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Primaquine Tablets

DESCRIPTION

Primaquine, an 8-aminoquinoline derivative, is a synthetic antimalarial agent. Its chemical formula is (R,S)-N4-
(6-Methoxy-8-quinolinyl)-1,4-pentanediamine diphosphate. Its molecular formula is C15H21N3O.2H3PO4.

COMPOSITION

Malirid
Each tablet contains:
Primaquine Sulphate IP …7.5 mg

Malirid-DS
Each tablet contains:
Primaquine Sulphate IP …15 mg

PHARMACOLOGY

An 8-aminoquinoline, primaquine is structurally similar to the 4-aminoquinolines but possesses markedly

different antimalarial activities.

Primaquine is a tissue schizonticidal agent and is active against the preerythrocytic and exoerythrocytic forms of
Plasmodium falciparum, P. malariae, P. ovale and P. vivax. Primaquine is also gametocytocidal against
plasmodia, especially the gametocytes of P. falciparum. Although primaquine has some activity against the
asexual erythrocytic forms of P. vivax, the drug is generally inactive against the erythrocytic forms of plasmodia.
Hence a blood schizonticidal agent, preferably chloroquine, is always given in conjunction with primaquine for
the treatment of P. ovale or P. vivax malaria.

The exact mechanism of antimalarial activity of primaquine has not been determined, but the drug appears to
interfere with the function of plasmodial DNA.

Primaquine may disrupt the parasite's mitochondria and bind to native DNA. The resulting structural changes
create a major disruption in the metabolic process. The gametocyte and exoerythrocyte forms are inhibited.
Some gametocytes are destroyed while others are rendered incapable of undergoing maturation division in the
mosquito gut. By eliminating tissue (exoerythocyte) infection, primaquine prevents development of blood
(erythrocytic) forms responsible for relapses in P. vivax malaria.

PHARMACOKINETICS

Primaquine is well absorbed from the GI tract. After oral administration, peak plasma concentrations of
primaquine are reached in 1 to 3 hours. Primaquine as compared to other antimalarials, is found in relatively
low concentrations in the tissues. Highest concentrations are in the liver, lungs, brain, heart and skeletal
muscle.

Primaquine is rapidly metabolized to a carboxylic acid derivative and then to further metabolites which have
varying degrees of activity. Approximately 1% is excreted unchanged in the urine.

Primaquine has a plasma half life of 3.7 - 9.6 hours in healthy adults.

INDICATIONS

Primaquine is recommended for the radical cure of P. vivax malaria, the prevention of relapse in P. vivax
malaria or following the termination of chloroquine phosphate suppressive therapy in an area where P. vivax
malaria is endemic.
Because primaquine is not generally active against asexual erythrocytic forms of plasmodia, a blood
schizonticidal agent, preferably chloroquine, is always given in conjunction with primaquine.

CONTRAINDICATIONS

Concomitant administration of quinacrine and primaquine, the acutely ill suffering from systemic disease
manifested by tendency to granulocytopenia (e.g. rheumatoid arthritis and lupus eythematosus), concurrent
administration of other potentially hemolytic drugs or bone marrow depressants are contraindications to
primaquine.

WARNINGS

Hemolytic reactions (moderate to severe): May occur in the following groups of people while receiving
primaquine: Glucose-6-phosphate dehydrogenase (G-6-PD) deficient patients; individuals with idiosyncratic
reactions (manifested by hemolytic anemia, methemoglobinemia or leukopenia); individuals with nicotinamide
adenine dinucleotide (NADH) methemoglobin reductase deficiency; or individuals with a family or personal
history of favism.

In such cases, the individual should be monitored closely. Discontinue if marked darkening of the urine or
sudden decrease in hemoglobin concentration or leukocyte count occurs.

PRECAUTIONS

Monitoring: Anemia, methemoglobinemia and leukopenia have occurred following large doses; do not exceed
recommended dose. Perform routine blood examinations (particularly blood cell counts and hemoglobin
determinations) during therapy.

Primaquine induced hemolysis in patients with G6PD deficiency can be worsened by liver or renal disease,
which may delay elimination of the drug.

Usage in pregnancy and lactation

Safety for use during pregnancy has not been established. Use only when clearly needed and when potential
benefits outweigh potential hazards to the fetus.

Some clinicians and the CDC recommend that for the prevention or treatment of relapsing malaria in pregnant
women, chloroquine be given prophylactically or to treat each relapse, respectively, until after delivery when
primaquine can be administered for radical cure.

(As per WHO, primaquine is contraindicated in pregnancy.

Usage in paediatrics

Appropriate studies on the relationship of age to the effects of primaquine have not been performed in the
geriatric population. However, no geriatrics-specific problems have been documented to date. No special
precautions are required in elderly patients.

Drug interactions

Quinacrine: May potentiate the toxicity of antimalarial compounds which are structurally related to primaquine.
Do not administer primaquine to patients who have recently received quinacrine.

ADVERSE EFFECTS

GI : Nausea, vomiting, epigastric distress, abdominal cramps. Adverse GI effects may be lessened by
administering primaquine with meals.

Hematologic : Leukopenia, hemolytic anemia in G-6-PD deficient individuals, methemoglobinemia in NADH

methemoglobin reductase deficient individuals.

Other adverse effects : Headache, interference with visual accomodation and pruritus have been reported with
primaquine. Hypertension and arrhythmias have also been reported rarely.

DOSAGE AND ADMINISTRATION

Patients suffering from an attack of P. vivax malaria or having parasitized red blood cells should receive a
course of chloroquine phosphate, which quickly destroys the erythrocytic parasites and terminates the
paroxysm.

Radical treatment
Adults : 0.25mg/Kg or 15mg daily for 14 days following standard chloroquine therapy, or if glucose-
6- phosphate dehydrogenase deficiency is known or suspected, 0.75mg/Kg weekly for 8 weeks
Children over 1 year - 0.25mg/Kg daily for 14 days after standard chloroquine therapy

Gametocytocidal therapy

Adults and children - 0.5 - 0.75mg/Kg in a single dose.

OVERDOSAGE

Symptoms : Abdominal cramps, vomiting, burning, epigastric distress, CNS and cardiovascular disturbances,
cyanosis, methemoglobinemia, moderate leukocytosis or leukopenia, anemia. The most striking symptoms are
granulocytopenia and acute hemolytic anemia in sensitive persons. Acute hemolysis occurs, but patients
recover completely if dosage is discontinued.

Treatment : Symptomatic

Storage

Store in cool dry dark place.

Presentation

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