primaquine
An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances.
Mechanism of effect
Primaquine's mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite. Also, although its mechanism of action is unclear, primaquine may bind to and alter the properties of protozoal DNA.
Pharmacodynamic
Primaquine is an antimalarial agent and is the essential co-drug with chloroquine in treating all cases of malaria. In the blood, malaria parasites break down a part of the red blood cells known as haemoglobin. When this happens haemoglobin is divided into two parts; haem and globin. Haem is toxic to the malaria parasite. To prevent it from being damaged, the malaria parasite produces an chemical which converts the toxic haem into a non-toxic product. Primaquine acts by interfering with a part of the parasite (mitochondria) that is responsible for supplying it with energy. Without energy the parasite dies. This stops the infection from continuing and allows the person to recover.
Primaquine kills the intrahepatic form of Plasmodium vivax and Plasmodium ovale, and thereby prevents the development of the erythrocytic forms that are responsible for relapses (it also kills gametocytes). Primaquine is not used in the prevention of malaria, only in the treatment. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent. Primaquine has gametocytocidal activity against all plasmodia, including P. falciparum.
Pharmacokinetics
- Absorption: Not Available
- Volume of distribution: Not Available
- Protein binding: Not Available
- Metabolism: Not Available
- Route of elimination: Not Available
- Half life: 3.7-7.4 hours.
Drug indications
Malaria ProphylaxisDosage
Usual Adult Dose for Malaria
Manufacturer Recommendations: 15 mg base (26.3 mg salt) orally once a day for 14 days
Usual Adult Dose for Malaria Prophylaxis
Manufacturer Recommendations: 15 mg base (26.3 mg salt) orally once a day for 14 days.
Usual Adult Dose for Pneumocystis Pneumonia
US CDC, National Institutes of Health (NIH), and HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA) Recommendations for HIV-infected Patients: 30 mg base (52.6 mg salt) orally once a day
Duration of therapy: 21 days.
Usual Pediatric Dose for Malaria
US CDC Recommendations: 0.5 mg/kg base (0.8 mg/kg salt) orally once a day for 14 days
Maximum dose: 30 mg base/dose.
Usual Pediatric Dose for Malaria Prophylaxis
US CDC Recommendations: 0.5 mg/kg base (0.8 mg/kg salt) orally once a day
Maximum dose: 30 mg base/dose.
Usual Pediatric Dose for Pneumocystis Pneumonia
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
Duration of therapy: 21 days
Side effects
vertigo , cardiac arrhythmias , itching , gastrointestinal disturbances , Abdominal pain , RashInteractions
Levamisole , pyrvinium pamoate , Dolasetron , vandetanib , Dofetilide , Pirfenidone , Halofantrine , Grepafloxacin , Tasimelteon , Entrectinib , Bepridil , bedaquiline , BromazepamQuinacrine: potentiates toxicity of antimalarials structurally related to primaquine.
Alerts
- Cardiovascular effects: May cause QT prolongation; monitor ECG in patients with cardiac disease, long QT syndrome, a history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia (<50 beats per minute), and during concomitant administration with QT interval prolonging agents.
- Hematologic effects: Anemia, methemoglobinemia, and leukopenia have been associated with primaquine use; monitor during treatment; do not exceed recommended dosage and duration. Closely monitor patients who have a family or personal history of hemolytic anemia or who have had a prior hematologic adverse reaction attributed to primaquine. Immediately discontinue if marked darkening of the urine or sudden decrease in hemoglobin concentration or leukocyte count occurs.
- Hemolytic anemia: Promptly discontinue with signs of hemolytic anemia (darkening of urine, marked fall in hemoglobin or erythrocyte count). Moderate to severe hemolytic reactions may occur in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and personal or familial history of favism. Geographic regions with a high prevalence of G6PD deficiency (eg, Africa, southern Europe, Mediterranean region, Middle East, southeast Asia, Oceania) are associated with a higher incidence of hemolytic anemia.
- G6PD deficiency: Screen for G6PD deficiency prior to therapy initiation. Use is contraindicated in patients with severe G6PD deficiency. Assess benefits/risks of treatment when considering use in patients with mild to moderate G6PD deficiency or those patients whose G6PD status is unknown and testing is not available. Also assess risk factors for G6PD deficiency or favism in patients with unknown G6PD status. If a decision is made to administer primaquine to a patient with mild to moderate G6PD deficiency or unknown G6PD status (when testing is not available), perform baseline hematocrit and hemoglobin testing and closely monitor hematological parameters (eg, at day 3 and 8). Immediately discontinue treatment if signs of hemolytic anemia occur.
- NADH methemoglobin reductase deficiency: Use with caution in patients with a personal or family history of NADH methemoglobin reductase deficiency; methemoglobinemia may occur.
Points of recommendation
To make sure this medicine is safe for you, tell your doctor if you have:
- If you have an allergy to primaquine or any other part of primaquine.
- If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
- If you have any of these health problems: Lupus or rheumatoid arthritis.
- If you have G6PD deficiency.
- If you are taking or have recently taken quinacrine.
- If you are taking any drugs that can stop your bone marrow from making some of the cells that your body needs. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
- If you are pregnant or may be pregnant. Do not take primaquine if you are pregnant.
- If you are breast-feeding or plan to breast-feed.
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 primaquine 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 primaquine. 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 primaquine.
If you are pregnant or you get pregnant while taking primaquine, call your doctor right away.
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.
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.
Ask a Pharmacist