Sibutramine

Sibutramine Uses, Dosage, Side Effects, Food Interaction and all others data.

Sibutramine produces its therapeutic effect by norepinephrine, serotonin and dopamine reuptake inhibition. Sibutramine exerts its pharmacological actions predominantly via its secondary (M1) and primary (M2) amine metabolites. The parent compound Sibutramine is a potent inhibitor of serotonin and norepinephrine reuptake in vivo. However metabolites M1 and M2 inhibit the reuptake of these neurotransmitters both in vivo and in vitro.

Sibutramine is an orally administered agent for the treatment of obesity. Sibutramine exerts its pharmacological actions predominantly via its secondary (M1) and primary (M2) amine metabolites. The parent compound, sibutramine, is a potent inhibitor of serotonin and norepinephrine reuptake in vivo, but not in vitro. However, metabolites M1 and M2 inhibit the reuptake of these neurotransmitters both in vitro and in vivo. In human brain tissue, M1 and M2 also inhibit dopamine reuptake in vitro, but with ~3-fold lower potency than for the reuptake inhibition of serotonin or norepinephrine. Sibutramine, M1 and M2 exhibit no evidence of anticholinergic or antihistaminergic actions. In addition, receptor binding profiles show that sibutramine, M1 and M2 have low affinity for serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C), norepinephrine (b, b1, b3, a1 and a2), dopamine (D1 and D2), benzodiazepine, and glutamate (NMDA) receptors. These compounds also lack monoamine oxidase inhibitory activity in vitro and in vivo.

Trade Name Sibutramine
Availability Discontinued
Generic Sibutramine
Sibutramine Other Names Sibutramina, Sibutramine, Sibutraminum
Related Drugs phentermine, semaglutide, Wegovy, Saxenda, liraglutide, Alli
Type
Formula C17H26ClN
Weight Average: 279.848
Monoisotopic: 279.175377544
Protein binding

97% (to human plasma proteins)

Groups Approved, Illicit, Investigational, Withdrawn
Therapeutic Class Appetite suppressant drugs/Anti-obesity drugs
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Sibutramine
Sibutramine

Uses

Sibutramine is used in the management of obesity, including weight loss and management of weight loss. It should be used in conjunction with a reduced caloric diet. Sibutramine is recommended for obese patients with an initial body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (e.g., hypertension, diabetes, dyslipidemia)

Sibutramine is also used to associated treatment for these conditions: BMI >30 kg/m2

How Sibutramine works

Sibutramine produces its therapeutic effects by inhibition of norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT), and to a lesser extent, dopamine reuptake at the neuronal synapse. By inhibiting the reuptake of these neurotransmitters, sibutramine promotes a sense of satiety and decrease in appetite, thereby reducing food intake. Data from animal studies also suggest that sibutramine may also increase energy expenditure through thermogenic effects in both the basal and fed states, but this has not been confirmed in humans. Sibutramine and its major pharmacologically active metabolites (M1 and M2) do not act via release of monoamines.

Dosage

Sibutramine dosage

The recommended starting dose is 10 mg administered once daily with or without food. If there is inadequate weight loss, the dose may be titrated after 4 weeks to a total of 15 mg once daily. The 5 mg dose should be reserved for patients who do not tolerate the 10 mg dose. Blood pressure and heart rate changes should be taken into account when making decisions regarding dose titration. Analysis of numerous variables has indicated that ≈ 60% of patients who lose at least 4 lbs in the first 4 weeks of treatment with a given dose of Sibutramine in combination with a reduced-calorie diet lose at least 5% (placebo-subtracted) of their initial body weight by the end of 6 months to 1 year of treatment on that dose. Conversely, ≈ 80% of patients who do not lose at least 4 lbs in the first 4 weeks of treatment with a given dose do not lose at least 5% (placebo-subtracted) of their initial body weight by the end of 6 months to 1 year of treatment on that dose. If a patient has not lost at least 4 lbs in the first 4 weeks of treatment, consider reevaluation of therapy which may include increasing the dose or discontinuing Sibutramine. The safety and efficacy of Sibutramine have not been determined beyond 1 year at this time.

Side Effects

Commonly reported side-effects of Sibutramine are dry mouth, headache, insomnia and constipation; diarrhoea, dizziness, drowsiness and rhinitis have also occurred. Less frequently reported side-effects include dysmenorrhoea, oedema, influenza-like symptoms, and depression. Abnormal bleeding, acute interstitial nephritis, emotional lability, migraine, seizures and skin rashes have been reported rarely. Clinically significant increases in heart rate and blood pressure may occur. Sibutramine may decrease salivary flow and therefore increase the risk of dental caries, periodontal disease, or other oral disorders. It may also produce mydriasis. Increases in liver enzyme have been reported.

Toxicity

Side effects include dry mouth, anorexia, insomnia, constipation and headache.

Precaution

Use caution when prescribing Sibutramine with other agents that may raise blood pressure or heart rate including certain decongestant, cough, cold and allergy medications that contain agents such as phenylpropanolamine, ephedrine or pseudoephedrine.

