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Dantrium 25mg Capsules
Pharmacodynamic properties - Pharmacokinetic properties
Preclinical safety data Carcinogenicity Dantrolene sodium showed some evidence of tumourgenicity at high dose levels in Sprague-Dawley female rats. However, these effects were not seen in other studies in Fischer 344 rats or HaM/ICR mice. There is no clinical evidence of carcinogenicity in humans; however, this possibility cannot be absolutely excluded. Sprague-Dawley female rats fed dantrolene sodium for 18 months at dosage levels of 15, 30 and 60 mg/kg/day showed an increased incidence of benign and malignant mammary tumours compared with concurrent controls. At the highest dose level, there was an increase in the incidence of benign hepatic lymphatic neoplasms. In a 30-month study at the same dose levels also in Sprague-Dawley rats, dantrolene sodium produced a decrease in the time of onset of mammary neoplasms. Female rats at the highest dose level showed an increased incidence of hepatic lymphangiomas and hepatic angiosarcomas. The only drug-related effect seen in a 30-month study in Fischer-344 rats was a dose-related reduction in the time of onset of mammary and testicular tumours. A 24-month study in HaM/ICR mice revealed no evidence of carcinogenic activity. The significance of carcinogenicity data relative to use of dantrolene sodium in humans is unknown. Mutagenicity Dantrolene sodium has produced positive results in the Ames S.Typhimurium bacterial mutagenesis assay in the presence and absence of a liver activating system. Reproductive toxicity Dantrolene sodium administered to male and female rats at dose levels up to 45 mg/kg/day showed no adverse effects on fertility or general reproductive performance. 6.
Dantrium 25mg Capsules
Pharmaceutical particulars - List of excipients
List of excipients Capsule content Wheat starch Talc Magnesium stearate Lactose monohydrate Capsule Shell Gelatine Titanium dioxide (E171) Erythrosine (127) Iron oxide 6.2
Dantrium 25mg Capsules
Pharmaceutical particulars - Incompatibilities
Incompatibilities Not applicable. 6.3
Dantrium 25mg Capsules
Pharmaceutical particulars - Shelf life
Shelf life 3 years 6.4
Dantrium 25mg Capsules
Pharmaceutical particulars - Special precautions for storage
Special precautions for storage Store capsules in the blister and outer packaging away from light and moisture. 6.5
Dantrium 25mg Capsules
Pharmaceutical particulars - Nature and contents of container
Nature and contents of container Polyvinyl chloride/aluminium Blister Packs. . 6.6
Dantrium 25mg Capsules
Pharmaceutical particulars - Special precautions for disposal and other handling
Special precautions for disposal and other handling No special requirements. A patient leaflet is provided for details of use and handling of the product. 7.
Dantrium 25mg Capsules
Marketing authorisation holder
Norgine Pharmaceuticals Limited Norgine House Widewater Place Moorhall Road Harefield Uxbridge UB9 6NS UK 8. Marketing authorisation number(s) PL 20011/0032 9.
Dantrium 25mg Capsules
Date of first authorisation/renewal of the authorisation
25 October 1989 10.
Dantrium 25mg Capsules
Date of revision of the text
04th January 2022
Dantrium IV 20 mg powder for solution for injection
Name of the medicinal product
Dantrium® IV 20mg 2.
Dantrium IV 20 mg powder for solution for injection
Qualitative and quantitative composition
Each vial contains 20mg dantrolene sodium. For the full list of excipients, see 6.1. 3.
Dantrium IV 20 mg powder for solution for injection
Pharmaceutical form
Powder for solution for injection. 4.
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Therapeutic indications
Therapeutic indications In combination with adequate support measures, Dantrium IV is indicated in adults and children in the treatment of malignant hyperthermia. 4.2
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Posology and method of administration
Posology and method of administration Posology Dantrium IV should be administered by rapid intravenous injection at least 2.5mg/kg body weight (8-10 vials in adults). As long as the main clinical symptoms of tachycardia, hypoventilation, sustained hyperacidity (pH and pCO2 monitoring required) and hyperthermia persist, bolus injection should be repeated. In most cases, a total dose of 10mg/kg body weight per 24hr is sufficient. This dose (10mg/kg) may need to be exceeded in individual cases. Safe uses up to 40mg/kg have been described. Based on this experience, higher dosages can be administered in isolated cases if required. Paediatric population No dosage adjustment required. Method of administration For intravenous administration. Each vial should be prepared by adding 60ml of sterile water for injection and the vial shaken until the solution is dissolved. The reconstituted solution should be filtered using the single use filter provided. For instructions on reconstitution and filtration of the medicinal product before administration, see section 6.6. 4.3
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Contraindications
Contraindications Hypersensitivity to dantrolene or to any of the excipients listed in section 6.1. 4.4
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Special warnings and precautions for use
Special warnings and precautions for use The use of Dantrium IV in the management of malignant hyperthermic crisis is not a substitute for other supportive measures. These must be individually continued in their various forms. Dantrium IV may only be infused intravenously. Due to the high pH value of the solution (pH 9.5), extravascular injection/infusion must be avoided as it can lead to tissue necrosis. Due to the risk of vascular occlusion, intraarterial injections must be avoided. Spill of the solution on skin should be avoided. If solution gets on the skin, it must be removed with sufficient water. In addition, due to the potential for undissolved crystals/particles to appear in the re-constituted product and the subsequent potential risk of exacerbation of injection site reactions/tissue necrosis from crystals within affected vials, use of the filtration device when drawing up the solution is required at all times. Each vial of Dantrium IV contains 3g mannitol (for adjustment of isotonic solutions). This amount should be considered if mannitol is used to prevent and treat renal complications related to malignant hyperthermia. Caution should be exercised if hyperkalaemia symptoms occur (muscular paralysis, ECG changes, bradycardic arrhythmias) or in cases of pre-existing hyperkalaemia (renal insufficiency, digitalis intoxication etc.), as an increase in serum potassium has been demonstrated in animal trials as a result of dantrolene. Liver damage may occur during dantrolene therapy. This is dependent on the dosage and duration of therapy and may run a lethal course. This medicine contains less than 1mmol sodium (23mg) per vial that is to say essentially “sodium free”. 4.5
