Monograph: |
Mepacrine Hydrochloride
A bright yellow odourless crystalline powder. Soluble I in 35
of water: soluble in alcohol. A I % solution in water has a pH
of about 4.5. Store in airtight containers. Protect from light.
Adverse Effects
The most common adverse effects associated with mepacrine
are dizziness, headache, and gastro-intestinal disturbances
such as nausea and vomiting. Reversible yellow discoloration
of the skin and urine may occur during long-term administra-
tion or after large doses: blue/black discoloration of the palate
and nails has also been reported. Doses such as those used in
the treatment of giardiasis may occasionally cause transient
acute toxic psychosis and CNS stimulation. Convulsions have
been reported at high doses. Ocular toxicity similar to that
seen with chloroquine and chronic dermatoses, in-
cluding severe exfoliative dermatitis and lichenoid eruptions.
have also occurred after prolonged administration of mepa-
crine. Hepatotoxicity and aplastic anaemia occur rarely.
Effects on the blood. In endemic malarial areas mepacrine
has been a significant cause of aplastic anaemia with an inci-
dence of about I in 20 000.
Effects on the nervous system. Two patients had convul-
sions a few hours after the intrapleural administration of
mepacrine hydrochloride 400 mg for malignant effusions.
One developed status epilepticus and died and the other was
successfully treated with anticonvulsants.
Precautions
Mepacrine should be used with caution in elderly patients or
patients with a history of psychosis, or in the presence of he-
patic disease or porphyria. Mepacrine can cause exacerbation
of psoriasis and should be avoided in psoriatic patients.
Interactions
Mepacrine has been reported to produce a mild disulfiram-
like reaction when taken with alcohol.
Theoretically, mepacrine may increase the plasma concentra-
tions of primaquine resulting in a higher risk of toxicity. and
it has been recommended that these drugs should not be used
concomitantly.
Pharmacokinetics
Mepacrine is readily absorbed from the gastro-intestinal tract
and widely distributed throughout the body. It accumulates in
body tissues particularly the liver and is liberated slowly.It is
excreted slowly mainly in the urine, and is still detectable in
the urine after 2 months. Mepacrine crosses the placenta.
Intrapleural administration. Peak plasma concentrations
of mepacrine far above those associated with CNS effects
were rapidly attained in 3 of 4 patients following intrapleural
instillation of a solution of mepacrine hydrochloride and re-
mained at these levels for several hours.
Uses and Administration
Mepacrine hydrochloride is a 9-aminoacridine antiprotozoal
used mainly as an alternative to one of the nitroimidazoles in
the treatment of giardiasis . It is no longer used to treat
malaria.
In giardiasis, mepacrine hydrochloride is given by mouth in
doses of 100 mg three times daily after food for 5 to 7 days.
A second course of treatment after 2 weeks may sometimes
be required. A suggested dose for children is f. mg per kg
body-weight given three times daily (maximum 300 mg dai-
ly)Mepacrine hydrochloride has also been used locally in the
treatment of some forms of cutaneous leishmaniasis. as a ster-
ilisation technique for contraception, and in the management
of malignant effusions.
Contraception. Sterilisation with intra-uterinc mepacrine
has been attempted as an irreversible method of contraception.
This technique produces occlusion of the fallopian
tube and has been reported to be an effective nonsurgical
means of female sterilisation. There has been speculation
about the risk of cancer from this technique but there ap-
peared to be no evidence to confirm such a risk. However,
the method remains controversial and some authorities have
recommended that a full evaluation of its safety and efficacy
is still needed. More recently it was reported that the Indian
government had banned the use of mepacrine for sterilisa-
tion.
Leishmaniasis. Mepacrine has been suggested for intrale-
sional injection in the treatment of early noninflamed nodular
lesions of cutaneous leishmaniasis (p.575) due to Leishmania
tmpica. L. major, L. mexicana. L. panamensis. or L. peruvi-
ana. ' A suggested course of treatment is 3 intralesional injec-
tions of a 5% solution of mepacrine given at intervals of 3 to
5 days. However, local infiltration of drugs can be difficult
and painful, and a number of other local and systemic treat-
ments have been tried.
Malignant effusions. Intrapleural instillations of mepacrine
hydrochloride have been used as sclerosants in the manage-
ment of malignant pleural effusions and recurrent pneumoth-
orax but the treatment is associated with pain and a high
frequency of toxic effects and tetracycline is generally pre-
ferred ; mepacrine mesylate has been used similar-
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