Levomepromazine

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Levomepromazine
Systematic (IUPAC) name
3-(2-methoxyphenothiazin-10-yl)- N, N,2-trimethyl-propan-1-amine
Identifiers
CAS number 60-99-1
(7104-38-3 [maleate], 1236-99-3 [HCl])
ATC code N05AA02
PubChem 72287
Chemical data
Formula C19H24N2OS 
Mol. mass 328.473 g/mol
Pharmacokinetic data
Bioavailability approx. 50 to 60%
Metabolism Hepatic
Half life ~ 20 hours
Excretion feces and urine (metabolites), unchanged drug only 1%
Therapeutic considerations
Pregnancy cat.

Only if clearly needed
Legal status

Rx-only (n.a. in the USA)
Routes oral, seldom i.m.

Contents

[edit] General Remarks and Pharmacology

Levomepromazine (sold as Levoprome) is an aliphatic phenothiazine neuroleptic drug. It is a low potent antipsychotic (approximately half as potent as chlorpromazine). It was formerly known as methotrimeprazine. It has low intrinsic antidepressant[citation needed], strong analgesic and also strong antiemetic properties.

  • Absorption, and other characteristics : Levomepromazine has an incomplete oral bioavailability, because it undergoes considerable first-pass-metabolism in the liver. It has a halflife of approximately 20 hours (15 to 30 hours). Maximum plasma levels are reached 1 to 4 hours after oral dosing. After i.m.-doses maximum plasma levels are seen after 30 to 90 minutes.
  • Distribution : The approximate distribution volume is 30 l/kg. Levomepromazin is lipophilic and crosses easily the blood-brain-barrier and the placenta, and can also be found in the milk of breast-feeding mothers. Liquor concentration usually exceeds the plasma concentrations.
  • Metabolism : Levomepromazine is metabolized in the liver and degraded to a Sulfoxid-, a Glucuronid- and a Demethyl-moiety.
  • Elimination : Drug elimination (as metabolites, only 1% of unchanged levomepromazin is recovered) is relatively slow. The metabolites are found in feces and urine.
  • Mode of Action : Levomepromazine blocks the following postsynaptic receptors:

The mode of action explains the particular pharmacological effects of levomepromazine.

Currently, levomepromazine is not registered in the USA. In Europe it has been marketed for decades as Neurocil® and Nozinan®. Nozinan® is also available in Canada.

Some American physicians are currently conducting studies regarding the strong analgesic effect of levomepromazine.

[edit] Indications

Levomepromazine is used for the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder, as well as for the treatment of agitated depressions in general. It is one of the most useful drugs to treat patients with severe suicidal impulses (3 times 25mg oral or i.m. initially, gradually increasing to 150mg to 300mg daily). The combination treatment of severe and/or chronic pain is also an on-label indication. Here low initial doses of 30mg to 75mg daily are indicated, slowly increased to 100 to 300mg daily. Levomepromazine has off-label uses as an antiemetic for cancer patients and for the treatment of cases of treatment-resistant insomnia. Antiemetic doses may be as low as 3 times 5mg. For the treatment of insomnia 25 to 50mg 2 to 3 hours before bedtime are usually used.

[edit] Side effects

Levomepromazine has prominent sedative and anticholinergic/sympatholytic effects (dry mouth, hypotension, sinus tachycardia, extreme night sweats) and causes massive weight gain. These side effects normally preclude prescribing the drug in doses needed for full remission of schizophrenia, so it has to be combined with a more potent antipsychotic. In any case, blood pressure and EKG should be monitored regularly.

Other symptoms include muscle stiffness, fever and neuroleptic malignant syndrome.

[edit] Important Interactions

If levomepromazine is given concomitantly with opioids, the opioid-dose should be reduced (by approx. 50%), because levomepromazine massively amplifies the therapeutic actions and side-effects of opioids.

Avoid the concomitant use of levomepromazine and tramadol (Ultram®). Massive seizures may be encountered with this combination.

Additive sedative effects and confusional states may emerge if levomepromazine is given with benzodiazepines or barbiturates. This may be avoided by using the lowest dose possible with the substances in question.

Exert particular caution in combining levomepromazine with other anticholinergic drugs (tricyclic antidepressants and antiparkinsonian-agents): Particularly the elderly may develop delirium, high fever, severe obstipation, even ileus and glaucoma. Reduce both the dose of levomepromazine and the dose of the other drug. If possible, avoid such combinations.

Caffeine and/or stimulantes of the ephedrine/amphetamine type may counteract the specific actions of levomepromazine. Concomitant use of these substances should be avoided.

Coffee and black tea should be avoided because they decrease the absorption of levomepromazine considerably. The same is true for antacids; these should be given 1 to 2 hours before or after oral administration of leveomepromazine.

[edit] References

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