Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability.
The only U.S. Food and Drug Administration (FDA)-approved indication for the use of doxycycline for malaria is for prophylaxis of Plasmodium falciparum in short-term travelers (< 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine-resistant strains. Although not FDA approved, doxycycline is recommended for prophylaxis of other species of malaria and may be used long term. When used in conjunction with other medications, doxycycline can be used for the treatment of malaria in non-pregnant adults and children ≥ 8 years of age: with quinine sulfate for uncomplicated, chloroquine-resistant P. falciparum; with both quinine sulfate and primaquine for uncomplicated chloroquine-resistant Plasmodium vivax; and with parenteral quinidine for severe malaria.
Available in multiple dosage forms and strengths, doxycycline tablets or capsules of 100 mg are most often used for malaria prophylaxis or treatment. Tablets or capsules should be swallowed with an adequate amount of fluid and should be taken with food. Intravenous (IV) formulation is available for patients unable to take oral medications for treatment. For IV, avoid rapid administration.
Prophylaxis: 100 mg base once daily starting 1–2 days before travel, then daily during travel, and daily for 4 weeks after leaving the malarious area.
Treatment: 100 mg twice a day for 7 days; must be used in conjunction with a fast acting schizontocide. Primaquine is also required if treating P. vivax or Plasmodium ovale.
For children ≥ 8 years of age.
Prophylaxis: 2.2 mg/kg (up to adult dose of 100 mg) daily starting 1–2 days before travel, daily during travel, and daily for 4 weeks after leaving the malarious area.
Treatment: 2.2 mg/kg (up to adult dose of 100 mg) twice a day for 7 days; must be used in conjunction with a fast acting schizontocide. Primaquine is also required if treating P. vivax or P. ovale.
Prophylaxis: Protective efficacy of doxycycline has been shown in three randomized placebo-controlled trials to be between 92% and 96% for P. falciparum and 98% for primary P. vivax infection.
Treatment: When used in combination with a fast acting schizontocide, treatment efficacy of doxycycline has been shown to be 96–100% in three open-label trials.
Limited data suggest that milk and other dairy products may limit the bioavailability of doxycycline. It is recommended to separate doxycycline and ingestion of dairy products by 2–3 hours.
Adverse drug reactions.
Most common mild/moderate adverse drug reactions (ADRs): nausea, vomiting, abdominal pain, photosensitivity, and vaginitis. Women prone to candidal vaginitis should consider carrying a self-treatment course of an anti-fungal. Severe ADRs are uncommon and include esophagitis and esophageal ulcerations. Doxycycline monohydrate has been observed to have less gastrointestinal side effects than doxycycline hyclate.
Doxycycline is contraindicated in those who have known hypersensitivity to tetracyclines.
Decreased absorption of doxycycline can occur if taken concurrently with medications with divalent or trivalent cations such as antacids, laxatives, and oral iron preparations. Although the current FDA label states “concurrent use of tetracycline may render oral contraceptives less effective,” recent studies have failed to show a significant association between oral contraceptive failure and tetracyclines. Tetracyclines may potentiate the effect of oral anticoagulants, therefore patients on oral anticoagulants should have prothrombin times monitored closely and dose adjusted as needed. Concurrent use of tetracyclines and methoxyflurane anesthesia is not recommended. Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.
Pregnancy category D: Do not use in pregnancy except for the treatment of life-threatening multidrug-resistant P. falciparum when no other treatment options are available. Not recommended for children < 8 years of age.
Use during breastfeeding.
Excreted in low concentrations in breast milk; noted to be compatible with breastfeeding by the American Academy of Pediatrics.