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Interaction with other medicinal products and other forms of interaction
Interaction with other medicinal products and other forms of interaction Isolated case reports and animal studies indicate an interaction between dantrolene and calcium channel blockers, such as verapamil and diltiazem, in the form of heart failure. It is recommended that Dantrium IV and calcium channel blockers should not be used at the same time. Concomitant administration of Dantrium IV with non-depolarising muscle relaxants such as vecuronium can enhance their effect. 4.6
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Fertility, pregnancy and lactation
Fertility, pregnancy and lactation Pregnancy There are no or limited data from the use of dantrolene in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Dantrolene crosses the placenta, and should be given only when the potential benefits have been weighed against the possible risk to mother and child. Breast-feeding No information is available on the use of dantrolene sodium during breastfeeding. According to its safety profile, a risk to a breastfed infant cannot be excluded as dantrolene is excreted in breastmilk. Therefore, breastfeeding should be discontinued during administration of Dantrium IV. Based on the elimination half-life of dantrolene, breastfeeding can be restarted 60 hours after the last dose. Fertility Data on the effects of dantrolene on fertility in humans are not available. 4.7
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Effects on ability to drive and use machines
Effects on ability to drive and use machines Dantrium IV has major influence on the ability to drive and use machinery, as it can lead to weakness, dizziness and light-headedness. This applies particularly in combination with alcohol or other medicines that depress the central nervous system. 4.8
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Undesirable effects
Undesirable effects Tabulated list of adverse reactions Adverse Drug Reactions related to dantrolene sodium are presented below according to system organ class and frequency. Frequencies are defined according to: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1000 to < 1/100) Rare (≥ 1/10000 to < 1/1000) Very rare (<1/10000) Not known: frequency could not be estimated due to the present data System Organ Class Frequency Adverse Drug Reaction Immune system disorders Unknown Allergic reactions, anaphylaxis Metabolism and nutrition disorders Unknown Hyperkalaemia Nervous system disorders Unknown Drowsiness, dizziness, general weakness, somnolence, convulsion, speech disorder, headache Cardiac disorders Unknown Cardiac failure, bradycardia, tachycardia Vascular disorders Unknown Thrombophlebitis Respiratory, thoracic and mediastinal disorders Unknown Pulmonary oedema, Pleural effusion, respiratory failure, respiratory depression Gastrointestinal disorders Unknown Abdominal pain/cramps, nausea, vomiting, gastrointestinal bleeding, diarrhoea Hepatobiliary disorders Unknown Jaundice, hepatitis, hepatic dysfunction including fatal hepatic failure, idiosyncratic or hypertensive liver diseases Skin and subcutaneous disorders Unknown Urticaria, erythema, hyperhidrosis Musculoskeletal and connective tissue disorders Unknown Muscle weakness, muscle fatigue Renal and urinary disorders Unknown Crystalluria Reproductive system and breast disorders Unknown Uterine hypotonia General disorders and administration site conditions Unknown Fatigue, administration site reactions Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. 4.9
Dantrium IV 20 mg powder for solution for injection
Clinical particulars - Overdose
Overdose None stated. 5. Pharmacological properties 5.1
Dantrium IV 20 mg powder for solution for injection
Pharmacodynamic properties - Pharmacodynamic properties
Pharmacokinetic properties Distribution Dantrolene is reversibly bound to plasma albumin; as an in vitro binding constant, a value of 4.3x104M -1 was established. For the transplacental passage of dantrolene, a factor of 0.4 was found. Metabolism Metabolism in the liver takes place through microsomal enzymes both via 5-hydroxylation at the hydantoin ring and via reduction of the nitro group to amine with subsequent acetylation. 5-hydroxydantrolene has similar activity to that of the parent substance, while the aceamino dantrolene does not have any muscle relaxant effect. Elimination Excretion is mainly renal and biliary, whereby renal excretion takes place, even in long-term use, at a ration of 79% 5-hydroxydantrolene, 17% acetylamino-dantrolene and 1 to 4% unchanged dantrolene. Renal clearance (5-OH-dantrolene) is 1.8 to 7.8L/h. Following intravenous administration, the average elimination half-life of dantrolene is variable, generally it is between 4 and 8 hours, in a malignant hyperthermia patient it is 12 hours. Pharmacokinetic studies in children have shown an average elimination half-life of approximately 7.4 to 12.6 hours. 5.3
Dantrium IV 20 mg powder for solution for injection
Pharmacodynamic properties - Pharmacokinetic properties
Preclinical safety data Acute toxicity Non clinical data for intravenous administration are not available. Following intraperitoneal administration, the LD50 is around 800 mg/kg body weight in rats (human equivalent dose 129 mg/kg) and following oral administration the LD50 is around 3 g/kg in newborn rats (human equivalent dose 484 mg/kg). No LD50 values could be determined following oral administration to adult animals, due to a lack of mortality. With subacute intravenous administration of dantrolene at doses of up to 20 mg/kg/day, the sole observations were reduced body weight gain in rats (human equivalent dose 3.2 mg/kg) and hepatic changes in dogs (human equivalent dose 11.1 mg/kg). Chronic toxicity In chronic toxicity studies, rats, dogs and monkeys oral administration of >30 mg/kg/day (human equivalent dose 4.8 mg/kg, 16.2 mg/kg and 9.6 mg/kg, respectively) for 12 months led to a reduction of growth or body weight gain. Hepatotoxic effects and possibly renal obstruction were observed, which were reversible. Mutagenicity Dantrolene yielded positive results in the Ames S. typhyimurium test both in the present and absence of a liver activating system. Carcinogenicity Dietary doses of dantrolene sodium in rats at doses of up to 60 mg/kg/day (human equivalent dose 9.6 mg/kg) for to 18 months resulted in increases in benign hepatic lymphatic neoplasms, increased hepatic lymphangiomas and hepatic angiosarcomas, and in females only, an increase in mammary tumours. The relevance of these data for clinical use of dantrolene is not known. Reproductive toxicity In male and female adult rats dantrolene up to an oral dose of 45 mg/bodyweight/day (human equivalent dose 7.3 mg/kg/day) did not have any adverse effects on fertility or general reproductive capability Administration of dantrolene to pregnant rabbits (45 mg/kg/day; human equivalent dose 14.5 mg/kg/day) led to increased formation of unilateral or bilateral supernumerary ribs in the pups. 6.
