Primaquine

Oral
Radical cure of ovale malaria, Radical cure of vivax malaria

Patients with mild to moderate G6PD deficiency: May consider 45 mg once weekly for 8 weeks with close monitoring for haemolysis.

Should be taken with food. Take w/ meals to avoid GI discomfort.

Acutely ill patients with systemic disease manifested by a tendency to develop granulocytopenia (e.g. SLE, rheumatoid arthritis); severe G6PD deficiency. Pregnancy. Concomitant use with other drugs causing haemolytic anaemia or myeloid bone marrow suppression; concomitant use with or recent use of mepacrine.

Patient with family or personal history of favism, haemolytic anaemia, or nicotinamide adenine dinucleotide (NADH) methaemoglobin reductase deficiency; mild to moderate G6PD deficiency or unknown G6PD status (when testing is unavailable); cardiac disease, long QT syndrome, bradycardia (<50 bpm), uncorrected hypokalaemia and/or hypomagnesaemia, history of ventricular arrhythmias; previous idiosyncratic reaction to primaquine. Children. Lactation.

Significant: Moderate to severe haemolytic reactions (particularly in patients with G6PD deficiency and those with family or personal history of favism), methaemoglobinaemia (in patients with NADH methaemoglobin reductase deficiency), leucopenia, anaemia, QT interval prolongation, cardiac arrhythmia.
Eye disorders: Visual disturbances.
Gastrointestinal disorders: Nausea, epigastric distress, vomiting, abdominal cramps.
Nervous system disorders: Headache, dizziness.
Skin and subcutaneous tissue disorders: Rash, pruritus.

Screen for G6PD deficiency before starting treatment. Obtain CBC (in G6PD normal patients), glucose, electrolytes, and visual colour check of urine periodically. If haemolysis is suspected, obtain haptoglobin, peripheral smear, CBC, and urinalysis dipstick for occult blood prior to starting treatment. In patients with mild to moderate G6PD deficiency or unknown G6PD status (when testing is unavailable), obtain haematocrit and Hb at baseline and monitor CBC periodically (e.g. at Day 3 and 8). Monitor ECG in patients at risk for QT prolongation. Assess for signs of haemolytic anaemia and other haematologic effects. Perform pregnancy test in sexually active females prior to treatment.

Symptoms: Vomiting, abdominal cramps, burning epigastric distress, CNS disturbances, CV disturbances including cardiac arrhythmia and QT interval prolongation, methaemoglobinaemia, cyanosis, anaemia, moderate leucocytosis or leucopenia; granulocytopenia and acute haemolytic anaemia in sensitive patients. Management: Supportive and symptomatic treatment. May consider administering activated charcoal within 1-2 hours after ingestion. Ascorbic acid may be given at a dose of 200 mg tid to treat methaemoglobinaemia after withdrawing primaquine.

May enhance the QTc-prolonging effect of QT-prolonging agents.
Potentially Fatal: May increase leucopenic effect with bone marrow depressants. Increased risk of toxic side effects with other haemolytic drugs. Mepacrine may enhance the toxicity of primaquine.

Description:
Mechanism of Action: Primaquine is an 8-aminoquinoline antimalarial which is active against exoerythrocytic stages of Plasmodium vivax and Plasmodium ovale, primary exoerythrocytic stages of Plasmodium falciparum, and gametocytes of Plasmodia. Its exact mechanism of action has not been determined but it appears to disrupt the mitochondria and bind to DNA.
Pharmacokinetics:
Absorption: Rapidly and well absorbed from the gastrointestinal tract. Time to peak plasma concentration: 1-3 hours.
Distribution: Widely distributed into body tissues. Enters breast milk (small amounts). Volume of distribution: Approx 150-250 L.
Metabolism: Rapidly metabolised in the liver by CYP1A2 isoenzyme to carboxyprimaquine (major active metabolite).
Excretion: Via urine (as unchanged drug in small amounts). Elimination half-life: 7 hours (range: 3.7-9.6 hours).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4908, Primaquine. https://pubchem.ncbi.nlm.nih.gov/compound/Primaquine. Accessed Nov. 24, 2022.

Store between 15-30°C. Protect from light.

Antimalarials

P01BA03 - primaquine ; Belongs to the class of aminoquinoline antimalarials.

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Primaquine Phosphate Tablet (PD-Rx Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 24/10/2022.

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Treatment of Malaria: Guidelines for Clinicians (United States). Centers for Disease Control and Prevention. https://www.cdc.gov. Accessed 24/10/2022.