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  • CLASSES

    Peripherally-Acting Antiobesity Products

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Gastrointestinal lipase inhibitor for obesity; non-systemically blocks the dietary fat absorption; may interfere with fat-soluble vitamin absorption; associated with GI effects like fecal urgency; available as a 120 mg prescription product and a 60 mg OTC product.

    COMMON BRAND NAMES

    alli, Xenical

    HOW SUPPLIED

    alli/Xenical Oral Cap: 60mg, 120mg

    DOSAGE & INDICATIONS

    For the treatment of obesity (including weight loss and weight maintenance) in conjunction with a reduced-calorie diet and appropriate exercise.
    NOTE: Orlistat is indicated for obese patients with a BMI >= 30 kg/m2 or a BMI >= 27 kg/m2 in the presence of other risk factors (e.g., hypertension, diabetes mellitus, or dyslipidemia). The BMI is calculated by dividing weight in kilograms by height in meters squared. Conversion factors for calculation; weight in pounds (lbs.) divided by 2.2 = kilogram weight (kg); height in inches x 0.0254 = height in meters (m).
    NOTE: Because orlistat may reduce the absorption of fat-soluble vitamins A, D, E, K, and beta-carotene, it is recommended patients take a daily multivitamin containing these vitamins at least 2 hours before or after orlistat.
    Oral dosage (120 mg capsules, e.g., Xenical)
    Adults and Adolescents >= 12 years

    One capsule (120 mg) PO 3 times per day with each main meal containing fat, taken during the meal or up to 1 hour after the meal. Doses greater than recommended did not increase weight loss. The results of a 2-year, randomized, double-blind, placebo-controlled study from 18 US research centers indicate orlistat plus reduced-calorie diet significantly increased weight loss and lessened weight gain in obese adults with BMIs of 30—43 kg/m2. Fasting insulin and low-density lipoprotein cholesterol (LDL-C) serum levels were also significantly decreased in the orlistat group. Similar results were observed in European trials. Pooled data from clinical trials also indicate improvement in cardiovascular risk parameters in treated patients. Another multicenter clinical trial showed significant improvement in glycemic control for obese patients with type 2 diabetes treated with orlistat; statistically significant decreases in HbA1c, fasting blood glucose, and sulfonylurea dosage were reported. Results from a 4-year study that involved 3304 obese patients with normal or impaired glucose tolerance indicated a 37% relative risk reduction in the development of type 2 diabetes in patients with impaired glucose tolerance and treated with orlistat vs. placebo. The results are hypothesized to be due to the additional weight loss vs. any metabolic alteration due to orlistat. Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years. In a 21-day study in adolescents, orlistat reduced fat absorption by roughly 27%, but no significant changes were noted in the balance of calcium, phosphorus, magnesium, copper or zinc in the active vs. placebo groups. Iron balance was decreased similarly in both the orlistat and placebo groups.

    Oral dosage (non-prescription 60 mg capsules, e.g., Alli)
    Adults

    One capsule (60 mg) PO 3 times per day with each main meal containing fat, taken during the meal or up to 1 hour after the meal. Do not exceed 3 capsules daily.

    MAXIMUM DOSAGE

    Adults

    360 mg/day PO (Xenical, Rx-only), 180 mg/day PO (Alli, OTC use).

    Geriatric

    360 mg/day PO (Xenical, Rx-only), 180 mg/day PO (Alli, OTC use).

    Adolescents

    >= 12 years: 360 mg/day PO (Xenical, Rx-only); OTC use (i.e., Alli) not recommended.

    Children

    Safety and efficacy have not been established.

    Infants

    Not indicated.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Administer orally with each main meal containing fat; can be administered up to one hour after the meal. May omit dose when a meal is missed or the meal contains no fat.
    Orlistat may decrease the absorption of some fat-soluble vitamins (A, D, E, K) and beta-carotene. To ensure adequate nutrition, patients should take a multivitamin supplement that contains fat-soluble vitamins. The multivitamin supplement should be taken orally once per day at least two hours before or after the administration of orlistat (i.e. bedtime).
    Patients should be on a reduced-calorie diet with approximately 30% of the calories from fat. Protein, carbohydrate, and fat intake should be balanced over 3 main meals.

