Primaquine

Dosage Forms & Strengths

tablet

• 26.3mg

Prevention of relapse of P. vivax malaria

30 mg PO qDay for 14 days

Uncomplicated P. vivax and P. ovale malaria (off-label)

30 mg PO qDay for 14 days with chloroquine or hydroxychloroquine

Alternatively, for mild G6PD deficiency or as alternative to daily regimen: 45 mg PO qDay for 8 weeks (only to be used after consultation with an infectious disease/tropical medicine expert

Chemoprophylaxis (Off-label)

P. vivax and P. ovale maleria: 30 mg PO qDay for 14 days after departure from malaria-endemic area

P. Jiroveci Pneumonia (Orphan)

For use in combination with clindamycin in the treatment of P. Jiroveci pneumonia associated with AIDS

15-30 mg base PO qD for 21 days (with clindamycin IV or PO)

Orphan indication sponsor

• Sanofi Winthrop, Inc; 90 Park Avenue; New York, NY 10016

Other Information

Monitor: CBC

Dosage Forms & Strengths

tablet

• 26.3mg

Uncomplicated P. vivax and P. ovale malaria (Off-label)

0.5 mg/kg (30 mg/day maximum) qDay for 14 days with chloroquine or hydroxychloroquine 

Chemoprophylaxis

0.5 mg/kg PO qDay (30 mg/day maximum); start 1-2 days prior to travel and continue for 7 days after departure from malaria endemic area 

Absorption: well absorbed

Metabolism: hepatic to carboxyprimaquine (active)

Half-life, Elimination: 3.7-9.6 hr

Peak Plasma Time: 1-2 hr

Excretion: urine (small amounts as unchanged drug)

Mechanism of Action

Disrupts Plasmodium mitochondria

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to primaquine.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking primaquine.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

You should not use primaquine if you have an autoimmune disorder, such as lupus or rheumatoid arthritis, or if you also use quinacrine (Atabrine).

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

The usual dose of primaquine is 1 tablet daily for 14 days.

Take primaquine for the entire length of time prescribed by your doctor. If you are taking this medicine to treat malaria, your symptoms may get better before the infection is completely treated.

Talk to your doctor if you stop taking this medicine early for any reason.

No medicine is 100% effective in treating or preventing malaria. For best results, keep taking primaquine as directed.

Contact your doctor as soon as possible if you have been exposed to malaria, or if you have fever or other symptoms of illness during or after a stay in an area where malaria is common.

In addition to taking primaquine, use protective clothing, insect repellents, and mosquito netting around your bed to further prevent mosquito bites that could cause malaria.

Store at room temperature away from moisture and heat.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop taking primaquine and call your doctor at once if you have:

• fever;

• dark colored urine;

• pale or yellowed skin; or

• confusion or weakness.

Common side effects may include:

• nausea, vomiting, stomach cramps;

• irregular heartbeats;

• rash; or

• dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Take primaquine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Keep using primaquine for the full treatment time, even if you feel better after the first few doses. Your infection may not clear up if you stop using primaquine too soon.

Dosing

The dose of primaquine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of primaquine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For malaria:
    • Adults— 15 milligrams (mg) once a day for 14 days.
    • Children— Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of primaquine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• Tell all of your health care providers that you take primaquine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
• Do not take this medicine for longer than you were told by your doctor.
• If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for 3 months after care ends. Use a condom.
• If you are a man and your sex partner gets pregnant while you take primaquine or within 3 months after your last dose, call your doctor right away.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting this medicine. Talk with your doctor.
• If you are able to get pregnant, use birth control that you can trust to prevent pregnancy while taking primaquine and for at least 1 monthly period (menstrual) cycle after stopping this medicine.
• If you are pregnant or you get pregnant while taking primaquine, call your doctor right away.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• To gain the most benefit, do not miss doses.
• Keep taking primaquine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Primaquine phosphate is indicated for the radical cure (prevention of relapse) of vivax malaria.

Persons with acute attacks of vivax malaria, provoked by the release of erythrocytic forms of the parasite, respond readily to therapy, particularly to chloroquine phosphate. Primaquine eliminates tissue (exoerythrocytic) infection and prevents relapses in experimentally induced vivax malaria in human volunteers and in persons with naturally occurring infections and is a valuable adjunct to conventional therapy in vivax malaria.

• Primaquine Phosphate
• Prymaccone

Primaquine is an antiprotozoal agent active against exoerythrocytic stages of Plasmodium ovale and P. vivax, also active against the primary exoerythrocytic stages of P. falciparum and gametocytes of Plasmodia; disrupts mitochondria and binds to DNA

Absorption

Well absorbed

Metabolism

Hepatic to carboxyprimaquine (active) via CYP1A2

Excretion

Urine (small amounts as unchanged drug)

Time to Peak

Serum: 1 to 3 hours

Half-Life Elimination

7 hours; reported range: 3.7 to 9.6 hours

Note: Screen for G6PD deficiency prior to initiating treatment. Dosage expressed as mg of base (15 mg base = 26.3 mg primaquine phosphate).