Dantrium IV 20 mg powder for solution for injection
Pharmaceutical particulars - List of excipients
List of excipients Mannitol Sodium hydroxide 6.2
Dantrium IV 20 mg powder for solution for injection
Pharmaceutical particulars - Incompatibilities
Incompatibilities Dantrium IV should not be mixed with other intravenous infusions. 6.3
Dantrium IV 20 mg powder for solution for injection
Pharmaceutical particulars - Shelf life
Shelf life Three years. The reconstituted solution should be used within six hours. 6.4
Dantrium IV 20 mg powder for solution for injection
Pharmaceutical particulars - Special precautions for storage
Special precautions for storage Unopened product: Do not store above 25°C. Reconstituted solution: store between 15 and 25°C. Do not refrigerate or freeze. Protect from direct light. 6.5
Dantrium IV 20 mg powder for solution for injection
Pharmaceutical particulars - Nature and contents of container
Nature and contents of container Type I glass vial with bromobutyl rubber stopper and an aluminium cap with a polypropylene flip-off disk. Each vial is provided with a single-use filtration device. Supplied in packs of 12 or 36 vials. Not all pack sizes may be marketed. 6.6
Dantrium IV 20 mg powder for solution for injection
Pharmaceutical particulars - Special precautions for disposal and other handling
Special precautions for disposal and other handling Reconstitution Each vial of Dantrium IV should be reconstituted by adding 60ml of water for injection Ph.Eur, and shaken until the powder is dissolved. Filter the reconstituted product with the single-use filtration device provided when drawing up the solution into the syringe. The reconstituted solution must be used within 6 hours but filtered immediately before use. Remove the filtration device from the syringe prior to attachment to an intravenous cannula or giving set. Discard the filtration device and product vial in an approved sharps collector. Use a new filtration device with every vial of Dantrium IV. Administer Dantrium IV immediately upon filtration. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Only use the filtration device provided. 7.
Dantrium IV 20 mg powder for solution for injection
Marketing authorisation holder
Norgine Pharmaceuticals Limited Norgine House, Widerwater Place Moorhall Road, Harefield Uxbridge UB9 6NS UK 8. Marketing authorisation number(s) PL 20011/0034 9.
Dantrium IV 20 mg powder for solution for injection
Date of first authorisation/renewal of the authorisation
14/02/1980 10.
Dantrium IV 20 mg powder for solution for injection
Date of revision of the text
30 November 2022
Dapsone 100mg
Name of the medicinal product
Dapsone 100 mg tablets 2.
Dapsone 100mg
Qualitative and quantitative composition
Each tablet contains 100 mg dapsone. Excipient with known effect: 27.50 mg of lactose per tablet of Dapsone 100 mg tablets. For the full list of excipients, see section 6.1. 3.
Dapsone 100mg
Pharmaceutical form
Tablets White or slightly yellowish, round, biconvex tablets, debossed with “D” on one side and with a score line on the other side. The tablet can be divided into equal doses. 4.
Dapsone 100mg
Clinical particulars - Therapeutic indications
Therapeutic indications 1) As part of a multi-drug regimen in the treatment of all forms of leprosy. 2) Treatment of dermatitis herpetiformis and other dermatoses. 3) Prophylaxis of malaria in combination with pyrimethamine. 4) Prophylaxis of Pneumocystis carinii pneumonia in immunodeficient subjects, especially AIDS patients. 4.2
Dapsone 100mg
Clinical particulars - Posology and method of administration
Posology and method of administration Posology Adults and children over 12 years: Multibacillary leprosy (3-drug regimen): 100mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 100mg daily for at least six months. Malaria prophylaxis: 100mg weekly with 12.5mg pyrimethamine. Dermatitis herpetiformis: Initially 50mg daily, gradually increased to 300mg daily if required. Once lesions have begun to subside, the dose should be reduced to a minimum as soon as possible, usually 25-50mg daily, which may be continued for a number of years. Maintenance dosage can often be reduced in patients receiving a gluten-free diet. Pneumocystis carinii pneumonia: In combination with trimethoprim, 50-100mg daily; 100mg twice weekly or 200mg once weekly. Children 6-12 years: Multibacillary leprosy (3-drug regimen): 50mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 50mg daily for at least six months. Children under the age of 6 years: The safety and efficacy of Dapsone in children aged less than six years has not been established. No data are available. Elderly: Dosage should be reduced in the elderly where there is an impairment of hepatic function. Method of Administration For oral administration. Tablets should be swallowed whole with a glass of water. 4.3
Dapsone 100mg
Clinical particulars - Contraindications
Contraindications • Hypersensitivity to dapsone or any of the excipients listed in section 6.1 • severe anaemia • porphyria • severe glucose-6-phosphate dehydrogenase deficiency. Dapsone contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. 4.4
Dapsone 100mg
Clinical particulars - Special warnings and precautions for use
Special warnings and precautions for use Dapsone should be used with caution in patients with cardiac or pulmonary disease. It is recommended that regular blood counts be performed during treatment with dapsone. Patients deficient in glucose-6-phosphate dehydrogenase, or methaemoglobin reductase, or with haemoglobin M are more susceptible to the haemolytic effects of dapsone. Dapsone should be used with caution in anaemia. Severe anaemia should be treated before starting Dapsone. 4.5
Dapsone 100mg
Clinical particulars - Interaction with other medicinal products and other forms of interaction
Interaction with other medicinal products and other forms of interaction Oral typhoid vaccine: should not be taken until at least three days after finishing a course of dapsone, because the dapsone could make this vaccine less effective. Probenecid: Excretion of dapsone is reduced and plasma concentrations are increased by concurrent administration of probenecid. Rifampicin/ Rifabutin: has been reported to increase the plasma clearance of dapsone. Saquinavir: should not be used in combination, as this could increase the risk of irregular heartbeat. Trimethoprim: Increased dapsone and trimethoprim concentrations have been reported following concurrent administration in AIDs patients. 4.6
Dapsone 100mg