    STORAGE

    alli:
    - Avoid excessive humidity
    - Protect from light
    - Store below 86 degrees F
    - Store between 68 to 77 degrees F
    Xenical:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Orlistat should not be used in patients who have demonstrated a hypersensitivity reaction to any of the active or inactive ingredients. Rare cases of hypersensitivity reactions have been reported.

    Cholelithiasis, cholestasis, gallbladder disease

    Orlistat is contraindicated for use in individuals with cholestasis. Substantial weight loss can increase the risk of cholelithiasis or gallbladder disease. In a clinical trial of orlistat, 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. The long-term effects on gallstone formation have not been determined; orlistat use does not appear to influence gallbladder motility.

    Hepatic disease, hepatitis, hepatotoxicity

    Reports of hepatotoxicity and liver-related adverse events have occurred with the use of prescription and over-the-counter (OTC) orlistat, and the drug is not recommended for use in patients with known hepatic disease. After a comprehensive review of all clinical data for orlistat, the FDA approved a labeling update for both prescription and OTC orlistat indicating that severe liver injury has been rarely reported. The FDA found 13 total reports of severe liver injury with orlistat, although in some patients, the liver injury may have been due to other drugs or factors; 12 of the reports were post-marketing foreign reports with use of prescription orlistat and 1 was a US report with over-the-counter orlistat. Of the 13 cases, 2 patients died from hepatic failure and 3 patients required liver transplantation. It should be noted that a cause and effect relationship of severe liver injury with orlistat use has not yet been established. Weigh the benefits of weight loss with orlistat against the potential risks when determining if orlistat is appropriate for patients. Patients with hepatitis infection that is treated with antiretroviral drugs should not use orlistat. In addition to the potential for hepatic toxicity in patients with pre-existing liver disease, loss of virological control has been reported in non-hepatitis patients treated with antiretroviral drugs for human immunodeficiency virus and some of these same medications may be used for patients infected with hepatitis or with co-infection with hepatitis. Patients and consumers currently taking orlistat should continue to do so as directed by their prescribing health care professional and/or in accordance with product labeling. Nonetheless, health care professionals should advise patients to immediately report any symptoms possibly associated with liver injury or hepatic disease. Symptoms of liver-related injury may include weakness, fatigue, fever, jaundice, brown urine, abdominal pain, nausea/vomiting, light-colored stools, itching, and/or loss of appetite. When these symptoms occur, orlistat and other suspect medications should be discontinued immediately and liver function tests and ALT and AST levels obtained. Clinicians and consumers are encouraged to submit reports through the FDA’s Adverse Event Reporting System.

    Malabsorption syndrome

    Orlistat has been shown to decrease nutrient and vitamin absorption; therefore, orlistat is contraindicated for use in patients with chronic malabsorption syndrome. Because orlistat can interfere with the absorption of fat-soluble vitamins, all patients should take a daily multivitamin that contains vitamins A, D, E, K, and beta-carotene; the supplement should be taken at least 2 hours before or after orlistat (see Drug Interactions).

    Anorexia nervosa, bulimia nervosa, malnutrition

    Patients who are of normal weight, underweight, or who suffer from malnutrition should not use orlistat. Patients taking orlistat for weight loss should be strongly encouraged to take a daily 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. Educate treated patients on the importance of maintaining a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat. Generally, the daily intake of fat, carbohydrate, and protein should be distributed over 3 main meals. Patients with eating disorders, such as anorexia nervosa or bulimia nervosa are generally not good candidates for treatment with orlistat.

    Hypothyroidism

    Organic causes of obesity, such as hypothyroidism, should be ruled out prior to prescribing orlistat, and should be treated as per clinical standards of care. Patients treated for hypothyroidism should be aware that orlistat can inhibit the proper absorption of thyroid hormones such as levothyroxine, and doses should be separated to help limit interactions. Thyroid function should be monitored routinely in such patients to ensure euthyroidism is maintained as weight loss efforts are continued.

    Nephrolithiasis

    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 kidney stone-related renal impairment and use orlistat with caution in those patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis. Patients taking orlistat who present with urinary tract pain or with difficulty passing urine may need to be evaluated for the presence of kidney stones.