Malaria: Oral:

Treatment or prevention of relapse of P. vivax malaria: 15 mg once daily in combination with chloroquine for 14 days (maximum dose: 15 mg/day)

Treatment of uncomplicated P. vivax and P. ovale malaria (off-label use): 30 mg once daily for 14 days with chloroquine or hydroxychloroquine; alternative regimen (for mild G6PD deficiency or as an alternative to daily regimen): 45 mg once weekly for 8 weeks (use only after consultation with an infectious disease/tropical medicine expert) (CDC 2013)

Chemoprophylaxis (off-label use): 30 mg once daily; start 1 to 2 days prior to travel and continue for 7 days after departure from malaria-endemic area (CDC Yellow Book 2014)

Presumptive antirelapse therapy for P. vivax and P. ovale malaria (off-label use): 30 mg once daily for 14 days after departure from malaria-endemic area (CDC Yellow Book 2014)

Pneumocystis pneumonia (PCP) treatment in HIV-infected patients (alternative to preferred therapy) (off-label use): Oral: 30 mg once daily for 21 days (in combination with clindamycin) (HHS [OI adult 2015])

Note: Screen for G6PD deficiency prior to initiating treatment. Dosage expressed as mg of base (15 mg base = 26.3 mg primaquine phosphate).

Malaria: Oral:

Treatment of uncomplicated P. vivax and P. ovale malaria (off-label use): 0.5 mg/kg (maximum: 30 mg/day) daily for 14 days with chloroquine or hydroxychloroquine (CDC 2013)

Chemoprophylaxis (off-label use): 0.5 mg/kg once daily (maximum dose: 30 mg/day); start 1 to 2 days prior to travel and continue for 7 days after departure from malaria-endemic area (CDC Yellow Book 2014)

Presumptive antirelapse therapy for P. vivax and P. ovale malaria (off-label use): 0.5 mg/kg (maximum dose: 30 mg/day) once daily for 14 days after departure from malaria-endemic area (CDC Yellow Book 2014)

Pneumocystis pneumonia (PCP) treatment in HIV-infected patients (alternative to preferred therapy) (off-label use) (alternative to preferred therapy):

Children: 0.3 mg/kg once daily for 21 days (in combination with clindamycin) (HHS [OI pediatric 2013])

Adolescents: Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling.

A 6 mg base/5 mL oral suspension may be made using tablets. Crush ten 15 mg base tablets and reduce to a fine powder. In small amounts, add a total of 10 mL Carboxymethylcellulose 1.5% and mix to a uniform paste; mix while adding Simple Syrup, NF to almost 125 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 125 mL. Label "shake well" and "refrigerate". Stable 7 days.

Primaquine is contraindicated in pregnant women.

Sexually active females should have a pregnancy test prior to treatment with primaquine. Females of reproductive potential should use effective contraception during therapy and until the next menses following discontinuation of treatment. Males with female partners of reproductive potential should use condoms during therapy and for 3 months after treatment is discontinued.

Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When treatment is needed, other agents are preferred (CDC Yellow Book 2016). Consult current CDC guidelines for the treatment of malaria during pregnancy.

US CDC, NIH, HIVMA/IDSA, Pediatric Infectious Diseases Society, and American Academy of Pediatrics Recommendations for HIV-exposed and HIV-infected Children: 0.3 mg/kg base (0.526 mg/kg salt) orally once a day
Maximum dose: 30 mg base/dose

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-infected Adolescents: 30 mg base (52.6 mg salt) orally once a day

Duration of therapy: 21 days

Comments:
-In combination with clindamycin, recommended as an alternative regimen for mild-to-moderate PCP (children and adolescents) and moderate-to-severe PCP (adolescents)
-Data not available for children; dosing based on use of these drugs to treat other infections.

Data not available

Storage requirements:
-Close bottle tightly; protect from light.

General:
-The dose of this drug is often expressed or calculated as the base. Each 26.3 mg tablet of primaquine phosphate is equivalent to 15 mg primaquine base.
-The US CDC recommends screening for G6PD deficiency before starting this drug.
-Current guidelines should be consulted for additional information.

Monitoring:
-Hematologic: Routine blood examinations, especially blood cell counts and hemoglobin values (during therapy)

In a trial, lactating mothers at risk for recurrent vivax malaria received 0.5 mg/kg/day. Preliminary results showed no drug-related side effects in their nursing infants (aged at least 28 days). Low but measurable levels of this drug were found in breast milk and infant plasma. The very small amounts of antimalarial drugs transferred in breast milk are insufficient to provide adequate protection against malaria. If prophylaxis is required, infants should receive recommended doses of antimalarial drugs. Current guidelines should be consulted for additional information.

This drug should not be used unless the breastfeeding mother and infant have normal glucose-6-phosphate dehydrogenase (G6PD) levels. Excreted into human milk: Yes (low levels) Comments: -If therapy is required, the mother and infant should be tested for G6PD deficiency before this drug is administered to a breastfeeding woman. -The effects in the nursing infant are unknown.