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Orlistat


General


Pronunciation

(OR li stat)


Brand Names: U.S.

  • Alli [OTC]
  • Xenical

Indications


Use: Labeled Indications

Obesity management:

OTC: For weight loss in overweight adults when used along with a reduced-calorie and low-fat diet.

Rx: For obesity management, including weight loss and weight maintenance, when used in conjunction with a reduced-calorie diet; to reduce the risk for weight regain after prior weight loss.

Limitations of use: Orlistat is indicated for obese patients with an initial body mass index of ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia).


Contraindications


Pregnancy; chronic malabsorption syndrome; cholestasis; hypersensitivity to orlistat or to any component of the formulation


Dosing and Administration


Dosing: Adult

Obesity management: Oral:

Xenical: 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.

Alli: OTC labeling: 60 mg 3 times daily with each main meal containing fat (maximum dose: 180 mg daily).

Dosing adjustment with concomitant therapy:

Cyclosporine: Administer cyclosporine 3 hours after orlistat.

Levothyroxine: Administer levothyroxine and orlistat at least 4 hours apart and monitor for changes in thyroid function.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Obesity management (Xenical): Children ≥12 years and Adolescents: Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied). However, dosage adjustment unlikely due to low systemic absorption.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied). However, dosage adjustment unlikely due to low systemic absorption.


Administration

Administer during or up to 1 hour after each main meal containing fat; separate dose by at least 2 hours from multivitamin daily supplement. Omit dose if a meal is missed or contains no fat.


Dietary Considerations

Multivitamin supplements that contain fat-soluble vitamins should be taken once daily at least 2 hours before or after the administration of orlistat (ie, bedtime). Gastrointestinal effects of orlistat may increase if taken with any one meal very high in fat. Distribute daily intake of carbohydrates, fat (~30% of daily calories), and protein over three main meals.


Storage

Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Alli: 60 mg [contains fd&c blue #2 (indigotine)]

Xenical: 120 mg [contains fd&c blue #2 (indigotine)]


Drug Interactions

Amiodarone: Orlistat may decrease the serum concentration of Amiodarone. Monitor therapy

Anticonvulsants: Orlistat may decrease the serum concentration of Anticonvulsants. Exceptions: Fosphenytoin; PENTobarbital; Thiopental. Monitor therapy

CycloSPORINE (Systemic): Orlistat may decrease the serum concentration of CycloSPORINE (Systemic). Management: Administer orlistat at least 3 hours before or after oral cyclosporine. Monitor for decreased serum concentrations of oral cyclosporine, even with the recommended dose separation. Consider therapy modification

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. Consider therapy modification

Multivitamins/Fluoride (with ADE): Orlistat may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Specifically, orlistat may impair absorption of fat-solube vitamins. Management: Administer oral fat soluble vitamins (such as vitamins A, D, E, and/or K that are contained in many multivitamin products) at least 2 hours before or after the administration of orlistat. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): Orlistat may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, orlistat may impair the absorption of fat-soluble vitamins. Management: Administer oral fat soluble vitamins (such as vitamins A, D, E, and/or K that are contained in many multivitamin products) at least 2 hours before or after the administration of orlistat. Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): Orlistat may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, orlistat may impair absorption of fat-solube vitamins. Management: Administer oral fat soluble vitamins (such as vitamins A, D, E, and/or K that are contained in many multivitamin products) at least 2 hours before or after the administration of orlistat. Consider therapy modification

Paricalcitol: Orlistat may decrease the serum concentration of Paricalcitol. Management: Monitor clinical response to paricalcitol closely when used with orlistat. When this combination must be used, consider administering paricalcitol at least 2 hours before or after the administration of orlistat. Consider therapy modification

Propafenone: Orlistat may decrease the serum concentration of Propafenone. Monitor therapy

Vitamin D Analogs: Orlistat may decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Exceptions: Calcipotriene. Consider therapy modification

Vitamins (Fat Soluble): Orlistat may decrease the serum concentration of Vitamins (Fat Soluble). Management: Administer oral fat soluble vitamins at least 2 hours before or after the administration of orlistat. Similar precautions do not apply to parenterally administered fat soluble vitamins. Exceptions: Calcipotriene. Consider therapy modification

Warfarin: Orlistat may enhance the anticoagulant effect of Warfarin. Monitor therapy


Monitoring Parameters

BMI; diet (calorie and fat intake); serum glucose in patients with diabetes; thyroid function in patient with thyroid disease; liver function tests in patients exhibiting symptoms of hepatic dysfunction


Adverse Reactions


The frequency of most adverse reactions (especially gastrointestinal effects) decreases over time. Frequency not always defined.

