Usage
Primaquine is prescribed for the radical cure (prevention of relapse) of Plasmodium vivax and Plasmodium ovale malaria. It eliminates the dormant liver stage of these parasites (hypnozoites), preventing future relapses. It is also effective against gametocytes of Plasmodium falciparum, thereby reducing transmission. Its pharmacological classification is antimalarial.
Primaquine’s mechanism of action involves the disruption of the parasite’s mitochondrial electron transport, leading to oxidative stress and ultimately parasite death.
Alternate Names
There are no widely used alternate names for Primaquine. Brand names may vary depending on the region.
How It Works
Pharmacodynamics: Primaquine acts primarily on the liver stages of P. vivax and P. ovale (hypnozoites) and the gametocytes of P. falciparum. The exact mechanism is not fully understood but involves the disruption of the parasite’s mitochondrial function. This leads to the formation of reactive oxygen species, causing oxidative damage and parasite death.
Pharmacokinetics: Primaquine is rapidly absorbed after oral administration and extensively metabolized in the liver. It is primarily eliminated via hepatic metabolism, with a small amount excreted renally. The specific CYP enzymes involved in its metabolism are not fully defined, but CYP 2D6 is thought to play a role.
Dosage
Standard Dosage
Adults:
- Malaria Treatment (Radical Cure): 15 mg base (equivalent to 26.3 mg primaquine phosphate) orally once daily for 14 days. A higher dose of 30 mg base daily for 14 days is recommended by the CDC due to concerns about the efficacy of the lower dose. For patients weighing ≥70 kg, a total dose of 6 mg/kg is recommended, divided into daily doses of 30 mg.
Children:
- Malaria Treatment (Radical Cure): 0.5 mg/kg base (maximum 30 mg/day) orally once daily for 14 days, given with chloroquine or hydroxychloroquine.
- Malaria Chemoprophylaxis: 0.5 mg/kg base orally once daily (maximum 30 mg/day), starting 1–2 days before travel and continuing for 7 days after departure from the malaria-endemic area.
Special Cases:
- Elderly Patients: Caution is advised due to potential age-related decline in hepatic and renal function. Dose adjustment may be necessary.
- Patients with Renal Impairment: Dose adjustment may be needed based on creatinine clearance.
- Patients with Hepatic Dysfunction: Dose reduction is required in patients with moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with G6PD deficiency, rheumatoid arthritis, lupus erythematosus, or conditions that prolong the QT interval.
Clinical Use Cases
Primaquine is not indicated for the acute treatment of malaria symptoms, intubation, surgical procedures, mechanical ventilation, ICU use, or other emergency situations. It targets the liver stages to prevent relapse and transmission, not immediate symptoms.
Side Effects
Common Side Effects
- Nausea
- Vomiting
- Abdominal cramps
- Dizziness
- Headache
Rare but Serious Side Effects
- Hemolytic anemia (especially in G6PD deficient patients)
- Methemoglobinemia
- Cardiac arrhythmias (QT prolongation)
- Granulocytopenia
Contraindications
- Severe G6PD deficiency
- Pregnancy
- Concurrent use of quinacrine or other drugs that cause hemolysis or bone marrow suppression
- Acute systemic illnesses associated with granulocytopenia (e.g., rheumatoid arthritis, lupus erythematosus)
Drug Interactions
Primaquine interacts with numerous medications, including:
- CYP3A4 inhibitors and inducers: May alter primaquine levels.
- Drugs that prolong the QT interval: Increased risk of cardiac arrhythmias.
- Other antimalarials (e.g., chloroquine): Additive effects and potential for increased toxicity.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated due to the risk of fetal harm.
- Breastfeeding: Contraindicated unless both mother and infant have normal G6PD levels. Primaquine is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Disrupts parasite mitochondrial function, leading to oxidative damage.
- Side Effects: Nausea, vomiting, abdominal cramps, dizziness, headache, hemolytic anemia (G6PD deficiency), methemoglobinemia, cardiac arrhythmias.
- Contraindications: Severe G6PD deficiency, pregnancy, concurrent quinacrine use.
- Drug Interactions: CYP3A4 inhibitors/inducers, drugs that prolong the QT interval, other antimalarials.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; use with caution during breastfeeding only if both mother and infant have normal G6PD levels.
- Dosage: Adults: 15-30 mg base daily for 14 days; Children: 0.5 mg/kg/day (maximum 30 mg) for 14 days.
- Monitoring Parameters: G6PD levels prior to initiating therapy, complete blood count, hemoglobin, methemoglobin levels.
Popular Combinations
Primaquine is often combined with chloroquine or an artemisinin-based combination therapy (ACT) for the treatment of P. vivax and P. ovale malaria. This combination provides both symptomatic relief and radical cure.
Precautions
- General Precautions: G6PD screening is mandatory before starting primaquine. Monitor for signs of hemolysis.
- Specific Populations: Contraindicated in pregnancy; use with caution during breastfeeding if both mother and infant have normal G6PD levels. Avoid use in infants less than 6 months old.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Primaquine?
A: Adults: 15 mg base once daily for 14 days. A higher dose of 30mg is recommended by CDC. Children: 0.5 mg/kg/day (max 30 mg) for 14 days.
Q2: What is the most serious side effect of Primaquine?
A: Hemolytic anemia, particularly in individuals with G6PD deficiency.
Q3: Can Primaquine be used during pregnancy?
A: No, Primaquine is contraindicated in pregnancy due to the risk of fetal harm.
A: Primarily through hepatic metabolism.
Q5: Can Primaquine be used to treat acute malaria symptoms?
A: No, Primaquine targets the liver stage to prevent relapse. It is not effective against the blood stages that cause acute symptoms.
Q6: What test is essential before starting Primaquine treatment?
A: G6PD deficiency testing.
Q7: What are the signs of hemolytic anemia associated with Primaquine?
A: Fatigue, pallor, shortness of breath, rapid heartbeat, jaundice, dark urine.
Q8: What are the drug interactions of Primaquine?
A: Interacts with CYP3A4 inhibitors/inducers, drugs that prolong the QT interval (e.g., some antibiotics and antipsychotics), and other antimalarials.
Q9: Can Primaquine be used in breastfeeding mothers?
A: Only if both the mother and infant have been tested and confirmed to have normal G6PD levels. Close monitoring is recommended.
Q10: Why is primaquine given with chloroquine?
A: Chloroquine treats the blood stage infection causing symptoms, while primaquine targets the liver stage to prevent relapse.
