Methotrimeprazine Hydrochloride, NOZINAN®

Brand name

  • NOZINAN®

Drug Class

  • Neuroleptic

Preparations

  • Tablets: 2 mg, 5 mg, 50 mg
  • Injection: 25 mg/mL

Indications

  • Anxiety and tension:
    • Autonomic disturbances
    • Personality disturbances
    • Emotional troubles secondary to such physical conditions as resistant pruritus, etc.
  • As an analgesic:
    • Management of terminal pain and accompanying restlessness or distress
    • Trigeminal neuralgia
    • Neurocostal neuralgia
    • Phantom pains and muscular discomforts
    • Cancer pain
    • Zona pain
  • As a potentiator of anesthetics:
    • Pre- and post-operative sedative and analgesic.
  • As an antiemetic:
    • For the treatment of nausea and vomiting of central origin.
  • As a sedative:
    • For the management of insomnia.
  • Psychotic disturbances:
    • Acute and chronic schizophrenias
    • Senile psychoses
    • Manic depressive syndromes

Metabolism

  • Liver P450 2d6 enzyme

Dosing

Oral:

  • 5 to 50 mg po Q4-8h

Injection:

  • Psychosis:
    • 75 to 100 mg given as 3 or 4 deep i.m. injections in a large muscle.
  • Pre and post-operative analgesic:
    • 75 to 100 mg given as 3 or 4 deep i.m. injections in a large muscle.
    • When given as a premedication or post-operative analgesic, the average dose varies from 10 to 25 mg every 8 hours, which is equivalent to 20 to 40 mg given orally.
    • The last dose during premedication, given 1 hour before surgery, can be 25 to 50 mg i.m.
  • during surgery or labour:
    • 10 to 25 mg in 500 mL of a 5% glucose solution administered at a rate of 20 to 40 drops/minute.

Drug Interactions

  • Nozinan® potentiates the action of other phenothiazines and CNS depressants (barbiturates, analgesics, narcotics and antihistaminics). The usual doses of these agents should be reduced by 50% if they are to be given concomitantly with Nozinan® until the dosage of the latter has been established.
  • Nozinan® and its non-hydroxylated metabolites are reported to be inhibitors of cytochrome P450 2D6. Coadministration of Nozinan and drugs primarily metabolized by the cytochrome P450 2D6 enzyme system may result in increased plasma concentrations of these drugs

Adverse Effects

  • CNS:
    • Drowsiness
  • Extrapyramidal effects
  • Autonomic Nervous System:
    • Dryness of the mouth and, in older patients, occasional urinary retention and tachycardia.
  • Cardiovascular:
    • Orthostatic hypotension (at the start of treatment by the parenteral route)
    • Very rare cases of QT interval prolongation have been reported.
    • Tachycardia
    • There have been isolated reports of sudden death, with possible causes of cardiac origin
  • Vascular disorder:
    • Cases of venous thromboembolism, including cases of pulmonary embolism
  • Blood:
    • Agranulocytosis
    • Neutropenia
  • Endocrine:
    • Weight gain
    • Hyperglycaemia or intolerance to glucose
  • Gastrointestinal:
    • Rare cases of cholestatic jaundice without liver damage have been observed.
    • Necrotizing enterocolitis, which can be fatal, has been very rarely reported in patients treated with Nozinan®.
  • Skin Reactions:
    • Skin reactions due to photosensitivity or allergies are extremely rare.

Contraindications

  • Levomepromazine will enhance the activity of any sedative or hypnotic.
  • Avoid alcohol.
  • Coma or CNS depression due to alcohol, hypnotics, analgesics or narcotics.
  • In patients with blood dyscrasia, hepatic troubles or a sensitivity to phenothiazines.

Pregnancy and Breastfeeding

  • Neonates exposed to antipsychotic drugs including Nozinan® during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.

Warning

  • Increased death rate in patient with dementia
  • Avoid driving or performing jobs that requires high attention because Nozinan® reduce psychomotor activity
  • QT interval prolongation
  • Tardive Dyskinesia
  • Neuroleptic Malignant Syndrome
  • Priapism
  • Venous thromboembolism
  • Simultaneous administration of desferrioxamine and prochlorperazinehas been observed to induce a transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours. It is possible that this may occur with Nozinan since it shares many of the pharmacological activities of prochlorperazine.
  • Avoid giving “Adrenaline” to patients overdosed with neuroleptics.
  • Coadministration of levomepromazine and drugs primarily metabolised by the cytochrome P450 2D6 enzyme system may result in increased plasma concentrations of these drugs.

