ARAKODA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARAKODA (ARAKODA).
ARAKODA (tafenoquine) is an 8-aminoquinoline antimalarial agent that inhibits the conversion of Plasmodium protozoa from liver stage to blood stage, thereby preventing relapses. Its exact mechanism may involve interference with electron transport or generation of reactive oxygen species.
| Metabolism | Primarily metabolized by CYP2D6 and monoamine oxidase (MAO). Tafenoquine undergoes extensive metabolism including N-dealkylation and oxidation. |
| Excretion | Biliary/fecal: ~90% unchanged; renal: <1% unchanged (dose-proportional urinary excretion of tafenoquine is minimal, with most eliminated via feces as unchanged drug and minor metabolites). |
| Half-life | Terminal elimination half-life: approximately 14-16 days (range 12-19 days) in healthy adults; this long half-life is due to extensive tissue distribution and slow release from tissues, providing prophylactic coverage for up to 4 weeks after a single dose. |
| Protein binding | ~99.5% bound to human serum albumin (HSA); binding is high and saturable, with unbound fraction slightly increasing at high concentrations. |
| Volume of Distribution | Apparent Vd: ~2000 L (or ~24-30 L/kg based on 70 kg), indicating extensive tissue distribution (concentrated in red blood cells, liver, lungs, and adipose tissue). |
| Bioavailability | Oral: ~100% (absolute bioavailability not formally determined, but absorption is complete with minimal first-pass metabolism; relative bioavailability is high based on AUC and clinical efficacy). |
| Onset of Action | Oral: Maximal plasma concentrations reached 12-15 hours after single dose; antimalarial effect (radical cure of P. vivax) begins within 1-2 days, with clinical improvement typically within 48 hours. |
| Duration of Action | Oral: Single-dose relapse prevention (radical cure) for P. vivax malaria; prophylactic effect persists for 4 weeks after a single dose of 200 mg (two 100 mg tablets). |
400 mg orally once daily for 3 days, then 200 mg once daily for maintenance (up to 12 months).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Contraindicated in Child-Pugh Class B or C. Use with caution in mild hepatic impairment (Child-Pugh Class A) with no dose adjustment. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment; use with monitoring for renal function due to age-related decline and potential for increased adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ARAKODA (ARAKODA).
| Breastfeeding | Excreted in human milk; M/P ratio unknown. Potential for adverse effects in infant; use caution, consider discontinuing breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: animal studies show fetal harm; human data insufficient. Second/third trimester: risk of fetal growth restriction; consider risk-benefit. |
| Fetal Monitoring | Monitor maternal liver function tests, complete blood count, and fetal growth via ultrasound. |
■ FDA Black Box Warning
ARAKODA can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD testing must be performed before prescribing due to risk of hemolytic anemia.
| Serious Effects |
["G6PD deficiency (without confirmed normal G6PD activity)","Known hypersensitivity to tafenoquine or any 8-aminoquinoline","Use in children <16 years (safety not established)","Severe renal impairment (eGFR <30 mL/min)","Lactation in infants with G6PD deficiency or unknown G6PD status"]
| Precautions | ["Hemolytic anemia in G6PD-deficient patients (contraindicated in G6PD deficiency without prior testing)","Methemoglobinemia (rare, monitor for cyanosis and dyspnea)","Psychiatric effects including anxiety, depression, and insomnia","Hepatotoxicity (rare, monitor liver function)","Use in pregnancy: not recommended (risk of hemolysis in G6PD-deficient fetus)","Lactation: avoid if breastfeeding infant is G6PD deficient"] |
| Food/Dietary | Take with a fatty meal to increase absorption. No specific dietary restrictions. Avoid grapefruit juice as it may alter metabolism. |
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| Fertility Effects | No human data; animal studies show impaired fertility at high doses. |
| Clinical Pearls | ARAKODA (tafenoquine) is indicated for radical cure of Plasmodium vivax malaria. Assess G6PD status before prescribing; contraindicated in G6PD-deficient patients due to hemolytic anemia risk. Monitor for methemoglobinemia. Avoid use in pregnancy/lactation. Take with food to enhance absorption. |
| Patient Advice | Take with food to improve absorption. · You must be tested for G6PD deficiency before starting this medication. · Report any signs of anemia, dark urine, or yellowing of eyes/skin. · Avoid use during pregnancy or breastfeeding. · Do not drive if you experience dizziness or blurred vision. |