Acnamino MR 100 mg capsules are indicated for the treatment of acne.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Posology

Treatment of acne should be continued for a minimum of 6 weeks, and where possible limited to a maximum of six months. If, after six months, there is no satisfactory response, Acnamino MR should be discontinued and other therapies considered.

If Acnamino MR is to be continued for longer than six months, patients should be monitored (including laboratory investigations) at least three monthly thereafter for signs and symptoms of hepatitis or systemic lupus erythematosus (SLE) or unusual pigmentation (see section 4.4 Special Warnings and Precautions).

Method of Administration

To reduce the risk of oesophageal irritation and ulceration, the capsules should be swallowed whole with plenty of fluid, while sitting or standing. Unlike other tetraacyclines, absorption of minocycline is not significantly impaired by food or moderate amounts of milk.

Use of minocycline is contraindicated in the following:

• Hypersensitivity to the active substance minocycline, other tetracyclines or to any of the excipients listed in section 6.1.

• Pregnancy and lactation.

• Children under the age of 12 years.

• Complete renal failure.

Rare, anaphylaxis/anaphylactoid reactions including shock and fatalities have been associated with the administration of minocycline (see section 4.8 Undesirable effects).

Acnamino MR 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 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.

Other rare, serious events have occurred with minocycline including Stevens-Johnson Syndrome and toxic epidermal necrolysis (see section 4.8 Undesirable effects). Acnamino MR should be discontinued if either of these serious skin reactions is suspected.

Minocycline is contraindicated in persons with renal failure. 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. The anti-anabolic action of the tetracyclines may cause an increase in serum urea. In patients with significantly impaired renal function, higher serum levels of tetracyclines may lead to uraemia, hyperphosphataemia and acidosis. If renal impairment exists, even usual oral and parenteral doses may lead to excessive systemic accumulations of the drug and possible liver toxicity.

Caution is advised in patients with myasthenia gravis as tetracyclines can cause weak neuromuscular blockade.

Cross-hypersensitivity between tetracyclines may occur in patients (see section 4.3).

Cross-resistance between tetracyclines may develop in micro-organisms and cross-sensitisation in patients. Acnamino MR should be discontinued if there are signs/symptoms of overgrowth of resistant organisms, e.g. enteritis, glossitis, stomatitis, vaginitis, pruritus and or Staphylococcal enteritis.

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

Minocycline may cause hyperpigmentation at various body sites (see Administration and section 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 Acnamino MR should be discontinued.

If a photosensitivity reaction occurs, patients should be warned to avoid direct exposure to natural or artificial light and to discontinue therapy at the first signs of skin discomfort.

As with other tetracyclines, bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported. Presenting features were headache and visual disturbances including blurring of vision, scotoma and diplopia. Permanent vision loss has been reported.

Treatment should cease if evidence of raised intracranial pressure develops.

Elderly:

Dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Paediatric population:

Acnamino MR is contraindicated in children of less than 12 years of age.

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.

Laboratory monitoring:

Periodic laboratory evaluations of organ system function, including haematopoietic, renal and hepatic should be conducted.

Excipient information:

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially 'sodium-free'.

Tetracyclines depress plasma prothrombin activity and reduced doses of concomitant anticoagulants may be necessary.

Diuretics may aggravate nephrotoxicity by volume depletion.

Minocycline should not be used with beta-lactam antibacterial agents due to the possibility of antagonism.

Bacteriostatic drugs may interfere with the bactericidal action of penicillin. Avoid giving tetracycline-class drugs in conjunction with penicillin. Absorption of minocycline is impaired by the concomitant administration of antacids, iron, calcium, magnesium, aluminium, bismuth and zinc salts (interactions with specific salts, antacids, bismuth containing ulcer – healing drugs, quinapril which contains a magnesium carbonate excipient). 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 Acnamino MR. Unlike earlier tetracyclines, absorption of minocycline is not significantly impaired by food or moderate amounts of milk.

The concomitant use of tetracyclines may reduce the efficacy of oral contraceptives.

Administration of isotretinoin should be avoided shortly before, during and shortly after Acnamino MR therapy. Each drug alone has been associated with pseudotumor cerebri (benign intracranial hypertension) (see section 4.4 Special Warngings and Precautions).

Interference with laboratory and other diagnostic tests:

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

Pregnancy

Minocycline is contraindicated during pregnancy as it can cause fetal harm (see section 4.3).

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. Acnamino MR therefore, should not be used in pregnancy unless considered essential.