Cardiovascular: Pedal edema ( ≤3%)

Central nervous system: Headache ( ≤31%), fatigue (3% to 7%), anxiety (3% to 5%), sleep disorder ( ≤4%)

Dermatologic: Xeroderma ( ≤2%)

Endocrine & metabolic: Menstrual disease ( ≤10%), hypoglycemia (in patients with diabetes)

Gastrointestinal: Oily rectal leakage (4% to 27%), abdominal distress ( ≤26%), abdominal pain ( ≤26%), flatulence with discharge (2% to 24%), bowel urgency (3% to 22%), steatorrhea (6% to 20%), oily evacuation (2% to 12%), frequent bowel movements (3% to 11%), nausea (4% to 8%), fecal incontinence (2% to 8%), infectious diarrhea ( ≤5%), rectal pain (3% to 5%), gingival disease (4%), cholelithiasis (3%), abdominal distension (in patients with diabetes)

Genitourinary: Urinary tract infection (6% to 8%), vaginitis (3%)

Infection: Influenza ( ≤40%)

Neuromuscular & skeletal: Back pain ( ≤14%), leg pain ( ≤11%), myalgia ( ≤4%)

Otic: Otitis (4%)

Respiratory: Upper respiratory tract infection (38%), lower respiratory tract infection ( ≤8%)

<1% (Limited to important or life-threatening): Acute renal failure, bullous skin disease, calcium oxalate nephrolithiasis, hepatic failure, hepatitis, hypersensitivity, hypersensitivity angiitis, increased serum alkaline phosphatase, increased serum transaminases, kidney injury (acute), pancreatitis, renal disease (secondary to increased urinary oxalate excretion)


Warnings/Precautions


Concerns related to adverse effects:

- Cholelithiasis: Substantial weight loss may increase the risk of cholelithiasis.

- Hepatotoxicity: Cases of severe liver injury (some fatal) with hepatocellular necrosis or acute hepatic failure have been reported; liver transplantation has been required in some patients. Patients should be instructed to report any symptoms of hepatic dysfunction (eg, anorexia, pruritus, jaundice, dark urine, light colored stools, right upper quadrant pain); discontinue therapy and obtain liver function test immediately if symptoms occur.

- Increased urinary oxalate: Increased levels of urinary oxalate following treatment may occur in some patients; cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure have been reported. Monitor renal function in patients at risk for renal impairment; use with caution in patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis.

Disease-related concerns:

- Diabetes: Monitor patients with diabetes closely; weight loss may affect glycemic control. Dosage adjustments of antidiabetic medications may be necessary.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Pediatric: When used in adolescents, weight related to growth is accounted for in BMI, therefore, reduction in BMI is a better indicator of weight loss.

Other warnings/precautions:

- Appropriate use: Prior to use, other causes for obesity (eg, hypothyroidism) should be ruled out. According to Endocrine Society practice guidelines, weight loss medication should be discontinued and alternative treatment considered if weight loss is <5% of body weight at 3 months or if safety/tolerability issues arise (Apovian, 2015).

- Dietary guidelines: Patients should be advised to adhere to dietary guidelines; if taken with a diet high in fat (>30% total daily calories from fat), gastrointestinal adverse events may increase. Distribute daily fat intake over 3 main meals. If taken with any 1 meal very high in fat, the possibility of gastrointestinal effects increases. Counsel patients to take a multivitamin supplement that contains fat-soluble vitamins ≥2 hours before or after orlistat administration to ensure adequate nutrition; orlistat has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene.

- Potential for misuse: The potential exists for misuse in inappropriate patient populations (eg, patients with anorexia nervosa or bulimia) similar to any weight loss agent.

- Self-medication (OTC use): Prior to use, patients should contact their healthcare provider if they have ever had kidney stones, gall bladder disease, or pancreatitis. Patients taking medications for diabetes or thyroid disease, seizures, anticoagulants, or other weight-loss products should consult their healthcare provider or pharmacist before use. Patients who have had an organ transplant should not use orlistat. If severe and/or continuous abdominal pain, itching, yellowing of the eyes or skin, dark urine, loss of appetite occurs, or seizures worsen, use should be discontinued and healthcare provider consulted.


Pregnancy Risk Factor

X


Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Although orlistat is minimally absorbed, weight-loss therapy is not recommended for pregnant women. Obese and overweight women should be encouraged to participate in weight reduction programs prior to attempting pregnancy; weight gain during pregnancy should be determined by their prepregnancy BMI and current guidelines (ADA, 2009; IOM, 2009). Use of orlistat is contraindicated in pregnant women.


Actions


Pharmacology

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


Absorption

Minimal


Metabolism

Metabolized within the gastrointestinal wall; forms inactive metabolites


Excretion

Feces (~97%, 83% as unchanged drug); urine (<2%)


Onset of Action

24-48 hours


Time to Peak

Serum: ~8 hours


Duration of Action

48-72 hours


Half-Life Elimination

1-2 hours


Protein Binding

>99% (lipoproteins and albumin)


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache, diarrhea, fecal incontinence, or flatulence with discharge. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), black, tarry, or bloody stools; painful urination; hematuria; polyuria; severe back pain; severe groin or thigh pain; swelling of arms or legs; severe nausea; severe vomiting; or severe abdominal pain (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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