PRIMAQUINE​ ​TABLETS

Indications

• Adjunct in the treatment of non-falciparum malaria caused by Plasmodium vivax
• Adjunct in the treatment of non-falciparum malaria caused by Plasmodium ovale
• Treatment of mild to moderate pneumocystis infection in combination with clindamycin

Mechanism of action

The precise mechanism of action of primaquine is not fully understood. However, it is believed to generate reactive oxygen species and interfere with electron transport within the parasite. Additionally, primaquine may bind to and alter the properties of protozoal DNA, disrupting the metabolic processes of the parasites by affecting their mitochondria and energy production. This results in the death of the parasites, halting the infection and enabling recovery.

Pharmacodynamics

Primaquine is essential in the treatment of malaria, particularly as a co-drug with chloroquine. It targets the intrahepatic forms of Plasmodium vivax and Plasmodium ovale, preventing the development of erythrocytic forms responsible for relapses. The drug exhibits gametocytocidal activity, effectively killing the sexual forms of the parasites to reduce transmission risk. Without sufficient energy, the malaria parasites cannot survive, allowing the host to recover from the infection.

Pharmacokinetics

Primaquine is rapidly absorbed after oral administration, with peak plasma concentrations typically achieved within 1 to 2 hours. It is metabolized in the liver, primarily through cytochrome P450 enzymes, and has a half-life of approximately 3 to 8 hours. The drug is excreted mainly in the urine as metabolites. Caution is advised in patients with renal impairment, as elimination may be prolonged, and dosing adjustments may be necessary in such populations.

Contra-indications

• Severe G6PD deficiency
• Hypersensitivity to primaquine or any of its components

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Headache
• Dizziness
• Hemolytic anemia (in G6PD-deficient patients)
• Methemoglobinemia
• Psychiatric effects (e.g., anxiety, depression)
• Visual disturbances
• Cardiac conduction disorders

Interactions

• Mepacrine (increases concentration of primaquine)
• Antimalarials (may have additive effects or altered pharmacokinetics)
• Caution with other medications that can cause hemolysis in G6PD deficiency

Precautions

• Use with caution in patients with G6PD deficiency
• Monitor for hemolysis in patients with a history of G6PD deficiency
• Caution in patients with cardiac conduction disorders
• Consider alternative therapies in patients with systemic diseases associated with granulocytopenia
• Screening for G6PD activity recommended before starting treatment

Pregnancy

Manufacturer advises avoiding use during pregnancy, particularly in the first trimester, unless the potential benefit outweighs the risk due to teratogenicity in animal studies.

Breast-feeding

No specific information available; theoretical risk of hemolysis in G6PD-deficient infants.

Storage

Store at room temperature, away from moisture and direct light.

Formulations

• Primaquine phosphate 7.5 mg tablet
• Primaquine phosphate 15 mg tablet

Mechanism of action

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. The precise mechanism of action has not been determined, but may be based on primaquine's ability to bind to and alter the properties of DNA. Primaquine is highly active against the exoeryhrocytic stages of plasmodium vivax and plasmodium ovale and against the primary exoerythrocytic stages of plasmodium falciparum. It is also highly active against the sexual forms of (gametocytes) plasmodia, especially P. falciparum, disrupting transmission of the disease by eliminating the reservoir from which the mosquito carrier is infected. /Primaquine/ disrupts the parasitic mitochondria, thereby interrupting metabolic processes requiring energy. ... /Primaquine is one/ of /aromatic amine-containing/ xenobiotics ... capable to inducing oxidative injury in erythrocytes. These agents appear to potentiate the normal redox reactions and are capable of overwhelming the usual protective mechanisms. The interaction between these xenobiotics and hemoglobin leads to the formation of free radicals that denature critical proteins, including hemoglobin, thiol-dependent enzymes, and components of the erythrocyte membrane ... Oxidative denaturation of the globin chain decreases its affinity for the heme group, which may dissociate from the globin chain during oxidative injury ... The generation of free radicals may also lead to peroxidation of membrane lipids. This may affect the deformability of the erythrocyte and the permeability of the membrane to potassium. The alteration of the Na(+)/K(+) gradient is ... potentially lethal to the affected erythrocyte. Oxidative injury also impairs the metabolic machinery of the erythrocyte, resulting in a decrease in the concentration of ATP. Damage to the membrane can also permit leakage of denatured hemoglobin from the cell. Such free denatured hemoglobin can be toxic on its own. Free hemoglobin may irreversibly bind nitric oxide, resulting in vasoconstriction. Released hemoglobin may form nephrotoxic hemoglobin dimers, leading to kidney damage. /Oxidative hemolysis/

Pharmacodynamics

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 <i>Plasmodium vivax</i> and <i>Plasmodium ovale</i>, 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 <i>P. falciparum</i>.