マジンドール

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Concurrent use /of other CNS stimulation-producing medications or thyroid hormones with appetite suppressants/ may increase the CNS stimulant effects of either these medications or the appetite suppressant. /Appetite suppressants, sympathomimetic/

The sympathomimetic effects of appetite suppressants /when used with monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline/ may be potentiated, possibly resulting in a hypertensive crisis; concurrent use is contraindicated; appetite suppressant should not be administered during or within 14 days following the administration of and MAO inhibitor. /Appetite suppressants, sympathomimetic/

Vasopressant effect may be potentiated; if necessary to administer a pressor amine agent to a patient who has recently received an appetite suppressant, initiating pressor therapy in reduced dosage and monitoring blood pressure at frequent intervals are recommended. /Appetite suppressants, sympathomimetic/

Anorectic effects of the appetite suppressant may be antagonized /when use with phenothiazines/. /Appetite suppressants, sympathomimetic/

For more Interactions (Complete) data for MAZINDOL (10 total), please visit the HSDB record page.

Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

Although the mechanism of action of the sympathomimetics in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Unlike other sympathomimetic appetite suppressants such as phentermine, mazindol is thought to inhibit the reuptake of norepinephrine rather than to cause its release.

/HUMAN EXPOSURE STUDIES/ Approximately half of the overdosage cases involved accidental ingestion in children 1-4 years of age. The reported doses ingested ranged from 4-40 mg. All recovered.

/SIGNS AND SYMPTOMS/ In cases in which overdosages have been reported, the symptoms listed below were cited: irritability, agitation, hyperactivity, tachycardia, arrhythmia (premature ventricular contractions occurred in the patient also taking phenmetrazine), tachypnea.

/SIGNS AND SYMPTOMS/ Chronic toxicity resulting from anorexigenic agents may produce severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. Psychosis, often clinically indistinguishable from schizophrenia, may also occur. Withdrawal symptoms including extreme fatigue, mental depression, and changes in the EEG during sleep have been reported when amphetamines and related drugs were abruptly discontinued following excessive use of these agents.

/CASE REPORTS/ A 25 year-old female died after ingesting a massive dose of 200 mg mazindol and an undetermined amount of ethanol.

For more Human Toxicity Excerpts (Complete) data for MAZINDOL (7 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Mazindol

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Treatment of dogs with high doses of mazindol for long periods resulted in some corneal opacities which were reversible when the drug was withdrawn.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Teratogenicity studies in rats and rabbits showed an increase in neonatal mortality and in rats a possible increase in rib anomalies.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... After prolonged administration of mazindol in dogs, withdrawal symptoms were observed when the drug was abruptly discontinued. In addition, monkeys have self-administered the drug.

While data specific to mazindol were not located(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).

Maintain open airway and assist ventilation if necessary. Treat agitation, seizures, coma, and hypothermia if they occur. Continually monitor temperature, other vital signs, and the ECG for a minimum of 6 hours. Hypertension is best treated with parenteral vasodilator such as phentolamine or nitroprusside. Treat tachyarrhythmias with propranolol or esmolol. Treat arterial vasospasm /with/ nitroglycerin sublingually ... /or/ iv. Intracoronary artery nitroglycerin may be required if there is no response to intravenous infusion. Also consider using a calcium antagonist. /Amphetamines/

Do not induce vomiting because of the risk of abrupt onset of seizures. Administer activated charcoal. Gastric emptying is not necessary if activated charcoal can be given promptly. Dialysis and hemoperfusion are not effective. Repeat dose charcoal has not been studied... /Amphetamines/

LD50 Mouse oral 106 mg/kg

LD50 Rat oral 180 - 320 mg/kg

LD50 Rabbit oral 98 mg/kg

LD50 Dog oral 9 mg/kg

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: Mazindol, Schedule IV, DEA Code #: 1605.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products, incl mazindol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Food and Drug Administration (FDA) is withdrawing approval of 80 new drug applications (NDAs) and 75 abbreviated new drug applications (ANDAs). /Mazindol listed in table/ The holders of the applications notified the agency in writing that the drug products were no longer marketed and requested that the approval of the applications be withdrawn. EFFECTIVE DATE: September 17, 2003.

THERAP CAT: anorexic; CNS stimulant /Former/

Appetite suppressant /Former/

MEDICATION

Mazindol is used in short-term (a few weeks) treatment of exogenous obesity in conjunction with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of 30 kg of body weight per height in meters squared (kg/m²) or in patients with a body mass index of 27 kg/m² in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia.

Preparation: W.J. Houlihan, DE 1814540; W.J. Houlihan, M.K. Eberle, DE 1930488; eidem US 3597445 (1969, 1970, 1970 all to Sandoz)

Preperation: T.S. Sulkowski, US 3763178 (1973 to American Home Prod.)

Mazindol is prepared by treating the dilithio reagent, obtained from 2-phenylimidazoline, with methyl 4-chlorobenzoate.

DOSAGE FORMS: TABLETS: 2 MG.

Mazanor(R), Sanorex (R): tablets, 1 and 2 mg

Controlled substance 21CFR1308.14

The Food and Drug Administration (FDA) is withdrawing approval of 80 new drug applications (NDAs) and 75 abbreviated new drug applications (ANDAs). /Mazindol listed in table/ The holders of the applications notified the agency in writing that the drug products were no longer marketed and requested that the approval of the applications be withdrawn. EFFECTIVE DATE: September 17, 2003.