COMPOSITION: Each tablet contains:
Minocycline hydrochloride equivalent to Minocycline 50 mg.
PHARMACOLOGICAL CLASSIFICATION: A20.1.1 Broad and medium spectrum antibiotics.
PHARMACOLOGICAL ACTION: Tetracyclines are bacteriostatic antibiotics which inhibit bacterial growth by binding to the 30s ribosomal sub unit with consequent misreading of information for protein synthesis. They are effective in vitro against the following organisms (In vitro activity does not necessarily imply in vivo efficacy):
Vibrio cholerae, Ureaplasma urealyticum, Mycoplasma pneumoniae; Chlamydia trachomatis, Chlamydia psittaci, Borrelia recurrentis, Calymmatobacterium granulomatis, Borrelia burgdorferi, penicillin-sensitive Neisseria gonorrhoeae and Rickettsiae;
Tetracyclines are also effective against the following organisms in vitro:
Haemophilus ducreyi, Actinomyces israelii; Francisella tularensis; Treponema pertenue. RESISTANT PATHOGENS Many of the following strains are resistant:
Fungi and yeasts (except Actinomyces)
Pseudomonas aeruginosa (all strains)
Minocycline is well absorbed and its half-life is long (16 18 hour). Plasma concentrations at the usual dosage range, are between 1 3 µg/mL.
Minocycline is widely distributed into pleural and peritoneal fluid, saliva, semen and prostatic fluid.
It passes the placental barrier readily and is also present in the milk of lactating patients.
It is concentrated by the liver and excreted, by way of bile, into the intestine from which it is partially re-absorbed.
Minocycline is recoverable from both urine and faeces and it appears to be metabolised to a considerable extent. Renal clearance of minocycline is low. Minocycline persists in the body after its administration is stopped, this may be due to retention in fatty tissues.
INDICATIONS: Infections caused by susceptible strains of pathogens: Upper and lower respiratory tract infections: Sinusitis, pharyngitis, Mycoplasma pneumonia, psittacosis and chronic bronchitis. Genito-urinary tract infections: Non-specific urethritis (only if the strain is sensitive), lymphogranuloma venereum, chancroid and granuloma inguinale, gonococcal salpingitis, epididymitis, acute epididymo-orchitus, endocervical infections, syphilis and gonorrhoea (in cases of penicillin allergy); Soft tissue: Acne Ophthalmic: Trachoma and inclusion conjunctivitis. Intestinal: Cholera, Whipple's disease and tropical sprue. Miscellaneous: Rickettsial infections, brucellosis, tularaemia, actinomycosis, Lyme disease, yaws, relapsing fever, leptospirosis during the early ineffective phase.
CONTRA-INDICATIONS: In patients with impaired renal function.
Allergy to any tetracycline. Tetracyclines should not be given in pregnancy. Tetracyclines cross the placenta and are deposited in foetal bones and teeth.
Pregnant women are particularly susceptible to severe tetracycline-induced liver damage.
Should not be given to lactating women or to children younger than 12 years of age as permanent discoloration of the child's teeth may occur.
Should not be given to patients with systemic lupus erythematosus.
WARNINGS: Care should be taken if tetracyclines are given to patients with impaired liver function and high doses should be avoided. Potentially hepatotoxic medicine (including erythromycin, chloramphenicol, isoniazid, and sulphonamides) should not be given concomitantly; the risk of nephrotoxicity may be increased if given with methoxyflurane or other potentially nephrotoxic medications.
Patients who may be exposed to direct sunlight should be warned of the risk of photosensitivity.
Care is advisable in patients with myasthenia gravis, who may be at risk of neuromuscular blockade. Vestibular side-effects including dizziness or vertigo may occur with minocycline, particularly in women. Patients should be advised not to drive or operate machinery if affected.
Minocycline has also been associated with pigmentation of the skin and other tissues. Pigmentation may occur as blue-black macules occurring in areas of inflammation and scarring and possibly due to an iron-chelate of minocycline within macrophoges, as blue-grey macules or hyperpigmentation affecting normal skin and which may be due to a break-down product of minocycline, or as a greyish-brown discoloration occurring particularly in sun-exposed areas of skin (muddy skin syndrome) apparently due to melanin deposition. Skin pigmentation appears to resolve slowly in discontinuing the agent.
DOSAGE AND DIRECTIONS FOR USE:
200 mg initially, followed by 100 mg every 12 hours.
