Version May 2024
Note: Screen for G6PD deficiency prior to initiating treatment. Dosage expressed as mg of base (15 mg base = 26.3 mg primaquine phosphate).
Malaria:
Treatment, P. vivax or P. ovale malaria: Oral: 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) (Ref).
Prophylaxis (primary) (off-label use): Oral: 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 (Ref).
Presumptive anti-relapse therapy (terminal prophylaxis) for P. vivax and P. ovale malaria (off-label use):
Temperate strains: Oral: 0.25 mg/kg once daily for 14 days after departure from malaria-endemic area. Total recommended dose: 3.5 mg/kg given over 14 days (Ref).
Tropical, frequent-relapsing P. vivax: Oral: 0.5 mg/kg (maximum daily dose: 30 mg) once daily for 14 days after departure from malaria-endemic area. Total recommended dose: 7 mg/kg given over 14 days; in patients ≥70 kg, extend treatment duration to achieve total recommended dose without exceeding the maximum daily dose (Ref).
Pneumocystis pneumonia, treatment (alternative agent) (off-label use): Oral: 30 mg once daily in combination with clindamycin for 21 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
(For additional information see "Primaquine: Pediatric drug information")
Note: Screen for G6PD deficiency prior to initiating treatment (Ref). Dosage expressed as mg of base (15 mg base = 26.3 mg primaquine phosphate):
Malaria, uncomplicated; relapse prevention (radical cure) ( P. vivax or P. ovale) : Limited data available:
Patients without G6PD-deficiency:
14-Day Regimen:
Infants, Children, and Adolescents: Note: Guideline-recommended regimen (Ref):
<70 kg: Oral: 0.5 mg base/kg/dose once daily for 14 days; maximum dose: 30 mg base/dose; must be used in combination with appropriate acute antimalarial treatment; consult guidelines to determine the appropriate agent (Ref).
≥70 kg: Oral: 30 mg base/day once daily to complete a total course of 6 mg base/kg (duration is the number of days it takes to complete total dose of 6 mg base/kg divided into 30 mg doses); must be used in combination with appropriate acute antimalarial treatment; consult guidelines to determine the appropriate agent (Ref).
7-Day Regimen: Note: This regimen has only been studied in patients with P. vivax.
Infants ≥6 months weighing ≥5 kg, Children, and Adolescents: Limited data available: Oral: 1 mg base/kg daily for 7 days; dosing based on 2 randomized noninferiority trials in which primaquine was given concomitantly with chloroquine or dihydroartemisinin-piperaquine for the treatment of uncomplicated P. vivax monoinfection; primaquine was administered for either 7 days at a dose of 1 mg/kg/day or at the same total dose divided over 14 days; malaria recurrence was similar between groups and gastrointestinal symptoms were more common in patients who received the 7-day regimen (Ref).
Patients with G6PD-deficiency:
Note: Recommended for patients with mild to moderate or intermediate G6PD deficiency; if patient has more severe G6PD deficiency or is not expected to tolerate primaquine, see guidelines for treatment options (Ref). Must be used in combination with appropriate acute antimalarial treatment; consult guidelines to determine the appropriate agents (Ref).
Infants ≥6 months, Children, and Adolescents: Limited data available: Oral: 0.75 mg base/kg/dose once weekly for 8 weeks under close medical supervision and monitoring for hemolysis; maximum dose: 45 mg base/dose (Ref).
Malaria, prophylaxis: Limited data available:
Primary prophylaxis for short-duration travel (<6 months) for travelers going to areas with primarily P. vivax: Infants, Children, and Adolescents (independent of HIV status): Oral: 0.5 mg base/kg/dose once daily; maximum dose: 30 mg base/dose; initiate 1 to 2 days prior to travel, and continue while in the area with malaria risk and for 7 days after departure(Ref).
