Action And Clinical Pharmacology: Methotrimeprazine possesses antipsychotic, tranquilizing, anxiolytic, sedative and analgesic properties and it is also a potent potentiator of anesthetics.
Methotrimeprazine possesses strong sedative properties. It potentiates ether and hexobarbital anesthesia as well as morphine analgesia. It also exerts a potent anti-apomorphine effect, a hypothermic action 3 times more potent than that of chlorpromazine and strong antispasmodic and anti-histaminic effects. Methotrimeprazine is capable of reversing epinephrine-induced hypertension but has practically no effect against norepinephrine and acetylcholine. It readily protects rats against traumatic shock and produces deep local anesthesia following parasciatic injections.
Indications And Clinical Uses: Psychotic disturbances: acute and chronic schizophrenias, senile psychoses, manic-depressive syndromes.
Conditions associated with anxiety and tension: autonomic disturbances, personality disturbances, emotional troubles secondary to such physical conditions as resistant pruritus, etc.
Methotrimeprazine is also employed: As an analgesic: In pain due to cancer, zona, trigeminal neuralgia and neurocostal neuralgia and in phantom limb pains and muscular discomforts.
As a potentiator of anesthetics: In general anesthesia where it can be used as both a 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.
Contra-Indications: In cases of coma or CNS depression due to alcohol, hypnotics, analgesics or narcotics.
It is also contraindicated in patients with blood dyscrasia, hepatic troubles or a sensitivity to phenothiazines.
Manufacturers’ Warnings In Clinical States: Occupational Hazards: Methotrimeprazine can reduce psychomotor activity especially during the first few days of treatment. Patients should therefore be cautioned not to drive a motor vehicle or to participate in activities requiring total mental alertness.
Pregnancy: The drug should be used with caution in pregnant women, particularly during the first trimester, unless the benefit to the patient outweighs any possible risk to the fetus.
Precautions: In high oral or parenteral doses, orthostatic hypotension may be encountered at the start of treatment. Patients whose treatment is started by the parenteral route should be kept in bed during the first few days.
Methotrimeprazine therapy should be initiated at low doses in patients with arteriosclerosis or cardiovascular problems.
Methotrimeprazine potentiates the action of other phenothiazines and CNS depressants (barbiturates, analgesics, narcotics and antihistaminics). The usual doses of these agents should be reduced by half if they are to be given concomitantly with methotrimeprazine until the dosage of the latter has been established.
Because of its anticholinergic effects, methotrimeprazine must be administered with caution in patients with glaucoma or prostatic hypertrophy.
During long-term therapy, periodic liver function tests should be performed. In addition, blood counts should be conducted regularly, particularly during the first 2 or 3 months of treatment, and physicians should watch for any signs of blood dyscrasia.
Methotrimeprazine does not alter EEG activity. Nevertheless, since phenothiazines can lower the threshold of cortical excitation, it is advisable to administer an appropriate anticonvulsant medication to epileptic patients receiving Nozinan therapy.
Adverse Reactions: May be classified as follows: CNS: Drowsiness may appear early in treatment but will gradually disappear during the first weeks or with an adjustment in the dosage.
Extrapyramidal effects are rare and usually appear only after prolonged therapy at high doses. These reactions may be corrected either by reducing the dose of Nozinan or by administering an antiparkinsonian agent.
Autonomic Nervous System: Dryness of the mouth and, in older patients occasional urinary retention, constipation and tachycardia.
Cardiovascular: Orthostatic hypotension may be encountered at the start of treatment by the parenteral route or with high oral doses.
Blood: Rare instances of agranulocytosis have been reported.
Endocrine: Weight gain has been occasionally reported in patients during prolonged treatment with high doses.
Gastrointestinal: Rare cases of cholostatic jaundice without liver damage have been observed.
Skin Reactions: Skin reactions due to photosensitivity or allergies are extremely rare.
Symptoms And Treatment Of Overdose: Symptoms: Symptoms of acute intoxication may include: simple CNS depression, spasms, tremor or tonic and clonic convulsions, coma accompanied by hypotension and respiratory depression.
Treatment: There is no specific antidote. After gastric lavage, treatment is symptomatic. Centrally acting emetics are ineffective because of the anti-emetic action of methotrimeprazine.
