Products and withdrawal from the market
Sibutramine was approved in 1999 and was commercially available in many countries in 10- and 15-mg capsule form (Reductil, Abbott AG). On March 29, 2010, Abbott AG, in consultation with Swissmedic, informed the public that the marketing authorization had been suspended. Since then, sibutramine may no longer be prescribed or dispensed in many countries. In the past, other appetite suppressants with a phenylethylamine structure, such as amphetamine, phenylpropanolamine and phentermine, have been withdrawn from the market due to cardiovascular risks. The cannabinoid receptor antagonist rimonabant has been off the market since 2008. In the EU, on January 21, 2010, the CHMP of the European Medicines Agency (EMA) recommended that marketing authorizations for sibutramine be withdrawn throughout Europe. The drug should no longer be prescribed and dispensed. The CHMP based its decision on results of the large safety study SCOUT (Sibutramine Cardiovascular Outcome Trial) and concluded that the benefits of the treatment did not outweigh the cardiovascular risks. Moderate weight loss was simultaneously found to increase the risk of serious non-fatal cardiovascular events such as myocardial infarction and stroke. However, this was also against the background that the drug was not used according to the precautions in the expert information (!)
Structure and Properties
Sibutramine (C17H26ClN, Mr = 279.8 g/mol) is a tertiary amine and is present in drugs as sibutramine hydrochloride, as monohydrate and racemate. It has a phenylethylamine structure like the older appetite suppressants, all of which are no longer commercially available (see above). The ADHD drug methylphenidate also has a structural similarity to sibutramine.
Effects
Sibutramine (ATC A08AA10) is appetite suppressant and increases the feeling of fullness. The effects are due to reuptake inhibition of the neurotransmitters norepinephrine and serotonin and, to a lesser extent, dopamine (Figure 1). They are mediated predominantly by the two amine metabolites formed via CYP3A4. Whether the increase in thermogenesis is involved in the effect is debated but controversial. Sibutramine belongs to the selective serotonin and norepinephrine reuptake inhibitor (SSNRI) group and was originally developed as an antidepressant but has not been studied or approved as such. The SSNRIs venlafaxine and duloxetine are marketed as antidepressants and also have appetite suppressant effects.
Indications
Dietary supportive treatment of obesity in patients BMI of at least 30 kg/m² (obesity) who have had an inadequate response to appropriate weight-reducing measures alone.
Abuse
Sibutramine is included in the doping list as a stimulant.
Dosage
Sibutramine is taken in the morning with or without food and with sufficient fluid. Unless a weight loss of at least 5% has been achieved within 3 months, therapy should be discontinued.
Contraindications and interactions
Sibutramine is contraindicated in numerous conditions and diseases, for example, in children and adolescents <18, mental illness, previous and existing cardiovascular disease, severe renal and hepatic dysfunction, hyperthyroidism, narrow-angle glaucoma, pregnancy, and lactation. Drug-drug interactions are possible with numerous active ingredients. Refer to the drug information leaflet for details.
Adverse effects
Common possible adverse effects include constipation, loss of appetite, dry mouth, insomnia, headache, tachycardia, palpitations, increase in blood pressure, arterial hypertension, vasodilatation, flushing, nausea, increased appetite, increase in hemorrhoidal symptoms, dyspepsia, drowsiness, nervousness, paresthesias, anxiety, drowsiness, taste disturbances, sweating, and skin rash. Others according to the professional information.
