-free'.
4.5 Interaction with other medicinal products and other forms of interaction
Aminoglutethimide administered concurrently with Depo-Provera may significantly depress the bioavailability of Depo-Provera.
Interactions with other medicinal treatments (including oral anticoagulants) have rarely been reported, but causality has not been determined. The possibility of interaction should be borne in mind in patients receiving concurrent treatment with other drugs.
The clearance of medroxyprogesterone acetate is approximately equal to the rate of hepatic blood flow. Because of this fact, it is unlikely that drugs which induce hepatic enzymes will significantly affect the kinetics of medroxyprogesterone acetate. Therefore, no dose adjustment is recommended in patients receiving drugs known to affect hepatic metabolising enzymes.
Medroxyprogesterone acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects with CYP3A4 inducers or inhibitors on MPA have not been conducted and therefore the clinical effects of CYP3A4 inducers or inhibitors are unknown.
4.6 Fertility, pregnancy and lactation
Fertility:
Depo-Provera is indicated for the prevention of pregnancy.
Women may experience a delay in return to fertility (conception) following discontinuation of Depo-Provera (see section 4.4).
Pregnancy:
Depo-Provera is contraindicated in pregnancy.
Doctors should check that patients are not pregnant before initial injection of Depo-Provera, and also if administration of any subsequent injection is delayed beyond 89 days (12 weeks and five days).
Infants from accidental pregnancies that occur 1-2 months after injection of Depo-Provera may be at an increased risk of low birth weight, which in turn is associated with an increased risk of neonatal death. The attributable risk is low because such pregnancies are uncommon.
Children exposed to medroxyprogesterone acetate in utero and followed to adolescence, showed no evidence of any adverse effects on their health including their physical, intellectual, sexual or social development.
Lactation:
Medroxyprogesterone acetate and/or its metabolites are secreted in breast milk Infants exposed to medroxyprogesterone acetate via breast milk have been studied for developmental and behavioural effects to puberty. No adverse effects have been noted. However, due to limitations of the data regarding the effects of MPA in breastfed infants less than six weeks old, Depo-Provera should be given no sooner than six weeks post-partum when the infant's enzyme system is more developed.
4.7 Effects on ability to drive and use machines
Depo-Provera may cause headaches and dizziness. Patients should be advised not to drive or operate machinery if affected.
4.8 Undesirable effects
The table below provides a listing of adverse drug reactions with frequency based on all-causality data from clinical studies that enrolled more than 4200 women who received DMPA for contraception for up to 7 years. Those most frequently (>5%) reported adverse drug reactions were weight increased (69%), weight decreased (25%), headache (16%), nervousness (11%), abdominal pain or discomfort (11%), dizziness (6%), and decrease in libido (6%).
The following lists of adverse reactions are listed within the organ system classes, under headings of frequency (number of patients expected to experience the reaction), using the following categories:
Very common (≥1/10)
Common (≥1/100 to <1/10);
Uncommon (≥1/1000 to <1/100);
Rare (≥1/10,000 to <1/1000);
Very rare (<1/10,000);
Not known (cannot be estimated from the available data)
System Organ Class
Very Common ≥1/10
Common ≥ 1/100 to < 1/10
Uncommon ≥ 1/1000 to < 1/100
Rare ≥ 1/10,000 to < 1/1000
Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps)
Breast cancer
Blood and lymphatic system disorders
Anaemia, Blood disorder
Immune system disorders
Drug hypersensitivity
Anaphylactic reaction, Anaphylactoid reaction, Angioedema
Metabolism & Nutrition Disorder
Increased appetite, decreased appetite
Psychiatric disorders
Nervousness
Depression, Libido decreased
Insomnia
Anorgasmia, Emotional disturbance, Effective disorder, Irritability, Anxiety
Nervous system disorders
Headache
Dizziness
Seizure, Somnolence, Paraesthesia
Migraine, Paralysis, Syncope
Ear and Labyrinth Disorder
Vertigo
Cardiac disorder
Tachycardia
Vascular disorders
Hot flush
Embolism and thrombosis, Deep vein thrombosis, Thrombophlebitis, Hypertension, Varicose veins
Respiratory, thoracic, and mediastinal disorders
Dyspnoea
Pulmonary embolism
Gastrointestinal disorders
Abdominal pain, Abdominal discomfort
Nausea, Abdominal distension
Rectal haemorrhage, Gastrointestinal disorder
Hepatobiliary disorders
Hepatic function abnormal
Jaundice, Hepatic enzyme abnormal
Skin and subcutaneous tissue disorders
Alopecia, Acne, Rash
Hirsutism, Urticaria, Pruritus, Chloasma
Lipodystrophy acquired*, Dermatitis, Ecchymosis, Scleroderma, Skin striae
Musculoskeletal and connective tissue disorders