    Seizure disorder

    Use caution when orlistat is used in patients with a concurrent seizure disorder. During post marketing surveillance of orlistat therapy, seizures have been reported in patients treated concomitantly with orlistat and anticonvulsant drugs. Patients should be monitored for possible changes in the frequency and/or severity of convulsions.

    Human immunodeficiency virus (HIV) infection

    Patients with human immunodeficiency virus (HIV) infection should consult with their health care professional prior to non-prescription use of orlistat. Use prescription orlistat with caution in patients receiving antiretroviral therapy for human immunodeficiency virus (HIV) infection. Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs. The exact mechanism for this is unclear, but may include inhibition of systemic absorption of the antiretroviral drug. If orlistat use is prescribed, the patients HIV RNA levels should be frequently monitored. If there is a confirmed increase in HIV viral load, then orlistat should be discontinued.

    Organ transplant

    Patients who have undergone organ transplant must not take non-prescription orlistat, as use may cause interference with medications that prevent transplant rejection. Prescription use of orlistat should be carefully monitored in such patients. Data from an orlistat and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma concentrations when the drugs are coadministered. Dose of orlistat and cyclosporine must be separated to limit this interaction. More frequent monitoring of cyclosporine concentrations should be considered.

    Diabetes mellitus

    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. Patients with diabetes should be advised to continue to routinely monitor blood glucose and report any changes in blood glucose control to their healthcare provider.

    Anticoagulant therapy

    Nonprescription self-use of orlistat is not advised in patients receiving anticoagulant therapy with warfarin; patients are advised to discuss use and receive approval from their health care professionals prior to using orlistat for weight loss. Vitamin K absorption may be decreased with use of orlistat. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant therapy resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and warfarin. More frequent monitoring of the INR or other parameters may be needed in such patients.

    Pregnancy

    Orlistat is a FDA pregnancy risk category X drug and is therefore contraindicated in pregnancy. Because weight loss offers no potential benefit to a pregnant woman and this coupled with reduced absorption of fat-soluble vitamins (vitamins A, D, E, K) may result in fetal harm, orlistat should not be used in pregnancy. Patients who are pregnant should consult a qualified health care provider during pregnancy; patients should not self-treat with orlistat. 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. No data are available on the use of orlistat during human pregnancy; however, animal studies at doses up to 800 mg/kg/day of orlistat show no teratogenicity or embryotoxicity. In general weight loss during pregnancy would not be encouraged in most women, due to the need to provide appropriate nutrition to the developing fetus.

    Breast-feeding

    The minimal systemic bioavailability of orlistat suggests that the drug is not expressed in breast milk; however, it is not known, with certainty, if orlistat is secreted into human milk, or if the effects of orlistat on maternal availability of fat-soluble vitamins would affect breast milk quality. Overall, the drug characteristics suggest that is does not represent a significant risk to the infant and the benefits of breast-feeding outweigh any risk this drug might pose to the baby. Mothers who are breast-feeding should be encouraged to take proper vitamin supplementation as suggested by orlistat product labeling to avoid deficiencies of fat-soluble vitamins.

    Children

    The safety and efficacy of orlistat has not been evaluated in children less than 12 years of age. Because orlistat may reduce the absorption of certain nutrients, use in children under 12 years of age has not been advised. Use of orlistat in older children should be in conjunction with a healthcare professionals approval and prescription; nonprescription use is not advised. Monitor weight and growth, and, ensure the use of a properly selected multivitamin supplement daily. Use in children and adolescents 12 years and older is supported by studies in adults and additional data from a 54-week safety and efficacy study conducted in obese adolescents.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    vasculitis / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known

    Moderate

    fecal incontinence / Early / 1.8-7.7
    depression / Delayed / 3.4-3.4
    cholelithiasis / Delayed / 2.9-2.9
    edema / Delayed / 2.8-2.8
    vaginitis / Delayed / 2.6-2.6
    bullous rash / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    hypothyroidism / Delayed / Incidence not known