Terminal prophylaxis (presumptive antirelapse therapy [PART]): Infants, Children, and Adolescents (independent of HIV status): Oral: 0.5 mg base/kg/dose once daily for 14 days after departure from malaria-endemic area; maximum dose: 30 mg base/dose (Ref).
Malaria, reduction in transmissibility in low transmission endemic areas (P. falciparum): Limited data available:
Infants ≥6 months, Children, and Adolescents: Oral: 0.25 mg base/kg as a single dose on the first day of malaria treatment, in addition to recommended malaria therapy (Ref). Note: G6PD testing is not required for single dose.
Pneumocystis jirovecii pneumonia (PCP), treatment (alternative) (HIV-exposed/-infected patients): Limited data available:
Infants and Children (doses extrapolated from use in other indications): Mild to moderate disease: Oral: 0.3 mg base/kg/dose once daily for 21 days in combination with clindamycin; maximum dose: 30 mg base/dose (Ref).
Adolescents: Oral: 30 mg base once daily for 21 days in combination with clindamycin (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Cardiac arrhythmia, dizziness, prolonged QT interval on ECG
Dermatologic: Pruritus, skin rash
Gastrointestinal: Abdominal cramps, epigastric distress, nausea, vomiting
Hematologic & oncologic: Anemia, hemolytic anemia (in patients with G6PD deficiency), leukopenia, methemoglobinemia (in NADH-methemoglobin reductase-deficient individuals)
Severe G6PD deficiency; pregnancy; use in acutely ill patients with a systemic illness manifested by tendency to develop granulocytopenia (eg, rheumatoid arthritis, systemic lupus erythematosus); concurrent use with other medications causing hemolytic anemia or myeloid bone marrow suppression; concurrent use of quinacrine.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to primaquine or any component of the formulation.
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 nicotinamide adenine dinucleotide (NADH) methemoglobin reductase deficiency, 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.
Disease-related concerns:
• G6PD deficiency: 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. Screen for G6PD deficiency prior to therapy initiation. Use is contraindicated in patients with severe G6PD deficiency. Assess benefits/risks of treatment when considering use in patients with mild to moderate G6PD deficiency or those patients whose G6PD status is unknown and testing is not available. Also assess risk factors for G6PD deficiency or favism in patients with unknown G6PD status. If a decision is made to administer primaquine to a patient with mild to moderate G6PD deficiency or unknown G6PD status (when testing is not available), perform baseline hematocrit and hemoglobin testing and closely monitor hematological parameters (eg, at day 3 and 8). Immediately discontinue treatment if signs of hemolytic anemia occur.
• Nicotinamide adenine dinucleotide methemoglobin reductase deficiency: Use with caution in patients with a personal or family history of NADH methemoglobin reductase deficiency; methemoglobinemia may occur.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as phosphate:
Generic: 26.3 mg (equivalent to primaquine base 15 mg)
Yes
Tablets (Primaquine Phosphate Oral)
26.3 (15 Base) mg (per each): $1.80 - $2.46
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as phosphate:
Generic: 26.3 mg (equivalent to primaquine base 15 mg)
Oral: Administer with food to decrease adverse GI effects (Ref).
Oral: Administer with meals to decrease adverse GI effects (Ref). Tablet may be crushed and mixed with a small amount of applesauce, chocolate syrup, or jelly (Ref).
Malaria, treatment: Radical cure (prevention of relapse) of malaria caused by Plasmodium vivax. Note: CDC guidelines also recommend primaquine for radical cure (prevention of relapse) of malaria caused by Plasmodium ovale (CDC 2022).
