SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Minocycline 50mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains minocycline hydrochloride equivalent to 50mg minocycline.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablet.

Brown-yellow film coated round tablets with an approximate diameter of 7mm, embossed GL50

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Minocycline is a broad spectrum antibiotic used for treatment of infections caused by tetracycline sensitive organisms. Tetracyclines, including minocycline, are the treatment of choice for infections caused by:

•    Chlamydia (trachoma, non-gonococcal urethritis, pelvic inflammatory disease, prostatitis, epididymitis, lymphogranuloma venereum and psittacosis).

•    Rickettsia (typhus, Q-Fever, Rocky mountain spotted fever).

•    Mycoplasma (respiratory and genital).

•    Brucella (normally in combination with other antibiotics such as streptomycin).

•    Borrelia burgdorferi (Lyme disease).

Other uses include:

• acute and chronic bronchitis

acne and, in cases of penicillin allergy

treatment of actinomycosis, nocardiosis, leptospirosis and syphilis.

Minocycline is also used for meningococcal prophylaxis.

4.2 Posology and method of administration

Posology

If, after six months, there is no satisfactory response Minocycline should be discontinued and other therapies considered. If minocycline is to be continued for longer than six months, patients should be monitored at least three monthly thereafter for signs and symptoms of hepatitis or SLE (see section 4.4).

Adults

Routine use:    100mg twice daily

Acne:    50mg twice daily or 100mg once daily, for at least 6 weeks.

Prophylaxis of asymptomatic meningococcal carriers:

100mg twice daily for 5 days, usually followed by a course of rifampicin.

Paediatric population

Minocycline is not recommended for children under 12 years.

For children above 12 years of age the recommended dose of Minocycline is 50mg twice daily.

Older people

The normal adult dose of Minocycline is appropriate for the elderly. However caution is advised in patients with severe renal impairment.

Method of administration

For oral administration

4.3 Contraindications

•    Hypersensitivity to the active substance, or to any of the excipients listed in section 6.1

•    Known hypersensitivity to tetracyclines

•    Pregnancy andlactation,

•    Systemic lupus erythematosus (SLE)

•    Complete renal failure

Paediatric population

Not recommended for children under 12 years.

4.4 Special warnings and precautions for use

Renal Impairment: Minocycline should be used with caution in patients with severe renal impairment

Use in Hepatic Dysfunction: Minocycline should be used with caution in patients with hepatic dysfunction and in conjunction with alcohol and concomitant use of hepatotoxic drugs avoided.

Cross-sensitivities: Cross-resistance between tetracyclines may develop in microorganisms and cross-sensitisation in patients. Minocycline should be discontinued if there are signs or symptoms of overgrowth of resistant organisms, eg enteritis, glossitis, stomatitis, vaginitis, pruritus ani or staphylococcal enteritis.

Auto -immune Disorders: Rare cases of auto-immune hepatotoxicity and isolated cases of systemic lupus erythematosus (SLE) and also exacerbation of pre-existing SLE have been reported. If patients develop signs or symptoms of SLE or hepatotoxicty, or suffer exacerbation or pre-existing SLE, Minocycline should be discontinued.

Hyperpigmentation: Higher doses may cause hyperpigmentation in acne lesions.

Contraceptive failure: Patients taking oral contraceptives should be warned that if diarrhoea or breakthrough bleeding occur there is a possibility of contraceptive failure.

Paediatric population : Use of Mincoycline in children under 12 years may lead to permanent discoloration of the teeth and enamel hypoplasia.

Myasthenia Gravis: Caution should be exercised in patients with Myasthenia Gravis as tetracyclines can cause weak neuromuscular blockade.

4.5 Interaction with other medicinal products and other forms of interaction

Antibacterials: Minocycline should not be used with penicillin's or cephalosporins as it may antagonise the antibacterial effect of these agents.

Anticoagulants: Minocycline/tetracyclines reduces plasma prothrombin activity and therefore reduced doses of concomitant anticoagulants may be necessary.

Antacids and Adsorbents: Minocycline absorption is not significantly impaired by food or moderate amounts of milk, but is reduced by concomitant administration of antacids and preparations containing salts of iron, calcium, aluminium, magnesium, bismuth and zinc.

Diuretics: may aggravate nephrotoxicity by volume depletion.

4.6 Fertility, pregnancy and lactation

Pregnancy

Minocycline should not be used in pregnancy unless essential. Animal studies have indicated that tetracyclines cross the placenta, are found in foetal tissues, and can cause toxicity in the foetus usually related to a retardation of skeletal development. Yellowbrown discolouration of the teeth and enamel hypoplasia can occur when drugs of the tetracycline group are administered after the first trimester of pregnancy. Minocycline should be avoided during pregnancy because of the effects on the bones of the developing foetus.

Breast-feeding

Minocycine is known to pass into breast milk and may cause growth impairment and bone discoloration in the neonate. It should therefore be avoided by breast feeding mothers.

4.7 Effects on ability to drive and use machines

Due to reports of dizziness, light-headedness and vertigo with Minocycline, patients should be warned about possible hazards of driving or operating machinery while on treatment.

4.8 Undesirable effects

Blood and lymphatic system disorders: Haemolytic anaemia, thrombocytopenia, neutropenia and eosinophilia have been reported with tetracyclines.

Hypersensitivity reactions: Urticaria, fever, arthralgia, angioneurotic oedema, anaphylaxis and anaphylactoid purpura. Isolated cases of systemic lupus erythematosus (SLE) and exacerbations of pre-existing SLE have also been reported in patients receiving Minocycline.

