Drug points: Interaction of thyroxine sodium with antimalarial drugsBMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7094.1593 (Published 31 May 1997) Cite this as: BMJ 1997;314:1593
Every year over 25 million non-immune people visit areas of the world where the prevalence of malaria is high. AlthoughPlasmodium falciparum is resistant to the combination of chloroquine and proguanil, this type of prophylaxis is still common. To date, few adverse side effects and hardly any drug interactions have been described with these drugs. We report a case of interaction between thyroxine sodium and chloroquine and proguanil.
A 52 year old white woman, who had no history of medical illness except for hypothyroidism, which was stabilised by treatment with thyroxine sodium 125 μg daily, went to Mali for two weeks. As prophylaxis against malaria she was given chloroquine 100 mg daily and proguanil 200 mg daily for two months, starting on the day of intended travel. Four weeks after starting prophylaxis her thyroid stimulating hormone concentration was 44.8 mU/l (normal range 0.35-6.0 mUI/l) at a routine visit. The regimen for thyroxine sodium was not changed. Chloroquine and proguanil were stopped as intended two months after the day of intended travel, and a week later her concentration of thyroid stimulating hormone was back to normal.
After 16 months–during which she had received the same regimen of thyroxine sodium–she spent two weeks in Indonesia. The same prophylaxis was prescribed. Because of what had happened the previous year her concentration of thyroid stimulating hormone was checked before her departure (3.2 mU/ml), when she came back (26 mU/l), and eight weeks after starting the prophylaxis (54.7 mU/l). When she came back free tri-iodothyronine concentration was 2.7 pmol/l (normal range 2.6-5.9), free thyroxine concentration 11 pmol/l (6-18), and thyroglobulin concentration 1.1 pg/l (<25). The dose of thyroxine sodium remained unchanged. Four weeks after the end of prophylaxis her concentrations of thyroid stimulating hormone and free tri-iodothyronine had returned to normal (0.7 mU/l and 14.6 pmol/l, respectively).
One of the antimalarial drugs might have had a central effect on the hypothalamus, but a drug interaction between thyroxine sodium and chloroquine and proguanil seems more likely to have enhanced the induction of liver enzymes. In this case chloroquine probably increased the catabolism of thyroid hormones by enzymatic induction. Chloroquine reduces the sedation produced by diazepam,1 but it enhances the effect of cyclosporin.2
Intrinsically, such an interaction3 is likely because it recurred when the drug was reintroduced and because the concentration of thyroid stimulating hormone was normal before antimalarial treatment. To our knowledge, this is the first reported case of an interaction between chloroquine and thyroxine sodium, although interactions with chloroquine have been reported in association with ciprofloxacin and methotrexate.1 2 4 5