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Primaquine

Medically reviewed by Drugs.com. Last updated on Apr 13, 2020.

Pronunciation

(PRIM a kwin)

Index Terms

  • Primaquine Phosphate
  • Prymaccone

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as phosphate:

Generic: 26.3 mg

Pharmacologic Category

  • Aminoquinoline (Antimalarial)
  • Antimalarial Agent

Pharmacology

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

Excretion

Urine (small amounts as unchanged drug)

Time to Peak

Serum: 1 to 3 hours

Half-Life Elimination

7 hours; reported range: 3.7 to 9.6 hours

Use: Labeled Indications

Malaria, treatment: Radical cure (prevention of relapse) malaria caused by Plasmodium vivax. Note: CDC guidelines also recommend primaquine for radical cure (prevention of relapse) of malaria caused by Plasmodium ovale (CDC 2020).

Off Label Uses

Malaria, prophylaxis

Based on the Centers for Disease Control and Prevention Health Information for International Travel, primaquine is effective and recommended for primary prophylaxis of malaria when the travel is of short duration to areas with principally P. vivax malaria and last-minute travelers and for presumptive antirelapse therapy (terminal prophylaxis) (CDC Yellow Book 2020).

Pneumocystis pneumonia (PCP) in HIV-infected patients

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, primaquine in combination with clindamycin is an effective and recommended alternative agent in the treatment of Pneumocystis pneumonia (PCP) in HIV-infected patients.

Contraindications

Severe G6PD deficiency; pregnancy; use in acutely ill patients who have a 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 with or recent use of quinacrine

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to primaquine or any component of the formulation

Documentation of allergenic cross-reactivity for aminoquinolines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Screen for G6PD deficiency prior to initiating treatment. Dosage expressed as mg of base (15 mg base = 26.3 mg primaquine phosphate).

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]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Screen for G6PD deficiency prior to initiating treatment (CDC 2019a; CDC 2019b; WHO 2015). 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 (CDC 2019a; CDC 2019b):

<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 (CDC 2019a; CDC 2019b).

≥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 (CDC 2019a; CDC 2019b).

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 (Chu 2019; Taylor 2019).

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 (CDC 2019a; CDC 2019b; WHO 2015). Must be used in combination with appropriate acute antimalarial treatment; consult guidelines to determine the appropriate agents (CDC 2019a; CDC 2019b).

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 (CDC Yellow Book 2020; WHO 2015).

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 (CDC Yellow Book 2020; HHS [OI adult 2020]; HHS [OI pediatric 2019]).

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 (CDC Yellow Book 2020; HHS [OI adult 2020]; HHS [OI pediatric 2019]).

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 (WHO 2015). 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 (HHS [OI pediatric 2019]).

Adolescents: Oral: 30 mg base once daily for 21 days in combination with clindamycin (HHS [OI adult 2020]).

Extemporaneously Prepared

6 mg base/5 mL Oral Suspension

A 6 mg base/5 mL oral suspension may be made using tablets. Crush ten 15 mg base tablets and reduce to a fine powder. In small amounts, add a total of 10 mL Carboxymethylcellulose 1.5% and mix to a uniform paste; mix while adding Simple Syrup, NF to almost 125 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 125 mL. Label "shake well" and "refrigerate". Stable 7 days.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

Administer with meals to decrease adverse GI effects. If patient vomits within 30 minutes of taking a dose, then they should repeat the dose (CDC 2013).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Antipsychotic Agents (Phenothiazines): Antimalarial Agents may increase the serum concentration of Antipsychotic Agents (Phenothiazines). Monitor therapy

Artemether: May enhance the QTc-prolonging effect of Primaquine. Artemether may increase the serum concentration of Primaquine. Monitor therapy

Artesunate: May enhance the QTc-prolonging effect of Primaquine. Artesunate may increase the serum concentration of Primaquine. Monitor therapy

Beta-Blockers: Aminoquinolines (Antimalarial) may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Carteolol (Ophthalmic); Levobunolol; Metipranolol; Nadolol; Sotalol. Monitor therapy

Cardiac Glycosides: Aminoquinolines (Antimalarial) may increase the serum concentration of Cardiac Glycosides. Monitor therapy

Chloroquine: May increase the serum concentration of Primaquine. 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. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

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. 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. 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. 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: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy

Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

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. Mefloquine may increase the serum concentration of Aminoquinolines (Antimalarial). Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial when possible. Avoid combination

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. 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. 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. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

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)

Warnings/Precautions

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.

Disease-related concerns:

• G6PD deficiency: 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.

• NADH methemoglobin reductase deficiency: Use with caution in patients with a personal or family history of NADH methemoglobin reductase deficiency; methemoglobinemia may occur.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Monitoring Parameters

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 sexually active females.

Reproductive Considerations

Sexually active females should have a pregnancy test prior to treatment with primaquine. Females of reproductive potential should use effective contraception during therapy and until the next menses following discontinuation of treatment. Males with female partners of reproductive potential should use condoms during therapy and for 3 months after treatment is discontinued.

Pregnancy Considerations

Primaquine 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).

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 2020; CDC Yellow Book 2020). Consult current CDC guidelines for the treatment of malaria during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat or prevent malaria.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal cramps

• Abdominal pain

• Vomiting

• Nausea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Methemoglobinemia like blue or gray color of the lips, nails, or skin; arrhythmia; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath

• Dark urine

• Chills

• Yellow skin

• Dizziness

• Fast heartbeat

• Abnormal heartbeat

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.