Tafenoquine
Tafenoquine Uses, Dosage, Side Effects, Food Interaction and all others data.
Tafenoquine is an 8-aminoquinoline analogue of primaquine which varies only on the presence of a 5-phenoxy group. It was discovered by the scientists at the Walter Reed Army Institute of Research in 1978 as a substitute for primaquine that would be more effective against relapsing vivax malaria. Tafenoquine was further developed collaboratively between GlaxoSmithKline and Medicines for Malaria Venture. It was FDA approved on July 20, 2018.
In vitro studies have shown that tafenoquine presents an average 50% inhibitory concentration of 0.436 mcg against blood stages of seven strains of P. falciparum. In chloroquine-resistant P. falciparum strains the IC50 of tafenoquine was greater when compared with primaquine and it ranged from 0.5 to 33.1 mcg. In studies evaluating the transmission-blocking activity of tafenoquine against the sporogonic stage of P. vivax, it was showed a reduced transmission at doses higher than 25 mg/kg.
In clinical trials, it was reported a tafenoquine-induced relapse prevention of 91.9% in cases of vivax malaria when pretreated with chloroquine. In prophylactic studies, tafenoquine showed an efficacy range from 84 to 87% against falciparum malaria and 99.1% against vivax malaria.
| Trade Name | Tafenoquine |
| Availability | Prescription only |
| Generic | Tafenoquine |
| Tafenoquine Other Names | Tafenoquine |
| Related Drugs | doxycycline, clindamycin, hydroxychloroquine, Plaquenil, Cleocin, Vibramycin, Malarone |
| Weight | 100mg, 150mg |
| Type | Oral tablet |
| Formula | C24H28F3N3O3 |
| Weight | Average: 463.501 Monoisotopic: 463.208276263 |
| Protein binding | The plasma protein binding of tafenoquine in humans is very high and it represents about 99.5%. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Tafenoquine is an antiparasitic agent used for the treatment and prevention of relapse of Vivax malaria.
Tafenoquine is used for the treatment and prevention of relapse of Vivax malaria in patients 16 years and older. Tafenoquine is not indicated to treat acute vivax malaria.
Malaria is a disease that remains to occur in many tropical countries. Vivax malaria, caused by Plasmodium vivax, is known to be less virulent and seldom causes death. However, it causes a substantive illness-related burden in endemic areas and it is known to present dormant forms in the hepatocytes named hypnozoites which can remain dormant for weeks or even months. This dormant form produces ongoing relapses.
Tafenoquine is also used to associated treatment for these conditions: Malaria caused by plasmodium vivax
How Tafenoquine works
The mechanism of action of tafenoquine is not well established but studies have reported a longer and more effective action when compared to primaquine. The active moiety of tafenoquine, 5,6 ortho quinone tafenoquine, seems to be redox cycled by P. falciparum which are upregulated in gametocytes and liver stages. Once inside, the oxidated metabolite produces hydrogen peroxide and hydroxyl radicals. It is thought that these radicals produce leads to the parasite death.
On the other hand, tafenoquine inhibits heme polymerase in blood stage of parasites which explains the activity against blood stages of parasites.
Toxicity
Tafenoquine can cause hemolysis in people with glucose-6-phosphate dehydrogenase deficiency. In preclinical studies, renal cell adenomas and carcinomas are increased in male rats with an overdose administration. However, this drug does not seem to be carcinogenic in humans and it was shown to lack mutagenic potential. In fertility studies, tafenoquine resulted in a reduced number of viable fetuses, implantation sites and corpora lutea.
Food Interaction
- Take with food.
[Moderate] ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of tafenoquine.
According to the manufacturer, tafenoquine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 31% and 41%, respectively, when administered as an investigational capsule formulation with a high-calorie, high-fat meal (approximately 1000 calories; 15% protein, 25% carbohydrate, 60% fat) relative to the fasted state.
MANAGEMENT: Tafenoquine should be administered with food.
Tafenoquine Disease Interaction
Major: G6PD deficiency, psychotic disordersModerate: hepatic/renal
Volume of Distribution
Tafenoquine presents a high volume of distribution of approximately 2 560 L.
Elimination Route
The first-in-human pharmacokinetic study showed a tmax of 13.8 hours and this study suggested that the prolonged absorption from the gut can be due to absorption in the distal gastrointestinal tract combined with a slow clearance. The AUC and Cmax demonstrated an intersubject variability. The bioavailability of tafenoquine is increased in the presence of a high-fat meal by modifying the amount of drug absorbed rather than the rate of absorption. Once absorbed, the concentration of tafenoquine in the whole body is two-fold higher than the corresponding concentration in plasma and it seems to be highly distributed in the liver showing an AUC of approximately 80 times more than what is found in the plasma.
Half Life
Tafenoquine presents a long half-life of approximately 14 days.
Clearance
Tafenoquine presents a low clearance of approximately 6 L/h.
Elimination Route
After degradation by different metabolic pathways, tafenoquine is slowly excreted from the body primarily in the feces and renal elimination of the unchanged form is very low.
Innovators Monograph
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