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 applied under the following circumstances:

• for patients who are at least 18 years old and need chemoprophylaxis against malaria.
• For the complete treatment of plasmodium vivax malaria in patients 16 years of age and older who are receiving antimalarial medication, or for the avoidance of relapse. It shouldn't be applied to plasmodium vivax-related acute malarial infections.

Tafenoquine Dose in Adults

Tafenoquine Dose in the treatment of malaria chemoprophylaxis (Arakoda):

• Before traveling to a place where malaria is common, you take a "loading regimen." That means you take 200 mg of tafenoquine once a day for three days before your trip.
• Once you're in the area where malaria is a risk, you switch to the "maintenance regimen." This means you take 200 mg of tafenoquine once a week. You start this regimen seven days after your last dose of the loading regimen.
• When you leave the malaria area, you take a "terminal prophylaxis regimen" to make sure you're still protected. This is just one 200 mg dose of tafenoquine, taken seven days after your last maintenance dose.

If you miss a dose:

• If you miss one dose during the loading regimen, take a single 200 mg dose as soon as you remember, and then start the maintenance regimen a week later.
• If you miss two loading doses, take one 200 mg dose each day for two days, and then start the maintenance regimen a week later.
• If you miss one maintenance dose, take it whenever you remember, up to the time of your next scheduled weekly dose.
• If you miss two maintenance doses, take one dose when you remember, up to your next scheduled dose.
• If you miss three or more maintenance doses, take one 200 mg dose each day for two days, up to your next scheduled dose.
• If you miss the terminal prophylaxis dose, take one 200 mg dose as soon as you remember.

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

• You take a single dose of 300 mg orally, either on the first or second day of your antimalarial treatment.
• This helps prevent the recurrence of the P. vivax infection.

Tafenoquine Dose in Children

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

• Teenagers older than 16 years old:
  • Refer to adult dosage.

Pregnancy Risk Factor: D

• Tafenoquine isn't recommended for use during pregnancy because it could potentially cause hemolytic anemia in a fetus that has G6PD deficiency.
• If someone is considering using tafenoquine and they're capable of becoming pregnant, they should make sure they're not pregnant before starting the treatment.
• Additionally, effective contraception should be used during the treatment and for three months after the last dose to prevent pregnancy during this time.
• It's important to prioritize safety for both the individual and any potential future pregnancy.

Tafenoquine use during breastfeeding:

• We're not sure if tafenoquine can pass into breast milk, so it's essential to check if the baby has G6PD deficiency before breastfeeding.
• If the baby is G6PD-deficient or their status isn't known, breastfeeding shouldn't happen until three months after the last dose of tafenoquine.
• For babies with normal G6PD status, the decision to breastfeed during tafenoquine therapy should weigh the risks of exposing the baby to the medicine against the benefits of breastfeeding and the mother's need for treatment.

Tafenoquine Dose in Renal Disease:

• The manufacturer's instructions don't offer specific dose adjustments for people with kidney problems because tafenoquine hasn't been studied in this group.
• If someone with renal impairment needs to take tafenoquine, they should use it carefully and watch out for any negative reactions.

Tafenoquine Dose in Liver Disease:

• The manufacturer's instructions don't give specific dose adjustments for people with liver issues because tafenoquine hasn't been studied in this group.
• If someone with liver problems needs to use tafenoquine, they should do so cautiously and keep an eye out for any negative reactions.

Tafenoquine's common side effects include:

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

Tafenoquine's less common side effects include:

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

Contraindications to Tafenoquine include:

• Tafenoquine shouldn't be used if someone has a known hypersensitivity to tafenoquine itself, other medications in the same class (like other 8-aminoquinolines), or any ingredient in the medicine.
• It's also not recommended for individuals with G6PD deficiency or if the G6PD status isn't known, and breastfeeding shouldn't occur if the baby is G6PD deficient or if their status isn't known.
• Additionally, for preventive use, it's not suitable for individuals with a history of psychotic disorders or if they're experiencing psychotic symptoms like hallucinations or delusions.
• These precautions are essential for ensuring the safety and effectiveness of the medication.

Warnings and Precautions

Hemolytic anemia

• Hemolytic anemia, where red blood cells are destroyed faster than they can be produced, is a risk with tafenoquine, especially in people with G6PD deficiency.
• Even those without this deficiency might experience a decrease in their hemoglobin levels.
• It's crucial to screen for G6PD deficiency before starting treatment with tafenoquine, and the medicine shouldn't be used if the patient has this deficiency or if it's not known.
• Since G6PD tests might not catch all cases, it's important to keep an eye out for signs of hemolysis (the breakdown of red blood cells) in all patients, regardless of their G6PD status.
• These signs can sometimes take a while to show up or last longer because tafenoquine stays in the body for a while.
• Patients need access to proper medical care and follow-up to manage this risk effectively.

Hypersensitivity reactions

• Serious allergic reactions, like angioedema (swelling) or urticaria (hives), have been reported with tafenoquine use.
• These reactions might take some time to appear or last longer because tafenoquine stays in the body for a while.
• If someone experiences a hypersensitivity reaction, it's essential to stop using tafenoquine and start appropriate treatment.
• Tafenoquine shouldn't be given again to patients who have had allergic reactions to it in the past.
• Prompt action and avoidance of re-exposure are crucial for managing these reactions effectively.

