Sebomin MR

1. Name Of The Medicinal Product

Sebomin 100mg MR Capsules.

2. Qualitative And Quantitative Composition

Each capsule contains 100mg anhydrous minocycline (as the hydrochloride).

For excipients, see 6.1

3. Pharmaceutical Form

Prolonged-release capsule, hard.

Orange, opaque, hard gelatin capsules (size 2) printed “C” and “MR” in white.

4. Clinical Particulars

4.1 Therapeutic Indications

The treatment of acne.

4.2 Posology And Method Of Administration

Dosage:

Adults: One 100mg capsule every 24 hours.

Children over 12 years: One 100mg capsule every 24 hours.

Children under 12 years: Sebomin MR is not recommended.

Elderly: No special dosing requirements.

Treatment of acne should be continued for a minimum of 6 weeks. If there is no satisfactory response to Sebomin MR after six months, the treatment should be discontinued and other therapies considered. If Sebomin MR 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 Special warnings and precautions for use).

Administration:

The capsules should be swallowed whole with plenty of fluid, while sitting or standing in order to reduce the risk of oesophageal irritation and ulceration. They should not be taken with food as this affects the absorption of minocycline.

4.3 Contraindications

• Known hypersensitivity to tetracyclines

• Pregnancy

• Lactation

• Children under the age of 12 years

• Complete renal failure.

4.4 Special Warnings 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 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 in patients with renal impairment there is no significant drug accumulation when they are treated with minocycline in the recommended doses. However, reduction of dosage and monitoring of renal function may be required in cases of severe renal insufficiency.

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 there is a possibility of contraceptive failure if diarrhoea or breakthrough bleeding occurs.

Minocycline may cause hyperpigmentation at various body sites. Hyperpigmentation may be present regardless of dose or duration of treatment 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 a photosensitivity reaction occurs, patients should be warned to avoid direct exposure to natural or artificial light and to discontinue therapy at the first sign of skin discomfort.

The capsule shell contains sunset yellow (E110), which can cause allergic - type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.

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.

4.5 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, 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. The capsules should not be taken with food as this affects the absorption of minocycline.

4.6 Pregnancy And Lactation

Pregnancy:

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.

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

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 has been observed following repeated short term courses however it is more common during long term use of the drug. Enamel hypoplasia has also been reported.

Lactation:

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.

4.7 Effects On Ability To Drive And Use Machines

Minocycline has been associated with headache, light-headedness, dizziness and vertigo and rarely impaired hearing. Patients should be warned about the possible hazards of driving or operating machinery during treatment.

4.8 Undesirable Effects

Common

As with other tetracyclines, gastrointestinal disturbances including nausea, anorexia, vomiting and diarrhoea may occur. 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. Hypersensitivity reactions can include urticaria, fever, arthralgia, myalgia, arthritis, pulmonary infiltration, wheezing, angioneurotic oedema, anaphylaxis and anaphylactoid purpura.

Cases of systemic lupus erythematosus (SLE) and also exacerbation of pre-existing SLE have been reported (see also Special warnings and precautions for use).

In common with other tetracyclines, bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported. If evidence of raised intracranial pressure develops, treatment should cease.

Blood haemolytic anaemia, thrombocytopenia, neutropenia and eosinophilia have been reported with tetracyclines.

As with other tetracyclines, transient increases in liver function test values have been reported. Some hepatic reactions have an auto-immune basis, and may occur after several months of minocycline treatment (see Posology and method of administration). When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discolouration of thyroid tissue.

Uncommon

There have been isolated incidences of pancreatitis.

Hyperpigmentation of skin, nails or discolouration of teeth and buccal mucosa have been reported occasionally. These are generally reversible on cessation of therapy.

There are isolated cases of discolouration of conjunctiva, lacrimal secretions, breast secretions and perspiration.

Rare

Hepatitis and acute liver failure have been reported.

Fixed drug eruptions have been observed.

Pericarditis, myocarditis, vasculitis and renal failure including interstitial nephritis have been reported.

Bone discolouration has been observed.

(See also Pregnancy and Lactation).

4.9 Overdose

No specific antidote. Gastric lavage plus appropriate supportive treatment.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotheraputic group: Tetracycline, ATC code: J01A A08

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

Minocycline has a long serum half-life and can be administered at 12 hour intervals, the modified release form can be given once daily.