Back pain, Pain in extremity
Arthralgia, Muscle spasms, Osteoporosis, Osteoporotic fractures
Reproductive system and breast disorders
Vaginal discharge, Breast tenderness, Dysmenorrhea, Genitourinary tract infection
Dysfunctional uterine bleeding (irregular, increase, decrease, spotting, Galactorrhoea Pelvic pain, Dyspareunia, Suppressed lactation
Vaginitis, Amenorrhoea, Breast pain, Metrorrhagia, Menometrorrhagia, Menorrhagia,Vulvovaginal dryness, Breast atropy, Ovarian cyst, Premenstrual syndrome, Endometrial hyperplasia, Breast mass, Nipple exudate bloody, Vaginal cyst, Breast enlargement, Lack of return to fertility, Sensation of pregnancy
General disorders and administration site conditions
Oedema/Fluid retention, Asthenia
Chest pain
Pyrexia, Fatigue, Injection site reaction*, Injection site persistent atrophy/indentation/dimpling*, Injection site nodule/lump*, Injection site pain/tenderness* Thirst, Dysphonia, VIIth nerve paralysis, Axillary swelling
Investigation
Weight increased, Weight decreased
Bone density decreased, Glucose tolerance decreased, Cervical smear abnormal
*ADR identified post-marketing
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 at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
No positive action is required other than cessation of therapy.
5. Pharmacological properties
5.1 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
Parenteral medroxyprogesterone acetate (MPA) is a long acting progestational steroid. The long duration of action results from its slow absorption from the injection site. Immediately after injection of 150 mg/ml MPA, plasma levels were 1.7 ± 0.3 nmol/l. Two weeks later, levels were 6.8 ± 0.8 nmol/l. Concentrations fell to the initial levels by the end of 12 weeks. At lower doses, plasma levels of MPA appear directly related to the dose administered. Serum accumulation over time was not demonstrated. MPA is eliminated via faecal and urinary excretion. Plasma half-life is about six weeks after a single intramuscular injection. At least 11 metabolites have been reported. All are excreted in the urine, some, but not all, conjugated.
5.3 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
No data held.
6. |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmaceutical particulars - List of excipients | List of excipients
Methyl parahydroxybenzoate (E218)
Macrogol 3350
Polysorbate 80
Propyl parahydroxybenzoate (E216)
Sodium chloride
Hydrochloric acid
Sodium hydroxide
Water for injections
6.2 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmaceutical particulars - Incompatibilities | Incompatibilities
Not applicable.
6.3 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmaceutical particulars - Shelf life | Shelf life
Syringe: 3 years. Vial: 5 years.
6.4 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmaceutical particulars - Special precautions for storage | Special precautions for storage
Do not store above 25°C. Do not refrigerate or freeze. Vial: store upright.
6.5 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmaceutical particulars - Nature and contents of container | Nature and contents of container
1 ml suspension for injection in a pre-filled glass syringe with halobutyl rubber plunger stopper and halobutyl rubber tip cap, packed singly.
1 ml suspension for injection in glass vials with halobutyl rubber stopper and aluminium cap with a plastic flip off in pack sizes of 1 or 25 vials.
Not all pack sizes may be marketed.
6.6 |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Pharmaceutical particulars - Special precautions for disposal and other handling | Special precautions for disposal and other handling
No special requirements for disposal.
7. |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Marketing authorisation holder | Pfizer Limited Ramsgate Road Sandwich CT13 9NJUK
8. Marketing authorisation number(s)
PL 00057/0965
9. |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Date of first authorisation/renewal of the authorisation | Date of first authorisation: 27 August 1991 Date of latest renewal: 6 February 1997
10. |
Depo-Provera 150mg/ml Injection Sterile suspension for injection | Date of revision of the text | 07/2021
Ref.: DP 21_1 |
Dermacort Hydrocortisone Cream | Name of the medicinal product | Dermacort Hydrocortisone Cream
2. |
Dermacort Hydrocortisone Cream | Qualitative and quantitative composition | Dermacort Hydrocortisone Cream contains hydrocortisone B.P. 0.1% w/w in a specially formulated, lanolin-free cream base.
3. |
Dermacort Hydrocortisone Cream | Pharmaceutical form | Cream.
4. |
Dermacort Hydrocortisone Cream | Clinical particulars - Therapeutic indications | Therapeutic indications
Topical treatment of skin irritations, contact dermatitis, allergic contact dermatitis and rashes due to reactions to plants, insect bite, jewellery, toiletries, deodorants, soaps and detergents. Dermacort is also indicated for the treatment of mild to moderate eczema.
