Mepacrine Hydrochloride

(BANM, rINNM)
Mepacrine Hydrochloride Chemical formula
Synonyms: Acrichinum; Acrinamine; Antimalarinae Chlorhydras; Chinacrina; Hidrocloruro de mepacrina; Mépacrine, Chlorhydrate de; Mepacrini Hydrochloridum; Mepakrin Hidroklorür; Quinacrine Hydrochloride. 6-Chloro-9-(4-diethylamino-1-methylbutylamino)2-methoxyacridine dihydrochloride dihydrate.
Cyrillic synonym: Мепакрина Гидрохлорид.

💊 Chemical information

Chemical formula: C23H30ClN3O,2HCl,2H2O = 508.9.
CAS — 83-89-6 (mepacrine); 69-05-6 (anhydrous mepacrine dihydrochloride); 6151-30-0 (mepacrine dihydrochloride dihydrate).
ATC — P01AX05.

💊 Adverse Effects

The most common adverse effects associated with mepacrine are dizziness, headache, and gastrointestinal disturbances such as nausea and vomiting. Reversible yellow discoloration of the skin, conjunctiva, and urine may occur during long-term use or after large doses; blue/black discoloration of the palate and discoloration of the nails have 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, including severe exfoliative dermatitis and lichenoid eruptions, have also occurred after prolonged use of mepacrine. Hepatotoxicity and aplastic anaemia occur rarely.

Effects on the nervous system.

Two patients had convulsions a few hours after mepacrine hydrochloride 400 mg was given intrapleurally for malignant effusions. One developed status epilepticus and died and the other was successfully treated with anticonvulsants.1
1. Borda I, Krant M. Convulsions following intrapleural administration of quinacrine hydrochloride. JAMA 1967; 201: 1049–50.

💊 Precautions

Mepacrine should be used with caution in elderly patients or patients with a history of psychosis, or in the presence of hepatic disease. Mepacrine can cause exacerbation of psoriasis and should be avoided in psoriatic patients.

Porphyria.

Mepacrine should be used with caution in patients with porphyria.

💊 Interactions

Mepacrine has been reported to produce a mild disulfiram-like reaction when taken with alcohol. Theoretically, mepacrine may increase the plasma concentrations of primaquine resulting in a higher risk of toxicity, and it has been recommended that these drugs should not be used together.

💊 Pharmacokinetics

Mepacrine is readily absorbed from the gastrointestinal 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 after intrapleural instillation of a solution of mepacrine hydrochloride and remained at these levels for several hours.1
1. Björkman S, et al. Pharmacokinetics of quinacrine after intrapleural instillation in rabbits and man. J Pharm Pharmacol 1989; 41: 160–73.

💊 Uses and Administration

Mepacrine is a 9-aminoacridine antiprotozoal used as the hydrochloride mainly as an alternative to the nitroimidazoles in the treatment of giardiasis. In giardiasis, mepacrine hydrochloride is given orally in doses of 100 mg three times daily after food for 5 to 7 days. A dose for children is 2 mg/kg given three times daily (maximum 300 mg daily). Mepacrine hydrochloride may also be used, alone or with hydroxychloroquine, for the treatment of discoid and subcutaneous lupus erythematosus. It has also been used locally in the treatment of some forms of cutaneous leishmaniasis, as a sterilisation technique for contraception, and in the management of malignant effusions. It was formerly used to treat malaria. The mesilate was also formerly used. Mepacrine is under investigation for the treatment of variant Creutzfeldt-Jakob Disease.

Contraception.

Sterilisation with intra-uterine mepacrine has been attempted as an irreversible method of contraception. It produces occlusion of the fallopian tube and has been reported to be an effective nonsurgical means of female sterilisation,1 although it may be less effective than other methods.2There has been speculation about the risk of cancer from this technique but there appeared to be no evidence to confirm such a risk.3-5 However, the method remains controversial and a full evaluation of its safety and efficacy has been recommended.6The Indian government has banned the use of mepacrine for sterilisation.
1. Hieu DT, et al. 31 781 Cases of non-surgical female sterilisation with quinacrine pellets in Vietnam. Lancet 1993; 342: 213–17
2. Sokal DC, et al. Contraceptive effectiveness of two insertions of quinacrine: results from 10-year follow-up in Vietnam. Contraception 2008; 78: 61–5
3. Anonymous. Death of a study: WHO, what, and why. Lancet 1994; 343: 987–8
4. Hieu DT. Quinacrine method of family planning. Lancet 1994; 343: 1040
5. Sokal DC, et al. Safety of quinacrine contraceptive pellets: results from 10-year follow-up in Vietnam. Contraception 2008; 78: 66–72
6. Benagiano G. Sterilisation by quinacrine. Lancet 1994; 344: 689.

Leishmaniasis.

Mepacrine has been suggested for intralesional injection in the treatment of early noninflamed nodular lesions of cutaneous leishmaniasis due to Leishmania tropica, L. major, L. mexicana, L. panamensis, or L. peruviana.1 The suggested course of treatment was 3 intralesional injections of a 5% solution of mepacrine given at intervals of 3 to 5 days. However, local infiltration of drugs can be difficult and painful.
1. WHO. Control of the leishmaniases. WHO Tech Rep Ser 793 1990.

Sclerotherapy.

Intrapleural instillations of mepacrine hydrochloride or mesilate have been used as sclerosants in the management of malignant pleural effusions and recurrent pneu mothorax but the treatment is associated with pain and a high frequency of toxic effects.

💊 Preparations

Proprietary Preparations

India: Maladin.
Published December 01, 2018.