References

  • Nozinan: Retrieved from: http://products.sanofi.ca/en/nozinan.pdf
  • Capron M, Lafitte B, Benedit M, Camard CN, Nicolas F, Beligon C, et al. Necrotizing colitis in a 29-year-old man under high-dose neuroleptics. Reanimation Urgences 1999;8(8):701-4.
  • Cubeddu LX. QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs. American Journal of Therapeutics 2003;10(6):452-7.
  • Courvoisier S, Ducrot R, Fournel J, Julou L. Propriétés pharmacodynamiques générales de la lévomépromazine (7044 R.P.). C.R. Soc Biologie 1957;151(7):1378-82.
  • Divry P, Boron J, Collard J. La lévomépromazine dans les cures de sommeil potentialisées et les cures neuroleptiques. Acta Neurol Psych Belgica 1959;59(3):325-36.
  • Fekete Z. Control of pruritus with levomepromazine. Appl Therap 1963;5(4):3334.
  • Fenichel RR, Malik M, Antzelevitch C, Sanguinetti M, Roden DM, Priori SG, et al. Drug-induced torsades de pointes and implications for drug development. J Cardiovasc Electr 2004;15(4):475-95.
  • Filloux MC, Marechal K, Bagheri H, Morales J, Nouvel A, Laurencin G. Phenothiazine-induced acute colitis: A positive rechallenge case report. Clin Neuropharmacol 1999;22(4):244-5.
  • Flamant J. Utilisation à faibles doses d’un nouveau neuroleptique (lévomépromazine, 7044 R.P.) dans le traitement des dystonies neuro-végétatives. L’Hôpital 1960;March H.S.
  • Gram LF, Hansen MG, Sindrup SH, Brösen K, Poulsen JH, Aaes-Jörgensen T, et al. Citalopram: interaction studies with levomepromazine, imipramine and lithium. Ther Drug Monitoring 1993;15:18-24.
  • Hals PA, Dahl SG. Effect of levomepromazine and metabolites on debrisoquine hydroxylation in the rat. Pharmacology & Toxicology 1994;75:255-60.
  • Huot JM, Kristof AC. Lévomépromazine (Nozinan) – a new neuroleptic agent for treatment of senile patients. CMAJ 1959;81:546-8.
  • Kenbubpha K, Silpakit C. Association between antipsychotics and sudden death in psychotic in-patients. International Medical Journal 2002;9(1):27-31.
  • Lambert PA, Beaujard M, Achaintre A, Broussolle P, Perrin J, Berthier C, et al. Essais thérapeutiques d’un nouveau dérivé de la phénothiazine, la lévomépromazineou 7044 R.P. Ann Medico-Psychol 1957;115(2):291-6.
  • Larrey D, Lainey E, Blanc P, Diaz D, David R, Biaggi A. Acute colitis associated with prolonged administration of neuroleptics. J Clin Gastroenterol 1992;14(1):64-7.
  • Levy L, Ban T. Phenothiazine drugs and the general practitioner. CMAJ 1962;86:415-7.
  • Mehtonen OP, Aranko K, Malkonen L, Vapaatalo H. A survey of sudden death associated with the use of antipsycgotic or antidepressant drugs: 49 cases in Finland. Acta Psychiatr Scand 1991;84:58-64.
  • Muller D. The treatment of restless psychotics with methotrimeprazine (Veractil). J Ment Sci 1961;107(449):783-6.
  • Panaccio V. La lévomépromazine dans le traitement des dermatoses prurigineuses. Union Med Canada 1964;93(3):317-9.
  • Paradis B. La lévomépromazine en anesthésie. Anesthésie-Analgésie 1959;16(1):185-93.
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  • Payne P, Veringer D. Levomepromazine in the treatment of neuroleptic resistant psychotics. J Ment Sci 1960;106:1429-31.
  • Ray WA, Meredith S, Thapa PB, Meador KG, Hall K, Murray KT. Antipsychotics and the risk of sudden cardiac death. Arch Gen Psychiat 2001;58(12):1161-7.
  • Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SHL. Thioridazine and sudden unexplained death in psychiatric in-patients. Brit J Psychiat 2002;180:515-22.
  • Sakurai T, Nishizono M, Nothohara N, Kitahara N. The treatment of schizophrenia with large doses of levomepromazine. Clin Psychiat 1963;4(10):741-54.
  • Sarwer-Foner GJ, Hajnsek F, Groszman M, Grauer H, Koranyi EK. Clinical investigation of levomepromazine (Nozinan) in open psychiatric settings. Med Services J Canada 1961;17(11):798-817.
  • Sigwald J, Bouttier D, Caille F. Le traitement du zona et des algies zostériennes. Étude des résultats obtenus avec la lévomépromazine. Thérapie 1959;14(5):818-24.
  • Sigwald J, Bouttier D, Solignac J. Essai de traitement de la névralgie essentielle du trijumeau par la lévomépromazine. Rev Neurol 1958;99(5):580-1.
  • Sigwald J, Bouttier D, Solignac J, Dumezil. L’action antialgique des phénothiazines. I- Le traitement par la lévomépromazine des algies intenses ou irréductibles. Thérapie 1959;14(6):978-84.
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Note

This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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