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Round, biconvex, beige coloured, film coated tablets, 6 mm in diameter, engraved with interlocking script LL on one side and M50 on the other.
Microbiology
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis.
Minocycline is a semisynthetic derivative of tetracycline and is active against many tetracycline resistant strains of organisms such as staphylococci, streptococci and E. coli. Thus the combined results of many studies show its activity against approximately 87% of tetracycline resistant staphylococci. Minocycline is also active against many strains of staphylococci which are resistant to penicillin G and certain semisynthetic penicillins.
Tube dilution testing. Microorganisms may be considered susceptible if the MIC (minimum inhibitory concentration) is not more than 4 mg/mL, partially resistant if the MIC is 4 to 12.5 mg/mL and resistant if the MIC is more than 12.5 mg/mL.
Susceptibility plate testing. If the Kirby-Bauer method (using a 30 mg minocycline disc) gives a zone of 18 mm or more, the bacterial strain is considered to be susceptible to any tetracycline. For strains resistant to other tetracyclines, minocycline susceptibility powder may be used for additional susceptibility testing.
Minocycline is rapidly absorbed after oral administration and absorption is not significantly impaired by ingestion of food or milk. After single oral doses of 150 mg in humans, minocycline yields serum levels that are generally 2 to 4 times higher than those of most other tetracyclines at all time intervals. When serum activity is determined against a standard of tetracycline, 150 mg of minocycline gives activity levels 16 or more times higher than 250 mg of tetracycline at 24 to 48 hours, this difference being largely due to the much longer serum half life of minocycline.
Minocycline is widely distributed in body tissues, with higher concentrations being found in cerebrospinal fluid and sputum than with other tetracycline analogues. As in blood, the concentration in tissues is generally 2 to 4 times higher with minocycline than with tetracycline.
Following a single dose of two 100 mg minocycline HCL capsules administered to ten normal adult volunteers, serum levels ranged from 0.74 to 4.45 mg/mL in one hour and attained peak levels between 2 and 3 hours; after 12 hours, they ranged from 0.34 to 2.36 mg/mL. Therapeutic levels are 1-2 mg/mL. The serum half life following a 200 mg dose in 12 normal volunteers ranged from 11 to 17 hours, in 7 patients with hepatic dysfunction ranged from 11 to 16 hours and in 5 patients with renal dysfunction ranged from 18 to 69 hours. Between 55% and 76% of an administered dose is bound by serum proteins.
Minocycline is excreted via the faeces primarily and via the urine at a low rate. High serum protein binding and the lipophylic properties contribute to this low excretion rate. The urinary and faecal recovery of minocycline when administered to 12 normal volunteers is one half to one third that of tetracycline.
In the treatment of a variety of infections due to susceptible Gram-positive and Gram-negative organisms. These infections include:
Respiratory tract infections: Laryngotracheitis, tracheobronchitis, bronchitis, bronchiolitis, bronchiectasis, bronchopneumonia, pneumonia (single lobe and multilobe), lung abscess.
Genitourinary tract infections: Pyelonephritis, cystitis, prostatitis, gonococcal urethritis, nonspecific urethritis.
Skin and soft tissue infections: Abscess, acne (including cystic and pustular types), cellulitis, infected dermatitis, folliculitis, furunculosis, impetigo, lymphadenitis, suppurative hydradenitis, paronychia, infected wounds.
Ear, nose and throat infections: Otitis media and externa, bacterial rhinitis, sinusitis, tonsillitis, pharyngitis.
Ophthalmological infections: Dacryocystitis, internal hordeolum associated with susceptible staphylococci, streptococci, Escherichia coli, Aerobacter strains and Haemophilus influenzae.
Tetracyclines including minocycline are not the substances of choice in the treatment of staphylococcal infection. Culture and sensitivity studies should be performed whenever feasible and should be done routinely in suspected streptococcal infections.
In cases of acute gonococcal urethritis where a primary or secondary lesion of syphilis is suspected, proper diagnostic procedures including darkfield examination should be followed. In all other cases where concomitant syphilis is suspected, serological tests should be made monthly for at least four months.
Therapy should continue for at least 24 to 48 hours after symptoms have subsided.
ADULTS
Acne vulgaris: 100 mg daily, given as a single dose or 50 mg twice daily. Duration of therapy varies depending upon response. Acne patients have been safely treated with minocycline for periods over 6 months.
Non-gonococcal urethritis: 100 mg daily for 10-14 days.
Gonorrhoea: Adult males: 200 mg initially followed by 100 mg every 12 hours for a minimum of 4 days with post-therapy cultures within 2-3 days. Adult females may require therapy for 10-14 days at the same dosage indicated for males.
Systemic infections: The usual dosage of minocycline is 100 mg every 12 hours.
Prophylaxis of asymptomatic meningococcal carriers: 100 mg bid for five days, usually followed by a course of rifampicin.
(See Warnings and Precautions)
Usual paediatric dose: 4 mg/kg followed by 2 mg/kg every 12 hours. Use sufficient liquids when taking medicine to prevent oesophageal irritation.
Minocycline may be used at the normal recommended dosage in elderly patients even with mild to moderate renal impairment.
Total dosage in patients with severe renal impairment should be decreased by reduction of recommended doses and/or by extending time intervals between doses.
