OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Primaquine	63-45-6	C15-H21-N3-O.2H3-O4-P

ANNOTATED BIBLIOGRAPHY

References updated: 02 February 2017

• Zimmerman HJ. Antiprotozoal agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 623-5.

  (Expert review of hepatotoxicity published in 1999; states that primaquine has not been linked to instances of clinically apparent liver disease).
• Vinetz JM, Clain J, Bounkeua V, Eastman RT, Fidock D. Chemotherapy of malaria.l In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman.s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1383-418.

  (Textbook of pharmacology and therapeutics).
• Thornsvard CT, Guider BA, Kimball DB. An unusual reaction to chloroquine-primaquine. JAMA 1976; 235: 1719-20. [PubMed: 946467]

  (39 year old woman developed fever, abdominal pain, myalgias and red urine 2 days after starting chloroquine-primaquine prophylaxis [bilirubin 0.8 mg/dL, AST >300 U/L, Alk P 60 U/L]; porphyrin testing indicated porphyria cutanea tarda).
• Taylor WR, White NJ. Antimalarial drug toxicity: a review. Drug Saf 2004; 27: 25-61. [PubMed: 14720085]

  (Review of the toxicities and side effects of antimalarials; quinine can cause a characteristic hypersensitivity reaction with liver injury; chloroquine can cause worsening of acute porphyria; primaquine can cause hemolysis, but has not been linked to cases of hepatitis).
• Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, Rowland M. A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of plasmodium vivax in Northwest Frontier Province, Pakistan. PLoS One 2008; 3: e2861. [PMC free article: PMC2481394] [PubMed: 18682739]

  (Among 200 patients with vivax malaria infection randomized to receive two regimens of primaquine in addition to chloroquine therapy for vivax malaria infection, primaquine reduced failure rates and there were "no serious or notable non-serious adverse events" except for anemia in one G6PD deficient patient).
• Ebringer A, Heathcote G, Baker J, Waller M, Shanks GD, Edstein MD. Evaluation of the safety and tolerability of a short higher-dose primaquine regimen for presumptive anti-relapse therapy in healthy subjects. Trans R Soc Trop Med Hyg. 2011 Oct; 105 (10): 568-73. [PubMed: 21890160]

  (Among 203 Australian soldiers treated with primaquine as a higher dose 7 day regimen, there were no "clinically significant differences ... in biochemical indices before and after treatment").
• John GK, Douglas NM, von Seidlein L, Nosten F, Baird JK, White NJ, Price RN. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malar J 2012; 11: 280. [PMC free article: PMC3489597] [PubMed: 22900786]

  (Review of the activity, efficacy and safey of primaquine as therapy and means of prevention of relapse of vivax malaria).
• Baird KJ, Maguire JD, Price RN. Diagnosis and treatment of Plasmodium vivax malaria. Adv Parasitol 2012; 80: 203-70. [PubMed: 23199489]

  (Extensive review of the history and modern approach to diagnosis and treatment of vivax malaria; primaquine has been shown to be effective in preventing relapse and might play a role in the reaching of a goal of elimination of malaria transmission; side effects are few and usually minor except in persons with G6PD deficiency, a problem for the developing world).
• Sutanto I, Tjahjono B, Basri H, Taylor WR, Putri FA, Meilia RA, Setiabudy R, et al. Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia. Antimicrob Agents Chemother 2013; 57: 1128-35. [PMC free article: PMC3591862] [PubMed: 23254437]

  (Prospective trial of three regimens for vivax malaria among 116 Indonesian soliders; primaquine was 92-98% effective in preventing relapse and "most laboratory findings" including serum ALT and alkaline phosphatase levels remained normal before, during and after treatment).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, none were attributed to an antimalarial agent).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25. (In a. [PubMed: 23419359]

  population based study from Iceland, 96 cases of drug induced liver injury were identified over a 2 year period [2010 and 2011], but none were attributed to an antimalarial agent).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to an antimalarial agentl).
• Advice for travelers. Treat Guidel Med Lett 2015: 57 (1466): 52-8.

  (Concise guidelines on prevention of malaria in travelers indicates that primaquine is an appropriate prophylactic agent for patients who cannot tolerate chloroquine).