1. NAME OF THE MEDICINAL PRODUCT. Each tablet contains 100mg minocycline (as hydrochloride).

Transcription

1 1. NAME OF THE MEDICINAL PRODUCT Minocycline 100 mg Film-coated Tablets. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 100mg minocycline (as hydrochloride). For excipients, see section PHARMACEUTICAL FORM Film-coated tablet. The tablets are light yellow round, biconvex tablets. 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Minocycline is a broad spectrum antibiotic used for the treatment of infections caused by tetracycline-sensitive organisms. Some tetracycline-resistant strains of staphylococci are also sensitive. Typical indications include: Gonorrhoea, non-gonococcal urethritis, prostatitis, acne, acute and chronic bronchitis, bronchiectasis, lung abscess, pneumonia, ear, nose and throat infections, urinary tract infections, pelvic inflammatory disease (e.g. salpingitis, oophoritis), skin and soft tissue infections caused by minocycline-sensitive organisms, ophthalmological infections, nocardiosis, prophylactic treatment of asymptomatic meningococcal carriers, preand post-operative prophylaxis of infection Posology and method of administration Adults Routine antibiotic use: The recommended adult dose is 200 mg daily in divided doses. Acne: The recommended adult dose for acne is 50 mg twice daily for a minimum of 6 weeks. Gonorrhoea: In adult males, the recommended dose for Gonorrhoea is 200 mg initially, followed by 100mg every 12 hours for a minimum of 4 days with post-therapy cultures within 2-3 days. Adult females may require more prolonged therapy.

2 Prophylaxis of asymptomatic meningococcal carriers: The recommended adult dose is 100 mg twice daily for 5 days, usually followed by a course of rifampicin. Use in patients with renal impairment Minocycline may be used at the normal recommended dosage in patients with mild to moderate renal impairment. However, in cases of severe renal insufficiency, reduction of dosage and monitoring of renal function may be required. Use in patients with impaired hepatic function See under Special Warning and Precautions for Use Use in the elderly: Minocycline may be used in the normal recommended dose in elderly patients. Children over 12 years of age For children above 12 years of age, the recommended dosage of minocycline is 50 mg every 12 hours. Children under 12 years of age Minocycline is not recommended for children under 12 years old. Administration To reduce the risk of oesophageal irritation and ulceration, the tablets should be swallowed whole with plenty of fluid, while sitting or standing. Unlike earlier tetracyclines, absorption of minocycline is not significantly impaired by food or moderate amounts of milk. Treatment of acne should be continued for a minimum of 6 weeks. If, after 6 months, there is no satisfactory response minocycline should be discontinued and other therapies considered. If minocycline is to be continued for longer than 6 months, patients should be monitored at least 3 monthly thereafter for signs and symptoms of hepatitis or SLE or unusual pigmentation (see 4.4 Special warning and precautions for use) Contraindications Patients with a known hypersensitivity to minocycline, any of the tablet excipients or to any of the tetracyclines. Minocycline is contraindicated in pregnancy and lactation (see under 4.6 Pregnancy and lactation) and in children under 12 years old. Patients with complete renal failure Special warning and precautions for use Minocycline should be used with caution in patients with hepatic dysfunction and in conjunction with alcohol and other hepatotoxic drugs. It is recommended that alcohol consumption should remain within the Government s recommended limits. Rare cases of auto-immune hepatotoxicity and isolated cases of systemic lupus erythematosus (SLE) and

3 also exacerbation of pre-existing SLE have been reported. If patients develop signs or symptoms of SLE or hepatotoxicity, or suffer exacerbation of pre-existing SLE, minocycline should be discontinued. Clinical studies have shown that there is no significant drug accumulation in patients with renal impairment when they are treated with minocycline in the recommended doses. In cases of severe renal insufficiency, reduction of dosage and monitoring of renal function may be required. Cross-resistance between tetracyclines may develop in micro-organisms and cross sensitisation in patients. Minocycline should be discontinued if there are signs/symptoms of overgrowth of resistant organisms e.g. enteritis, glossitis, stomatitis, vaginitis, pruritus ani or staphylococcal enteritis. Patients taking oral contraceptives should be warned that if diarrhoea or break through bleeding occur there is a possibility of contraceptive failure. As with other tetracyclines, minocycline may cause hyperpigmentation at various body sites (see under 4.2 Posology and method of administration and 4.8 Undesirable effects). Hyperpigmentation may present regardless of dose or duration of therapy but develops more commonly during long term treatment. Patients should be advised to report any unusual pigmentation without delay and minocycline should be discontinued. If photosensitivity occurs, patients should be warned to avoid exposure to natural or artificial light and to discontinue therapy at the first sign of discomfort. Use in children: the use of tetracyclines during tooth development in children under the age of 12 years may cause permanent discolouration. Enamel hypoplasia has also been reported Interaction with other medicinal products and other forms of interaction Minocycline should not be used with penicillins. Tetracyclines depress plasma prothrombin activity and reduced doses of concomitant anticoagulants may be necessary. Absorption of minocycline is impaired by the concomitant administration of antacids, bismuth, iron, calcium, magnesium, aluminium and zinc salts. It is recommended that any indigestion remedies, vitamins or other supplements containing these salts are taken at least 3 hours before or after a dose of minocycline. Unlike earlier tetracyclines, absorption of minocycline is not significantly impaired by food or moderate amounts of milk. Diuretics may aggravate nephrotoxicity by volume depletion. Tetracyclines bind to di-/tri-valent cations. The concomitant use of tetracyclines may decrease the efficacy of oral contraceptives Pregnancy and lactation

