(British Approved Name, US Adopted Name, rINN)
Pharmacopoeias. In US. Also in British Pharmacopoeia (Vet).
British Pharmacopoeia (Vet) 2008 (Levomepromazine). A white or slightly cream-coloured crystalline powder. Practically insoluble in water slightly soluble in alcohol freely soluble in ether. Protect from light.
The United States Pharmacopeia 31, 2008 (Methotrimeprazine). A fine white, practically odourless, crystalline powder. Soluble 1 in 10 of water, of alcohol, and of methyl alcohol, and 1 in 2 of chloroform freely soluble in ether sparingly soluble in alcohol at 25° but freely soluble in boiling alcohol. Store at a temperature of 25°, excursions permitted between 15° and 30°. Protect from light.
(BANM, US Adopted Name, rINNM)
Pharmacopoeias. In Europe.
European Pharmacopoeia, 6th ed. (Levomepromazine Hydrochlonde). A white or very slightly yellow, slightly hygroscopic crystalline powder. It deteriorates on exposure to air and light. Freely soluble in water and in alcohol. Store in airtight containers. Protect from light.
Incompatibility. Levomepromazine hydrochloride is reported to be incompatible with alkaline solutions.
(BANM, US Adopted Name, rINNM)
Pharmacopoeias. In Europe and Japan.
European Pharmacopoeia, 6th ed. (Levomepromazine Maleate). A white or slightly yellowish crystalline powder. It deteriorates when exposed to air and light. Slightly soluble in water and in alcohol sparingly soluble in dichloromethane. The supernatant of a 2% dispersion in water has a pH of 3.5 to 5.5. Protect from light.
Adverse Effects, Treatment, and Precautions
As for Chlorpromazine, although it may be more sedating. See also Adverse Effects of Antihistamines.
Levomepromazine may cause severe orthostatic hypotension, and patients taking large initial doses, patients over 50 years of age, or those given injections, should be lying down. Children are very susceptible to the hypotensive and sedative effects of levomepromazine.
As for Chlorpromazine.
Although MAOIs have been used with phe-nothiazines without untoward effects, the use of levomepromazine with MAOIs should probably be avoided as this combination has been implicated in 2 fatalities.
In a study involving 5 psychiatric patients peak plasma concentrations of levomepromazine were noted 1 to 4 hours after oral doses and 30 to 90 minutes after injection into the gluteal muscle. About 50% of an oral dose reached the systemic circulation. Although the metabolite levomepromazine sulfoxide could not be detected after a single intramuscular injection, it was found in concentrations higher than unmetabolised levomepromazine after single and multiple oral dosage, both substances reaching a steady state in the plasma within 7 days of starting multiple-dose oral therapy. Fluctuations in plasma concentration during multiple-dose oral therapy indicated that until the correlation between acute adverse effects and peak plasma concentration of levomepromazine had been further studied the total daily dose should be divided into 2 or 3 portions when larger oral doses of levomepromazine are used.
In 8 psychiatric patients given levomepromazine 50 to 350 mg daily the plasma half-life showed wide variation, from 16.5 to 77.8 hours, and did not correlate with the dose given.
Uses and Administration
Levomepromazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has antihistaminic actions as well as CNS effects resembling those of chlorpromazine. It is also reported to have analgesic activity. It is used in the treatment of various psychoses including schizophrenia, as an analgesic for moderate to severe pain usually in non-ambulatory patients, and for premedication. It is also used in palliative care for the control of symptoms such as restlessness, agitation, and as an adjunct to opioid analgesia, as well as being an effective broad-spectrum antiemetic in nausea and vomiting.
Levomepromazine is also used in veterinary medicine.
Levomepromazine is given orally as the maleate or the hydrochloride or by injection as the hydrochloride. In the UK, doses such as those given below are expressed in terms of the appropriate salt. However, in some countries, the dose of levomepromazine may be expressed in terms of the base. The embonate has also been used. Care is required in elderly patients because of the risk of severe hypotension if levomepromazine is given to such patients reduced doses may be necessary.
The usual initial oral dose of levomepromazine maleate for the treatment of schizophrenia is 25 to 50 mg daily the daily dosage is usually divided into 3 portions with a larger portion taken at night. Doses of 100 to 200 mg have been given to non-ambulant patients increased gradually up to 1 g daily if necessary. Children are very susceptible to the hypotensive and sedative effects of levomepromazine: a suggested oral dose for a 10-year-old is 12.5 to 25 mg of the maleate daily in divided doses a dose of 37.5 mg daily should not be exceeded.
When used in palliative care as an adjunct to analgesics in the management of severe terminal pain and for the control of nausea and vomiting, levomepromazine maleate may be given orally in a dose of 12.5 to 50 mg every 4 to 8 hours. The BNFalso includes an oral dose of levomepromazine maleate 6 to 25 mg daily given in 1 or 2 divided doses for the management of nausea and vomiting where first-line antiemetics have proved inadequate. Alternatively 12.5 to 25 mg of levomepromazine hydrochloride may be given intramuscularly every 6 to 8 hours but patients should remain in bed for at least the first few doses doses of up to 50 mg have been given for severe agitation.
Levomepromazine hydrochloride may also be given intravenously in similar doses after dilution with an equal volume of sodium chloride 0.9% injection. Alternatively it may be given, suitably diluted with sodium chloride 0.9% injection, by continuous subcutaneous infusion via a syringe driver doses range from a total of 25 to 200 mg daily although lower doses of 5 to 25 mg daily may also be effective against nausea and vomiting. Experience with parenteral use of levomepromazine hydrochloride in children is limited but a dose of 100 to 400 micrograms/kg daily by continuous intravenous or subcutaneous infusion has been suggested for children aged 1 month and over in the management of nausea and vomiting in palliative care it has also been used in the treatment of restlessness and confusion in palliative care in a dose of 0.35 to 3 mg/kg daily by continuous subcutaneous infusion in those aged 1 year and over.
Levomepromazine hydrochloride given intramuscularly has been used in some countries for the control of acute pain, as a premedicant, and for postoperative analgesia. In some countries levomepromazine is also licensed for use as an anxiolytic and sedative, and in the management of other types of pain, including labour pain.
As levomepromazine appears to possess intrinsic analgesic activity in addition to its antiemetic and antipsychotic actions it has been used for the symptomatic control of restlessness and vomiting and as an adjunct to opioid analgesics in pain control (see Choice of Analgesic) in terminally ill patients.
BP 2008: Levomepromazine Injection; Levomepromazine Tablets
The United States Pharmacopeia 31, 2008: Methotrimeprazine Injection.
Argentina: Detenler Levolam Nozinan Togrel
Brazil: Levozine Neozine
Canada: Apo-Methoprazine Novo-Meprazine Nozinan
Czech Republic: Tisercin
Finland: Levozin Nozinan
Germany: Levium Neurocil
Greece: Nozinan Prazine Sinogan
Israel: Methozane Nozinan Ronexine
Mexico: Levocina Sinogan
The Netherlands: Nozinan
New Zealand: Nozinan
United Kingdom: Levinan Nozinan