sage adjustments are needed in patients with mild to moderate renal impairment. In patients with severe renal impairment (creatine clearance <30 mL/min) alternatives to Malarone for treatment of acute P. falciparum malaria should be recommended whenever possible (See Sections 4.4 and 5.2). For prophylaxis of P. falciparum malaria in patients with several renal impairments see Section 4.3.
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Malarone is contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min).
4.4 Special warnings and precautions for use
Persons taking Malarone for prophylaxis or treatment 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 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 eva luated 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. If patients experience an allergic reaction (see section 4.8) 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, patients should be treated with a different blood schizonticide as such events can reflect a resistance of the parasite.
Parasitaemia should be closely monitored in patients receiving concurrent tetracycline (see section 4.5).
The concomitant administration of Malarone and efavirenz or boosted protease-inhibitors should be avoided whenever possible (see section 4.5).
The concomitant administration of Malarone and rifampicin or rifabutin is not recommended (see section 4.5).
Concurrent use of metoclopramide is not recommended. Another antiemetic treatment should be given (see section 4.5).
Caution is advised when initiating or withdrawing malaria prophylaxis or treatment with Malarone in patients on continuous treatment with warfarin and other coumarin based anticoagulants (see section 4.5).
Atovaquone can increase the levels of etoposide and its metabolite (see section 4