    Mild

    infection / Delayed / 46.0-46.0
    headache / Early / 31.0-31.0
    abdominal pain / Early / 25.5-25.5
    flatulence / Early / 4.4-23.9
    fecal urgency / Early / 2.8-22.1
    steatorrhea / Delayed / 6.0-20.0
    back pain / Delayed / 13.9-13.9
    increased defecation / Early / 2.6-10.8
    menstrual irregularity / Delayed / 9.8-9.8
    nausea / Early / 8.1-8.1
    fatigue / Early / 7.2-7.2
    diarrhea / Early / 5.3-5.3
    dizziness / Early / 5.2-5.2
    rash (unspecified) / Early / 4.3-4.3
    myalgia / Early / 4.2-4.2
    vomiting / Early / 3.1-3.1
    anxiety / Delayed / 2.8-2.8
    musculoskeletal pain / Early / Incidence not known
    hypovitaminosis / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    purpura / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    maculopapular rash / Early / Incidence not known

    DRUG INTERACTIONS

    Abacavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Abacavir; Dolutegravir; Lamivudine: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Abacavir; Lamivudine, 3TC: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Acitretin: (Moderate) Due the effect of orlistat on fat absorption and the lower serum levels of fat-soluble vitamins noted during clinical trials, the bioavailability of acitretin may be decreased. Close monitoring of patients receiving acitretin with orlistat is recommended.
    Albiglutide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Alogliptin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group.
    Alogliptin; Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group.
    Alogliptin; Pioglitazone: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group.
    Alpha-glucosidase Inhibitors: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients which may be additive to the effects of antidiabetic agents. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of antidiabetic agents with time. Both orlistat and the alpha-glucosidase inhibitors exert their effects locally in the intestine; it is not known if orlistat would interfere with the proper action of acarbose. An increase in gastrointestinal side effects with the concurrent use of orlistat and acarbose could potentially limit the use of these medications concurrently.
    Amiodarone: (Major) In one pharmacokinetic study of healthy volunteers, administration of orlistat 120 mg three times daily for 13 days and a single orlistat dose of 120 mg on the morning of Day 14 in addition to a single dose of 1200 mg amiodarone on Day 4 resulted in a 23% to 27% reduction in the systemic exposure to amiodarone and its metabolite desethylamiodarone. The effect of initiating treatment with orlistat in patients stable on amiodarone therapy has not been studied; however, a reduced therapeutic effect of amiodarone is possible. The clinical response to amiodarone should be monitored closely if orlistat is initiated during chronic amiodarone therapy.
    Amprenavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Anticonvulsants: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Apixaban: (Moderate) Patients on chronic stable doses of anticoagulants, like apixaban, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Aspirin, ASA; Pravastatin: (Moderate) Serum concentrations of pravastatin increased by approximately 30% when administered with orlistat in a parallel study of 24 normal-weight, mildly hypercholesterolemic subjects. Orlistat produced additive lipid-lowering effects when used concomittantly with pravastatin. However, another study failed to show any changes in pravastatin pharmacokinetics when coadministered with orlistat. Use caution and monitor patients carefully if using these drugs together.
    Atazanavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Atazanavir; Cobicistat: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Beta-Carotene: (Moderate) Due to orlistat's mechanism of action, the potential exists for the malabsorption of drugs and dietary supplements. Patients should be advised to take a multivitamin supplement once per day that contains fat soluble vitamins A, D, E, K and beta-carotene. The manufacturer recommends that fat-soluble vitamin supplements be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Bexarotene: (Moderate) Due the effect of orlistat on fat absorption and the lower serum levels of fat-soluble vitamins noted during clinical trials, the bioavailability of orally administered retinoids, such as bexarotene may also be decreased.
    Canagliflozin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Canagliflozin; Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Carbamazepine: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Cod Liver Oil: (Moderate) Due to orlistat's mechanism of action, the potential exists for the malabsorption of drugs and dietary supplements. Patients should be advised to take a multivitamin supplement once per day that contains fat soluble vitamins A, D, E, K and beta-carotene. The manufacturer recommends that fat-soluble vitamin supplements be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption. (Moderate) Orlistat can decrease the intestinal absorption of fat, including omega-3 fatty acids, and fat-soluble vitamins including vitamin A and vitamin D. If cod liver oil is used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Orlistat has been shown to inhibit the absorption of a vitamin E acetate supplement by 60%. Patients should be advised to take adaily multiple vitamin supplement that contains vitamin E while receiving orlistat.
    Cranberry, Vaccinium macrocarpon Ait.: (Moderate) Orlistat has been shown to inhibit the absorption of a vitamin E acetate supplement by 60%. Patients should be advised to take adaily multiple vitamin supplement that contains vitamin E while receiving orlistat.
    Cyclosporine: (Major) Orlistat decreases the absorption of fat by inhibiting gastrointestinal lipases and as cyclosporine is dependent on lipid absorption, especially the Sandimmune formulation, the absorption of cyclosporine is inhibited. Caution is advised with the concomitant use of orlistat and cyclosporine therapy. More frequent cyclosporine concentration monitoring may be needed. To reduce the chance of a drug-drug interaction, cyclosporine should be administered at least 2 hours before or after orlistat in patients taking both drugs; although, as noted, separation of administration times may not always alter the course of the interaction.