Clinical particulars - Fertility, pregnancy and lactation
Fertility, pregnancy and lactation Pregnancy It is now generally considered that the benefits of dapsone in the treatment of leprosy outweigh any potential risk to the pregnant patient. Some leprologists recommend 5mg folic acid daily for leprosy patients receiving dapsone during pregnancy. Breast-feeding Dapsone diffuses into breast milk and there has been a report of haemolytic anaemia in a breast fed infant. While some feel that dapsone should not be used in lactating mothers, in general treatment for leprosy is continued in such patients. Fertility There is limited information available on the effect of dapsone on fertility; it may reduce the numbers and / or motility of sperm, thereby rendering impregnation less likely. 4.7
Dapsone 100mg
Clinical particulars - Effects on ability to drive and use machines
Effects on ability to drive and use machines Dapsone has no or negligible influence on the ability to drive and use machines. 4.8
Dapsone 100mg
Clinical particulars - Undesirable effects
Undesirable effects Dapsone should be discontinued, or reduced in dosage, if severe lepra reactions affecting the eyes or nerve trunks occur. The frequencies of undesirable effects are reported according to the following convention: Very common ≥ 1/10 users Rare ≥1/10,000users; <1/1000 users Common ≥1/100users; <1/10 users Very rare <1/10,000 users Uncommon ≥1/1000users; <1/100 users Unknown Cannot be estimated System Organ Class(SOC) Frequency Undesirable effect Blood Disorders: Common Haemolysis1 Methaemoglobinaemia1 Uncommon Haemolytic anaemia Rare Agranulocytosis2 Cardiac Disorders: Uncommon Tachycardia Gastrointestinal Disorders: Uncommon Anorexia Nausea Vomiting General Disorders: Rare Dapsone Syndrome3 Hepatic Disorders: Uncommon Hepatitis Jaundice Changes in liver function tests Metabolic Disorders: Uncommon Hypoalbuminaemia Nervous System Disorders: Uncommon Headache Neuropathy peripheral4 Peripheral motor neuropathy4 Psychiatric Disorders: Uncommon Insomnia Psychoses Skin Disorders: Uncommon Photosensitivity Pruritis Rash Rare Exfoliative dermatitis Maculopapular rash Toxic epidermal necrolysis Stevens – Johnson syndrome Very rare Fixed drug eruptions 1) – these are the most frequently reported adverse effects of dapsone and are dose related; occurring in most subjects administered more than 200 mg daily; doses of up to 100 mg daily do not cause significant haemolysis, but subjects deficient in glucose-6-phosphate dehydrogenase are affected by doses above about 50 mg daily. 2) – this is rare when dapsone is used alone; reports are more common when dapsone has been used with other medicines for malarial prophylaxis. 3) – this may occur following 3 – 6 weeks of therapy; symptoms include rash (always present), fever and eosinophilia. Id dapsone is not stopped immediately; the syndrome may progress to exfoliative dermatitis, hepatitis, albuminuria, and psychosis. Deaths have been recorded. The majority of patients require steroid therapy for several weeks; this is possibly due to prolonged elimination time of dapsone. 4) – peripheral neuropathy may occur as part of leprosy reaction states and it is not an indication to discontinue dapsone. 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
Dapsone 100mg
Clinical particulars - Overdose
Overdose Symptoms:hypoxia, methaemoglobinaemia and haemolytic anaemia. Treatment: In severe over-dosage the stomach should be emptied by gastric lavage. Administration of activated charcoal by mouth has been shown to enhance the elimination of dapsone and its monoacetyl metabolite. Methaemoglobinaemia has been treated with slow IV injections of methylene blue 1-2mg/kg bodyweight, repeated after one hour if necessary. Methylene blue should not be administered to patients with glucose-6-phosphate dehydrogenase deficiency since it will not be effective. Haemolysis has been treated by infusion of concentrated human red blood cells to replace the damaged cells. Supportive therapy includes oxygen to alleviate hypoxia, and administration of fluids to maintain renal flow and promote the elimination of dapsone. 5. Pharmacological properties 5.1
Dapsone 100mg
Pharmacodynamic properties - Pharmacodynamic properties
Pharmacokinetic properties Absorption Following oral administration, dapsone is almost completely absorbed from the gastrointestinal tract, with reported bioavailability exceeding 86 %. Peak serum concentrations are reached within 2 h – 8 h. Post ingestion of a single 50 mg – 300 mg dose of dapsone, maximum serum concentrations range from 0.63 mg/L to 4.82 mg/L. Under steady state conditions, the most frequently used dose of 100 mg/day, results in serum concentrations of maximum 3.26 mg/L, and a minimum, at 24 h, of 1.95 mg/L. Steady state concentrations are not achieved until after at least 8 days daily administration. Distribution Dapsone is 50% – 80% bound to plasma proteins, whereas the principal metabolite, monoacetyldapsone is almost completely bound to plasma proteins. Dapsone is distributed to almost all organs, and is retained in the skin, muscle, kidneys, and liver, with trace concentrations present in these tissues up to 3 weeks post discontinuation. Dapsone is distributed into sweat, saliva, sputum, tears, and bile. It crosses the blood – brain barrier, and the placenta, and is excreted in breast milk. The half-life ranges from 10 h – 80 h. Biotransformation Post absorption, dapsone undergoes enterohepatic recirculation. It is metabolised by the liver, and additionally by activated polymorphonuclear leukocytes and mononuclear cells. In the liver dapsone is primarily metabolised via acetylation by Nacetyltransferase to monoacetyldapsone, and through hydroxylation by cytochrome P450 enzymes, resulting in the generation of dapsone hydroxylamine. Dapsone hydroxylamine may be responsible for dapsone associated methaemoglobinaemia and haemolysis. Acetylation exhibits genetic polymorphism, with both rapid and slow acetylators. Elimination Around 20 % of dapsone is excreted, unchanged, via urine, with 70 % – 80 % of the dose being eliminated as water soluble metabolites following conjugation with glucuronic acid. A small amount of the dose may be excreted in faeces, including some unidentified metabolites. Linearity/non-linearity The drug shows linear pharmacokinetics within the therapeutic range. 5.3
Dapsone 100mg
Pharmacodynamic properties - Pharmacokinetic properties
Preclinical safety data There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC. 6.
