Drug Information

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:

Exogenous obesity

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.

Sibutramine @ Anorexiants- (Sep 2007)

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Interaction with Food

Pregnancy and lactation