    Dabigatran: (Moderate) Patients on chronic stable doses of anticoagulants, like dabigatran, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Dalteparin: (Moderate) Patients on chronic stable doses of anticoagulants, like dalteparin, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Dapagliflozin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Dapagliflozin; Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Dapagliflozin; Saxagliptin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Darunavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Darunavir; Cobicistat: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Delavirdine: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Desiccated Thyroid: (Major) Patients treated with orlistat and thyroid hormones should be monitored for changes in thyroid function; orlistat may interfere with the absorption of thyroid hormones from the gastrointestinal tract. A recommendation regarding the separation of thyroid hormones and orlistat administration by at least 4 hours has not been made, but may be prudent.
    Didanosine, ddI: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Dulaglutide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Edoxaban: (Moderate) Patients on chronic stable doses of anticoagulants like edoxaban should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Efavirenz: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Efavirenz; Emtricitabine; Tenofovir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Empagliflozin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Empagliflozin; Linagliptin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, such as linagliptin. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Empagliflozin; Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Emtricitabine: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Emtricitabine; Tenofovir alafenamide: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Emtricitabine; Tenofovir disoproxil fumarate: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Enoxaparin: (Moderate) Patients on chronic stable doses of anticoagulants, like enoxaparin, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Entecavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Etravirine: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Exenatide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Orlistat has been shown to inhibit the absorption of a vitamin E acetate supplement by 60%. Patients should be advised to take adaily multiple vitamin supplement that contains vitamin E while receiving orlistat.
    Fondaparinux: (Moderate) Patients on chronic stable doses of anticoagulants, like fondaparinux, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Fosamprenavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Gabapentin: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Glimepiride; Pioglitazone: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Glimepiride; Rosiglitazone: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Glipizide; Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time.
    Glyburide; Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time.
    Heparin: (Moderate) Patients on chronic stable doses of anticoagulants, like heparin, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Incretin Mimetics: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Indinavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Insulin Degludec; Liraglutide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Insulin Glargine; Lixisenatide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Insulins: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Isotretinoin: (Moderate) The bioavailability of orally administered retinoids may be decreased during coadministration with isotretinoin. In patients receiving orally-administered retinoids along with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamin analogues be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Lacosamide: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Lamivudine, 3TC: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Lamivudine, 3TC; Zidovudine, ZDV: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Lamotrigine: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Levetiracetam: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Levothyroxine: (Major) Patients treated with orlistat and thyroid hormones should be monitored for changes in thyroid function; orlistat may interfere with the absorption of thyroid hormones from the gastrointestinal tract. A recommendation regarding the separation of thyroid hormones and orlistat administration by at least 4 hours has not been made, but may be prudent.
    Linagliptin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, such as linagliptin.
    Linagliptin; Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. A statistically significant number of obese, type 2 diabetics stabilized on sulfonylureas who received orlistat during a one-year double-blind, placebo-controlled study required a reduction in dose or discontinuation of drug therapy compared to the placebo group. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, such as linagliptin.
    Liothyronine: (Major) Patients treated with orlistat and thyroid hormones should be monitored for changes in thyroid function; orlistat may interfere with the absorption of thyroid hormones from the gastrointestinal tract. A recommendation regarding the separation of thyroid hormones and orlistat administration by at least 4 hours has not been made, but may be prudent.
    Liotrix: (Major) Patients treated with orlistat and thyroid hormones should be monitored for changes in thyroid function; orlistat may interfere with the absorption of thyroid hormones from the gastrointestinal tract. A recommendation regarding the separation of thyroid hormones and orlistat administration by at least 4 hours has not been made, but may be prudent.
    Liraglutide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Lixisenatide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Lopinavir; Ritonavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Lorcaserin: (Moderate) The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Co-use of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome.
    Metformin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time.