4.2 |
Dermacort Hydrocortisone Cream | Clinical particulars - Posology and method of administration | Posology and method of administration
For cutaneous use.
Method of administration
Adults and children over 10 years:
Apply a thin layer to cover the affected area once or twice a day.
Rub in gently until the cream disappears.
Do not use for more than one week.
4.3 |
Dermacort Hydrocortisone Cream | Clinical particulars - Contraindications | Contraindications
For external use only.
Hypersensitivity to hydrocortisone or to any other excipients listed in section 6.1.
Do not use on the eyes or face, the ano-genital region, on broken or infected skin.
As with all topical steroids, Dermacort is contra-indicated in the presence of viral, bacterial and fungal diseases of the skin.
4.4 |
Dermacort Hydrocortisone Cream | Clinical particulars - Special warnings and precautions for use | Special warnings and precautions for use
Instruct patients not to smoke or go near naked flames - risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.
Withdrawal and Misuse
Long term continuous or inappropriate use of topical steroids can result in the development of rebound flares after stopping treatment (topical steroid withdrawal syndrome). A severe form of rebound flare can develop which takes the form of a dermatitis with intense redness, stinging and burning that can spread beyond the initial treatment area. It is more likely to occur when delicate skin sites such as the face and flexures are treated. Should there be a reoccurrence of the condition within days to weeks after successful treatment a withdrawal reaction should be suspected. Reapplication should be with caution and specialist advise is recommended in these cases or other treatment options should be considered.
Visual disturbance
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
4.5 |
Dermacort Hydrocortisone Cream | Clinical particulars - Interaction with other medicinal products and other forms of interaction | Interaction with other medicinal products and other forms of interaction
None known
4.6 |
Dermacort Hydrocortisone Cream | Clinical particulars - Fertility, pregnancy and lactation | Fertility, pregnancy and lactation
Pregnancy
There is inadequate evidence of safety in human pregnancy. Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intrauterine growth retardation.
Dermacort should not be used during pregnancy.
4.7 |
Dermacort Hydrocortisone Cream | Clinical particulars - Effects on ability to drive and use machines | Effects on ability to drive and use machines
Not applicable.
4.8 |
Dermacort Hydrocortisone Cream | Clinical particulars - Undesirable effects | Undesirable effects
Eye disorders: Frequency uncommon: Vision, blurred (see also section 4.4).Dermacort is normally well tolerated, but if signs of hypersensitivity appear application should stop immediately.
Skin and Subcutaneous Tissue Disorders: Not known (cannot be estimated from available data) Withdrawal reactions - redness of the skin which may extend to areas beyond the initial affected area, burning or stinging sensation, itch, skin peeling, oozing pustules. (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 website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 |
Dermacort Hydrocortisone Cream | Clinical particulars - Overdose | Overdose
Acute overdosage is very unlikely to occur, however, in the case of chronic overdosage or misuse, the features of hypercorticism may appear and in this situation topical steroids should be discontinued.
5. Pharmacological properties
5.1 |
Dermacort Hydrocortisone Cream | Pharmacodynamic properties - Pharmacodynamic properties | Pharmacokinetic properties
The cream formulation of Dermacort was developed in order to optimise the release and partition of its active ingredient, hydrocortisone, into the skin. The hydrocortisone is presented as a saturated or near saturated solution in aqueous propylene glycol, which represents the continuous phase of the emulsion system. It has been shown, by the vasoconstrictor assay on normal skin, that in this environment, a 0.1% concentration of the hydrocortisone is equivalent to the 1% concentration where the drug substance is in suspension. Clinical studies have confirmed that 0.1% Dermacort is equivalent to 1.0% hydrocortisone cream BP/BPC whilst the reduced strength of Dermacort increases the margin of safety.
5.3 |
Dermacort Hydrocortisone Cream | Pharmacodynamic properties - Pharmacokinetic properties | Preclinical safety data
None applicable.
6. |
Dermacort Hydrocortisone Cream | Pharmaceutical particulars - List of excipients | List of excipients
Propylene Glycol
Emulsifying Ointment
Citric Acid
Purified Water
6.2 |
Dermacort Hydrocortisone Cream | Pharmaceutical particulars - Incompatibilities | Incompatibilities
None applicable.
6.3 |
Dermacort Hydrocortisone Cream | Pharmaceutical particulars - Shelf life | Shelf life
24 months.
6.4 |
Dermacort Hydrocortisone Cream | Pharmaceutical particulars - Special precautions for storage | Special precautions for storage
None.
6.5 |
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