Frequency unknown: Polyarteritis nodosa

Nervous system disorders: Hyperaesthesia, paraesthesia have rarely been reported.

Headache, dizziness, vertigo and ataxia may occur. These disturbances are reversible within 3-48 hours of discontinuing therapy and occur less frequently when a low dose is given.

As with other tetracyclines, bulging fontanelles in infants and benign intracranial hypertension in adults have been reported. Treatment should be stopped if evidence of raised intracranial pressure develops. Headache and visual disturbance can signify benign intracranial hypertension; treatment should cease if this develops.

Eye disorders: There are isolated cases of discolouration of the conjunctiva and lacrimal secretions. (See Section 4.6).

Ear and labyrinth disorders: Impaired hearing has rarely been reported. Tinnitus may occur.

Cardiac disorders: Rarely pericarditis has been reported.

Respiratory, thoracic and mediastinal disorders: Rarely pulmonary infiltration has been reported. Frequency unknown: pulmonary eosinophilia

Gastrointestinal disturbances: Disturbances like anorexia, including epigastric burning, nausea, vomiting, dyspepsia, dysphagia, antibiotic-associated colitis and diarrhoea may occur; these effects appear to be dose related. Any diarrhoea must be differentiated from that due to bacterial overgrowth. Overgrowth with candida may also occur.

There have been isolated incidences of pancreatitis. A few cases of oesophagitis and oesophageal ulceration have been reported. To reduce the risk of oesophageal irritation and ulceration the capsules should be administered with adequate amount of fluids and probably not be given at bedtime or to patients with oesophageal obstruction or compression.

Hepato-biliary disorders: In common with other tetracyclines transient increases in liver function test values and, rarely, hepatitis have been reported. Some hepatic reactions have an auto-immune basis, and may occur after several months of Minocycline treatment (See section 4.2).

Frequency unknown: Acute hepatic failure, liver injury, jaundice, hyperbilirubinaemia.

Skin and subcutaneous tissue disorders: Skin reactions are rare, however erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, alopecia and photosensitivity have been reported.

Hyperpigmentation of skin have been reported occasionally.

Frequency unknown: Rash (including rash maculo-papular), drug rash with eosinophilia and systemic symptoms (DRESS)

Renal and urinary disorders: Rarely acute renal failure has been reported.

Other: when given over prolonged periods of administration Minocycline/ tetracyclines have been reported to produce brownish-black microscopic discolouration of thyroid tissue; no abnormalities of thyroid function are known to occur.

Discolouration of teeth,buccal mucosa and tongue discolouration have been reported occasionally. These are generally reversible on cessation of therapy. There are isolated cases of breast secretions and perspiration. (See 4.6).

Reporting of suspected adverse reactions

Reporting suspected adverse drug reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9. Overdose

No specific antidote. Gastric lavage and appropriate supportive treatment are recommended.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Tetracycline ATC code: J01AA

Tetracyclines, including Minocycline, are broad spectrum antibiotics with a wide range of bacteriostatic activity including Chlamydia, Mycoplasmas, Rickettsias and Spirochaetes, and also any aerobic and anaerobic Gram-positive and Gram-negative pathogenic bacteria, and some protozoa.

Tetracyclines penetrate bacterial cell walls as a result of both passive diffusion and an active transport process. Once within the cell they bind to the 30s subunit of the ribosome, preventing the binding of aminoacyl transfer RNA and inhibiting protein synthesis and hence cell growth.

5.2 Pharmacokinetic properties

Minocycline is readily absorbed from the GI tract and is not significantly affected by the presence of food or moderate amounts of milk, though it may be impaired by iron salts or antacids. Steady-state plasma concentrations of 2.3 to 3.5mg/l are reported following doses of 100mg every 12 hours. Minocycline is more lipophilic than other tetracyclines and is widely distributed in body tissues and fluids, though CSF penetration is still relatively poor. About 75% of Minocycline is bound to plasma proteins and the normal plasma half-life is in the range of 11-26 hours. Only 5-10% of a dose is excreted in the urine and up to 34% in the faeces; some metabolism occurs in the liver, mainly to 9-hydroxyminocycline.

5.3. Preclinical Safety Data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Core tablet: Povidone (K-25)

Sodium starch glycollate Microcrystalline cellulose (PH101) Colloidal anhydrous silica Magnesium stearate Purified water

Film coating

Hydroxypropylmethylcelullose Macrogol 6000 Titanium dioxide (E171)

Yellow ferric oxide (E172).

6.2    Incompatibilities

None applicable.

6.3    Shelf life

3 years

6.4    Special precautions for storage

Store below 25°C in a dry place. Store in the original package in order to protectfrom light.

6.5    Nature and contents of container

Strips-Blister Packs

PVC (250 micrometres) heat sealed to aluminium foil (20 micrometres).

Packs Sizes: 2, 28, 56, 84, 98 tablets.

Not all packs sizes may be marketed.

6.6    Special precautions for disposal    and other handling

No special requirements for disposal. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

MARKETING AUTHORISATION HOLDER

Tillomed Laboratories Ltd 3 Howard Rd Eaton Socon St. Neots. Cambs PE198ET UK

8. MARKETING AUTHORISATION NUMBER(S)

PL 11311/0146

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

Date of first authorisation: 19/07/1999 Date of latest renewal: 13/03/2009

10 DATE OF REVISION OF THE TEXT

22/12/2015