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Sibutramine
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DRUG INFO
Sibutramine
Drug Name:
Sibutramine
Indication: For the treatment of obesity
Pharmacology: 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.
Mechanism Of Action: Sibutramine produces its therapeutic effects by norepinephrine (NE), serotonin reuptake (5-hydroxytryptamine, 5-HT) and dopamine reuptake inhibition. Sibutramine and its major pharmacologically active metabolites (M1 and M2) do not act via release of monoamines.
Drug Category: Appetite Depressants; Antidepressants; Anorexigenic Agents; Stimulants; ATC:A08AA10
Brand Names/Synonyms: Reductil; Medaria; Sibutraminum [Latin]; Sibutramina [Spanish]; Cyclobutanemethanamine, 1-(4-chlorophenyl)-N,N-dimethyl-alpha-(2-methylpropyl)-; Meridia; Medaria
Dosage Forms: CAPSULE
Absorption: Rapid absorption following oral administration. Absolute bioavailability is not know, but at least 77% of a single oral dose of sibutramine is absorbed.
Interactions: Interactions for Sibutramine:
CNS Active Drugs
The use of Sibutramine in combination with other CNS-active drugs, particularly serotonergic agents, has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of Sibutramine with other centrally-acting drugs is indicated.
In patients receiving monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, selegiline) in combination with serotonergic agents (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine), there have been reports of serious, sometimes fatal, reactions ("serotonin syndrome;" see below). Because Sibutramine inhibits serotonin reuptake, Sibutramine should not be used concomitantly with a MAOI. At least 2 weeks should elapse between discontinuation of a MAOI and initiation of treatment with Sibutramine. Similarly, at least 2 weeks should elapse between discontinuation of Sibutramine and initiation of treatment with a MAOI.
The rare, but serious, constellation of symptoms termed "serotonin syndrome" has also been reported with the concomitant use of selective serotonin reuptake inhibitors and agents for migraine therapy, such as Imitrex (sumatriptan succinate) and dihydroergotamine, certain opioids, such as dextromethorphan, meperidine, pentazocine and fentanyl, lithium, or tryptophan. Serotonin syndrome has also been reported with the concomitant use of two serotonin reuptake inhibitors. The syndrome requires immediate medical attention and may include one or more of the following symptoms: excitement, hypomania, restlessness, loss of consciousness, confusion, disorientation, anxiety, agitation, motor weakness, myoclonus, tremor, hemiballismus, hyperreflexia, ataxia, dysarthria, incoordination, hyperthermia, shivering, pupillary dilation, diaphoresis, emesis, and tachycardia.
Because Sibutramine inhibits serotonin reuptake, in general, it should not be administered with other serotonergic agents such as those listed above. However, if such a combination is clinically indicated, appropriate observation of the patient is warranted.
Drugs That May Raise Blood Pressure and/or Heart Rate: Concomitant use of Sibutramine and other agents that may raise blood pressure or heart rate have not been evaluated. These include certain decongestants, cough, cold, and allergy medications that contain agents such as ephedrine, or pseudoephedrine. Caution should be used when prescribing Sibutramine to patients who use these medications.
Drugs That Inhibit Cytochrome P450(3A4) Metabolism: In vitro studies indicated that the cytochrome P450(3A4)-mediated metabolism of sibutramine was inhibited by ketoconazole and to a lesser extent by erythromycin. Clinical interaction trials were conducted on these substrates. The potential for such interactions is described below.
Ketoconazole: Concomitant administration of 200 mg doses of ketoconazole twice daily and 20 mg sibutramine once daily for 7 days in 12 uncomplicated obese subjects resulted in moderate increases in AUC and Cmax of 58% and 36% for M1 and of 20% and 19% for M2, respectively.
Erythromycin: The steady-state pharmacokinetics of sibutramine and metabolites M1 and M2 were evaluated in 12 uncomplicated obese subjects following concomitant administration of 500 mg of erythromycin three times daily and 20 mg of sibutramine once daily for 7 days. Concomitant erythromycin resulted in small increases in the AUC (less than 14%) for M1 and M2. A small reduction in Cmax for M1 (11%) and a slight increase in Cmax for M2 (10%) were observed.
Cimetidine: Concomitant administration of cimetidine 400 mg twice daily and sibutramine 15 mg once daily for 7 days in 12 volunteers resulted in small increases in combined (M1 and M2) plasma Cmax (3.4%) and AUC (7.3%); these differences are unlikely to be of clinical significance.
Alcohol: In a double-blind, placebo-controlled, crossover study in 19 volunteers, administration of a single dose of ethanol (0.5 mL/kg) together with 20 mg of sibutramine resulted in no psychomotor interactions of clinical significance between alcohol and sibutramine. However, the concomitant use of Sibutramine and excess alcohol is not recommended.
Oral Contraceptives: The suppression of ovulation by oral contraceptives was not inhibited by Sibutramine. In a crossover study, 12 healthy female volunteers on oral steroid contraceptives received placebo in one period and 15 mg sibutramine in another period over the course of 8 weeks. No clinically significant systemic interaction was observed; therefore, no requirement for alternative contraceptive precautions are needed when patients taking oral contraceptives are concurrently prescribed sibutramine.
