MALARONE PAEDIATRIC

Method of administration The daily dose should be taken once daily with food or a milky drink (to ensure maximum absorption) at the same time each day. If patients are unable to tolerate food Malarone paediatric tablets should be administered, but systemic exposure of atovaquone will be reduced.

In the event of vomiting within 1-hour of dosing a repeat dose should be taken. Malarone paediatric tablets should preferably be swallowed whole. If difficulties are encountered when dosing young children, the tablets may be crushed and mixed with food or a milky drink just prior to administration.

Posology The dosage for the prophylaxis and treatment of acute, uncomplicated P. falciparum malaria in children is based on body weight. 5 75 Three Malarone paediatric tablet >40 250 100 Subjects of >40 kg should receive ONE Malarone 250/100 mg tablet daily Refer to Malarone 250/100 mg Tablets SmPC The safety and effectiveness of Malarone paediatric tablets for prophylaxis of malaria in children who weigh less than 11 kg has not been established.

Prophylaxis should • commence 24 or 48 hours prior to entering a malaria-endemic area, • continue during the period of the stay, • continue for 7 days after leaving the area. The safety and effectiveness of Malarone paediatric tablets have been established in studies of up to 12 weeks in residents (semi-immune) of endemic areas.

1). In non-immune subjects, the average duration of exposure in clinical studies was 27 days. 5 75 Three Malarone paediatric tablets daily for 3 consecutive days. ≥11 Refer to Malarone 250/100 mg Tablets SmPC The safety and effectiveness of Malarone paediatric tablets for the treatment of malaria in children who weigh less than 5 kg has not been established.

For individuals who weigh 11 kg or more, the first choice for the treatment of acute, uncomplicated P. falciparum malaria is Malarone tablets (250/100 mg). Please consult the Malarone tablets SmPC for the recommended dosage for this weight range.

Malarone tablets are four-times the strength of Malarone paediatric tablets. In circumstances when sufficient Malarone tablets are not available, then Malarone paediatric tablets may be used. Dosage in Hepatic Impairment There are no studies in children with hepatic impairment.

However, a pharmacokinetic study in adults indicates that no dosage adjustments are needed in patients with mild to moderate hepatic impairment. 2). Dosage in Renal Impairment There are no studies in children with renal impairment. However, pharmacokinetic studies in adults indicate that no dosage adjustments are needed in those with mild to moderate renal impairment.

2).

In clinical trials of Malarone paediatric tablets for prophylaxis of malaria, 357 children or adolescents 11 to ≤40 kg body weight received Malarone paediatric tablets. Most of these were residents of endemic areas and took Malarone paediatric tablets for about 12 weeks.

The rest were travelling to endemic areas, and most took Malarone paediatric tablets for 2-4 weeks. Open label clinical studies investigating the treatment of children weighing between ≥5 kg and <11 kg have indicated that the safety profile is similar to that in children weighing between 11 kg and 40 kg, and adults.

There are limited long term safety data in children. In particular, the long-term effects of Malarone on growth, puberty and general development have not been studied. In clinical trials of Malarone for treatment of malaria, the most commonly reported adverse reactions were abdominal pain, headache, anorexia, nausea, vomiting, diarrhoea and coughing.

In clinical trials of Malarone for prophylaxis of malaria, the most commonly reported adverse reactions were headache, abdominal pain and diarrhoea. The following table provides a summary of adverse reactions that have been reported to have a suspected (at least possible) causal relationship to treatment with atovaquone-proguanil in clinical trials and spontaneous post-marketing reports.

The following convention is used for the classification of frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known (cannot be estimated from the available data).

4) Vasculitis3 Metabolism and nutrition disorders Hyponatraemia1 Anorexia Elevated amylase levels1 Psychiatric disorders Abnormal dreams Depression Anxiety Hallucinations Panic attack Crying Nightmares Psychotic disorder Nervous system disorders Headache Insomnia Dizziness Seizure Cardiac disorders Palpitations Tachycardia Gastrointestinal disorders Nausea1 Vomiting Diarrhoea Abdominal pain Stomatitis Gastric intolerance3 Oral ulceration3 Hepatobiliary disorders Elevated liver enzymes1 Hepatitis Cholestasis3 Skin and subcutaneous tissue disorders Pruritus Rash Hair loss Urticaria Stevens-Johnson syndrome Erythema multiforme Blister Skin exfoliation Photosensitivity reactions General disorders and administration site conditions Fever Respiratory, thoracic and mediastinal disorders Cough 1.

Frequency taken from atovaquone label. Patients participating in clinical trials with atovaquone have received higher doses and have often had complications of advance Human Immunodeficiency Virus (HIV) disease. These events may have been seen at a lower frequency or not at all in clinical trials with atovaquone-proguanil.

2. Observed from post-marketing spontaneous reports and the frequency is therefore unknown 3. Observed with proguanil. 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. uk/yellowcard.

Persons taking Malarone paediatric tablets for prophylaxis or treatment of malaria should take a repeat dose if they vomit within 1hour of dosing. In the event of diarrhoea, normal dosing should be continued. Absorption of atovaquone may be reduced in individuals with diarrhoea or vomiting, but diarrhoea or vomiting was not associated with reduced efficacy in clinical trials of Malarone for malaria prophylaxis.

However, as with other antimalarial agents, subjects with diarrhoea or vomiting should be advised to continue with malaria prevention measures by complying with personal protection measures (repellants, bednets). In patients with acute malaria who present with diarrhoea or vomiting, alternative therapy should be considered.

If Malarone is used to treat malaria in these patients, parasitaemia and the patient’s clinical condition should be closely monitored. Malarone has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria including hyperparasitaemia, pulmonary oedema or renal failure.

Occasionally, severe allergic reactions (including anaphylaxis) have been reported in patients taking Malarone. 8) Malarone should be discontinued promptly and appropriate treatment initiated. Malarone has been shown to have no efficacy against hypnozoites of Plasmodium vivax as parasite relapse occurred commonly when P.

vivax malaria was treated with Malarone alone. Travellers with intense exposure to P. vivax or P. ovale, and those who develop malaria caused by either of these parasites, will require additional treatment with a drug that is active against hypnozoites.

In the event of recrudescent infections due to P. falciparum after treatment with Malarone, or failure of chemoprophylaxis with Malarone paediatric tablets, patients should be treated with a different blood schizonticide as such events can reflect a resistance of the parasite.

5). 5). 5). Concurrent use of metoclopramide is not recommended. 5). 5). 5). In patients with severe renal impairment (creatinine clearance
30 mL/min) alternatives to Malarone for treatment of acute P. 2). The safety and effectiveness of Malarone paediatric tablets for the prophylaxis of malaria in children who weigh less than 11 kg and the treatment of malaria in children who weigh less than 5 kg have not been established.

Malarone paediatric tablets are not indicated for the treatment of acute uncomplicated P. falciparum malaria in individuals weighing 11-40 kg. 2). This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

1. Malarone paediatric tablets are contraindicated for prophylaxis of P. min).