Rimonabant

Structural formula
General
Non-proprietary name	Rimonabant
other names	5- (4-Chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl- N - (piperidin-1-yl) -1 H -pyrazole-3-carboxamide SR141716A
Molecular formula	C 22 H 21 Cl 3 N 4 O
External identifiers / databases
CAS number 168273-06-1 158681-13-1 (hydrochloride) EC number 685-399-5 ECHA InfoCard 100.210.978 PubChem 104850 DrugBank DB06155 Wikidata Q412529
Drug information
ATC code	A08 AX01
Drug class	Anorectics
Mechanism of action	Selective cannabinoid receptor CB 1 antagonist
properties
Molar mass	463.79 g · mol -1
solubility	2 mg l −1 in water
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 372-410 P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Rimonabant is a drug that was used as an appetite suppressant to treat obesity , but was actually developed by the pharmaceutical company Sanofi-Aventis for smoking cessation . Rimonabant intervenes in the body's own cannabinoid system ( endocannabinoid system ) and mediates its effect by inhibiting cannabinoid receptors of the subtype CB ₁ . Rimonabant was marketed under the Acomplia brand name between 2006 and October 2008 . The substance was not approved in the USA because of its psychiatric side effects; in the EU, an intensive discussion of the risks of rimonabant led in October 2008 to the recommendation of the European Medicines Agency to suspend approval (see approval ).

Indications

Rimonabant was used as a drug in addition to diet and exercise for the treatment of obesity ( BMI > = 30 kg / m ² ) or overweight patients ( BMI > 27 kg / m ² ) who also had one or more risk factors such as type 2 diabetes or Have dyslipidemia , approved.

Contraindications

Rimonabant must not be used in patients with depression and must not be prescribed if the patient is also taking an antidepressant . If symptoms of depression occur, Acomplia must be discontinued immediately.

Efficacy, clinical studies

In the pivotal clinical studies , the patients treated with rimonabant lost slightly more weight (4–5%) than those participants who received a dummy drug ( placebo ). After stopping the drug, the body weight increases again ( yo-yo effect ).

In the RIO studies carried out with over 6,600 patients, a positive effect on metabolic risk factors was shown in addition to weight reduction . The values ​​of the colloquially “good cholesterol” HDL rose, while the triglyceride values ​​and insulin resistance in type 2 diabetics fell. In the non-pivotal SERENADE study lowered rimonabant in non-treated type 2 diabetics the HbA _1c value and weight. The informative value of these studies is severely limited by the high dropout rates of 40 to 50%.

Side effects

The most commonly observed side effects during the clinical trials were nausea , diarrhea , dizziness and respiratory infections . Cardiovascular side effects were not observed.

If the prescribed dose (20 mg) is taken, adverse psychological effects can occur: depression (in 2.9% of patients, under placebo: 1.5%), feeling of anxiety (1.1%, under placebo: 0.4%) and Nausea (1.3%, with placebo: <0.1%). Patients who have previously been treated for depression should not take this drug. A dangerous side effect is rimonabant-induced suicidal ideation . In the UK, five patients died after taking the appetite suppressant Acomplia®. Other possible undesirable effects are memory impairment and probably also seizures.

Admission

Rimonabant was originally developed for smoking cessation . Appropriate approval was rejected by both the European Medicines Agency and the American Food and Drug Administration , because clinical studies did not provide sufficient evidence for the effectiveness of rimonabant in smoking cessation.

Because of the increased risk of suicide, rimonabant is currently not approved in the USA. An FDA panel of experts unanimously rejected the approval in June 2007; the final decision was announced for July 27, 2007. The manufacturing company Sanofi-Aventis withdrew the application for approval on June 29, 2007.

The review panel of the European Medicines Agency has reassessed the risks of rimonabant based on the FDA decision. As a result, Acomplia may no longer be prescribed to depressed patients, and the simultaneous use of antidepressants is now considered a contraindication . Acomplia was approved in the EU in 2006 without a detailed examination of possible risks; these should be determined using a pharmacovigilance program.

On July 27, 2007, the BfArM announced a red-hand letter about the intended restriction of the use of rimonabant.

