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Primaquine is the essential co-drug with chloroquine in treating
all cases of malaria. It is highly effective against the gametocytes of all plasmodia and
thereby prevents spread of the disease to the mosquito from the patient. It is also
effective against the dormant tissue forms of P. vivax and P. ovale malaria, and thereby
offers radical cure and prevents relapses. 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.
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.
Absorption, fate and excretion: It
is well absorbed after oral administration and rapidly metabolised. Its elimination
half-life is about 6 hours. The metabolites of primaquine have oxidative properties and
can cause hemolysis in susceptible patients.
Adverse effects: In therapeutic
doses, primaquine is well tolerated. At larger doses, it may cause occasional epigastric
distress and abdominal cramps. This can be minimised by taking the drug with a meal. Mild
anemia, cyanosis and methemoglobinemia may also occur. Severe methemoglobinemia can occur
rarely in patients with deficiency of NADH methemoglobin reductase. Granulocytopenia and
agranulocytosis are rare complications.
Patients with deficiency of Glucose 6-phosphate dehydrogenase will develop hemolytic anemia on
taking usual doses of primaquine. This problem is restricted to certain
sections of the population. It
may not be practical to test each and every patient for G 6 PD deficiency before
administering primaquine. If a patient is known to be severely G6PD deficient, then primaquine should not be given. For the majority of
patients with mild variants of the deficiency, primaquine should be given in
a dose of 0.75 mg base/kg bw once a week for 8 weeks. If significant haemolysis
occurs on treatment, then primaquine should be stopped.[Guidelines for the treatment of malaria. World Health Organization.
Geneva, 2006. pp 62-68. Available at
http://apps.who.int/malaria/docs/TreatmentGuidelines2006.pdf]
Primaquine should not be used in patients
who have severe systemic illness that is likely to cause leukopenia (severe rheumatoid
arthritis, SLE etc.). It should not be used with other drugs likely to cause bone marrow
depression.
Patients with G6PD deficiency may develop
hemolysis with quinine. (Mosby's Drug Consult, 2002 p.III-2387-2388). A study in healthy
subjects indicates that concurrent administration of primaquine can increase blood
concentrations of mefloquine and may increase the adverse effects due to mefloquine.
(Martindale 31st Edition, 1996; 468-469). Therefore, simultaneous use of quinine or
mefloquine is contra indicated.
Availability: Primaquine is
available as tablets containing 2.5, 7.5 and 15 mg of the salt.
Dose of Primaquine |
| Age in
years |
P.
vivax/mixed infection
(once daily for 5 days*) |
P.
falciparum infection
(Single Dose) |
| 0-1 |
Nil |
Nil |
| 1-5 |
2.5 mg |
7.5 mg |
| 5-9 |
5 mg |
15 mg |
| 9-14 |
10 mg |
30 mg |
| >14 |
15 mg |
45 mg |
(*See table below)
The Primaquine Questions - Confusions in Primaquine
Use In Malaria |
To use or not? |
Often
primaquine is not prescribed for falciparum malaria because it is not needed for attaining
a cure of the infection. But it is required to prevent the spread of falciparum infection
because unlike in case of P. vivax malaria, chloroquine does not sterilize the
gametocytes of falciparum species. Therefore, if primaquine is not used in falciparum
malaria, there will be a selective spread of P. falciparum malaria, which may be
even resistant to drugs. Therefore, do not forget to use primaquine in P. falciparum
malaria- prevent the spread of P. falciparum, prevent the spread of drug
resistant strains! Primaquine is hence a must for both P.vivax and P.falciparum
infections. |
What is the dose? |
0.25mg/kg/day
(once a day) for 5 days in P. vivax; 0.75 mg/kg as single dose in P.
falciparum. |
*5 days or 14 days? |
In cases of P.
vivax malaria, the National Malaria Eradication Programme (N.M.E.P.) in India
recommends Primaquine therapy for 5 days, whereas the standard literature recommends for
14 days. 5 days therapy is adequate in most cases. In cases of relapse, a 14-day treatment
is advisable. |
What is the alternative to primaquine? |
At present,
Primaquine is the only drug available for tissue schizonticidal activity in P. vivax
malaria and gametocytocidal activity in P. falciparum infection. Therefore, it
must be used in both these infections. Therefore, at present there are no alternatives to
primaquine. Newer anti malarials like mefloquine or artemisinin derivatives are NOT
substitutes for primaquine! |
Is there primaquine resistance? |
Although
resistance to primaquine has been reported from SE Asia and Africa, it is rare. Such
cases are managed with a higher dose of primaquine. |
Primaquine or 'parda'? (Mosquito nets) |
In some
hospitals, patients with malaria are made to lie inside mosquito nets, with the idea of
preventing the spread of the infection to the 'hospital mosquitoes' and hence to other
patients. Often these patients are not administered primaquine. Remember, mosquito nets
may not prevent the spread of falciparum malaria, but Primaquine WILL. |
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