Dapsone 100mg
Pharmaceutical particulars - List of excipients
List of excipients Lactose monohydrate; Maize starch; Sodium laurilsulfate (E 487); Colloidal anhydrous silica (E 551); Magnesium stearate (E 470b). 6.2
Dapsone 100mg
Pharmaceutical particulars - Incompatibilities
Incompatibilities Not applicable. 6.3
Dapsone 100mg
Pharmaceutical particulars - Shelf life
Shelf life 36 months 6.4
Dapsone 100mg
Pharmaceutical particulars - Special precautions for storage
Special precautions for storage This medicinal product does not require any special storage conditions. 6.5
Dapsone 100mg
Pharmaceutical particulars - Nature and contents of container
Nature and contents of container Dapsone 100 mg Tablets are packed in white Alu-PVC blister. Pack containing 28 tablets is available. 6.6
Dapsone 100mg
Pharmaceutical particulars - Special precautions for disposal and other handling
Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 7.
Dapsone 100mg
Marketing authorisation holder
Rivopharm UK Ltd., 30th Floor, 40 Bank Street, Canary Wharf London E14 5NR United Kingdom 8. Marketing authorisation number(s) PL 33155/0084 9.
Dapsone 100mg
Date of first authorisation/renewal of the authorisation
02/07/2020 10.
Dapsone 100mg
Date of revision of the text
02/07/2020
Dapsone 100mg Tablets
Name of the medicinal product
Dapsone 100 mg Tablets 2.
Dapsone 100mg Tablets
Qualitative and quantitative composition
Each tablet contains 100mg of dapsone. For the full list of excipients, see section 6.1. 3.
Dapsone 100mg Tablets
Pharmaceutical form
Tablet White to off white, round tablets, debossed with "HP" on one side and scored on the other side with debossing "99" as "9 │ 9". The tablet can be divided into equal doses. 4.
Dapsone 100mg Tablets
Clinical particulars - Therapeutic indications
Therapeutic indications Dapsone is indicated for the treatment of the following infections (see section 5.1): 1) As part of a multidrug regimen in the treatment of all forms of leprosy. 2) Treatment of dermatitis herpetiformis and other dermatoses. 3) Prophylaxis of Pneumocystis carinii pneumonia in immunodeficient subjects, especially AIDS patients. Consideration should be given to official guidance on the appropriate use of antibacterial agents. 4.2
Dapsone 100mg Tablets
Clinical particulars - Posology and method of administration
Posology and method of administration Posology Adults and children over 12 years: Multibacillary leprosy (3-drug regimen): 100mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 100mg daily for at least six months. Dermatitis herpetiformis: Initially 50mg daily, gradually increased to 300mg daily if required. Once lesions have begun to subside, the dose should be reduced to a minimum as soon as possible, usually 25-50mg daily, which may be continued for a number of years. Maintenance dosage can often be reduced in patients receiving a gluten-free diet. Pneumocystis carinii pneumonia: In combination with trimethoprim, 50-100mg daily; 100mg twice weekly or 200mg once weekly. Paediatric population Children 6-12 years: Multibacillary leprosy (3-drug regimen): 50mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 50mg daily for at least six months. Elderly population: Dosage should be reduced in the elderly where there is an impairment of hepatic function. Method of administration For oral administration. 4.3
Dapsone 100mg Tablets
Clinical particulars - Contraindications
Contraindications Hypersensitivity to dapsone, sulfonamides, sulfones or any of the excipients listed in section 6.1. Severe anaemia; porphyria; severe glucose-6-phosphate dehydrogenase deficiency. 4.4
Dapsone 100mg Tablets
Clinical particulars - Special warnings and precautions for use
Special warnings and precautions for use Dapsone should be used with caution in patients with cardiac or pulmonary disease. It is recommended that regular blood counts be performed during treatment with dapsone. Patients deficient in glucose-6-phosphate dehydrogenase, or methaemoglobin reductase, or with haemoglobin M are more susceptible to the haemolytic effects of dapsone. Dapsone should be used with caution in anaemia. Severe anaemia should be treated before starting Dapsone. 4.5
Dapsone 100mg Tablets
Clinical particulars - Interaction with other medicinal products and other forms of interaction
Interaction with other medicinal products and other forms of interaction Excretion of dapsone is reduced and plasma concentrations are increased by concurrent administration of probenecid. Rifampicin has been reported to increase the plasma clearance of dapsone. Increased dapsone and trimethoprim concentrations have been reported following concurrent administration in AIDS patients. 4.6
Dapsone 100mg Tablets
Clinical particulars - Fertility, pregnancy and lactation
Fertility, pregnancy and lactation Pregnancy It is now generally considered that the benefits of dapsone in the treatment of leprosy outweigh any potential risk to the pregnant patient. Some leprologists recommend 5mg folic acid daily for leprosy patients receiving dapsone during pregnancy. Breast-feeding Dapsone diffuses into breast milk and there has been a report of haemolytic anaemia in a breast fed infant. While some feel that dapsone should not be used in lactating mothers, in general treatment for leprosy is continued in such patients. 4.7
Dapsone 100mg Tablets
Clinical particulars - Effects on ability to drive and use machines
Effects on ability to drive and use machines None known. 4.8
Dapsone 100mg Tablets
Clinical particulars - Undesirable effects