A therapeutic dose of minocycline should be administered for at least 10 days.
Gonorrhoea patients sensitive to penicillin may be treated with minocycline administered as 200 mg initially followed by 100 mg every 12 hours for a minimum of 4 days, with post-therapy cultures within 2-3 days. In the treatment of uncomplicated gonococcal urethritis in men, 100 mg twice a day orally for 5 days is recommended. Adult females with acute gonococcal infections require more extended therapy.
Patients with a history of hypersensitivity to any of the tetracycline antibiotics.
Severe renal insufficiency.
Pregnancy and lactation.
Children under 12 years of age.
If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulation of the substance and possible liver toxicity. Under such conditions, lower than usual total doses are indicated and, if therapy is prolonged, serum level determinations may be advisable.
The antianabolic action of the tetracyclines may cause an increase in plasma urea. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracyclines may lead to uraemia, hyperphosphataemia and acidosis.
The use of tetracyclines during tooth development (last half of pregnancy, infancy and childhood to the age of 12 years) may cause permanent discolouration of the teeth (yellow/grey/brown). This adverse reaction is more common during long term use but has been observed following repeated short term courses. Enamel hypoplasia has also been reported. Tetracyclines therefore, should not be used in this age group unless alternatives are not likely to be effective or are contraindicated.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracyclines and treatment should be discontinued at the first evidence of skin erythema. Studies to date indicate that photosensitivity occurs rarely with minocycline hydrochloride.
CNS side effects including lightheadedness, dizziness or vertigo have been reported. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. These symptoms may disappear during therapy and always disappear rapidly when the substance is discontinued.
Minocycline has been found to produce thyroid hyperplasia in rats and dogs. Dietary administration of minocycline in a long-term tumourgenicity study in rats resulted in evidence of thyroid tumour production. Minocycline causes goitre in rats and this species appears to be uniquely susceptible to developing thyroid tumours following long-term administration of agents that cause goitre.
Segment I (fertility and general reproduction) studies have shown that at a dose level more than 50 times the highest human therapeutic dose, minocycline impairs fertility in male rats. There were no effects on fertility or reproduction in female rats or male or female rabbits.
As with other antibiotic preparations, use of minocycline may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy should be instituted.
In venereal disease when coexistent syphilis is suspected, darkfield examination should be done before treatment is started and the blood serology repeated monthly for at least 4 months.
(See WARNINGS AND PRECAUTIONS about use during tooth development). 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. The safety of minocycline hydrochloride for use during pregnancy has not been established.
Tetracyclines have been shown to be present in the milk of lactating women.
(See WARNINGS AND PRECAUTIONS about use during tooth development). All tetracyclines form a stable calcium complex in any bone forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the substance was discontinued.
Gastrointestinal: Anorexia, nausea, vomiting, diarrhoea, glossitis, dysphagia, enterocolitis, pancreatitis and inflammatory lesions (with monilial overgrowth) in the anogenital region. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Rarely, oesophagitis and oesophageal ulceration.
Hepatic: Increases in liver enzymes and rarely, hepatitis and acute liver failure have been reported.
Skin: Maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Fixed drug eruptions have been rarely reported. Lesions occurring on the glans penis have caused balanitis. Erythema multiforme and rarely Stevens-Johnson syndrome have been reported. Pigmentation of the skin and mucous membranes, as well as nail discolouration, have been reported.
Photosensitivity (see WARNINGS AND PRECAUTIONS).
Dental: Tooth discolouration in children less than 8 years of age and also, rarely, in adults has been reported.
Renal toxicity: Rise in plasma urea has been reported and is apparently dose related (See WARNINGS AND PRECAUTIONS). Reversible acute renal failure has been reported.
Hypersensitivity reactions: Urticaria, angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis, polyarthralgia, and exacerbation of systemic lupus erythematosus. Pulmonary infiltrates with oesinophilia has been rarely reported.
Blood: Haemolytic anaemia, thrombocytopenia, neutropenia and eosinophilia have been reported.
Endocrine: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discolouration of thyroid glands. No abnormalities of thyroid function studies are known to occur.
CNS effects: (See WARNINGS AND PRECAUTIONS) Dizziness, vertigo.
Bulging fontanelles have been reported in young infants following full therapeutic dosage. Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Headache, alone, has also been reported. Decreased hearing has been rarely reported in patients on minocycline therapy.
In long-term therapy, a periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies, should be performed.
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
All infections due to group A b-haemolytic streptococci should be treated for at least 10 days. Since bacteriostatic substances may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline in conjunction with penicillin.
The concomitant administration of antacids, iron, calcium, magnesium, aluminium and zinc salts may impair the absorption of tetracyclines. The absorption of MINOMYCIN MR is not significantly impaired by food or moderate amounts of milk.
Reduced efficacy and increased incidence of breakthrough bleeding has been suggested with concomitant use of tetracycline and oral contraceptive preparations.
There is no specific antidote. Gastric lavage plus appropriate supportive treatment should be performed.
Store below 25°C.
Prescription Medicine.
50 mg tablets: Blister packs of 28 tablets, 3 strips to a carton.
Nil.
Zuellig Pharma Limited
54 Carbine Road
Mt Wellington
Auckland
Telephone: (09) 570 1080
19 May 2002