In humans, minocycline like other tetracycline-class antibiotics, crosses the placenta and may cause foetal harm when administered to a pregnant woman. In addition, there have been post marketing reports of congenital abnormalities including limb reduction. If Acnamino MR is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the foetus.

The use of drugs of the tetracycline class during tooth development (last half of pregnancy) 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 administered during the last trimester form a stable calcium complex throughout the human skeleton. A decrease in fibula growth rate has been observed in premature human infants given oral tetracyclines in doses up to 25mg/kg every 6 hours. Changes in fibula growth rate were shown to be reversible when the drug was discontinued.

Breast-feeding

Minocycline is contraindicated during breast-feeding (see section 4.3).

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.

Headache, light-headedness, dizziness, tinnitus and vertigo (more common in women) and, rarely, impaired hearing have occurred with minocycline. Patients should be warned about the possible hazards of driving or operating machinery during treatment. These symptoms may disappear during therapy and usually disappear when the drug is discontinued.

The assessment of side effects is based on the following frequency information:

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).

The following syndromes have been reported. In some cases involving these syndromes, death has been reported. As with other serious adverse reactions, if any of these syndromes are recognised, the drug should be discontinued immediately:

• Hypersensitivity syndrome consisting of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following: hepatitis, pneumonitis, nephritis, myocarditis, pericarditis.

• Fever and lymphadenopathy may be present.

• Lupus-like syndrome consisting of positive antinuclear antibody, arthralgia, arthritis, joint stiffness or joint swelling, and one or more of the following: fever, myalgia, hepatitis, rash, vasculitis.

• Serum sickness-like syndrome consisting fever, urticaria or rash, and arthralgia, arthritis, joint stiffness or joint swelling. Eosinophilia may be present.

• 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 in 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.

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.

Dizziness, nausea and vomiting are the adverse effects most commonly seen with overdose. There is no specific antidote. In cases of overdose, discontinue medication, treat symptomatically with gastric lavage and appropriate supportive measures. Minocycline is not removed in significant quantities by haemodialysis or peritoneal dialysis.

Pharmacotherapeutic group: Antibacterial for Systemic Use, ATC code: J01AA08

Acnamino MR Capsules contain the active ingredient minocycline as minocycline hydrochloride, a semi-synthetic derivative of tetracycline.

Mechanism of action

Minocycline inhibits protein synthesis in susceptible bacteria. In common with other tetracyclines it is primarily bacteriostatic and has a similar spectrum of activity to other tetracyclines.

Breakpoints

The general MIC breakpoint to identify organisms susceptible to minocycline is ≤ 0.5 mg/l. All organisms for which the MIC of minocycline is ≥ 1 mg/l are considered resistant (European Committee on Antimicrobial Susceptibility Testing (EUCAST), 2004).

Susceptibility

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable. Minocycline is usually active in vitro against Propionibacterium acnes, which is implicated in the pathogenesis of acne.

Resistance

Bacterial resistance to the tetracyclines is now common in some species and usually involves cross-resistance between the different tetracyclines.

After a single 100 mg dose of Minocycline Capsules administered to fasting male subjects a maximum concentration of 608 (± 162) ng/ml was achieved at 3.2 (± 1.1) hours after dosing and was eliminated with a plasma half-life of 18.4± 6.2 hours. When administered to male subjects in the fed state a maximum concentration of 750.9 (± 223.8) ng/ml was achieved at 3.7 (± 1.3) hours after dosing and was eliminated with a plasma half-life of 18.8± 3.1 hours.

There is no other relevant information from pre-clinical studies that has not already been mentioned in the preceding sections.

Core:

Microcrystalline cellulose

Povidone

Croscarmelose sodium

Magnesium stearate

Iron oxide red (E-172)

Silica colloidal anhydrous

Iron oxide yellow (E-172)

Coating:

Hypromellose phthalate

Triethyl citrate

Opadry OY-S-24932 pink (which contains Hypromellose 2910, Macrogol 6000, Titanium dioxide (E-171), Talc, Iron oxide red (E-172))

Polishing:

Carnauba wax

Hard Gelatin Capsule (which contains Gelatin, Titanium dioxide (E-171), Iron oxide yellow (E-172), Black iron oxide (E-172), Red iron oxide (E-172))

Not applicable.

4 years.

Store in the original package

The capsules are presented in aluminium/aluminium blisters, strips of which are contained within a printed cardboard carton. Each carton contains 56 capsules.

No special requirements.