Drugs Highly Bound to Plasma Proteins: Although sibutramine and its active metabolites M1 and M2 are extensively bound to plasma proteins (94%), the low therapeutic concentrations and basic characteristics of these compounds make them unlikely to result in clinically significant protein binding interactions with other highly protein bound drugs such as warfarin and phenytoin. In vitro protein binding interaction studies have not been conducted.
Chemical IUPAC Name: 1-[1-(4-chlorophenyl)cyclobutyl]-N,N,3-trimethyl-butan-1-amine
Chemical Formula: C17H26ClN
Half Life: 1.1 hours
Drug Type: Approved Drug
# Accession No: APRD00456
CAS Registry Number: 106650-56-0
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Sibutramine News
(When available)
Publication of the evaluation report of the MEDA II programme Jan 11, 2006
EurofundingMag, This mid-term evaluation report of the MEDA II programme presents the results of an assignment conducted for the Commission by a team of experts. ...
19 army personnel awarded Sena medal Jan 15, 2006
Chennai Online, The other awardees of the Sena meda included Maj Neeraj Shukla of 9 JK Rifles, Capt Inderpreet Dhillon of Army Service Corps (both for the second time), Col ...
WEEKLY PLANNER Jan 15, 2006
Pioneer Press, ...$15 includes a boxed lunch and materials. Tim Wagner, 612-259-6576 or twagner@meda.net. Minnesota Concrete and Masonry Contractors Association. ...
Otsego County Economic Alliance: Ratcliffe honored by Economic ... Dec 19, 2005
Gaylord Herald Times, ...executive director of the Otsego County Economic Alliance, has been is the recipient of the Michigan Economic Developers Association (MEDA) President's Award. ...
Feed, seed store adpats to the changing times Jan 9, 2006
Hilton Head Island Packet, Smith's father, Edward Frampton Smith, was a railroad agent and owner of Lobeco Mercantile Company, along with Smith's mother, Meda. ...
Lecture looks at children, depression Jan 9, 2006
Corvallis Gazette Times, ...joined the Corvallis Clinic, where he worked for 27 years before retirement in 1994. He and his wife Meda still live in Corvallis.
The designer Ab Rogers lives in Wimbledon with his wife Sophie and ... Jan 10, 2006
Independent, She has bought me a designer chair each year, including an Alberto Meda chaise longue by Alias, and Martin Van Severen's chair for Vitra, both of which I adore ...
NEW ABRASION RESISTANT ELASTOMER SYSTEM Jan 11, 2006
dBusinessNews Newark (press release), Phone:+44-207-039-0034 Fax: +44-207-060-0628 E-mail: eutech@masterbond.com Middle East Phone: 972-2-652-8384 Fax: 972-2-652-8402 E-mail: meda@masterbond.com ...
Erkesso continues good form in Addis Ababa Jan 1, 2006
International Association of Athletics Foundation, ...short race) Teyiba Erkesso, and Werkitu Ayana were impressive winners respectively of the men’s and women’s races at the 22nd MOHA Jan Meda Addis Ababa ...
Calls for proposals Dec 16, 2005
European Commission's Delegation to Israel, ...cultural cooperation. These actions will benefit from a financial assistance from the MEDA programme of the European Communities. The ...
Integrated multimodal Euro-Mediterranean transport network to be ... Dec 24, 2005
Arabic News ...through the Euro-Mediterranean Transport Forum and its working groups, and the launching of several projects in the framework of the MEDA programme, notably ...
WEEKLY PLANNER Jan 8, 2006
Pioneer Press, Cloud. $25 per training session. Registration required, limited space. 1-320-202-6496 or cnebel@meda.net. North Central Business Travel Association. ...
Lil Kim Shows Hip Hop Love With Toy Giveaway Dec 19, 2005
Rap News Network ...be entertainment industry insider, Charles “Charlie Mack� Alston, Hillary Weston Manager for Lil’ Kim, Eddie Magic, 100.3 The Beat, Meda Judah, Fight for ...
Lil Kim Gives Back from Prison Dec 20, 2005
HipHopDX ...will be on hand including Charles “Charlie Mack� Alston, Hillary Weston Manager for Lil’ Kim, Eddie Magic, 100.3 The Beat, Meda Judah, Fight for Life ...
The Times' Joy Fund Dec 18, 2005
Shreveport Times, In memory of James Turner Harris, Henry F. Turner, Frank Bruner and Janilu Bruner, from Meda Bruner, $100. In memory of Jack Stein and Aymi Stein, $100. ...
Dec. 20, 2005 Joy Fund Dec 20, 2005
Shreveport Times, ...family, $100. In memory of James Turner Harris, Henry F. Turner, Frank Bruner and Janielu Bruner, from Meda W. Bruner, $100. In ...
Commissioner Dimas convenes high-level meeting to clean up the ... Dec 16, 2005
EurofundingMag, ...the EU has devoted €577 million to environmental cooperation with Mediterranean partner countries in the period 1995 to 2006 under the MEDA programme, the EU ...