Hypotension: A 5% glucose solution may be administered. If a hypertensive agent is required, norepinephrine or phenylephrine may be used, but not epinephrine which can aggravate hypotension.
Respiratory depression: Oxygen by inhalation or controlled respiration after tracheal intubation.
Respiratory infection: Wide spectrum antibiotics.
Extrapyramidal reactions: An antiparkinsonian agent or chloral hydrate, however the latter must be used with caution because of its depressant effect on respiration.
Any CNS stimulant should be used with caution.
Dosage And Administration: Dosage must be adjusted according to the indication and individual needs of the patient. If sedation during the day is too pronounced, lower doses may be given during the day and higher doses at night.
Adults: Oral: Minor conditions in which methotrimeprazine may be given in low doses as a tranquilizer, anxiolytic, analgesic or sedative: begin treatment with 6 to 25 mg/day in 3 divided doses at mealtimes. Increase the dosage until the optimum level has been reached. As a sedative, a single night time dose of 10 to 25 mg is usually sufficient.
Severe conditions: Such as psychoses or intense pain in which methotrimeprazine is employed at higher doses: Begin treatment with 50 to 75 mg/day divided into 2 or 3 daily doses; increase the dosage until the desired effect is obtained. In certain psychotics doses may reach 1 g or more/day. If it is necessary to start therapy with higher doses, i.e., 100 to 200 mg/day, administer the drug in divided daily doses and keep the patient in bed for the first few days.
Parenteral: I.M.: To be used primarily for the initial treatment of psychoses for certain severe pain as a premedication or for the treatment of postoperative pain. In psychoses and pain, doses vary from 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.
I.V.: To be used primarily as an infusion during surgery or labour. The dose may range from 10 to 25 mg in 500 mL of a 5% glucose solution administered at a rate of 20 to 40 drops/minute. If methotrimeprazine is administered with a barbiturate or narcotic, the doses of the latter must be reduced by at least one-half.
Children: Oral: The initial dose has been established at 1/4 mg/kg daily given in 2 or 3 divided doses. This dosage may be increased gradually until an effective level is reached which should not surpass 40 mg/day for a child less than 12 years of age.
Parenteral: I.M.: A dose of 1/16 to 1/8 mg/kg/day in one or divided among several injections. Oral medication should be substituted as soon as possible.
I.V.: In anesthesia, 1/16 mg/kg in 250 mL of a 5% glucose solution may be administered as a slow infusion (20 to 40 drops per minute) during surgery.
Availability And Storage: Injectable: Each mL contains: methotrimeprazine base 25 mg (as the hydrochloride). Nonmedicinal ingredients: ascorbic acid, sodium chloride, sodium sulfite and water for injection. Ampuls of 1 mL, boxes of 10. Protect from light or discoloration may occur.
Oral Drops: Each mL of brown solution contains: methotrimeprazine base 40 mg (as the hydrochloride). Nonmedicinal ingredients: alcohol 95%, ascorbic acid, caramel, citric acid, ethyl vanillin, glycerin, orange oil deterpine, purified water and sucrose. Alcohol: 16.5% v/v. Energy: 7.3 kJ (1.8 kcal)/mL. Sucrose: 200 mg/mL. Tartrazine-free. Bottles of 100 mL.
Liquid: Each 5 mL of brown liquid contains: methotrimeprazine base 25 mg (as the hydrochloride). Nonmedicinal ingredients: alcohol 95%, apricto essence, ascorbic acid, caramel, citric acid, glycerin, purified water and sucrose. Alcohol: 2.0% v/v. Energy: 62.3 kJ (14.9 kcal)/5 mL. Sucrose: 3.7 g/5 mL. Tartrazine-free. Bottles of 500 mL.
Tablets: Each yellow tablet contains: methotrimeprazine base 2, 5, 25 or 50 mg (as the maleate). Nonmedicinal ingredients: acetic anhydride, carnauba wax, cellulose, D&C Yellow No 10 aluminum lake, dicalcium phosphate, diethyl phthalate, FD&C Yellow No 6 aluminum lake, magnesium stearate, polacrilin potassium, silicon dioxide, sodium oleate, titanium dioxide, and zein. Tartrazine-free. Bottles of 100 and 500. (Shown in Product Recognition Section)
NOZINAN® Rhône-Poulenc Rorer Methotrimeprazine Neuroleptic