Malaria, prophylaxis; Pneumocystis pneumonia, treatment
Primaquine may be confused with primidone
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Artemether and Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Artemether and Lumefantrine. Management: Artemether/lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. If combined, monitor patients for increased toxicities of both agents, including QTc interval prolongation. Risk D: Consider therapy modification
Artesunate: May enhance the QTc-prolonging effect of Primaquine. Artesunate may increase the serum concentration of Primaquine. Risk C: Monitor therapy
Chloroquine: May increase the serum concentration of Primaquine. Risk C: Monitor therapy
ChlorproMAZINE: Antimalarial Agents may increase the serum concentration of ChlorproMAZINE. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May diminish the therapeutic effect of Primaquine. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Primaquine. Risk C: Monitor therapy
Dapsone (Systemic): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider therapy modification
Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Consider avoidance of this combination when possible. If combined, closely monitor for signs/symptoms of hemolytic reactions. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Mefloquine: Aminoquinolines (Antimalarial) may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial. Risk X: Avoid combination
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Quinacrine: May enhance the adverse/toxic effect of Primaquine. Risk X: Avoid combination
Rabies Vaccine: Aminoquinolines (Antimalarial) may diminish the therapeutic effect of Rabies Vaccine. Management: If coadministration is unavoidable during rabies post-exposure vaccination, give a 5th dose of the rabies vaccine. If coadministration is unavoidable during rabies pre-exposure vaccination, ensure antibody titers are greater than or equal to 0.5 IU/mL. Risk D: Consider therapy modification
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Pregnancy testing is recommended prior to use in patients who may become pregnant. Patients who could become pregnant should use effective contraception during therapy and until the next menses following discontinuation of treatment. Patients with partners who could become pregnant should use condoms during therapy and for 3 months after treatment is discontinued.
Primaquine is contraindicated during pregnancy.
Malaria infection in pregnant patients may be more severe than in nonpregnant patients 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 persons and persons who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant persons should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2022; CDC Yellow Book 2020).
Because primaquine may cause acute hemolytic anemia in a fetus with glucose-6-phosphate dehydrogenase deficiency, use is contraindicated in pregnancy. When treatment is needed, other agents are preferred (CDC 2022; CDC Yellow Book 2020). Consult current CDC guidelines for the treatment of malaria during pregnancy.
Primaquine and carboxyprimaquine are present in breast milk.
Data related to the presence of primaquine in breast milk are available following administration of oral primaquine 0.5 mg/kg/day for 14 days to 21 breastfeeding women for the radical cure of P. vivax malaria. All mothers and their children were G6PD-normal, and all infants were at least 28 days of age prior to the study. Maximum breast milk concentrations were 26.8 to 116 ng/mL for primaquine and 3.98 ng/mL to 28.4 ng/mL for carboxyprimaquine. Total daily infant doses via breast milk ranged from 1.06 mcg/kg/day to 9.10 mcg/kg/day and the relative infant dose (RID) ranged from 0.212% to 1.82% compared to a weight-adjusted infant dose of 0.5 mg/kg/day. Primaquine was measurable in the capillary plasma of one infant at one time point during the study; primaquine and carboxyprimaquine concentrations were below the limits of quantification in all other infant plasma samples obtained. Adverse events were not observed in the breastfed infants (Gilder 2018). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or the drug, considering the importance of treatment to the mother. If therapy is needed, the mother and infant should be tested for G6PD deficiency; primaquine may be used in breastfeeding mothers and infants with normal G6PD levels and concentrations (CDC 2022; CDC Yellow Book 2020). The World Health Organization also considers primaquine to be compatible with breastfeeding in G6PD-normal infants; infants should be monitored for hemolysis and jaundice, especially if premature or <1 month of age (WHO 2002).
Periodic CBC (in G6PD normal patients), visual color check of urine, glucose, electrolytes; if hemolysis suspected, monitor CBC, haptoglobin, peripheral smear, urinalysis dipstick for occult blood, G6PD deficiency screening (prior to initiating treatment); baseline hematocrit and hemoglobin testing and periodic CBC (eg, at day 3 and 8) in patients with mild to moderate G6PD deficiency or unknown G6PD status (when testing is not available); ECG (in patients at risk for QT prolongation). Pregnancy test prior to therapy in patients who could become pregnant.
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
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)
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