Interaction

Sibutramine should not be given concurrently with, or within at least two weeks of stopping an MAOI; at least two weeks should elapse between discontinuation of Sibutramine and starting therapy with an MAOI. There is a risk of the serotonin syndrome developing if Sibutramine is administered together with other serotonergic drug such as selective serotonin reuptake inhibitors (SSRIs), sumatriptan, lithium, pethidine, fentanyl, dextromethorphan and pentazocine. Sibutramine should not be used with other drugs that may increase heart rate or blood pressure such as ephedrine, phenylpropanolamine, and pseudoephedrine (which may be ingredients of some cough and cold remedies). Alcohol should be avoided. Inhibitors of the cytochrome P450 isoenzyme CYP3A4, such as ketoconazole and erythromycin, may increase plasma concentrations of Sibutramine.

Food Interaction

[Moderate] GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants.

In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm

This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone.

Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected.

The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease.

Patients should be counselled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Elimination Route

Rapid absorption following oral administration. Absolute bioavailability is not known, but at least 77% of a single oral dose of sibutramine is absorbed.

Half Life

1.1 hours

Clearance

  • Oral cl=1750 L/h [oral administration]

Elimination Route

Sibutramine is metabolized in the liver principally by the cytochrome P450 (3A4) isoenzyme, to desmethyl metabolites, M1 and M2. These active metabolites are further metabolized by hydroxylation and conjugation to pharmacologically inactive metabolites, M5 and M6. Approximately 85% (range 68-95%) of a single orally administered radiolabeled dose was excreted in urine and feces over a 15-day collection period with the majority of the dose (77%) excreted in the urine. The primary route of excretion for M1 and M2 is hepatic metabolism and for M5 and M6 is renal excretion.

Pregnancy & Breastfeeding use

The use of Sibutramine is not recommended during pregnancy. Women of child-bearing potential should use adequate contraception while taking this drug. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. It is not known whether Sibutramine or its active metabolites are excreted in breast milk. It is not recommended for use in nursing mothers. Patients should be advised to notify their physician if they are breast-feeding.

Contraindication

Patients receiving monoamine oxidase inhibitors (MAOIs), hypersensitivity to Sibutramine or any of the active ingredients of Sibutramine; patients with anorexia nervosa, patients taking other centrally acting appetite-suppressant drugs. Give with caution to those patients with a history of hypertension and do not give to patients with uncontrolled or poorly controlled hypertension.

Storage Condition

Should be protected from light. Store in a dry place and between 15˚ to 30˚C temperature.

Innovators Monograph

You find simplified version here Sibutramine

Sibutramine contains Sibutramine see full prescribing information from innovator Sibutramine Monograph, Sibutramine MSDS, Sibutramine FDA label

FAQ

What is Sibutramine used for?

Sibutramine is used together with diet and exercise to treat obesity that may be related to diabetes, high cholesterol, or high blood pressure.Sibutramine may also be used for other purposes not listed in this medication guide.

How safe is Sibutramine?

Sibutramine is safe, well tolerated, and produces statistically and clinically significant body weight loss in obese patients whose hypertension is well controlled with an ACE inhibitor.

What are the common side effects of Sibutramine?

The common side effects of Sibutramine are include:

  • A Stuffy And Runny Nose
  • Dry Mouth
  • Constipation
  • Dizziness
  • Difficulty Sleeping
  • Decreased Appetite
  • Headache
  • Nervousness
  • Irritability
  • Anxious Feelings

How does Sibutramine work in the body?

Sibutramine blocks the reuptake of the neurotransmitters dopamine, norepinephrine, and serotonin.

Is Sibutramine safe during pregnancy?

The use of Sibutramine is considered contraindicated during pregnancy. It is recommended that women of child bearing potential use adequate contraception while on Sibutramine therapy. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy.

Is Sibutramine safe during breastfeeding?

Sibutramine is considered contraindicated during breast-feeding by the manufacturer. Patients should be advised to notify their physician if they are breast-feeding.

Can I drink alcohol with Sibutramine?

Using Sibutramine with alcohol can increase the risk of cardiovascular side effects such as increased heart rate, chest pain, or blood pressure changes.

How long does Sibutramine stay in my system?

Sibutramine is metabolized stay in your system half-lives of 14 and 16 hours, respectively.

Does Sibutramine give mecenergy?

it reduces energy intake by increasing satiety and it increases energy expenditure.

Does sibutramine get me high?

Sibutramine has no abuse potential since it does not enhance dopamine release at the synapse.

Does Sibutramine affect fertility?

Sibutramine is associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility.

Is Sibutramine a stimulant?

It is a centrally acting stimulant chemically.

Can Sibutramine cause heart problems?

Sibutramine is one such agent and potentially causes cardiac arrest even in subjects without pre-existing cardiovascular disease, particularly when combined with drugs that lead to QT prolongation.

Is Sibutramine an antidepressant?

Sibutramine was initially developed as an antidepressant.

Can I take Sibutramine long time?

Sibutramine should not be taken for longer than 2 years.

When is the best time to take Sibutramine?

Sibutramine is taken once daily, generally in the morning.

What happens if I miss a dose of Sibutramine?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose of Sibutramine?

Seek emergency medical attention.
Overdose symptoms may include headache, dizziness, and fast heart rate.

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*** Taking medicines without doctor's advice can cause long-term problems.
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