Primaquine

General

Pronunciation
(PRIM a kween)

Trade Name(s)

• Primaquine Phosphate
• Prymaccone

• Aminoquinoline (Antimalarial)

Indications

Use: Labeled Indications
Prevention of relapse of P. vivax malaria

Use: Unlabeled
Prevention of relapse of P. ovale malaria; prevention of malaria; treatment of uncomplicated P. vivax and P. ovale malaria; treatment of Pneumocystis jirovecii pneumonia (PCP); prevention of malaria

Contraindications

Use in acutely-ill patients who have a tendency to develop granulocytopenia (eg, rheumatoid arthritis, SLE); concurrent use with other medications causing hemolytic anemia or myeloid bone marrow suppression; concurrent use with or recent use of quinacrine

Dosing and Administration

Oral: Dosage expressed as mg of base (15 mg base = 26.3 mg primaquine phosphate). Note: The CDC requires screening for G6PD deficiency prior to initiating treatment with primaquine.

Malaria:

Treatment or prevention of relapse of P. vivax malaria: Adults: 30 mg once daily for 14 days

Treatment of uncomplicated P. vivax and P. ovale malaria (unlabeled use):

Children: 0.5 mg /kg (maximum: 30 mg/day) daily for 14 days with chloroquine or hydroxychloroquine (CDC, 2009)

Adults: 30 mg once daily for 14 days with chloroquine or hydroxychloroquine; alternative regimen (for mild G6PD deficiency or as an alternative to daily regimen): 45 mg once weekly for 8 weeks (use only after consultation with an infectious disease/tropical medicine expert) (CDC, 2009)

Chemoprophylaxis (unlabeled use):

Children: 0.5 mg/kg once daily (maximum dose: 30 mg/day); start 1-2 days prior to travel and continue for 7 days after departure from malaria-endemic area (CDC, 2012)

Adults: 30 mg once daily; start 1-2 days prior to travel and continue for 7 days after departure from malaria-endemic area (CDC, 2012)

Presumptive antirelapse therapy for P. vivax and P. ovale malaria (unlabeled use):

Children: 0.5 mg/kg (maximum dose: 30 mg/day) once daily for 14 days after departure from malaria-endemic area (CDC, 2012)

Adults: 30 mg once daily for 14 days after departure from malaria-endemic area (CDC, 2012)

Pneumocystis jirovecii pneumonia treatment (unlabeled use): CDC recommendation (as alternative):

Children: 0.3 mg/kg once daily for 21 days (in combination with clindamycin)

Adults: 30 mg once daily for 21 days (in combination with clindamycin)

General Administration
Take with meals to decrease adverse GI effects. Drug has a bitter taste.

Dosage Forms/Strengths

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

Tablet, oral, as phosphate: 26.3 mg [15 mg base]

Interactions

Anthelmintics: Aminoquinolines (Antimalarial) may decrease the serum concentration of Anthelmintics. Monitor therapy

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

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. Monitor therapy

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

Bendamustine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Monitor therapy

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

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

CYP1A2 Substrates: CYP1A2 Inhibitors (Strong) may decrease the metabolism of CYP1A2 Substrates. Consider therapy modification

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Monitor therapy

Dapsone: May enhance the adverse/toxic effect of Antimalarial Agents. More specifically, dapsone may increase the risk for hemolytic reactions. Antimalarial Agents may enhance the adverse/toxic effect of Dapsone. More specifically, 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. Consider therapy modification

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. 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. Monitor therapy

Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. 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

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Adverse Reactions

Frequency not defined.

Cardiovascular: Arrhythmias (rare)

Central nervous system: Headache

Dermatologic: Pruritus

Gastrointestinal: Abdominal cramps, dyspepsia, nausea, vomiting

Hematologic: Agranulocytosis, anemia, hemolytic anemia (in patients with G6PD deficiency), leukopenia, leukocytosis, methemoglobinemia (in NADH-methemoglobin reductase-deficient individuals)

Ocular: Interference with visual accommodation

Precautions

Boxed warnings:

• Experienced physician: See “Other warnings/precautions” below.

Concerns related to adverse effects:

• 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.

• Other hematologic effects: Anemia, methemoglobinemia, and leukopenia have been associated with primaquine use; monitor during treatment; do not exceed recommended dosage and duration.

Disease-related concerns:

• G6PD deficiency: Use with caution in patients with known G6PD; use of aminoquinolines has been associated with hemolysis. The CDC recommends screening for G6PD deficiency prior to therapy initiation.

• NADH methemoglobin reductase deficiency: Use with caution in patients with NADH methemoglobin reductase deficiency; methemoglobinemia may occur.

Other warnings/precautions:

• Experienced physician: [U.S. Boxed Warning]: Should be prescribed by physicians familiar with its use.

Monitoring
Periodic CBC, 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; CDC recommendation)

Pregnancy Considerations
Animal reproduction studies have not been conducted. Primaquine use is not recommended in pregnant women per CDC Guidelines. Consult current CDC guidelines for the treatment of malaria during pregnancy.

Lactation
Excretion in breast milk unknown

Action

Excretion
Urine (small amounts as unchanged drug)

Patient and Family Education

It is important to complete full course of therapy for full effect. May be taken with meals to decrease GI upset and bitter aftertaste. Avoid excessive alcohol intake. You should have regular ophthalmic exams (every 4-6 months) if using this medication over extended periods. May cause nausea, vomiting, or loss of appetite. Report persistent GI disturbance, chest pain or palpitation, unusual fatigue, easy bruising or bleeding, visual or hearing disturbances, or changes in urine (darkening, tinged with red, decreased volume). Blood counts and immune system need to be monitored.