Undesirable effects Dapsone should be discontinued or reduced in dosage if severe lepra reactions affecting the eyes or nerve trunks occur. The frequencies of undesirable effects are reported according to the following convention: Very Common: ≥ 1 / 10 users; Common: ≥ 1 / 100; < 1 / 10 users; Uncommon: ≥ 1 / 1,000; < 1 / 100 users; Rare: > 1 / 10,000; < 1 / 1,000 users; Very Rare: < 1 / 10,000 users; Unknown: Cannot be estimated System Organ Class (SOC) Frequency Undesirable Effect Blood disorders Common   Uncommon Rare Haemolysis1 Methemoglobinaemia1 Haemolytic anaemia Agranulocytosis* Cardiac disorders Uncommon Tachycardia Gastrointestinal disorders Uncommon Anorexia Nausea Vomiting General disorders Rare Dapsone syndrome2 Hepatic disorders Uncommon Hepatitis Jaundice Changes in liver function tests Metabolic disorders Uncommon Hypoalbuminaemia Nervous system disorders Uncommon Headache Peripheral Neuropathy3 Peripheral motor neuropathy3 Psychiatric disorders Uncommon Insomnia Psychosis Skin disorders Uncommon    Rare     Very rare Rash Photosensitivity Pruritis Maculopapular rash Exfoliative dermatitis Toxic epidermal necrolysis Stevens-Johnson syndrome Fixed drug eruptions * Although agranulocytosis has been reported rarely with dapsone when used alone, reports have been more common when dapsone has been used with other agents in the prophylaxis of malaria. 1 these are the most frequently reported adverse effects of dapsone and occur in most subjects given more than 200mg daily; doses of up to 100mg daily do not cause significant haemolysis but subjects deficient in glucose-6-phosphate dehydrogenase are affected by doses above approximately 50mg daily. 2 this may occur after 3-6 weeks therapy; symptoms include rash, which is always present, fever, and eosinophilia. If dapsone is not stopped immediately, the syndrome may progress to exfoliative dermatitis, hepatitis, albuminuria and psychosis. Deaths have been recorded. Most patients require steroid therapy for several weeks, possibly due to the prolonged elimination time of the drug. 3 Peripheral neuropathy may occur as part of leprosy reaction states and it is not an indication to discontinue dapsone. 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
Dapsone 100mg Tablets
Clinical particulars - Overdose
Overdose Symptoms are hypoxia, methaemoglobinaemia and haemolytic anaemia. In severe overdosage the stomach should be emptied by gastric lavage. Administration of activated charcoal by mouth has been shown to enhance the elimination of dapsone and its monoacetyl metabolite. Methaemoglobinaemia has been treated with slow IV injections of methylene blue 1-2mg/kg bodyweight, repeated after one hour if necessary. Methylene blue should not be administered to patients with glucose-6-phosphate dehydrogenase deficiency, since it will not be effective. Haemolysis has been treated by infusion of concentrated human red blood cells to replace the damaged cells. Supportive therapy includes oxygen to alleviate hypoxia and administration of fluids to maintain renal flow and promote the elimination of dapsone. 5. Pharmacological properties 5.1
Dapsone 100mg Tablets
Pharmacodynamic properties - Pharmacodynamic properties
Pharmacokinetic properties Absorption: Following oral administration, dapsone is almost completely absorbed from the gastrointestinal tract, with reported bioavailability exceeding 86 %. Peak serum concentrations are reached within 2 h – 8 h. Post ingestion of a single 50 mg – 300 mg dose of dapsone, maximum serum concentrations range from 0.63 mg/L to 4.82 mg/L. Under steady state conditions, the most frequently used dose of 100 mg/day, results in serum concentrations of maximum 3.26 mg/L, and a minimum, at 24 h, of 1.95 mg/L. Steady state concentrations are not achieved until after at least 8 days daily administration. Distribution: Dapsone is 50 % – 80 % bound to plasma proteins, whereas the principal metabolite, monoacetyldapsone is almost completely bound to plasma proteins. Dapsone is distributed to almost all organs, and is retained in the skin, muscle, kidneys, and liver, with trace concentrations present in these tissues up to 3 weeks post discontinuation. Dapsone is distributed into sweat, saliva, sputum, tears, and bile. It crosses the blood – brain barrier, and the placenta, and is excreted in breast milk. The half life ranges from 10 h – 80 h. Biotransformation: Post absorption, dapsone undergoes enterohepatic recirculation. It is metabolised by the liver, and additionally by activated polymorphonuclear leukocytes and mononuclear cells. In the liver dapsone is primarily metabolised via acetylation by N-acetyltransferase to monoacetyldapsone, and through hydroxylation by cytochrome P-450 enzymes, resulting in the generation of dapsone hydroxylamine. Dapsone hydroxylamine may be responsible for dapsone associated methaemoglobinaemia and haemolysis. Acetylation exhibits genetic polymorphism, with both rapid and slow acetylators. Elimination: Around 20 % of dapsone is excreted, unchanged, via urine, with 70 % – 80 % of the dose being eliminated as water soluble metabolites following conjugation with glucuronic acid. A small amount of the dose may be excreted in faeces, including some unidentified metabolites. Linearity/non – linearity: The drug shows linear pharmacokinetics within the therapeutic range. 5.3
Dapsone 100mg Tablets
Pharmacodynamic properties - Pharmacokinetic properties
Preclinical safety data There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC. 6.
