Orlistat is a Lipase Inhibitor belonging to Drug for weight maintenance.

Orlistat is a reversible inhibitor of gastrointestinal lipases indicated for weight loss and weight maintenance.

Orlistat having a minimal absorption. Time to peak plasma concentration is approximately 8 hours. The onset and duration of action is about 24-48 hours and 48-72 hours respectively. Plasma protein binding of Orlistat is about >99% (mainly to lipoproteins and albumin). Metabolised within the gastrointestinal wall and forms inactive metabolites, M1 (primary metabolite, hydrolysed β-lactone ring product of orlistat) and M3 (secondary metabolite, sequential metabolite after M1’s cleavage of the N-formyl leucine side-chain). Excreted mainly via faeces (approx 97%, 83% as unchanged drug); via urine (<2%). The Elimination half-life is about 1-2 hours.

Orlistat shows side effects like Oily spotting on underwear or on clothing, gas with oily spotting, urgent need to have a bowel movement, loose stools, oily or fatty stools, increased number of bowel movements, difficulty controlling bowel movements, pain or discomfort in the rectum (bottom), stomach pain, irregular menstrual periods, headache, anxiety.

Orlistat is available in the form of Oral Capsule.

Orlistat is available in India, US, Canada, China, Singapore, Germany, Malaysia, France, Italy, Spain, and Australia.

Orlistat belongs to the Drug for weight maintenance acts as a Lipase Inhibitor.

Orlistat is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss.

The onset and duration of action of Orlistat is about 24-48 hours and 48-72 hours respectively.

The Tmax of Orlistat is approximately 8 hours.

Orlistat is available in the form of Oral Capsule.

Orlistat Capsule is taken orally, usually three times daily.

Orlistat is a medicine used to treat obesity, which is a medical problem involving an excessive amount of body fat. Being obese may increase your risk of developing other health problems, including diabetes and high blood pressure.

Orlistat is a Lipase Inhibitor belonging to Drug for weight maintenance.

Orlistat a reversible inhibitor of gastric and pancreatic lipases, thus inhibiting absorption of dietary fats by 30%.

Orlistat is approved for use in the following clinical indications

• Weight management, chronic in adults
• Obesity management in Pediatric

• Weight management, chronic (alternative agent)

Adult Oral Dose: 120 mg 3 times daily with each main meal containing fat (during or up to 1 hour after the meal); omit dose if meal is occasionally missed or contains no fat.

• Obesity management

Children ≥8 years to <12 years

Oral: 120 mg 3 to 4 times daily with each meal. Dosing based on a prospective, open-label study (n=11, age: 8.3 to 12.3 years) evaluating the efficacy of orlistat in obese prepubertal children defined as a BMI standard deviation score ≥4 standard deviations above normal and Tanner stage 1 to 2; median weight loss was 4 kg (range of weight change: –12.7 to +2.5 kg) and decreased fat intake was described.

Children ≥12 years and Adolescents:

Oral: 120 mg 3 times daily administered with each main meal containing fat (during or up to 1 hour after eating); omit dose if meal is occasionally missed or contains no fat.

Fat containing food should be avoided while taking orlistat.

Orlistat is contraindicated in patients with

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

• Drug Interactions And Decreased Vitamin Absorption

orlistat may interact with concomitant drugs including cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs, and antiretroviral drugs.

Data from a orlistat and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when orlistat was co-administered with cyclosporine. Therefore, orlistat and cyclosporine should not be simultaneously coadministered. To reduce the chance of a drug-drug interaction, cyclosporine should be taken at least 3 hours before or after orlistat in patients taking both drugs. In addition, in those patients whose cyclosporine levels are being measured, more frequent monitoring should be considered.

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 (e.g., sulfonylureas) or insulin may be required in some patients.

• Liver Injury

There have been rare post-marketing 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. Monitor renal function 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. In a clinical trial of orlistat for the prevention of type 2 diabetes, the rates of cholelithiasis as an adverse event were 2.9% (47/1649) for patients randomized to orlistat and 1.8% (30/1655) for patients randomized to placebo.

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

Orlistat is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. No embryotoxicity or teratogenicity was seen in animals that received orlistat at doses much higher than the recommended human dose. 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.

Fat containing food should be avoided while taking Orlistat.

