Primaquine is an antimalarial medication used to treat specific parasitic infections. It belongs to a class of drugs known as 8-aminoquinolines and is available as a generic medication. It was first synthesized in 1946 and is included on the World Health Organization’s List of Essential Medicines.
Medical Uses of Primaquine
The primary role of primaquine in malaria treatment is its ability to prevent relapses of infections caused by the parasites Plasmodium vivax and Plasmodium ovale. These two species of malaria are unique because they can leave dormant forms in the liver. If left untreated, these forms can reactivate weeks, months, or even years after the initial illness, causing a relapse of the disease. Primaquine is specifically effective at eliminating these dormant liver stages, which are known as hypnozoites.
Primaquine is almost always administered as part of a combination therapy. It follows or is given alongside another antimalarial drug, such as chloroquine, which targets the active, blood-stage parasites that cause the immediate symptoms of malaria. While the other drug clears the parasites from the bloodstream, primaquine works in the liver to eradicate the lingering hypnozoites, providing a “radical cure.”
Beyond preventing relapse, primaquine has other applications in malaria control. It can be used for primary prevention of malaria in certain circumstances where other options are not suitable. A single low dose of primaquine is sometimes used to prevent the transmission of Plasmodium falciparum, the most dangerous malaria parasite. This dose prevents the parasite from being passed to mosquitoes, reducing the spread of disease. It is also used as an alternative treatment for a type of fungal pneumonia called Pneumocystis pneumonia.
Mechanism of Action
The drug’s exact mechanism of action is not fully understood, but it is believed to function by disrupting the parasite’s cellular processes. Primaquine is a prodrug, meaning it must be metabolized by the body’s enzymes, specifically the cytochrome P450 system, to be converted into its active forms.
These active metabolites are thought to interfere with the parasite in a few ways. One leading theory is that they generate reactive oxygen species, which are chemically reactive molecules that cause significant oxidative stress. This stress damages the parasite’s cells, particularly its mitochondria, which are responsible for energy production. By disrupting the parasite’s energy supply and cellular integrity, primaquine effectively kills the dormant hypnozoites.
Required G6PD Deficiency Screening
Before a patient starts a standard course of primaquine, testing for a specific genetic condition is necessary. This condition is called Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. G6PD is an enzyme that plays a protective role in red blood cells. The enzyme helps shield these cells from damage caused by oxidative stress.
Individuals who have G6PD deficiency lack sufficient amounts of this protective enzyme. When they take primaquine, the drug’s metabolites generate high levels of oxidative stress that their red blood cells cannot handle. This leads to a rapid destruction of red blood cells, a dangerous condition known as acute hemolytic anemia. Symptoms can include fatigue, jaundice, dark urine, and shortness of breath.
Because of this serious risk, screening for G6PD deficiency is a standard safety measure before prescribing a full treatment course of primaquine. For patients with severe G6PD deficiency, standard primaquine therapy is contraindicated. In cases of mild G6PD deficiency, healthcare providers may recommend an alternative dosing schedule, such as a once-weekly dose for eight weeks under close medical supervision, to reduce the risk of hemolysis.
Side Effects and Risks
Aside from the significant risks associated with G6PD deficiency, primaquine can cause other side effects. The most frequently reported issues are gastrointestinal. These include nausea, vomiting, and stomach cramps. Taking the medication with food can help to lessen this discomfort.
Less common, but more serious, adverse effects can also occur. One such risk is methemoglobinemia, a condition where the blood’s ability to carry oxygen is reduced. This happens when primaquine interferes with the function of hemoglobin in red blood cells.
Overdosing can also impact blood cell counts, potentially leading to a reduction in red blood cells, white blood cells, and platelets. Patients with certain systemic diseases like rheumatoid arthritis may be more susceptible to these effects. It is also important to avoid taking primaquine with other specific drugs, as interactions can increase toxicity.
Dosage and Administration
Primaquine is administered as an oral tablet. The specific dosage and the length of the treatment course are determined by a healthcare professional based on the intended purpose of the medication. The patient’s body weight and the specific type of malaria parasite being targeted are also considered.
For the prevention of relapse in P. vivax or P. ovale malaria, a regimen involves taking a daily dose for 14 days. In other situations, such as for malaria prevention after leaving an endemic area, the dosage and duration might differ.