Drug Interaction:
Anorexiants include-
Phenetermine Hcl, Benzphentamine Hcl, phenetrazine Hcl, Phendimetrazine tartarate,
Diethylpropion Hcl, Mazindol, Fenfluramine, Sibutramine
Refer - Dexfenfluramine HCl
Interacting drugs- summary
+ Sibutramine
Alcohol
concomittant use of sibutramine and exces alcohol is not recommended
Cimetidine
coadmin. resulted in small increases in combined sibutramine metabolites
M1 and M2 plasma conc. Cmax 3.4% and AUC 7.3% , these differences
are unlikely to be of clinical significance
Erythromycin
comcomittant erythromycin resulted in small increases in sibutramine
metabolites AUC less than 14% for M1 and M2.
A small reduction in Cmax were observed
Ketoconazole
codmin. resulted in moderate increases in sibutramine
metabolites AUC and Cmax of 58% and 36% for M1 and of 20% and
19% for M2 respy.
Sibutramine +
Agents that raise blood pressure or increase heart rate eg. ephedrine,
pseudiephedrine other decongestant
these agents include decongestants, and cough and cold allergy products
that contain agents such as ephedrine or pseudoephedrine.
Use caution when using concurrently with subutramine
CNS active drugs
caution is adviced if coadmin. of sibutramine with other centrally acting
drugs is indicated
MAO inhibitors eg, phenelzine, selegiline
Sibutramine should not be used concomittantly with MAO inhibitors and
serotenergic drugs(selective serotonin reuptake inhibitors), since rare
serotonin syndrome is reported.
At least two weeks should elapse between discontinuation of MAO and
initiation of treatment with sibutramine.
Similarly, two weeks should elapse between discontinuation of subtramine
and MAO inhibitors.
Indication:
Anorexiants include- Phenetermine Hcl, Benzphentamine Hcl, phenetrazine Hcl, Phendimetrazine tartarate, Diethylpropion Hcl, Mazindol, Fenfluramine, Sibutramine
Refer - Dexfenfluramine HCl
LIST OF DRUGS DURING 2007
Sr.No- 133
Name of the Drug- R-Sibutramine Capsule
(2.5mg/5mg)
Pharmacological Classification- As an adjunct therapy for the management
of obesity including weight loss and
maintenence of weight loss in patients
whose BMI is 30kg/m2 or higher
Date of Approval- 26-09-07
Approved by U.S.FDA on 30-12-2007 (Ref- FDA approved List- 2007)
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
1.Sibutramine Hcl Anti-Obesity 23-12-1999
2.R-sibutramine capsule 26-09-2007
2.5mg/5mg
As an adjunctive therapy for the management of obesity including
weight loss and maintenance of weight loss in patients whose BMI
is 30kg/m2 or higher
Adverse Reaction:
Dry mouth, anorexia, insomnia, and constipation.
Convulsions in patients who have potentially
predisposing factors for seizures.
Ecchymosis/bleeding have been observed due to possible
effects on platelet function as a result of its effect on serotonin uptake.
Diarrhoea, flatulence, gastroenteritis, peripheral odema,
arthiritis, agitation, hypertonia, bronchitis,
pruritis and menstrual disorders.
Contra-Indications:
Hypersensitivity. Patients receiving MAO inhibitors. Patients taking other centrally acting appetite
supressants drugs. Anorexia nervosa.
Special Precautions:
Sibutramine substantially increases blood pressure in some patients.
Regular monitoring of blood pressure is required.
For patients who experience a sustained increase in blood pressure or pulse rate while receiving sibutramine, either dose reduction or discontinuation should be considered.
To be given with caution to patients with history of hypertension.
Sibutramine should not used in patients with history of coronary artery disease, congestive heart failure, arrhythmias, or stroke.
Use with caution in patients with narrow angle glaucoma.
Caution with patients with history of seizures
Not recommend for use during pregnancy
Not recommended for use in nursing mothers.
Safety in pediatric patients not established.
Dosages/ Overdosage Etc:
Dosage-
Recommended dose is 10mg once daily with or without food. If there is adequate weight loss, dose may be titrated after 4 weeks to a total of 15mg once daily. 5mg may given to patients who do not tolerate 10mg dose.
Patient Information:
Anorexiants include- Phenetermine Hcl, Benzphentamine Hcl, phenetrazine Hcl, Phendimetrazine tartarate, Diethylpropion Hcl, Mazindol, Fenfluramine, Sibutramine
Refer - Dexfenfluramine HCl
1.Regular monitoring of blood pressure.
2.Patients with narrow angle glaucoma
3.Patients with severe renal impairment
Pharmacology/ Pharmacokinetics:
Ref- Drug Facts And Comparisons (2010)
Pharmacology
Sibutramine is an orally administered centrally acting with apparently devoid of
amphetamine-like abuse potential. Its primary and secondary amine metabolites are
pharmacologically active and are thought to induce the natural processes leading to
enhancement of safety and thermogenesis by inhibiting serotonin(5-HT ) and noradrenaline reuptake.
Pharmacokinatics:
Sibutramine is rapidly absorbed from GIT following oral administration and undergoes first
pass metabolism in the liver. to form the pharmacologically active mono-and didesmethyl
metabolite M1 and M2. Peak plasma concenrations of M1 and M2 are reached within 3 to 4
hours.
On the basis of mass balance studies on average at least 77% of a single oral dose is
absorbed. The absolute bioavailabiliy of sibutaraine hs not been determined
Effect of food- administration of a single dose of sibutramine 20mg with a standard
breakfast resulted in reduced peak M1 and M2 concentration by 27% and 32% respy.
however the AUC area under the curve of M1 and M2 were not significantly altered.
Special Population Pharmacokinetic Parameters (15mg Dose)
Study Population Cmax Tmax AUC t 1/2
(ng/mL) (h) (ng*h/mL) (h)
Metabolite 1
Target population
Obese subjects
(n=18) 4 (42) 3.6(28) 25.5(63) -
3.2 to 4.8 3.1 to 4.1 18.1 to 32.9
Special population
Moderate hepatic 2.2(36) 3.3(33) 18.7 (65) -
function impairment 1.8 to 2.7 2.7 to 3.9 11.7 to 25.5
(n=12)
Metabolite 2
Target Population 6.4 (28) 3.5 (17) 92.1 (26) 17.2(58)
Obese subjects 5.6 to 7.2 3.2 to 3.8 81.2 to 103 12.5 to 21.8
(n=18)
Special population
Moderate hepatic 4.3(37) 3.8 (34) 90.5(27) 22.7 (30)
function impairment 3.5 to 5.2 3.1 to 4.5 76.9 to 104 18.9 to 26.5
Interaction with Food:
Not altered by the presence of food.
Pregnancy and lactation:
Pregnancy-
Use not recommended during pregnancy
Lactation-
Not recommended for use in nursing mothers.
Children-
Safety and efficacy in pediatric patients not established.