Common

• Vitamin deficiency (including decreased carotene levels [beta-carotene: 2% to 6%], vitamin A deficiency, vitamin D deficiency, vitamin E deficiency, Abdominal distress, abdominal pain, bowel urgency, flatulence with discharge, frequent bowel movements, oily evacuation, oily rectal leakage, steatorrhea, Influenza , Headache , Back pain, lower extremity pain, Upper respiratory tract infection, Pedal edema , Xeroderma, Menstrual disease, Cholelithiasis, fecal incontinence, gingival disease, infectious diarrhea, nausea, rectal pain, Urinary tract infection, vaginitis , Anxiety, fatigue, sleep disorder, Myalgia, Lower respiratory tract infection.

Rare

• Hypertension, Bullous skin disease, Hyperoxaluria, Gastrointestinal hemorrhage (lower), pancreatitis (including acute pancreatitis), Crystalluria (calcium oxalate) Macrocytic anemia, thrombocytopenia, Hepatic failure, hepatic necrosis, hepatitis, increased serum alkaline phosphatase, increased serum transaminases, Anaphylaxis, angioedema, hypersensitivity angiitis, hypersensitivity reaction, Myopathy, Acute kidney injury, calcium oxalate nephrolithiasis, renal tubular necrosis.

Amiodarone

Orlistat may decrease the serum concentration of Amiodarone.

Antiretroviral Agents

Orlistat may decrease the serum concentration of Antiretroviral Agents.

Antiseizure Agents: Orlistat may decrease the serum concentration of Antiseizure Agents.

Cyclosporine (Systemic)

Orlistat may decrease the serum concentration of Cyclosporine (Systemic). Management: Administer oral cyclosporine 3 hours after orlistat. Monitor for decreased serum concentrations of oral cyclosporine, even with the recommended dose separation.

Levothyroxine

Orlistat may decrease the serum concentration of Levothyroxine. Management: Separate administration of oral levothyroxine and orlistat by a least 4 hours. Monitor patients closely for signs and symptoms of hypothyroidism.

Propafenone

Orlistat may decrease the absorption of Propafenone.

Sincalide

Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.

Triheptanoin

Orlistat may decrease serum concentrations of the active metabolite(s) of Triheptanoin.

Vitamin K Antagonists (eg, warfarin)

Orlistat may enhance the anticoagulant effect of Vitamin K Antagonists.

Vitamins (Fat Soluble)

Orlistat may decrease the absorption of Vitamins (Fat Soluble). Management: Administer oral fat-soluble vitamins at least 2 hours before or 2 hours after the administration of orlistat. Avoid concomitant administration due to the risk of impaired vitamin absorption.

The common side effects of Orlistat include the following

Common side effects

• Oily spotting on underwear or on clothing, gas with oily spotting, urgent need to have a bowel movement, loose stools, oily or fatty stools, increased number of bowel movements, difficulty controlling bowel movements, pain or discomfort in the rectum (bottom), stomach pain, irregular menstrual periods, headache, anxiety.

Rare side effects

• Hives, rash, itching, difficulty breathing or swallowing, severe or continuous stomach pain, excessive tiredness or weakness, nausea, vomiting, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, dark-colored urine, light-colored stools.

• Pregnancy

Pregnancy Category X

orlistat is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. No embryotoxicity or teratogenicity was seen in animals that received orlistat at doses much higher than the recommended human dose. 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 in pediatric patients below the age of 12 have not been established.

• 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.

Pharmacodynamic

Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes.

Pharmacokinetics

• Absorption

Orlistat having a minimal absorption. Time to peak plasma concentration is approximately 8 hours. The onset and duration of action is about 24-48 hours and 48-72 hours respectively.

• Distribution

Plasma protein binding of Orlistat is about >99% (mainly to lipoproteins and albumin).

• Metabolism and Excretion

Metabolized within the gastrointestinal wall and forms inactive metabolites, M1 (primary metabolite, hydrolyzed β-lactone ring product of orlistat) and M3 (secondary metabolite, sequential metabolite after M1’s cleavage of the N-formyl leucine side-chain). Excreted mainly via faeces (approx 97%, 83% as unchanged drug); via urine (<2%). The Elimination half-life is about 1-2 hours.

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