Mazindol

Mazindol is a tricyclic anorexigenic agent belonging to central nervous system (CNS) stimulants

medication that is primarily used to treat obesity.

Mazindol is Readily absorbed from the GI tract. It gets excreted Via urine (as metabolite and unchanged drug).

Mazindol shows common side effects like Headache, Dry mouth, Fatigue or drowsiness, Nausea, Stomach upset, Nervousness, Difficulty sleeping, and Skin rash or itching.

Mazindol is available in Tablet.

Mazindol is available in India, Germany, Canada, France, USA

Mazindol is a tricyclic anorexigenic agent that is unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits the uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter.

Mazindol is available in the form of Tablet.

Oral: Administer with water 1 hour before or 2 hours after intake of food or fruit juices.

Mazindol is a central stimulant that acts by inhibiting the reuptake of dopamine and noradrenaline. It has been used as an anorectic in the treatment of obesity.

Mazindol is approved for use in the following clinical indications

Obesity

Oral

Obesity

Adult: Initially, 0.5-1 mg/day in the morning. May increase to 1.5-2 mg/day after 1 wk, depending on patient's response. Max dose: 3 mg/day in divided doses. Treatment duration: 4-6 wk. Max: 12 wk.

Child: >12 yr: Initially, 0.5-1 mg/day in the morning. May increase to 1.5-2 mg/day after 1 wk, depending on patient's response. Max dose: 3 mg/day in divided doses. Treatment duration: 4-6 wk. Max: 12 wk.

Mazindol is available in the dosage strength of 1 mg and 2 mg.

• Dosage Adjustment for Pediatric Patients:

Child: >12 yr: Initially, 0.5-1 mg/day in the morning. May increase to 1.5-2 mg/day after 1 wk, depending on patient's response. Max dose: 3 mg/day in divided doses. Treatment duration: 4-6 wk. Max: 12 wk.

Take after eating and with a full glass of water to decrease gastric upset.

Mazindol is contraindicated in patients with:

• A history of coronary artery disease, congestive heart failure, cardiac decompensation, cardiovascular disease including cardiac arrhythmias, or a history of such disease, or cerebrovascular disease (stroke or transient ischemic attack).

• Inadequately controlled (>145/90 mm hg) or unstable hypertension, severe arterial hypertension, pulmonary artery hypertension or elevated venous pressure

• A history of, or presence of, major eating disorder such as anorexia nervosa or bulimia nervosa. • psychiatric disorders, including depression, schizophrenia, hyperexcitability and states of agitation, or a history of such disorders

• Narrow-angle glaucoma.

• severe renal and hepatic insufficiency.

• uraemia, with a history of, and propensity to drug abuse or dependence

• known alcoholism.

• children under 12 years, and patients who are pregnant or lactating. 6 concomitant use of mazindol with other centrally acting anorectic agent is contraindicated due to the potentially increased risk of pulmonary artery hypertension.

Concomitant use of mazindol and mao inhibitors is contraindicated. At least 14 days should elapse between discontinuation of a mao inhibitor and initiation of treatment with mazindol (to avoid hypertensive crisis).

Concomitant use of mazindol and centrally-acting drugs for the treatment of psychiatric disorders (such as antidepressants, antipsychotics) or herbal remedies (such as st john’s wort) is contraindicated. At least 14 days should elapse between discontinuation of these drugs and initiation of treatment with mazindol. A 5 week discontinuation period is required for fluoxetine mazindol (mazindol) should not be given to patients who display hypersensitivity or idiosyncratic reactions to mazindol or any of the other components of this product.

Certain centrally-acting weight loss agents that cause both release and re-uptake inhibition of serotonin from nerve terminals have been associated with primary pulmonary hypertension (PPH), a rare but sometimes fatal disease, and cardiac valve dysfunction when used for more than 3 months. It is hypothesized that the mechanism by which these drugs cause PPH and cardiac valvulopathy is the release of serotonin from nerve terminals. MAZINDOL (mazindol) is a serotonin and norepinephrine re- uptake inhibitor and not a serotonin releasing agent. The yearly occurrence of PPH in the general population is estimated to be approximately 1-2 cases per 1,000,000 persons.

In view of this rare but serious risk, it must be emphasized that:

• careful compliance with the indication and the duration of treatment is required,

• a treatment period greater than 3 months increases the risk of pulmonary artery hypertension

• the onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema suggest the possibility of occurrence of pulmonary hypertension.

Under these circumstances, treatment should be immediately discontinued and the patient referred to a primary pulmonary hypertension specialist.

Cardiac Valve Dysfunction:

Cardiac valve disorders have been reported in association with the use of some centrally acting anorectic agents such as fenfluramine and dexfenfluramine.

Other factors possibly contributing to the development of cardiac valve disorders are prolonged exposure to centrally acting anorectic agents, exposure to doses higher than those recommended, and/or concomitant treatment with more than one centrally acting anorectic agent. Therefore the use of centrally acting anorectic agents is not recommended in patients known to have cardiac murmur or cardiac valve abnormalities.

Selective Serotonin Reuptake Inhibitors/ Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome:

Cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans. If concomitant treatment with mazindol and SSRIs (e.g., sertraline, escitalopram oxalate, and fluoxetine) or SNRIs (e.g., venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)

Hematologic:

There have been reports of bleeding abnormalities associated with agents that affect serotonin reuptake. Mazindol should be used with caution in patients treated concomitantly with drugs known to affect hemostasis or platelet function [e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, and non-steroidal anti-inflammatory drugs (NSAIDs)]. Caution is also advised in patients with a history of bleeding disorders or those with predisposing conditions. Hepatic/Biliary/Pancreatic:

Weight loss can precipitate or exacerbate gallstone formation.