A renewed discussion of the benefit-risk ratio in the Committee for Medicinal Products for Human Use of the European Medicines Agency led in October 2008 to the recommendation to suspend the approval. The basis for the reassessment was data from new clinical studies and from pharmacovigilance, which, compared to the approval studies, on the one hand showed a significantly higher risk of serious psychiatric disorders, and on the other hand showed a lower efficacy than expected in routine use. This made the risk-benefit ratio unfavorable. The European Commission still has to make a binding decision on the recommendation of the CHMP; in the meantime, further prescriptions are not recommended. Sanofi-Aventis then withdrew the drug from the market.

literature

RIO studies:

• Lipids: New England Journal of Medicine. 353, 2005, pp. 2121-2134. PMID 16291982 .
• Europe: The Lancet. 365, 2005, pp. 1389-1397. PMID 15836887 .
• North America: JAMA. 295, 2006, pp. 761-775. PMID 16478899 .
• Diabetes: The Lancet. 368, 2006, pp. 1660-1672. PMID 17098084 .

rating

• Cochrane Review: Rimonabant for Overweight or Obesity. In: Cochrane Database Syst Rev. (4), Oct 18, 2006, p. CD006162. PMID 17054276 .
• Drug treatments for obesity: orlistat, sibutramine, and rimonabant. In: The Lancet. 369, 2007, pp. 71-77. PMID 17208644 .

Web links

• rating
• RIO study
• Mens Health - Opinion of US pharmacologist Piomelli
• Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Rimonabant

Individual evidence

1. ↑ CL Schaich, HA Shaltout, KB Brosnihan, AC Howlett, DI Diz: Acute and chronic systemic CB1 cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2) 27 rats. In: Physiological reports. Volume 2, number 8, August 2014, no. E12108, doi: 10.14814 / phy2.12108 . PMID 25168868 .
2. ↑ Takács-Novák, K .; Urac, M .; Horváth, P .; Völgyi, G .; Anderson, BD; Avdeef, A .: Equilibrium solubility measurement of compounds with low dissolution rate by Higuchi's Facilitated Dissolution Method. A validation study in Eur. J. Pharm. Sci. 106 (2017) 133-144, doi : 10.1016 / j.ejps.2017.05.064 .
3. ↑ There is not yet a harmonized classification for this substance . A label of [No public or meaningful name is available] in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 1, 2018, is derived from a self-classification by the distributor .
4. ↑ Questions and Answers on the Safety of ACOMPLIA (RIMONABANT) (PDF; 43 kB), July 19, 2007.
5. ↑ FX Pi-Sunyer, LJ Aronne, HM Heshmati, J. Devin, J. Rosenstock; RIO-North America Study Group: Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. In: JAMA. 295, 2006, pp. 761-775. PMID 16478899 .
6. ↑ The weight loss medication rimonabant can trigger suicidal ideation. ( Memento from February 26, 2009 in the Internet Archive ) In: Deutsches Ärzteblatt. online, June 12, 2007.
7. ↑ Deaths after taking rimonabant. ( Memento from December 18, 2015 in the Internet Archive ) In: Deutsches Ärzteblatt. online, June 4, 2008.
8. ↑ European Public Assessment Report (EPAR) - ACOMPLIA ( Memento of March 15, 2010 in the Internet Archive )
9. ↑ Documents of the FDA assessment process .
10. ↑ FDA: No approval for rimonabant in the USA. ( Memento from September 30, 2007 in the Internet Archive ) In: Deutsches Ärzteblatt. online, June 14, 2007.
11. ↑ Ben Hirschler: Sanofi pulls obesity drug application in US Reuters news service, June 29, 2007.
12. ↑ Acomplia®: EMEA wants to react to non-approval in the USA. ( Memento from September 30, 2007 in the Internet Archive ) In: Deutsches Ärzteblatt. online, June 15, 2007.
13. ↑ Slimming medication: contraindications, but not a ban on Acomplia®. ( Memento from September 30, 2007 in the Internet Archive ) In: Deutsches Ärzteblatt. online, July 20, 2007.
14. ↑  ( page no longer available , search in web archives ) EPAR, Scientific Discussion, pp. 36–37.
15. ↑ BfArM: Acomplia (Rimonabant): European Medicines Agency recommends restrictions on use ( Memento of December 30, 2013 in the web archive archive.today ).
16. ↑ Red Hand Brief: Increased frequency of reports of depression in patients treated with ACOMPLIA ^® . ( Memento of December 31, 2013 in the Internet Archive ) July 27, 2007 (PDF).
17. ↑  ( Page no longer available , search in web archives ) The European Medicines Agency recommends suspension of the marketing authorization of Acomplia - Press release of the European Medicines Agency recommending that the approval be suspended (PDF; 51 kB).
18. ^ Off for slimming products from Sanofi-Aventis. on: handelsblatt.com , October 23, 2008.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !