JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
Regions with Plasmodium vivax or Plasmodium ovale malaria with or without Plasmodium falciparum malaria
Primaquine phosphate (generic only)
Two 26.3mg tabs (30mg base q day
Adult dose
Avoid in pregnancy
As soon as possible on return
14 days
•Hemolytic anemia with G6PD deficiency; pretherapy
testing required. • Gastric irritation • Methemoglobinemia • Contraindicated during pregnancy and breast-feeding unless the infant has normal G6PD levels • Failures in P. vivax therapy reported in patients with hepatic CYP2D6 polymorphisms.
Table 2: FDA Pregnancy Categories: Note: As of June 2015, the FDA no longer uses letter categories to describe pregnancy risks and makes recommendation statements only. A: Human studies have demonstrated no evidence of risk to the fetus. B: Animal studies have demonstrated no evidence of risk to the fetus. C: Animal studies have demonstrated adverse effects on the fetus. D: Investigational or marketing experiences or human studies have demonstrated adverse effects on the fetus, but potential benefits may warrant use of the drug in pregnancy despite the risks. X: Studies in animals or humans have demonstrated fetal abnormalities. N: FDA has not classified the drug.
In chemoprophylactic doses of mefloquine, the most severe neuropsychiatric side effects of seizures and acute psychoses with suicidal tendencies occur very rarely at rates of 1 in 6,500 to 1 in 10,600 persons. 13 Less serious neuropsychiatric effects including insomnia, nightmares, irritability, and depression do occur more commonly at rates of 1 in 200 to 1 in 500 users. 4, 12-15 The most common side effects appear to be colorful and vivid dreams that occur in 15 to 25% of users and are typically well tolerated. Over 90% of mefloquine users complete their prescribed courses of chemoprophylaxis without significant side effects. 14-16 In summary, the evidence has confirmed that mefloquine’s adverse effect profile is similar in frequency to other antimalarials. Given its rare potential for neuropsychiatric adverse effects, mefloquine chemoprophylaxis should not be recommended in persons with preexisting histories of epilepsy, seizures, depression, suicide attempts, or psychoses. 13 Although contraindicated in these cases, mefloquine is among the safest antimalarials for pregnant patients (Category B) and is recommended throughout pregnancy for travelers to chloroquine-resistant, P. falciparum -endemic regions. 14-16 The other antimalarials used in prophylaxis, doxycycline and atovaquone-proguanil, are not recommended in pregnancy. Doxycycline has known fetotoxic effects on bone and tooth development duringpregnancy; and atovaquone-proguanil, the newest antimalarial, has an unknown potential for fetotoxicity.
chloroquine, mefloquine, and doxycycline; and (6) an excellent medication compliance rate. 17 On the other hand, atovaquone- proguanil does have to be taken orally every day like doxycycline and not weekly like mefloquine. In addition, atovaquone- proguanil is the most expensive oral antimalarial which limits its use for long-term, cost-effective chemoprophylaxis. In a 2010 investigation designed to analyze adherence with atovaquone-proguanil chemoprophylaxis in short-term travelers, DePetrillo and coauthors prescribed atovaquone- proguanil prophylaxis to 124 adult travelers to malaria-endemic countries. 17 Most (n = 92, 89%) study subjects were compliant with their prophylaxis; and adverse effects were unusual (n = 6, 5%). Among the three travelers who discontinued atovaquone- proguanil, two experienced abdominal discomfort and diarrhea, andone reportednausea. The authors concluded that adherence to atovaquone-proguanil chemoprophylaxis was high and that serious adverse effects were uncommon. Given the effectiveness and high compliance profile of atovaquone-proguanil, clinicians nowquestion theneed for such a prolonged post-travel course of 7 days of chemoprophylaxis. In 2014, Leshem and coinvestigators reported the results of their retrospective telephone survey of 485 travelers to P. falciparum- hyperendemic sub-Saharan Africa over the reporting period 2010-2011 in comparison to P. falciparum cases reported to the passive surveillance registry run by the Israeli Ministry of Health (MOH). 18 Among the 485 travelers to sub-Saharan Africa, none developed malaria, and 421 (87%) discontinued atovaquone-proguanil one day after leavingAfrica. 18 Descriptive analysis of theMOH registry identified 363 cases of P. falciparum malaria, mostly in patients who did not use chemoprophylaxis (n = 305, 84%), and of those who did, none used atovaquone-proguanil. Nevertheless, at this stage, malaria experts caution that a post-travel atovaquone-
The Duration of Atovaquone-Proguanil Chemoprophylaxis
Atovaquone-proguanil, available in the U.S. since the late 1990s, is the among the most acceptable and well tolerated antimalarials for many reasons including: (1) a favorable side effect profile; (2) dual antimalarial actions in blood and liver stages; (3) no detectable parasite resistance worldwide; (4) a short pre-travel administration period of 2 days; (5) a post- travel administration period of a week compared to a month for
136 J La State Med Soc VOL 169 SEPTEMBER/OCTOBER 2017
Made with FlippingBook Digital Publishing Software