Neurologic:

MAZINDOL should be used with caution in epileptic patients. It should be discontinued in any patient who develops seizures. Psychiatric: Cases of depression, delirium and anxiety have been reported in patients on mazindol treatment. If signs or symptoms of such psychiatric events occur during treatment with mazindol, the discontinuation of mazindol and commencement of an appropriate treatment should be considered.

Drug Dependence:

Experience with anorectic drugs with amphetamine-like properties has established that their use over prolonged periods can produce severe psychological dependence and has led to extensive abuse. Abstinence effects and self-administration of mazindol have been observed in animals.

While the abuse potential of mazindol has not been further defined, the possibility of dependence should be kept in mind when evaluating the desirability of mazindol as part of a weight reduction program.

Tolerance:

Tolerance to the anorectic effect of mazindol may occur within a few weeks. If this occurs, discontinuation of the medication is indicated: the dose should not be increased.

PRECAUTIONS

It is recommended that treatment be carried out under the care of a physician experienced in the treatment of obesity. Secondary organic causes of obesity must be excluded by diagnosis before prescribing this product. The management of obesity should be undertaken using a global approach that includes dietary, medical and psychotherapeutic methods. Mazindol should be used with caution in patients with hypertension and frequent monitoring of blood pressure is indicated. There is insufficient evidence to indicate that MAZINDOL would not have an adverse effect in some hypertensive patients. Blood pressure and pulse rate should be measured prior to starting therapy with mazindol and should be monitored at regular intervals thereafter. For patients who experience a sustained increase in blood pressure or pulse rate while receiving mazindol, the drug should be discontinued. Mazindol should be given with caution to patients with well-controlled hypertension, and is contraindicated in patients with inadequately controlled or unstable hypertension. The drug is not recommended in individuals with symptomatic cardiovascular disease including arrhythmias. Insulin requirements in diabetes mellitus may be altered by mazindol administration and concomitant dietary regimens. It is recommended that mazindol be administered continuously for a period no greater than six weeks. Mazindol should be prescribed at the lowest effective dose in the smallest possible quantities to avoid possible overdosage. Evening dosing should be avoided, as this product may induce nervousness and insomnia. Patients should be cautioned against engaging in activities requiring rapid and precise responses, such as driving an automobile or operating machinery until their response to mazindol has been determined. Rarely, cardiac and cerebrovascular accidents have been reported, often following rapid weight loss. Special care should be taken to ensure gradual and controlled weight loss in obese patients, who are at risk of vascular disease. In view of general concerns with anti-obesity drugs, it is important to be on the look out for symptoms such as progressive dyspnea, chest pain and ankle edema in the course of routine check-ups. The patient should be advised to consult a doctor immediately if these symptoms occur.

Mazindol may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

There are no known food interactions with Mazindol . However, it is recommended to avoid drinking alcohol while taking Mazindol , as it can increase the risk of drowsiness and dizziness.

• Common Adverse effects:

Eye irritation or burning (when used as eye drops), Headache ,Taste disturbances, Dry mouth, Fatigue or drowsiness, Dizziness, Nausea

• Less Common Adverse effects:

Cardiovascular effects such as increased heart rate, palpitations, and high blood pressure.

Respiratory effects such as thickening of bronchial secretions, which can make it difficult to breathe, especially in patients with asthma or COPD.

Skin reactions such as rash, hives, and itching.

Allergic reactions such as anaphylaxis, which is a severe and potentially life-threatening allergic reaction.

Gastrointestinal effects such as abdominal pain and diarrhea.

Fatigue, weakness, and headache.

• Rare Adverse effects

Allergic reactions: In rare cases, Mazindol may cause an allergic reaction, which can be life-threatening. Symptoms of an allergic reaction may include difficulty breathing, swelling of the face, lips, tongue or throat, or a skin rash.

Liver injury: There have been rare reports of liver injury associated with the use of Mazindol , including cases of hepatitis and elevated liver enzymes.

Seizures: Mazindol may lower the seizure threshold in some people, especially those with a history of seizures or epilepsy.

Cardiac events: There have been rare reports of cardiac events associated with the use of Mazindol , including tachycardia, palpitations, and QT prolongation.

Concomitant use of mazindol with other centrally acting weight-reducing agents is contraindicate

• Concomitant use of mazindol and MAO inhibitors is contraindicated. At least 14 days should elapse between discontinuation of a MAO inhibitor and initiation of treatment with mazindol

• Concomitant use of mazindol and centrally-acting drugs for the treatment of psychiatric disorders (such as antidepressants, antipsychotics) or herbal remedies (such as St John’s Wort) is contraindicated. At least 14 days should elapse between discontinuation of these drugs and initiation of treatment with mazindol. A 5 week discontinuation period is required for fluoxetine

The common side effects of Mazindol include the following :

Eye irritation or burning (when used as eye drops), Headache, Taste disturbances, Dry mouth, Fatigue or drowsiness, Dizziness and Nausea.

• Pharmacodynamic

Mazindol is a sympathomimetic amine that stimulates the central nervous system (nerves and brain), leading to increased your heart rate and blood pressure, and decreased appetite. Since the appetite-suppressing effect of the drug tends to decrease after few weeks of treatment, sympathomimetic appetite suppressants are typically used short-term weight-loss program.

• Pharmacokinetics

Absorption: Readily absorbed from the GI tract.

Excretion: Via urine (as metabolite and unchanged drug).

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Mazindol -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Mazindol
5. https://europepmc.org/article/med/6988203