Lil Kim Holiday Giveaway in Philly Dec 21, 2005
NobodySmiling.com, Event coordinators include Charles “Charlie Mack� Alston, Lil Kim’s manager Hillary Weston, Eddie Magic, Meda Judah, Fight for Life' Foundation, Mothers ...
Web Ghana Music.com Dec 15, 2005
Ghana Music.com, Other songs on the album are 'Meka Nea Waye', 'Meda Woase', 'Enye Menko', 'Mebisa Dee', 'Yesu Gye Me', 'Dware Me' and 'Awurade Kasa'. ...
'Culture Watch 05' Project Launched Dec 19, 2005
AllAfrica.com, He also said the ministry was ready to cooperate with the No.1 Traditional Cloth Producers Association of Shiro Meda, an association of weavers, to enable ...
THE WEEKEND ENTERTAINER Dec 24, 2005
Fort Worth Star Telegram, By MEDA KESSLER. Although you've had months to prepare for this weekend's big happenings, the arrival of the new year sort of sneaks up on us. ...
EU To Unveil Sweeping Advertising Changes Dec 13, 2005
AdWorld, The EU commissioner responsible for meda, Viviane Reding, says the new regulations will allow TV companies compete on a more equal footing in the evolving ...
Conroe ISD briefs Dec 15, 2005
Conroe Courier, The school would like to thank Edward Lopez, Zaida Meda, Denise Stanley, and Rod Chaves for putting this wonderful evening together. ...
Design Within Reach to Offer Le Corbusier Designs From Cassina Dec 12, 2005
Yahoo! News (press release) ...force. Cassina SpA, founded in 1927 in Meda, Italy is the manufacturer and distributor of modern classics and contemporary furniture. ...
Weight-loss drug isn't for everyone Jan 15, 2006
Miami Herald, Meridia, available by prescription, is intended for people who need to lose 30 or more pounds. It makes them feel full, a signal to stop eating. ...
Pills can help win weight-loss fight Jan 10, 2006
Contra Costa Times, Meridia, on the market since 1997, curbs appetite. Xenical has been around for six years. It contributes to weight loss by inhibiting fat absorption. ...
Arena shares gain from results of weight-loss drug Dec 15, 2005
San Diego Union Tribune, If approved, Arena's drug would face competition from existing medicines such as Roche's Xenical and Abbott Laboratories' Meridia, both of which have side ...
Appetite Suppressants, The Big Hope, The Big Letdown Jan 5, 2006
NewsBlaze (press release), ...stroke. Sibutramine (Meridia) was approved for weight- loss treatment in 1998, just in time to fill the void left by Fen-Phen. Not ...
Glaxo's Weight-Loss Wait Dec 15, 2005
Motley Fool ...had worldwide sales of $496.6 million -- a disappointing level for a veteran product with only one competitor, the appetite suppressant Meridia from Abbott ...
Consumer Reports Examines Weaknesses of Current Drug-safety System Dec 27, 2005
Kansas City infoZine, Mefloquine (Lariam) to prevent malaria; Rosuvastatin (Crestor) for high cholesterol; Salmeterol* (Serevent) for asthma; Sibutramine (Meridia) for weight loss ...
America's Weight Problem - Where Is The Pharmaceutical Industry? Dec 19, 2005
Medical News Today (press release), Meridia® (sibutramine hydrochloride monohydrate) from Knoll Pharmaceuticals, one of two weight loss Rx drugs that have been approved by the Food and Drug ...
Whiny Whistleblower of the Year Award Dec 30, 2005
American Council on Science and Health, ...bans. Graham has made a career out of calling for the banning of drugs, including Accutane, Arava, Meridia, Serevent, and Bextra. ...
Rimonabant adds appetizing choice to slim obesity market Dec 30, 2005
Nature.com (subscription), The drugs on the market—Abbott's Meridia (sibutramine, marketed as Reductil in Europe) and Roche's Xenical (orlistat)—offer ho-hum effectiveness and side ...
The Skinny on Obesity Drugs Dec 22, 2005
Motley Fool As a serotonin 5-HT2C receptor agonist, APD356 is attempting to suppress appetite by essentially the same means employed by Abbott Labs' Meridia and the ...
Gut Reaction Dec 14, 2005
Smartmoney.com Currently, there are only two obesity drugs on the market: Meridia by Abbott Laboratories (ABT) and Xenical by Switzerland's Roche. ...
Wear PJs to library for stories Dec 13, 2005
Daily News Journal (subscription), ...stops will include the Roscoe Brown parking lot, Kurcher Court, Tombee Court, Headwater Court, Berkshire subdivision's pool, Apostle Lane, Meridia Court and ...
Group blasts Taiwan's top shopping Web sites Dec 31, 2005
eTaiwan News, ...survey results. The top 10 news stories also included the online sales of counterfeit weight loss medication Reductil. According ...
Rimonabant adds appetizing choice to slim obesity market Dec 30, 2005
Nature.com (subscription), The drugs on the market—Abbott's Meridia (sibutramine, marketed as Reductil in Europe) and Roche's Xenical (orlistat)—offer ho-hum effectiveness and side ...
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