Initially 50-100 mg twice daily; followed by a maintenance dose of 50 mg twice daily.
The absorption of minocycline from the gastro-intestinal tract is not significantly affected by the presence of food or moderate amounts of milk.
Therapy should be continued for at least 24 - 48 hours after symptoms of fever have subsided.
SIDE EFFECTS AND SPECIAL PRECAUTIONS: Gastro-intestinal effects including nausea, vomiting and diarrhoea are common especially with high doses and most are attributed to irritation of the mucosa. Other effects that have been reported include dry mouth, glossitis; stomatitis and dysphagia. Oral candidiasis, vulvovaginitis, and pruritis ani occur mainly due to overgrowth with candida albicans and there may be overgrowth of resistant coliform organisms; such as Pseudomonas spp., and Proteus spp. causing diarrhoea. More serious superinfection with resistant staphylococci causing enterocolitis, and also pseudomembranous colitis due to colostridium difficile have been reported.
Usual therapeutic doses given to patients with renal disease increases the diversity of uraemia with increased secretion of Nitrogen and losses of Sodium, accompanied by acidosis and hyperphosphataemia. These effects are related to the dose and severity of renal impairment and are probably due to the anti-anabolic effects of the minocycline. Severe and sometimes fatal hepatotoxicity associated with fatty changes in the liver and pancreatitis has been reported in patients with renal impairment or those given high doses.
Tetracyclines are deposited in deciduous and permanent teeth during their formation, causing discoloration and enamel hypoplasia. They are also deposited in calcifying areas in bone and the nails and interfere with bone growth when given in therapeutic doses to young infants or pregnant women.
An increase in intracranial pressure with headache; visual disturbances, and papilloedema has been reported in patients given minocycline; the use of minocycline in infants has been associated with a bulging fontanelle. If raised intracranial pressure occurs minocycline treatment should be stopped.
Hypersensitivity reactions, including rashes, fixed drug eruptions; exfoliative dermatitis; toxic epidermal necrolysis; drug fever, pericarditis, angioedema, urticaria, and asthma have been reported; anaphylaxis has occurred less frequently. Photosensitivity appears to be phototoxic and not photoallergic in nature. Paraesthesia may be an early sign of impending phototoxicity. Nail discoloration and onycholysis may occur. Abnormal pigmentation of the skin and eye has occurred rarely: permanent discoloration of the cornea has been reported in infants born to mothers given tetracycline in high doses during pregnancy. Myopia may be due to transient hydration of the lens.
Haemolytic anaemia, eosinophilia, neutropenia, and thrombocytopenia have been reported. Minocycline may produce hypoprothrombinaemia. Minocycline has also been associated with reductions in serum-vitamin B concentrations, including a case of folate deficiency and concomitant megaloblastic anaemia.
The use of out-of-date or deteriorated minocycline has been associated with the development of a reversible Fanconi-type syndrome characterised by polyuria and polydipsia with nausea, glycosuria, aminoaciduria, hypophosphataemia, hypokalaemia and hyperuricaemia with acidosis and proteinuria; these effects have been attributed to the presence of degradation products.
Other adverse effects that have been reported include myopathy, increased muscle weakness in patients with myasthenia gravis, and provocation of lupus erythematosus.
INTERACTIONS: The absorption of minocycline is reduced by the concomitant administration of iron preparations and antacids containing calcium, magnesium and aluminium salts. Doses of anticoagulant may need to be reduced if given concomitantly. Because of the possible antagonism of the action of the penicillins by predominately bacteriostatic tetracylines it has been recommended that the two types of antibiotic should not be given concomitantly.
Minocycline may diminish the effectiveness of oral contraceptives.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: In the event of sensitivity reactions treatment should be withdrawn. Symptoms should be treated symptomatically and supportively.
Brown-yellow bi-convex film-coated tablets. One sided score notch.
Diameter: +6,8 mm
PRESENTATION: 50 mg tablet: packs of 60 tablets
STORAGE INSTRUCTIONS: Store in airtight containers. Protect from light.
Keep out of reach of children.
REGISTRATION NUMBER: 29/20.1.1/0570
NAME AND BUSINESS ADDRESS OF APPLICANT: Hexal Pharma (SA) (PTY) Ltd
10 Fangio Road
DATE OF PUBLICATION OF THIS PACKAGE INSERT: August 1996