Malanil 250mg. 100mg Tablet

MALANIL is indicated for the prophylaxis of drug sensitive and drug resistant Plasmodium falciparum malaria. Official guidelines and local information on the prevalence of resistance to antimalarial drugs should be taken into consideration.

The daily dose should be taken with food or milk at the same time each day. In the event of vomiting within 1 hour of dosing, a repeat dose should be taken.

Prophylaxis: Prophylaxis should start 1 to 2 days before entering a malaria-endemic area, and be continued daily until 7 days after leaving the area.

Dosage in adults: One MALANIL tablet daily.

Dosage in the elderly: A pharmacokinetic study indicates that no dosage adjustments are needed in the elderly (see Pharmacokinetics).

Dosage in hepatic impairment: A pharmacokinetic study indicates that no dosage adjustments are needed in patients with mild to moderate hepatic impairment. No studies have been conducted in patients with severe hepatic impairment (see Pharmacokinetics in hepatic impairment).

Dosage in renal impairment: Pharmacokinetic studies indicate that no dosage adjustments are needed in patients with mild to moderate renal impairment. For prophylaxis of P. falciparum malaria in patients with severe renal impairment (see CONTRA-INDICATIONS).

MALANIL is contra-indicated in individuals with known hypersensitivity to atovaquone or proguanil hydrochloride or any component of the formulation. MALANIL is contra-indicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance < 30 ml/min).

Safety and effectiveness of MALANIL for the prophylaxis of malaria in patients who weigh less than 40 kg has not been established. In the event of recrudescent infections due to P. falciparum or failure of chemoprophylaxis, patients should be treated with a different blood schizonticide. Persons taking MALANIL for prophylaxis of malaria should take a repeat dose if they vomit within 1 hour of dosing. In the event of diarrhoea, normal dosing should be continued. Absorption of atovaquone may be reduced in patients with diarrhoea or vomiting, but diarrhoea or vomiting was not associated with reduced efficacy in clinical trials of MALANIL for malaria prophylaxis. However, patients with diarrhoea or vomiting should be advised to continue to comply with personal protection measures (repellents, bednets). The concomitant administration of MALANIL and rifampicin or rifabutin is not recommended (see INTERACTIONS). It is not recommended that mothers receiving MALANIL breastfeed their babies. MALANIL should be used with caution in patients with a history of epilepsy (see SIDE EFFECTS). Skin rashes ranging from photosensitivity rashes and urticaria to Stevens-Johnson syndrome have been reported. MALANIL must be stopped immediately at the first sign of a serious skin rash or where there is blistering or mucosal involvement. There have been no studies to investigate the effect of MALANIL on driving performance or the ability to operate machinery, but a detrimental effect on such activities is not predicted from the pharmacology of the component drugs.

Proguanil may potentiate the anticoagulant effect of warfarin and other coumarin based anticoagulants. The mechanism of this potential drug interaction has not been established. Caution is advised when initiating or withdrawing malaria prophylaxis with MALANIL in patients on continuous treatment with anticoagulants. Concomitant use of tetracycline, metoclopramide, rifampicin and rifabutin have been associated with significant decreases in plasma concentrations of atovaquone (see WARNINGS AND SPECIAL PRECAUTIONS). Concomitant administration of atovaquone and indinavir results in a decrease in the C min of indinavir (23 % decrease; 90 % CI 8-35 %). Caution should be exercised in prescribing atovaquone with indinavir due to the decrease in trough levels of indinavir. Atovaquone is highly protein bound (> 99 %) but does not displace other highly protein bound drugs in vitro, indicating that significant drug interactions arising from displacement are unlikely.

The safety of atovaquone and proguanil hydrochloride when administered concurrently in human pregnancy and lactation have not been established. The proguanil component of MALANIL acts by inhibiting parasitic dihydrofolate reductase. There are no clinical data indicating that folate supplementation diminishes drug efficacy. For women of childbearing age receiving folate supplements to prevent neural tube birth defects, such supplements may be continued while taking MALANIL.

There have been no studies to investigate the effect of MALANIL on driving performance or the ability to operate machinery, but a detrimental effect on such activities is not predicted from the pharmacology of the component drugs.

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common > 1/10, common > 1/100 and 1/1 000 and 1/10 000 and < 1/1 000, very rare < 1/10 000. Very common, common and uncommon frequencies were determined from clinical trial data. Rare and very rare frequencies were generally derived from spontaneous data. The frequency classification "Not known" has been applied to those reactions where a frequency could not be estimated from the available data. MALANIL contains atovaquone and proguanil hydrochloride, therefore, the adverse events associated with each of these compounds may be expected with MALANIL. At the doses employed for prophylaxis of malaria, adverse events are generally mild and of limited duration. There is no evidence of added toxicity following concurrent administration of atovaquone and proguanil. A summary of adverse events associated with the use of MALANIL, atovaquone or proguanil hydrochloride is provided below.

Blood & Lymphatic system disorders: Common: anaemia, neutropenia. Not Known: pancytopenia in patients with severe renal impairment.

Immune system disorders: Common: rash. Uncommon: urticaria. Not Known: angioedema, anaphylaxis, vasculitis, photosensitivity reactions, Stevens-Johnson syndrome.

Metabolism and nutritional disorders: Common: hyponatraemia, anorexia. Uncommon: elevated amylase levels.

Nervous system disorders: Very common: headache. Common: insomnia, dizziness. Not Known: Cases of convulsions have been reported (see WARNINGS AND SPECIAL PRECAUTIONS).

Psychiatric disorders: Not Known: depression, anxiety, mood disorders, and psychotic reactions including paranoid reactions and hallucinations have been reported.

Gastrointestinal disorders: Very common: abdominal pain, nausea, vomiting, diarrhoea. Uncommon: stomatitis. Not Known: gastric intolerance, oral ulceration.

Hepatobiliary disorders: Common: elevated liver enzyme levels. Not Known: hepatitis, cholestasis. Clinical trial data for MALANIL indicated that abnormalities in liver function tests were reversible and not associated with untoward clinical events.

Skin and subcutaneous tissue disorders: Uncommon: hair loss.

General disorders and administration site conditions: Common: fever.

Respiratory, thoracic and mediastinal disorders: Common: cough. In clinical trials of MALANIL for prophylaxis of malaria, the most commonly reported adverse events, independent of attributability, were headache, abdominal pain and diarrhoea, and were reported in a similar proportion of subjects receiving MALANIL or placebo.

In case of suspected overdosage, symptomatic and supportive therapy should be given as appropriate.