Doxycycline versus Atovaquone/Proguanil (Malarone®)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Difference between Doxycycline and Atovaquone/Proguanil
  Doxycycline Atovaquone/Proguanil
Drug class Tetracycline antibiotic Antimalarial,
Hydroxynaphthoquinone derivative and biguanide derivative
Antimalarial mode of action Doxycycline works as blood schizontocide -- kills the erythrocytic stages of the malaria parasite.

In P. falciparum, doxycycline blocks the expression of apicoplast genes, leading to nonfunctional apicoplasts in subsequent progeny, and impeding the development of viable parasites3.
Doxycycline also has some pre-erythrocytic activity in P. falciparum.

Doxycycline has no effect on the liver stage hypnozoites of the Plasmodium species.
Atovaquone/Proguanil works as causal prophylactics -- kills malaria parasites in the erythrocytic stage and liver stage.

Atovaquone inhibits parasite mitochondrial electron transport at the level of the cytochrome bc1 complex and collapses mitochondrial membrane potential.
Proguanil inhibits dihydrofolate reductase (via its metabolite cycloguanil). Atovaquone and proguanil have the synergistic antimalarial action.

Atovaquone/Proguanil has activity against liver stages of P . falciparum. Only limited activity against established P. vivax hypnozoites 1.
Uses and Dosing Prevention of Malaria

100 mg daily
Doxycycline should be taken 1-2 days before arrival in a malarious area, continued whilst you are there and for 4 weeks after leaving the area (to suppress liver forms of Plasmodium parasites that may be released into the blood after exposure ends).

Doxycycline is used in conjunction with quinine for the treatment of uncomplicated malaria caused P. falciparum or P. vivax.
Doxycycline is used in conjunction with quinidine for the treatment of severe malaria caused by P. falciparum.
Prevention of Malaria

1 fixed-combination tablet (250/100 mg) daily

Malarone is approved as chemoprophylactic agent for P. falciparum malaria in children weighing ≥ 11 kg.
Dosage is based on weight.

Malarone should be taken 1-2 days before arrival in a malarious area, continued whilst you are there and for 7 days after leaving the area.
Tablets should be taken at the same time each day ideally with food or a milky drink.

Treatment of Uncomplicated Malaria
4 tablets (1 g of atovaquone and 400 mg of proguanil) once daily for 3 consecutive days.
Long-term use Doxycycline can be used for up to two years. No evidence of harm in long-term use.
Licensed for up to 28 days but can be safely used longer.
Contraindications • Pregnancy or breast feeding
• Children under 8 years of age
• Hypersensitivity to tetracyclines
• Long-term use for more than 12 months
• Hypersensitivity proguanil or atovaquone
• Severe renal impairment
Efficacy Protective efficacy is about 92% and 96% for P. falciparum and 98% for primary P. vivax infection3. Protective efficacy is about 97% 4.

Cure rates of P. falciparum exceed 93% 4.
Side effects nausea, vomiting, abdominal pain, photosensitivity abdominal pain, nausea, vomiting, diarrhea, and headache
Special populations
Pregnancy category D
Pregnancy category C
Lactation Contraindicated May be considered if there is no suitable alternative
Renal impairment Can be used in normal dosage in patients with low creatinine clearance. Contraindicated in patients severe renal impairment (creatinine clearance less than 30 ml/minute).
Drug interactions Decreased absorption with antacids, iron, and zinc. Rifampicin and rifabutin significantly reduce plasma concentrations of atovaquone.
Metoclopramide reduces the bioavailability and absorption of atovaquone
Cost Very inexpensive Expensive

Malarone's 7-day posttravel intake requirement, compared to the 4 weeks required for doxycycline, offers advantage of better adherence, since adherence to prophylaxis is often reduced after return from travel.


Further reading

  • 1. Looareesuwan S, Wilairatana P, Glanarongran M, et al . Atovaquone and proguanil hydrochloride followed by primaquine for treatment of Plasmodium vivax malaria in Thailand . Trans R Soc Trop Med Hyg 1999 ; 93 :637-640 .
  • 2. Shapiro TA, Ranasinha CD, Kumar N, Barditch-Crovo P . Prophylactic activity of atovaquone against Plasmodium falciparum in humans. Am J Trop Med Hyg 1999 ; 60: 831-836 .
  • 3. Tan KR, Magill AJ, Parise ME, Arguin PM; Centers for Disease Control and Prevention. Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis . Am J Trop Med Hyg. 2011 Apr;84(4):517-31. PubMed
  • 4. Boggild AK, Parise ME, Lewis LS, Kain KC. Atovaquone-proguanil: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg. 2007 Feb;76(2):208-23. PubMed

Published: June 10, 2014
Last updated: February 01, 2016


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