Minocycline interferes with the third stage of bacterial protein synthesis. After amino acids are activated and attached to t-RNA (transfer RNA), the resulting amino acyl-t-RNA migrates to the bacterial ribosome for synthesis of proteins. Minocycline binds to the 30s subunit on the ribosome and inhibits binding of the aminoacyl-t-RNA molecules.

There is also evidence that minocycline may cause alterations in the cytoplasmic membrane, thereby allowing leakage of nucleotides and other compounds from the cell. This would explain the rapid inhibition of DNA replication that ensues when cells are exposed to concentrations of minocycline greater than that needed to inhibit protein synthesis.

In higher concentration, minocycline inhibits mammalian protein synthesis and may aggravate pre-existing renal functional impairment. The drug may interfere with parenteral nutrition in post operative patients by inhibiting utilization of amino acids for protein synthesis.

Minocycline is reported to be active against both Gram negative and Gram positive organisms.

5.2 Pharmacokinetic Properties

Absorption

Oral bioavailability for minocycline has been reported to be 90%.

One report has demonstrated that food did not significantly affect the absorption of minocycline following 50 mg oral doses. However, another study reported that minocycline absorption was decreased by 77%, 27% and 13% when given with iron, milk and food.

Distribution

Total protein binding of minocycline has been reported to be in the order of 76%.

Other sites of distribution of minocycline include the following:

AQUEOUS HUMOR

Minocycline administered orally with a loading dose of 200 mg followed by 2 doses of 100 mg 12 hours apart produce adequate drug concentration in the aqueous humor of noninflamed eyes. The plasma to aqueous humor ratio was approximately 2:1.

CEREBROSPINAL FLUID

Minocycline has been reported to cross the blood/brain barrier to a higher degree than doxycycline. However, passage of either drug has been shown to be significantly decreased in patients with uninflamed meninges.

GINGIVAL FLUID

The mean gingival crevicular fluid drug concentration of 8.03 +/- 1.64 mcg/ml was reported after 7 days of oral minocycline 200 mg in patients with moderate to severe periodontal disease. Mean serum concentration was 2.58 +/- 0.32 mcg/ml.

JOINT FLUID CONCENTRATIONS

Following 200 mg oral doses of minocycline, joint fluid levels 3 to 12 hours following the dose were 0.43 to 0.88 mcg/ml.

SALIVA/TEARS

Minocycline achieved significant levels in saliva and tears sufficient to inhibit most strains of meningococci. Following oral doses of 100 mg every 12 hours for 5 days, the concentration of drug in saliva and tear equalled or was greater than the average MIC for meningococci for up to 12 hours after the dose. Two hours following an oral dose, concentrations of minocycline in saliva and tears were at 0.3 mcg/mL and 0.4 mcg/mL, respectively.

SINUS SECRETIONS

Following a dose of 100 mg twice daily for 4 days in patients with sinusitis a sinus level of 1.06 mcg/5 mL was found. The mean minocycline serum level was 3.16 mcg/ml, giving a sinus secretion to serum level ratio of 0.34:1.

Metabolism

An inactive metabolite, 9-hydroxyminocycline has been isolated.

Elimination

Minocycline has a very low renal clearance as compared to other tetracyclines. However, urinary concentrations approximating 10 times that of serum are attained for the first 4 to 6 hours following an oral dose.

Minocycline is excreted 19% in the faeces, this level is much lower than most other tetracyclines.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

glycerol monostearate 40-55,

microcrystalline cellulose 101 (E460(i)),

povidone K-30 (E1201),

purified talc (E553b).

Capsule shell

gelatin,

purified water,

titanium dioxide (E171),

sunset yellow (E110),

quinoline yellow (E104).

Printing ink

shellac (E904),

ethyl alcohol,

isopropyl alcohol,

propylene glycol,

butyl alcohol,

povidone (E1201),

sodium hydroxide,

titanium dioxide (E171).

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Do not store above 30°C.

Polypropylene container - store in the original container,

PVC/aluminium blister pack - keep container in the outer carton.

6.5 Nature And Contents Of Container

PVC/aluminium blister pack in outer cardboard container

28, 30, 56, 60, 84, 90

Polypropylene container with polyethylene cap

100, 112, 120, 200, 250, 500

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Actavis UK Limited

(Trading style: Actavis)

Whiddon Valley

Barnstaple

North Devon

EX32 8NS

United Kingdom

8. Marketing Authorisation Number(S)

PL 00142/0526

9. Date Of First Authorisation/Renewal Of The Authorisation

20 June 2003

Renewed – 19.03.09

10. Date Of Revision Of The Text

19.03.09