Methemoglobinemia:

• Some cases of asymptomatic methemoglobinemia, where an abnormal amount of methemoglobin is present in the blood, have been reported with tafenoquine use.
• This condition might be of concern for patients with a deficiency in nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase.

Psychiatric effects

• Tafenoquine use has been associated with psychiatric effects like abnormal dreams, anxiety, depression, and insomnia.
• These effects might not appear right away and could last longer due to tafenoquine's long half-life in the body.
• In some cases, psychosis, which involves losing touch with reality, was reported in patients with a history of psychiatric disorders who received higher doses than recommended.
• If someone has a history of psychiatric illness, tafenoquine should be used cautiously.
• It's not recommended for preventing malaria in patients with a history of psychotic disorders or current psychotic symptoms.
• If psychotic symptoms occur, discontinuation of tafenoquine and prompt evaluation are necessary.
• Other psychiatric symptoms like anxiety, mood changes, or severe insomnia should also be evaluated promptly, especially if they last more than three days.
• Keeping an eye on mental health is crucial during tafenoquine treatment.

G6PD deficiency:

• Before starting therapy with tafenoquine, it's important to screen for G6PD deficiency.
• This condition affects the red blood cells' ability to function properly.
• Tafenoquine shouldn't be used if the patient has G6PD deficiency or if it's not known whether they have it or not.
• Screening helps ensure the safety of the treatment and reduces the risk of complications associated with G6PD deficiency.

Tafenoquine: Drug Interaction

Monitoring parameters:

Before Starting Tafenoquine:

• Pregnancy Testing (for Females): Before taking tafenoquine, it's important for females to get a pregnancy test. This helps make sure they're not pregnant before starting the medication.
• G6PD Testing: G6PD deficiency affects how red blood cells work. Testing for this condition before starting tafenoquine is crucial. If someone has G6PD deficiency or if it's not known, they shouldn't use tafenoquine.

During Tafenoquine Treatment, Watch Out for:

• Signs of Hemolysis: Keep an eye out for signs of hemolysis, where red blood cells break down too quickly. Symptoms might include fatigue, paleness, or dark urine. Even if someone doesn't have G6PD deficiency, this can still happen.
• Hypersensitivity Reactions: Allergic reactions like swelling or hives can occur. These reactions might not show up right away and could last longer because tafenoquine stays in the body for a while.
• Methemoglobinemia: This condition involves having too much methemoglobin in the blood. While it might not cause symptoms in everyone, it's essential to monitor for signs, especially in patients with a specific enzyme deficiency.
• Psychiatric Effects: Keep an eye out for changes in mood, trouble sleeping, or unusual dreams. These effects might not happen immediately and could last longer due to tafenoquine's long-lasting presence in the body.

How to administer tafenoquine

• Take with Food: It's best to take tafenoquine with food. This can help reduce the chance of stomach upset.
• Swallow Whole: The tablets should be swallowed whole, not broken, crushed, or chewed. This ensures the medication works as intended.
• If Vomiting Occurs: If someone vomits within an hour of taking tafenoquine for preventing the relapse of P. vivax malaria, they should take another dose. However, this should only be done once. Don't try to take more doses if vomiting occurs again.
• Completing the Course: When using tafenoquine for preventing malaria (chemoprophylaxis), make sure to finish the full course. This includes both the loading regimen before traveling to a malaria-prone area and the terminal dose after leaving the area. Completing the full course helps ensure the best protection against malaria.

Tafenoquine's Mechanism of Action:

• Tafenoquine is a type of antimalarial drug known as an 8-aminoquinoline.
• It works against different stages of the malaria parasite's life cycle.
• This includes the early stage in the liver (pre-erythrocytic forms) where the parasite can hide in a dormant state called hypnozoite, as well as the later stage in red blood cells (erythrocytic forms) and even the sexual forms (gametocytes) of the parasite.
• By targeting the liver stage, it helps prevent the recurrence of malaria caused by P.
• vivax.
• Additionally, tafenoquine has been observed to cause shrinkage of red blood cells in laboratory studies.

Absorption:

• Taking tafenoquine with a high-calorie, high-fat meal can boost its absorption into the body.

Distribution:

• The volume of distribution (V) of tafenoquine ranges from 1,600 to 2,470 liters. This means it's distributed widely throughout the body.

Protein Binding:

• Tafenoquine is highly bound to proteins in the blood, with more than 99.5% of the drug being bound.

Half-life Elimination:

• The elimination half-life of tafenoquine is long, ranging from 15 to 16.5 days. This means it takes a significant amount of time for half of the drug to leave the body.

Time to Peak:

• It takes around 12 to 15 hours for tafenoquine to reach its peak concentration in the blood after administration.

International brands available:

• Kodatef
• Kozenis
• Krintafel

Tafenoquine Brands in Pakistan:

No brands available in Pakistan