VULGA XR Tablets are indicated for the treatment of acne.

 Dosage:

Adults: One 100 mg tablet every 24 hours.

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

Children under 12 years: VULGA is not recommended.

Elderly: No special dosing requirements

Administration:

To reduce the risk of oesophageal irritation and ulceration, the tablets should be swallowed whole with plenty of fluid, while sitting or standing. Unlike earlier tetracyclines, absorption of Vulga xr is not significantly impaired by food or moderate amounts of milk.

Treatment of acne should be continued for a minimum of 6 weeks. If, after six months, there is no satisfactory response Vulga xr should be discontinued and other therapies considered. If Vulga xr 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 or unusual pigmentation (see Special Warnings and Precautions).

Vulga xr 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 there is no significant drug accumulation in patients with renal impairment when they are treated with Vulga xr 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-resistance between tetracyclines may develop in micro-organisms and cross-sensitisation in patients. Vulga xr 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 if diarrhoea or breakthrough bleeding occur there is a possibility of contraceptive failure.

Minocycline may cause hyperpigmentation at various body sites (see Administration and 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 Vulga 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 fontanelleles 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.

Use in the 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.

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.

Laboratory monitoring:

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

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

Diuretics may aggravate nephrotoxicity by volume depletion.

Bacteriostatic drugs may interfere with the bactericidal action of penicillin. Avoid giving tetracycline-class drugs in conjunction with penicillin. Absorption of Vulga xr 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 Vulga xr. Unlike earlier tetracyclines, absorption of Vulga xr is not significantly impaired by food or moderate amounts of milk.

There is an increased risk of ergotism when ergot alkaloids or their derivatives are given with tetracyclines.

The concomitant use of tetracyclines may reduce the efficacy of oral contraceptives. Administration of isotretinoin or other systemic retinoids or retinol should be avoided shortly before, during and shortly after minocycline therapy. Each of these agents alone has been associated with pseudotumor cerebri (benign intracranial hypertension) (see 4.4 Special warnings and precautions).

Interference with laboratory and other diagnostic tests:

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

Use in pregnancy: Pregnancy category D

Vulga xr should not be used in pregnancy unless considered essential

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. Vulga xr therefore, should not be used in pregnancy unless considered essential. In humans, Vulga, 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 Vulga 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.

Use in 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.

Headache, light-headedness, dizziness, tinnitus and vertigo (more common in women) and, rarely, impaired hearing have occurred with Vulga xr. 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.

Adverse reactions are listed in the Table in CIOMS frequency categories under MedDRA

system/organ classes:

Common: ≥ 1%

Uncommon: ≥ 0.1% and < 1%

Rare: ≥ 0.01% and < 0.1%

Very Rare: < 0.01%

Infections and Infestations

Very Rare: Oral and anogenital candidiasis, vulvovaginitis.

Blood and Lymphatic System Disorders

Rare: Eosinophilia, leucopenia, neutropenia, thrombocytopenia.

Very Rare: Haemolytic anaemia, pancytopenia.

There are also reports of: Agranulocytosis

Immune System Disorders

Rare: Anaphylaxis /anaphylactoid reaction (including shock), including fatalities.

There are also reports of: Hypersensitivity, pulmonary infiltrates, anaphylactoid purpura.

Endocrine Disorders

Very Rare: Abnormal thyroid function, brown-black discolouration ofthe thyroid.

Metabolism and Nutrition Disorders

Rare: Anorexia

Nervous System Disorders

Common: Dizziness (light-headedness).

Rare: Headache, hypesthesia, paraesthesia, intracranial hypertension, vertigo.

Very Rare: Bulging fontanelle.

There are also reports of: convulsions, sedation.

Ear and Labyrinth Disorders

Rare: Impaired hearing, tinnitus.

Cardiac Disorders

Rare: Myocarditis, pericarditis.

Respiratory, Thoracic and Mediastinal Disorders

Rare: Cough, dyspnoea.

Very Rare: Bronchospasm, exacerbation of asthma, pulmonary eosinophilia.

There are also reports of: Pneumonitis

Gastrointestinal Disorders

Rare: Diarrhoea, nausea, stomatitis, discolouration of teeth including adult tooth discolouration), vomiting.

Very Rare: Dyspepsia, dysphagia, enamel hypoplasia, enterocolitis, oesophagitis, oesophageal ulceration, glossitis, pancreatitis, pseudomembranous colitis.

There are also reports of: Oral cavity discolouration (including tongue, lip and gum).

Hepatobiliary Disorders

Rare: Increased liver enzymes, hepatitis, autoimmune hepatoxicity. (See Section 4.4 Special warnings and precautions for use).

Very Rare: Hepatic cholestatis, hepatic failure (including fatalities), hyperbilirubinaemia, jaundice.

There are also reports of: Autoimmune hepatitis.

Skin and Subcutaneous Tissue Disorders

Rare: Alopecia, erythema multiforme, erythema nodosum, fixed drug eruption, hyperpigmentation of skin, photosensitivity, pruritis, rash, urticaria, vasculitis.

Very Rare: Angioedema, exfoliative dermatitis, hyperpigmentation of nails, Stevens-Johnson Syndrome, toxic epidermal necrolysis.

Musculoskeletal, Connective Tissue and Bone Disorders

Rare: Arthralgia, lupus-like syndrome, myalgia.

Very Rare: Arthritis, bone discolouration, cases of or exacerbation of systemic lupus erythematosus (SLE) (See Section 4.4 Special warnings and precautions for use), joint stiffness, joint swelling.

Renal and Urinary Disorders

Rare: Increased serum urea, acute renal failure, interstitial nephritis.

Reproductive System and Breast Disorders

Very Rare: Balanitis.

General Disorders and Administration Site Conditions

Uncommon: Fever.

Very Rare: Discolouration of secretions.

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 mille, 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.

• Saudi Arabia:

− The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: +966-11-205-7662 Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free phone: 8002490000

E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

• Other GCC States: Please contact the relevant competent authority.

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 appropriate supportive measures. Vulga is not removed in significant quantities by haemodialysis or peritoneal dialysis.

ATC-Code: A01AB23

VULGA XR Tablets contain the active ingredient minocycline as minocycline hydrochloride, a semi-synthetic derivative of tetracycline.

VULGA XR Tablets have been formulated as a "double pulse" delivery system in which a portion of the minocycline dose is delivered in the stomach, and a second portion of the dose is available for absorption in the duodenum and upper GI tract.

None stated.

Methocel E50

Lactose monohydrate 200

Isopropyl alcohol

Colloidal silicon dioxide

Magnesium stearate

Purified Water

Opadry II85F240148 Pink: (Polyvinyl Alcohol, Titanium Dioxide, Polyethelene glycol/ Macrogol, Talc, Ponceau 4R Lake, Quinoline Yellow aluminum Lake, Yellow iron oxide non- irradiated.

None known.

Do not store above 30°C.

Protect from light.

Aluminium foil blister packs containing 30 tablets.

Not applicable.