Which malaria prophylaxis is preferable for patients with epilepsy on anticonvulsant therapy?/nThe

Fråga: Which malaria prophylaxis is preferable for patients with epilepsy on anticonvulsant therapy?

The questioner has a general concern about patients on anticonvulsant therapy who are in need of malaria prophylaxis, especially considering interaction risks and the effect on the seizure threshold.

Sammanfattning: The fixed combination of proguanil/atovaquone seems to be a preferable choice of malaria prophylaxis to patients with epilepsy. The substances have low interaction risk and no reported negative effect on seizure threshold.

Svar: Chloroquine or mefloquine are contraindicated in patients with epilepsy, because of their propensity to worsen seizures (1,2).

Doxycycline 100 mg daily can be used as malaria prophylaxis in patients with epilepsy (1,2). However, if the patient is treated with these enzyme inducing anticonvulsants, the dose of doxycycline should be doubled to 200 mg daily (3). Doxycycline also has a phototoxic potency that should be taken into account. The incidence is about 3 % in patients receiving 100 mg doxycycline daily (4).

An alternative to doxycycline is the fixed combination of proguanil/atovaquone, which was approved in Sweden in 2001 for malaria prophylaxis (5). Proguanil and atovaquone have low interaction risk and no reported negative effect on seizure threshold (2). Proguanil is a prodrug of which only a small part is metabolically converted by CYP2C19 into the active compound cycloguanil (6,7). Proguanil also acts as an enhancer to atovaquone and due to synergism between atovaquone and proguanil the presence of cycloguanil may not be required for an effective malaria prophylaxis (8). Up to 60 % of a proguanil dose is renally excreted (5,6). No metabolites of atovaquone have been found in humans (6,7). Less than 1% of atovaquone is excreted in the urine, and 94 % of an oral dose is excreted unchanged in the faeces over 21 days (7). Taylor WR, White NJ. Antimalarial drug toxicity. A review. Drug Saf 2004;27(1):25-61. Richens A, Andrews C. Clinical practice. Epilepsy Res 2001;51:1-4. Stockley IH. Drug interactions. 6th ed. London: The Pharmaceutical Press; 2002. p. 224. Layton AM, Cunliffe WJ. Phototoxic eruptions due to doxycycline - a dose-related phenomenon. Clin Exp Dermatol 1993;5:425-7 (abstract) Ahlqvist Rastad J, Melander H. Malarone övervärderat I Läkemedelsverkets produktmonografi? Information från Läkemedelsverket 2002;13(6). Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. Marra F, Salzman JR, Ensom MH. Atovaquone-proguanil for prophylaxis and treatment of malaria. Ann Pharmacother 2003;37:1266-75.