120 XENISTAT

  • Therapeutic Category
    • OTHER GASTROINTESTINAL DRUGS
    • GASTROINTESTINAL DRUGS
  • Pharmaceutical Form : Capsules
  • Composition : Orlistat 120 mg / Cap
  • Active Substance : Orlistat

Mechanism of Action:

Orlistat is a reversible inhibitor of gastrointestinal lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine residue site of gastric and pancreatic lipases. The inactivated enzymes are thus unavailable to hydrolyze dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides. As undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control.

Pharmacokinetic:

Absorption: plasma concentrations of intact orlistat were near the limits of detection (< 5 ng/mL), eight hours following oral administration of orlistat.

Distribution: it is > 99% bound to plasma proteins

Elimination: Approximately 97% of the administered dose was excreted in feces, 83% of that is found to be unchanged. The time to reach complete excretion (fecal plus urinary) was 3 to 5 days. The half-life of the absorbed orlistat is in the range of 1 to 2 hours.

INDICATIONS:

orlistat is indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet.

orlistat is also indicated to reduce the risk for weight regain after prior weight loss.

orlistat is indicated for obese patients with an initial body mass index (BMI) ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of other risk factors (e.g., hypertension, diabetes, dyslipidemia).

Contraindicated:

It is contraindicated in:

  • Pregnancy
  • Patients with chronic malabsorption syndrome
  • Patients with cholestasis
  • Patients with known hypersensitivity to orlistat or to any component of this product

Warning and precaution:

  • Decreased Vitamin Absorption: Patients should be strongly encouraged to take a multivitamin supplement that contains fat-soluble vitamins to ensure adequate nutrition because ORLISTAT has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene. In addition, the levels of vitamin D and beta-carotene may be low in obese patients compared with non-obese subjects. The supplement should be taken once a day at least 2 hours before or after the administration of ORLISTAT, such as at bedtime.
  • Weight-loss may affect glycemic control in patients with diabetes mellitus. A reduction in dose of oral hypoglycemic medication or insulin may be required in some patients.
  • Liver Injury: There have been rare postmarketing reports of severe liver injury with hepatocellular necrosis or acute hepatic failure in patients treated with ORLISTAT, with some of these cases resulting in liver transplant or death. Patients should be instructed to report any symptoms of hepatic dysfunction (anorexia,  pruritus,  jaundice, dark urine, light-colored stools or right upper quadrant pain) while taking ORLISTAT. When these symptoms occur, ORLISTAT and other suspect medications should be discontinued immediately and liver function tests and ALT and AST levels obtained.
  • Increases in Urinary Oxalate: Some patients may develop increased levels of urinary oxalate following treatment with ORLISTAT. Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure have been reported. Renal function should be monitored when prescribing ORLISTAT to patients at risk for renal impairment and use with caution in those with a history of hyperoxaluria or calcium oxalate nephrolithiasis.
  • Cholelithiasis: Substantial weight loss can increase the risk of cholelithiasis.
  • Gastrointestinal events may increase when ORLISTAT is taken with a diet high in fat (> 30% total daily calories from fat). The daily intake of fat should be distributed over three main meals.
  • Drug Abuse and Dependence: As with any weight-loss agent, the potential exists for abuse of orlistat in some patient populations (e.g., patients with anorexia nervosa or bulimia).

Pregnancy:

Pregnancy Category X

It is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus.

Nursing Mothers:

It is not known if ORLISTAT is present in human milk. Caution should be exercised when ORLISTAT is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness of ORLISTAT in pediatric patients below the age of 12 have not been established.

The safety and efficacy of ORLISTAT have been evaluated in obese adolescent patients aged 12 to 16 years

Geriatric Use:

Clinical studies of ORLISTAT did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients

SIDE EFFECTS:

Common with an incidence of ≥ 5%:

Oily Spotting, Flatus with Discharge, Fatty/Oily Stool, Fecal Urgency, Oily Evacuation, Increased Defecation, Fecal Incontinence

 GI adverse events may occur in some individuals over a period of 6 months or longer

Other Side effect with an incidence of ≥ 2%

Abdominal Pain/Discomfort, Nausea, Infectious Diarrhea, Rectal Pain/Discomfort, Tooth Disorder, Gingival Disorder, Vomiting, Influenza, Upper Respiratory Infection, Lower Respiratory Infection, Ear, Nose & Throat Symptoms, Back Pain, Lower Extremities Pain, Arthritis, Myalgia, Joint Disorder, Tendonitis, Headache, Dizziness, Fatigue, Sleep Disorder, Rash, Dry Skin, Menstrual Irregularity, Vaginitis, Urinary Tract Infection, Psychiatric Anxiety, Depression, Otitis, Pedal Edema

Drug interactions:

Cyclosporine: Data indicates a reduction in cyclosporine plasma levels when ORLISTAT was coadministered with cyclosporine. ORLISTAT and cyclosporine should not be simultaneously coadministered. Cyclosporine should be administered 3 hours after the administration of ORLISTAT.

Fat-soluble Vitamin Supplements: Data showed that the absorption of beta-carotene supplement is reduced when concomitantly administered with ORLISTAT. ORLISTAT inhibited absorption of a vitamin E acetate supplement.

Levothyroxine: Patients treated concomitantly with ORLISTAT and levothyroxine should be monitored for changes in thyroid function. Administer levothyroxine and ORLISTAT at least 4 hours apart.

Anticoagulants Including Warfarin: Vitamin K absorption may be decreased with ORLISTAT. Patients on chronic stable doses of warfarin or other anticoagulants who are prescribed ORLISTAT should be monitored closely for changes in coagulation parameters.

Amiodarone: A reduced therapeutic effect of amiodarone is possible where amiodarone is orally administered during orlistat treatment.

Antiepileptic Drugs: Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs. Patients should be monitored for possible changes in the frequency and/or severity of convulsions.

Antiretroviral Drugs: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs such as atazanavir, ritonavir, tenofovir, emtricitabine, and with the combinations lopinavir/ritonavir and emtricitabine/efavirenz/tenofovir. HIV RNA levels should be frequently monitored in patients who take ORLISTAT while being treated for HIV infection. If there is a confirmed increase in HIV viral load, ORLISTAT should be discontinued.

DOSAGE AND ADMINISTRATION:

  1. The recommended dose for orlistat 60 mg for overweight adults 18 years and older is 1 capsule with each meal containing fat and with doctor’s prescription.
  • Do not exceed 3 capsules daily.
  • Use with a reduced calorie, low fat diet to reach the weight loss goal.
  1. The recommended dose of ORLISTAT is one 120-mg three times a day with each main meal containing fat (during or up to 1 hour after the meal) and with doctor’s prescription.
  • The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat. The daily intake of fat, carbohydrate, and protein should be distributed over three main meals. If a meal is occasionally missed or contains no fat, the dose of ORLISTAT can be omitted.
  • Doses above 120 mg three times a day have not been shown to provide additional benefit.
  • Based on fecal fat measurements, the effect of ORLISTAT is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.

OVERDOSE:

If a significant overdose of ORLISTAT occurs, it is recommended that the patient be observed for 24 hours.

Storage conditions: store at (20-25) °c protect from light, moisture and heat.

 

How supplied: 20 capsules.