Dapsone 100mg Tablets
Pharmaceutical particulars - List of excipients
List of excipients Also contains: Maize starch Silica colloidal anhydrous Magnesium stearate Microcrystalline cellulose 6.2
Dapsone 100mg Tablets
Pharmaceutical particulars - Incompatibilities
Incompatibilities Not applicable 6.3
Dapsone 100mg Tablets
Pharmaceutical particulars - Shelf life
Shelf life 2 years 6.4
Dapsone 100mg Tablets
Pharmaceutical particulars - Special precautions for storage
Special precautions for storage This medicinal product does not require any special storage conditions. 6.5
Dapsone 100mg Tablets
Pharmaceutical particulars - Nature and contents of container
Nature and contents of container Unit Dose Blister packs consisting of Aluminium lidding material Foil Plain-Paper/PET/Al and base film PVC/PVDC. Dapsone 100mg Tablets are available in packs of 28 tablets. Not all pack sizes may be marketed. 6.6
Dapsone 100mg Tablets
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.
Dapsone 100mg Tablets
Marketing authorisation holder
Tillomed Laboratories Ltd220 Butterfield, Great Marlings, Luton, LU2 8DL United Kingdom 8. Marketing authorisation number(s) PL 11311/0576 9.
Dapsone 100mg Tablets
Date of first authorisation/renewal of the authorisation
10/04/2018 10.
Dapsone 100mg Tablets
Date of revision of the text
27/04/2023
Dapsone 100mg Tablets
Name of the medicinal product
Dapsone 100mg Tablets 2.
Dapsone 100mg Tablets
Qualitative and quantitative composition
Each tablet contains 100mg Dapsone 3.
Dapsone 100mg Tablets
Pharmaceutical form
White uncoated tablets. White to off-white, uncoated, circular, biconvex tablets debossed "100" above and “D” below the score on one side and plain on the other side. Tablet size: 7.5 mm The tablet can be divided into equal doses. 4.
Dapsone 100mg Tablets
Clinical particulars - Therapeutic indications
Therapeutic indications 1) As part of a multi-drug regimen in the treatment of all forms of leprosy. 2) Treatment of dermatitis herpetiformis. 3) Prophylaxis of Pneumocystis jirovecii pneumonia in immunodeficient subjects, especially AIDS patients. 4.2
Dapsone 100mg Tablets
Clinical particulars - Posology and method of administration
Posology and method of administration Posology Adults and children over 12 years: Multibacillary leprosy (3-drug regimen): 100mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 100mg daily for at least six months. Dermatitis herpetiformis: Initially 50mg daily, gradually increased to 300mg daily if required. Once lesions have begun to subside, the dose should be reduced to a minimum as soon as possible, usually 25-50mg daily, which may be continued for a number of years. Maintenance dosage can often be reduced in patients receiving a gluten-free diet. Pneumocystis jirovecii pneumonia: In combination with trimethoprim, 50-100mg daily; 100mg twice weekly or 200mg once weekly. Paediatric population: Children 6-12 years: Multibacillary leprosy (3-drug regimen): 50mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 50mg daily for at least six months. Children aged less than 6 years: The safety and efficacy of Dapsone in children aged less than six years has not been established. No data are available. Elderly: Dosage should be reduced in the elderly where there is an impairment of hepatic function. Method of Administration For oral administration. 4.3
Dapsone 100mg Tablets
Clinical particulars - Contraindications
Contraindications Hypersensitivity to dapsone, sulfonamides, sulfones, or any of the excipients listed in section 6.1. Severe anaemia; porphyria; severe glucose-6-phosphate dehydrogenase deficiency; severe liver disease. 4.4
Dapsone 100mg Tablets
Clinical particulars - Special warnings and precautions for use
Special warnings and precautions for use Dapsone should be used with caution in patients with cardiac or pulmonary disease. It is recommended that regular blood counts be performed during treatment with dapsone. Patients deficient in glucose-6-phosphate dehydrogenase, or methaemoglobin reductase, or with haemoglobin M are more susceptible to the haemolytic effects of dapsone. Dapsone should be used with caution in anaemia. Severe anaemia should be treated before starting Dapsone. 4.5
Dapsone 100mg Tablets
Clinical particulars - Interaction with other medicinal products and other forms of interaction
Interaction with other medicinal products and other forms of interaction Excretion of dapsone is reduced and plasma concentrations are increased by concurrent administration of probenecid. Rifampicin has been reported to increase the plasma clearance of dapsone. Increased dapsone and trimethoprim concentrations have been reported following concurrent administration in AIDs patients. Oral typhoid vaccine should not be taken until at least three days after finishing a course of dapsone, because the dapsone could make this vaccine less effective. Saquinavir should not be used in combination, as this could increase the risk of irregular heartbeat. 4.6
Dapsone 100mg Tablets
Clinical particulars - Fertility, pregnancy and lactation
Fertility, pregnancy and lactation Pregnancy It is now generally considered that the benefits of dapsone in the treatment of leprosy outweigh any potential risk to the pregnant patient. Some leprologists recommend 5mg folic acid daily for leprosy patients receiving dapsone during pregnancy. Breast-feeding Dapsone diffuses into breast milk and there has been a report of haemolytic anaemia in a breast fed infant. While some feel that dapsone should not be used in lactating mothers, in general treatment for leprosy is continued in such patients. Fertility There are no data on fertility in humans available. 4.7
Dapsone 100mg Tablets
Clinical particulars - Effects on ability to drive and use machines
Effects on ability to drive and use machines None known. 4.8
Dapsone 100mg Tablets
Clinical particulars - Undesirable effects
