Prescription Drugs

CLINICAL PHARMACOLOGY ACTIONS The pharmacodynamic action of TORECAN® (thiethylperazine) in humans is unknown. However, a direct action of TORECAN (thiethylperazine) on both the CTZ and the vomiting center may be concluded from induced vomiting experiments in animals.

Torecan® (thiethylperazine maleate) Tablets (thiethylperazine maleate) for Injection, USP For Intramuscular Use Only DESCRIPTION TORECAN (thiethylperazine) is a phenothiazine. Thiethylperazine is characterized by a substituted thioethyl group at position 2 in the phenothiazine nucleus, and a piperazine moiety in the side chain. The chemical designation is: 2-ethyl-mercapto-10-[3 †- (1 †-methyl-piperazinyl-4†)-propyl-1] phenothiazine. Tablet, 10 mg, for oral administration Active Ingredient: thiethylperazine maleate USP, 10 mg. Inactive Ingredients: acacia, carnauba wax, FD&C Yellow No.5 aluminum lake (tartrazine), FD&C Yellow No.6 aluminum lake, gelatin, lactose, magnesium stearate, povidone, sodium benzoate, sorbitol, starch, stearic acid, sucrose, talc, titanium dioxide. Ampul, 2 ml, for intramuscular administration Active Ingredient: thiethylperazine malate USP, 10 mg per 2 mL. Inactive Ingredients: sodium metabisulfite NF, 0.5 mg; ascorbic acid USP, 2.0 mg; sorbitol NF, 40 mg; carbon dioxide gas q.s.; water for injection USP, q.s.to 2 mL.

INDICATIONS TORECAN (thiethylperazine) is indicated for the relief of nausea and vomiting. DOSAGE AND ADMINISTRATION Adult Usual daily dose range is 10 mg to 30 mg. Oral: One tablet, one to three times daily. Intramuscular: 2 mL IM, one to three times daily. (See PRECAUTIONS.) Pediatric Patients Appropriate dosage of TORECAN (thiethylperazine) has not been determined in pediatric patients. HOW SUPPLIED Torecan (thiethylperazine maleate) Tablets, USP 10mg Each tablet contains 10 mg thiethylperazine maleate, USP. Bottles of 100 tablets (NDC 0054-4748-25). Storage: Below 86°F (30°C). Dispense in tight, light-resistant container as defined in the USP/NE Torecan (thiethylperazine malate) Injection, USP 2 mL Ampul Each 2 mL ampul contains aqueous solution 10 mg thiethylperazine malate, USP. Boxes of 20 ampuls (NDC 0054-1701-07). Boxes of 100 ampuls (NDC 0054-1701-25). Storage: Below 86°F (30°C); protect from light. Administer only if clear and colorless.

PATIENT INFORMATION Patients receiving TORECAN (thiethylperazine) should be cautioned about possible combined effects with alcohol and other CNS depressants. Patients should be cautioned not to operate machinery or drive a motor vehicle after ingesting the drug.

OVERDOSE Manifestations of acute overdosage of TORECAN (thiethylperazine) can be expected to reflect the CNS effects of the drug and include extrapyramidal symptoms (E.P.S), confusion and convulsions with reduced or absent reflexes, respiratory depression and hypotension. If the patient is conscious, vomiting should be induced mechanically or with emetics. Gastric lavage should be employed utilizing concurrently a cuffed endotracheal t.b. if the patient is unconscious to prevent aspiration and pulmonary complications. Maintenance of adequate pulmonary ventilation is essential. The use of pressor agents intravenously may be necessary to combat hypotension. The administration of epinephrine should be avoided since phenothiazines may induce a reversed epinephrine effect. The most suitable vasoconstrictive agents are norepinephrine and phenylephrine. Fluids should be administered intravenously to encourage diuresis. The value of dialysis has not been determined. If excitation occurs, barbiturates should not be used. It should be borne in mind that multiple agents may have been ingested. CONTRAINDICATIONS Severe central nervous system (CNS) depression and comatose states. Use of TORECAN (thiethylperazine) is contraindicated in patients who have demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) to phenothiazines. Because severe hypotension has been reported after the intravenous administration of phenothiazines, this route of administration is contraindicated. Usage in Pregnancy TORECAN (thiethylperazine) is contraindicated in pregnancy.

WARNINGS TORECAN (thiethylperazine) Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Phenothiazines are capable of potentiating CNS depressants (e.g., barbiturates, anesthetics, opiates, alcohol, etc.) as well as atropine and phosphorous insecticides. Since TORECAN (thiethylperazine) may impair mental and/or physical ability required in the performance of potentially hazardous tasks such as driving a car or operating machinery, it is recommended that patients be warned accordingly. Postoperative Nausea and Vomiting With the use of this drug to control postoperative nausea and vomiting occurring in patients undergoing elective surgical procedures, restlessness and postoperative CNS depression during anesthesia recovery may occur. Possible postoperative complications of a severe degree of any of the known reactions of this class of drug must be considered. Postural hypotension may occur after an initial injection, rarely with the tablet. The administration of epinephrine should be avoided in the treatment of drug-induced hypotension in view of the fact that phenothiazines may induce a reversed epinephrine effect on occasion. Should a vasoconstrictive agent be required, the most suitable are norepinephrifle bitartrate and phenylephrine. The use of this drug has not been studied following intracardiac and intracranial surgery. PRECAUTIONS Abnormal movements such as extrapyramidal symptoms (E.P.S.) (e.g., dystonia, torticollis, dysphasia, oculogyric crises, akathisia) have occurred. Convulsions have also been reported. The varied symptom complex is more likely to occur in young adults and children. Extrapyramidal effects must be treated by reduction of dosage or cessation of medication. TORECAN (thiethylperazine) tablets contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Use in patients with bone marrow depression only when potential benefits outweigh risks. Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with phenothiazine drugs. Clinical manifestations include: hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. The extrapyramidal symptoms which can occur secondary to TORECAN (thiethylperazine) may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g., Reye†s Syndrome or other encephalopathy. The use of TORECAN (thiethylperazine) and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye†s Syndrome. Phenothiazine drugs may cause elevated prolactin levels that persist during chronic administration. Since approximately one-third of human breast cancers are prolactin-dependent in vitro, this elevation is of potential importance if phenothiazine drug administration is contemplated in a patient with a previously-detected breast cancer. Neither clinical nor epidemiologic studies to date, however, have shown an association between the chronic administration of phenothiazine drugs and mammary tumorigenesis. Postoperative Nausea and Vomiting When used in the treatment of nausea and/or vomiting associated with anesthesia and surgery, it is recommended that TORECAN (thiethylperazine) should be administered by deep intramuscular injection at or shortly before the termination of anesthesia. Information for Patients Patients receiving TORECAN (thiethylperazine) should be cautioned about possible combined effects with alcohol and other CNS depressants. Patients should be cautioned not to operate machinery or drive a motor vehicle after ingesting the drug. Drug Interactions Phenothiazines are capable of potentiating CNS depressants (e.g., barbiturates, anesthetics, opiates, alcohol, etc.) as well as atropine and phosphorous insecticides. Laboratory Test Interactions The usual precautions should be observed in patients with impaired renal or hepatic function. Nursing Mothers Information is not available concerning the excretion of TORECAN (thiethylperazine) in the milk of nursing mothers. As a general rule, nursing should not be undertaken while the patient is on a drug, since many drugs are excreted in human milk. Pediatric Use Safety and effectiveness in pediatric patients have not been established.