4 Minocycline is contraindicated in pregnancy and in breast feeding mothers. Results of animal studies indicate that tetracyclines cross the placenta, are found in foetal tissues and can have toxic effects on the developing foetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy. There is a risk of skeletal development retardation in the unborn child. The use of drugs of the tetracycline class during tooth development (exposure during the last half of pregnancy, lactation and in developing children) may cause permanent discolouration of the teeth (yellow-grey-brown). This adverse reaction is more common during long term use of the drugs but has been observed following repeated short term courses. Enamel hypoplasia has also been reported. Tetracyclines have been found in the milk of lactating women who are taking a drug in this class. Permanent tooth discolouration may occur in the developing infant and enamel hypoplasia has been reported (See section 4.4 Warning and precautions for use) Effects on ability to drive and use machines Patients should be warned about the possible hazards of driving or operating machines during treatment due to the following undesirable effects which have occurred during treatment with minocycline: headache, light-headedness, dizziness, vertigo and rarely, impaired hearing and tinnitus Undesirable effects In common with other tetracyclines gastrointestinal disturbances including nausea, vomiting, anorexia and diarrhoea may occur. A few cases of oesophagitis and oesophageal ulceration have been reported, usually when tablets are taken before bed or with inadequate amounts of fluids. Dermatological reactions such as erythema multiforme, erythema nodosum, Stevens Johnson Syndrome, exfoliative dermatitis, hair loss and photosensitivity have been reported, as well as maculopapular and erythematous rashes and, rarely, fixed drug eruptions. The most commonly reported skin rash is hypersensitivity. Hypersensitivity reactions can include urticaria, fever, arthralgia, myalgia, arthritis, pulmonary infiltration, wheezing, angioneurotic oedema, anaphylaxis and anaphylactoid purpura. Rarely pericarditis, myocarditis, vasculitis and renal failure including interstitial nephritis have been reported. Cases of systemic lupus erythematosus (SLE) and also exacerbation of pre-existing SLE have been reported. Headache, light-headedness, dizziness, vertigo and rarely, impaired hearing and tinnitus have occurred with minocycline. As with other tetracyclines bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported. Some presenting symptoms are headache and visual disturbances including blurred vision, scotoma and diplopia. Treatment should cease if evidence of raised intracranial pressure develops. Blood: haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia have been reported with tetracyclines.

5 In common with other tetracyclines, transient increase in liver function test values and rarely hepatitis and acute liver failure have been reported. Some hepatic reactions have an auto-immune basis, and may occur after several months of minocycline treatment (see under 4.2 Posology and method of administration ). There have been some isolated incidences of pancreatitis. Hyperpigmentation of various body sites including the skin, nails, teeth, oral mucosa, bones, thyroid, eyes (including sclera and conjunctiva), breast milk, lacrimal secretions and perspiration has been reported. This blue/black/grey or muddy-brown discolouration may be localised or diffuse. The most frequently reported site is the skin. Pigmentation is often reversible on discontinuation of the drug, although it may take several months or may persist in some cases. The generalised muddy-brown skin pigmentation may persist, particularly in areas exposed to the sun. As with all antibiotics overgrowth of non-susceptible organisms may cause candidiasis, pseudominas colitis (Clostridium difficile overgrowth), glossitis, stomatitis, vaginitis or staphylococcal enterocolitis Overdose There is no specific antidote to overdose with minocycline. In the event of overdose, gastric lavage plus appropriate supportive treatment is indicated. 5. PHARMACOLOGICAL PROPERTIES 5.1. Pharmacodynamic properties Minocycline is an antibiotic with a broad spectrum of activity similar to other tetracyclines. Minocycline is more active against many species than tetracycline hydrochloride. Some tetracycline-resistant strains of staphylococci are also sensitive to minocycline. The efficacy of minocycline against some tetracycline-resistant staphylococci is reported in vitro, and also occurs against some tetracycline-resistant streptococci, Escherichia coli and Haemophilus influenza Pharmacokinetic properties Minocycline is almost completely absorbed after oral administration. Absorption is not significantly affected by the presence of food or milk. Doses of 200mg followed by 100mg every 12 hours produce plasma concentrations of 1 to 4 mg per ml. Minocycline has a lower renal clearance that doxycycline with a plasma half-life of hours in patients with normal renal function. Plasma half life increases in renal impairment and following continuous administration.

6 Minocycline is more lipid-soluble than doxycycline and other tetracyclines and is widely distributed in body tissues and fluids including the CSF. It crosses the placenta and is excreted in breast milk Preclinical safety data No relevant preclinical safety data to the prescriber have been generated apart from that already detailed in the Summary of Product Characteristics. 6. PHARMACEUTICAL PARTICULARS 6.1. List of excipients Povidone Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Colloidal silica, anhydrous Magnesium stearate Hypromellose Macrogol 6000 Yellow iron oxide E172 Titanium dioxide E Incompatibilities Not applicable Shelf life 36 months Special precautions for storage Do not store above 30 C. Store in the original package Nature and contents of container

7 PVC/PVDC // Aluminium blisters containing 28, 50, 56 or 84 tablets Instructions for use handling (, and disposal) Not applicable. 7. MARKETING AUTHORISATION HOLDER PLIVA Pharma Ltd. Vision House Bedford Road Petersfield Hampshire GU32 3QB United Kingdom 8. MARKETING AUTHORISATION NUMBER PL 10622/ DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 12/03/ DATE OF REVISION OF THE TEXT 12/03/2009