Undesirable effects Dapsone should be discontinued or reduced in dosage if severe lepra reactions affecting the eyes or nerve trunks occur. The frequencies of undesirable effects are reported according to the following convention: Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) not known (cannot be estimated from the available data) System Organ Class (SOC) Frequency Undesirable Effect Blood disorders Common Hemolysis1 Methemoglobinaemia1 Uncommon Hemolytic anaemia Rare Agranulocytosis2 Cardiac disorders Uncommon Tachycardia Gastrointestinal disorders Uncommon Anorexia Nausea Vomiting General disorders Rare Dapsone syndrome3 Hepatic disorders Uncommon Hepatitis Jaundice Changes in liver function tests Metabolic disorders Uncommon Hypoalbuminaemia Nervous system disorders Uncommon Headache Neuropathy Peripheral4 Peripheral motor neuropathy4 Psychiatric disorders Uncommon Insomnia Psychosis Skin disorders Uncommon Rash Photosensitivity Pruritis Rare Maculopapular rash Exfoliative dermatitis Toxic epidermal necrolysis Stevens-Johnson syndrome Very rare Fixed drug eruptions 1 these are the most frequently reported adverse effects of dapsone and occur in most subjects given more than 200mg daily; doses of up to 100mg daily do not cause significant haemolysis but subjects deficient in glucose-6-phosphate dehydrogenase are affected by doses above approximately 50mg daily. 2 although agranulocytosis has been reported rarely with dapsone when used alone, reports have been more common when dapsone has been used with other agents in the prophylaxis of malaria. 3 this may occur after 3-6 weeks therapy; symptoms include rash, which is always present, fever, and eosinophilia. If dapsone is not stopped immediately, the syndrome may progress to exfoliative dermatitis, hepatitis, albuminuria and psychosis. Deaths have been recorded. Most patients require steroid therapy for several weeks, possibly due to the prolonged elimination time of the drug. 4 peripheral neuropathy may occur as part of leprosy reaction states and it is not an indication to discontinue dapsone. 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
Dapsone 100mg Tablets
Clinical particulars - Overdose
Overdose Symptoms are hypoxia, methaemoglobinaemia and haemolytic anaemia. In severe overdosage the stomach should be emptied by gastric lavage. Administration of activated charcoal by mouth has been shown to enhance the elimination of dapsone and its monoacetyl metabolite. Methaemoglobinaemia has been treated with slow IV injections of methylene blue 1-2mg/kg bodyweight, repeated after one hour if necessary. Methylene blue should not be administered to patients with glucose-6-phosphate dehydrogenase deficiency since it will not be effective. Haemolysis has been treated by infusion of concentrated human red blood cells to replace the damaged cells. Supportive therapy includes oxygen to alleviate hypoxia, and administration of fluids to maintain renal flow and promote the elimination of dapsone. 5. Pharmacological properties 5.1
Dapsone 100mg Tablets
Pharmacodynamic properties - Pharmacodynamic properties
Pharmacokinetic properties Absorption: Following oral administration, dapsone is almost completely absorbed from the gastrointestinal tract, with reported bioavailability exceeding 86 %. Peak serum concentrations are reached within 2 h - 8 h. Post ingestion of a single 50 mg – 300 mg dose of dapsone, maximum serum concentrations range from 0.63 mg/L to 4.82 mg/L. Under steady state conditions, the most frequently used dose of 100 mg/day, results in serum concentrations of maximum 3.26 mg/L, and a minimum, at 24 h, of 1.95 mg/L. Steady state concentrations are not achieved until after at least 8 days daily administration. Distribution: Dapsone is 50-80% bound to plasma proteins, whereas the principal metabolite, monoacetyldapsone is almost completely bound to plasma proteins. Dapsone is distributed to almost all organs and is retained in the skin, muscle, kidneys and liver, with trace concentrations present in these tissues up to 3 weeks post discontinuation. Dapsone is distributed into sweat, saliva, sputum, tears and bile. It crosses the blood-brain barrier and the placenta, and is excreted in breast milk. The half-life ranges from 10 h - 80 h. Biotransformation: Post absorption, dapsone undergoes enterohepatic recirculation. It is metabolised by the liver, and additionally by activated polymorphonuclear leukocytes and mononuclear cells. In the liver dapsone is primarily metabolised via acetylation by N- acetyltransferase to monoacetyldapsone and through hydroxylation by cytochrome P-450 enzymes, resulting in the generation of dapsone hydroxylamine. Dapsone hydroxylamine may be responsible for dapsone associated methaemoglobinaemia and haemolysis. Acetylation exhibits genetic polymorphism, with both rapid and slow acetylators. Elimination: Around 20 % of dapsone is excreted, unchanged, via urine, with 70 % – 80 % of the dose being eliminated as water soluble metabolites following conjugation with glucuronic acid. A small amount of the dose may be excreted in faeces, including some unidentified metabolites. Linearity/non – linearity: The drug shows linear pharmacokinetics within the therapeutic range. 5.3
Dapsone 100mg Tablets
Pharmacodynamic properties - Pharmacokinetic properties
Preclinical safety data There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC. 6.
Dapsone 100mg Tablets
Pharmaceutical particulars - List of excipients
List of excipients Cellulose, microcrystalline (Grade – 102) Maize starch Silica colloidal anhydrous Magnesium stearate 6.2
Dapsone 100mg Tablets
Pharmaceutical particulars - Incompatibilities
Incompatibilities None known. 6.3
Dapsone 100mg Tablets
Pharmaceutical particulars - Shelf life
Shelf life 3 years 6.4
Dapsone 100mg Tablets
Pharmaceutical particulars - Special precautions for storage
Special precautions for storage This medicinal product does not require any special storage condition. 6.5
Dapsone 100mg Tablets
Pharmaceutical particulars - Nature and contents of container
Nature and contents of container Dapsone 100mg tablets are available in White opaque PVC-Aluminium foil blister pack Blister pack sizes: 28 tablets 6.6
Dapsone 100mg Tablets
Pharmaceutical particulars - Special precautions for disposal and other handling
Special precautions for disposal and other handling Not applicable. 7.
Dapsone 100mg Tablets
Marketing authorisation holder
Milpharm Limited Ares Block, Odyssey Business Park, West End Road, Ruislip, HA4 6QD United Kingdom 8. Marketing authorisation number(s) PL 16363/0646 9.