Piperaquine
Piperaquine is an antiparasitic drug used in combination with dihydroartemisinin to treat malaria. Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurually similar antimalarial drug chloroquine
Mechanism of effect
Primaquine is an antiprotozoal agent active against exoerythrocytic stages of Plasmodium ovale and P. vivax, also active against the primary exoerythrocytic stages of P. falciparum and gametocytes of Plasmodia; disrupts mitochondria and binds to DNA
Pharmacokinetics
Absorption: Well absorbed
Metabolism: Hepatic to carboxyprimaquine (active) via CYP1A2
Half-life elimination: 7 hours; reported range: 3.7 to 9.6 hours
Time to peak, serum: 1 to 3 hours
Excretion: Urine (small amounts as unchanged drug
Dosage
Malaria: Oral:
Treatment, P. vivax or P. ovale malaria: 30 mg once daily for 14 days in combination with another appropriate antimalarial agent; in patients weighing ≥70 kg, adjust to a total dose of 6 mg/kg, administered in daily doses of 30 mg once daily for the number of days required to complete the total calculated dose. For patients with intermediate G6PD activity, may consider 45 mg once weekly for 8 weeks, with close monitoring for hemolysis (use only after consultation with an infectious disease/tropical medicine expert) (CDC 2020).
Prophylaxis (primary) (off-label use): 30 mg once daily; start 1 to 2 days prior to travel and continue while in the malaria-endemic area and for 7 days after departure from the area (CDC Yellow Book 2020).
Presumptive antirelapse therapy (terminal prophylaxis) for P. vivax and P. ovale malaria (off-label use): 30 mg once daily for 14 days after departure from malaria-endemic area. Note: Presumptive antirelapse therapy is not needed if primaquine or tafenoquine are taken for primary prophylaxis (CDC Yellow Book 2020).
Pneumocystis pneumonia (PCP) treatment in HIV-infected patients (alternative to preferred therapy) (off-label use): Oral: 30 mg once daily for 21 days (in combination with clindamycin) (HHS [OI adult 2015]).
Side effects
nausea , vomiting , vertigo , cardiac arrhythmias , ECG prolonged QT , skin rush , Abdominal pain , LeukopeniaAlerts
Concerns related to adverse effects:
• Cardiovascular effects: May cause QT prolongation; monitor ECG in patients with cardiac disease, long QT syndrome, a history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia (<50 beats per minute), and during concomitant administration with QT interval prolonging agents.
• Hematologic effects: Anemia, methemoglobinemia, and leukopenia have been associated with primaquine use; monitor during treatment; do not exceed recommended dosage and duration. Closely monitor patients who have a family or personal history of hemolytic anemia or who have had a prior hematologic adverse reaction attributed to primaquine. Immediately discontinue if marked darkening of the urine or sudden decrease in hemoglobin concentration or leukocyte count occurs.
• Hemolytic anemia: Promptly discontinue with signs of hemolytic anemia (darkening of urine, marked fall in hemoglobin or erythrocyte count). Moderate to severe hemolytic reactions may occur in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and personal or familial history of favism. Geographic regions with a high prevalence of G6PD deficiency (eg, Africa, southern Europe, Mediterranean region, Middle East, southeast Asia, Oceania) are associated with a higher incidence of hemolytic anemia.
Points of recommendation
Concerns related to adverse effects:
• Cardiovascular effects: May cause QT prolongation; monitor ECG in patients with cardiac disease, long QT syndrome, a history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia (<50 beats per minute), and during concomitant administration with QT interval prolonging agents.
• Hematologic effects: Anemia, methemoglobinemia, and leukopenia have been associated with primaquine use; monitor during treatment; do not exceed recommended dosage and duration. Closely monitor patients who have a family or personal history of hemolytic anemia or who have had a prior hematologic adverse reaction attributed to primaquine. Immediately discontinue if marked darkening of the urine or sudden decrease in hemoglobin concentration or leukocyte count occurs.
• Hemolytic anemia: Promptly discontinue with signs of hemolytic anemia (darkening of urine, marked fall in hemoglobin or erythrocyte count). Moderate to severe hemolytic reactions may occur in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and personal or familial history of favism. Geographic regions with a high prevalence of G6PD deficiency (eg, Africa, southern Europe, Mediterranean region, Middle East, southeast Asia, Oceania) are associated with a higher incidence of hemolytic anemia.
Pregnancy level
rimaquine is contraindicated in pregnant women.
Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant women should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2020; CDC Yellow Book 2020)
Breast feeding warning
Primaquine and carboxyprimaquine are present in breast milk.
The relative infant dose (RID) of primaquine is <2% as calculated by the authors of a study and compared to a weight-adjusted infant dose of 0.5 mg/kg/day (Gilder 2018).
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