Tafenoquine single dose to prevent relapse of P.Vivax.

Tafenoquine is an antimalarial drug that is active against pre-erythrocytic forms including the dormant stage or hypnozoites and the erythrocytic or asexual forms, as well as gametocytes of Plasmodium falciparum and P. vivax. It is used in the following conditions:

For malaria chemoprophylaxis in patients 18 years of age or more.
For the radical cure or prevention of relapse of plasmodium vivax malaria in patients 16 years of age or older in patients receiving antimalarial therapy. It should not be used to treat acute malarial infection due to plasmodium vivax.

Tafenoquine Dose in Adults

Dose in the treatment of Malaria chemoprophylaxis (Arakoda):

Loading regimen:
- 200 mg orally once a day for 3 days prior to travel to a malaria-endemic area
Maintenance regimen:
- 200 mg orally once a week (while in the malaria-endemic area), starting after 7 days of the last dose of the loading regimen.
Terminal prophylaxis regimen:
- 200 mg orally as a single dose, 7 days after the last dose of the maintenance regimen (after leaving the malaria-endemic area).

Missed dose:

Missed one loading dose:
- Administer a single 200 mg dose so that a total of three daily loading doses have been taken.
Missed two loading doses:
- Administer 200 mg once a day for two consecutive days so that a total of 3 daily loading doses have been taken.
Missed one maintenance weekly dose:
- Administer one 200 mg dose on any day up to the time of the next scheduled weekly dose
Missed two maintenance weekly doses:
- Administer one 200 mg dose on any day up to the time of the next scheduled weekly dose
Missed 3 or more maintenance weekly doses:
- Administer 200 mg once a day for 2 days up to the time of the next scheduled weekly dose
Missed terminal prophylaxis dose:
- Administer 200 mg as a single dose as soon as remembered.

Dose for the prevention of relapse of P.Vivax malaria (Krintafel):

300 mg orally as a single dose on the first or second day of antimalarial therapy.

Tafenoquine Dose in Childrens

Dose for the prevention of relapse of P.Vivax malaria (Krintafel):

Adolescents older than 16 years of age:
- Refer to adult dosing.

Pregnancy Risk Factor: D

Because of the potential for adverse fetal outcomes (and hemolysis in G6PD deficient fetus), it is not recommended during pregnancy.
Before initiating therapy, it is important to have a pregnancy test.
Effective contraception should be used by female patients with reproductive potential during treatment and for 3 months following the last dose.

Tafenoquine use during breastfeeding:

It is unknown if the drug can be absorbed into breastmilk.
Manufacturers recommend that parents weigh the benefits and risks of drug exposure for their infants.
It is important to test the infant for G6PD deficiencies.
Breastfeeding should be avoided for infants with G6PD deficiency and those with undetermined status.

Tafenoquine Dose in Renal Disease:

It has not been studied in patients with renal disease and adjustment in the dose has not been provided by the manufacturer. However, it should be used with caution in patients with renal impairment.

Tafenoquine Dose in Liver Disease:

It has not been studied in patients with liver disease and adjustment in the dose has not been provided by the manufacturer. However, it should be used with caution in patients with hepatic impairment.

Common Side Effects Of Tafenoquine Include:

Central nervous system:
- Headache
Gastrointestinal:
- Diarrhea
Hematologic & Oncologic:
- Methemoglobinemia
Neuromuscular & Skeletal:
- Back Pain
Ophthalmic:
- Epithelial Keratopathy

Less Common Side Effects Of Tafenoquine Include:

Central Nervous System:
- Dizziness
- Sleep Disorder
- Drowsiness
- Abnormal Dreams
- Insomnia
- Anxiety
- Depressed Mood
- Depression
Gastrointestinal:
- Nausea
- Motion Sickness
- Vomiting
Hematologic & Oncologic:
- Decreased Hemoglobin
Hepatic:
- Increased Serum Alanine Aminotransferase
Hypersensitivity:
- Hypersensitivity Reaction
Ophthalmic:
- Photophobia
Renal:
- Increased Serum Creatinine

Contraindication to Tafenoquine Include:

Allergy reactions to tafenoquine or other 8-aminoquinolines or any component of this formulation
G6PD deficiency, or undetermined G6PD status
Breastfeeding an infant who is G6PD deficient or with undetermined G6PD status
Patients who have psychotic symptoms or a history psychotic disorders such as hallucinations, delusions and grossly disorganized behavior.

Warnings and Precautions

Hemolytic anemia
- Patients with G6PD deficiency may experience hemolysis.
- Before starting therapy with tafenoquine it is important to determine your G6PD levels.
- Patients with G6PD deficiencies or undetermined status should not be given tafenoquine.
Hypersensitivity reactions
- There have been reports of severe allergic reactions such as angioedema or urticaria.
- Rehallenge and discontinuation of treatment should be considered.
Methemoglobinemia:
- Methemoglobinemia can occur in patients.
- People with methemoglobin reductase-dependent nicotinamide dinucleotide(NADH) should be closely monitored.
Psychiatric effects
- High doses of marijuana have been linked to psychotic effects such as anxiety, depression, abnormal dreams, and insomnia.
- Patients with psychiatric symptoms lasting more than three days should be evaluated immediately and treated accordingly.
G6PD deficiency:
- Before starting treatment, patients should be tested for G6PD levels.
- Patients with undetermined G6PD status should not use it.

Tafenoquine: Drug Interaction

Risk Factor D (Consider therapy modification)
MATE1 Substrates	Tafenoquine may increase the serum concentration of MATE1 Substrates. Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling.
OCT2 Substrates	Tafenoquine may increase the serum concentration of OCT2 Substrates. Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling.

Monitoring parameters:

Perform a pregnancy test in females of reproductive age groups before administration of the drug
G6PD testing should be done before the treatment initiation.
Monitor for clinical features of hemolysis
Monitor for allergic reactions
Observe for methemoglobinemia
Monitor the patient for psychiatric effects.

How to administer Tafenoquine?

It is best administered orally with food. The tablets should be swallowed whole. Crushing, breaking, or chewing the tablets should be avoided.
If vomiting occurs in less than one hour of administering the tablet, the dose should be repeated. (The dose may be repeated only once).

Mechanism of action of Tafenoquine:

It is an 8-aminoquinoline, antimalarial drug. It is active against preerythrocytic forms such as the dormant or hypnozoites as well as the erythrocytic and asexual forms.
It prevents plasmodium viral malaria relapses by preventing the parasite's erythrocytic forms from the pre-erythrocytic liver stage.

AbsorptionThe effects of the drug are increased when combined with high-fat meals or high-calorie diets. The drug contains more than 99.5% protein. It has a half life of 15 to 16.5 hours.

The time to reach peak plasma concentration is 12 - 15 hours.