    Metformin; Pioglitazone: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Metformin; Repaglinide: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Metformin; Rosiglitazone: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Metformin; Saxagliptin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Metformin; Sitagliptin: (Moderate) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in obese diabetic patients, which may be additive to the effects of metformin. Lower blood glucose as a result of orlistat-induced changes in body composition may necessitate a dosage reduction of metformin with time. (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Nateglinide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Nelfinavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Nevirapine: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Non-nucleoside reverse transcriptase inhibitors: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Nucleoside reverse transcriptase inhibitors: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Oxcarbazepine: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Phentermine: (Moderate) The safety and efficacy of coadministration of phentermine with other products intended for weight loss has not been established.
    Phentermine; Topiramate: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated. (Moderate) The safety and efficacy of coadministration of phentermine with other products intended for weight loss has not been established.
    Phytonadione, Vitamin K1: (Moderate) Several drugs can interfere with the oral bioavailability of vitamin K including orlistat. In patients receiving orlistat routinely for a prolonged period of time (i.e., more than 2 weeks), vitamin K intake may need to be increased.
    Pioglitazone: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Pramlintide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Use orlistat with caution in patients taking pramlintide; patients should be advised to monitor blood glucose concentrations closely. A reduction in the dosage of pramlintide or other antidiabetic agents may be necessary to prevent hypoglycemia.
    Pravastatin: (Moderate) Serum concentrations of pravastatin increased by approximately 30% when administered with orlistat in a parallel study of 24 normal-weight, mildly hypercholesterolemic subjects. Orlistat produced additive lipid-lowering effects when used concomittantly with pravastatin. However, another study failed to show any changes in pravastatin pharmacokinetics when coadministered with orlistat. Use caution and monitor patients carefully if using these drugs together.
    Propafenone: (Major) Orlistat may limit the fraction of propafenone available for absorption. In post-marketing reports, abrupt cessation of orlistat in patients stabilized on propafenone therapy has resulted in severe adverse events including convulsions, AV block and acute circulatory failure.
    Protease inhibitors: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Repaglinide: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Ritonavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Rivaroxaban: (Moderate) Patients on chronic stable doses of anticoagulants like rivaroxaban should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Rosiglitazone: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Saquinavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Saxagliptin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Simvastatin; Sitagliptin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Sitagliptin: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Stavudine, d4T: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Sulfonylureas: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Telbivudine: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Tenofovir Alafenamide: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Tenofovir Alafenamide: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Tenofovir, PMPA: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Thyroid hormones: (Major) Patients treated with orlistat and thyroid hormones should be monitored for changes in thyroid function; orlistat may interfere with the absorption of thyroid hormones from the gastrointestinal tract. A recommendation regarding the separation of thyroid hormones and orlistat administration by at least 4 hours has not been made, but may be prudent.
    Tiagabine: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Tinzaparin: (Moderate) Patients on chronic stable doses of anticoagulants, like tinzaparin, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
    Tipranavir: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral protease inhibitors. Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Topiramate: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Tretinoin, ATRA: (Moderate) The bioavailability of orally administered retinoids may be decreased if coadministered with orlistat. In patients receiving orally-administered retinoids along with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamin analogues be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Valproic Acid, Divalproex Sodium: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Vigabatrin: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    Vitamin A: (Moderate) Due to orlistat's mechanism of action, the potential exists for the malabsorption of drugs and dietary supplements. Patients should be advised to take a multivitamin supplement once per day that contains fat soluble vitamins A, D, E, K and beta-carotene. The manufacturer recommends that fat-soluble vitamin supplements be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Vitamin D analogs: (Moderate) Orlistat reduced the absorption of fat-soluble vitamins absorption during clinical trials. The bioavailability of orally administered vitamin D analogs may also be decreased. In patients receiving orally-administered vitamin D analogs along with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamin analogs be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Vitamin D: (Moderate) Orlistat reduced the absorption of fat-soluble vitamins during clinical trials. The bioavailability of orally administered vitamin D may also be decreased. In patients receiving orally-administered vitamin D with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamins be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Vitamin E: (Moderate) Orlistat has been shown to inhibit the absorption of a vitamin E acetate supplement by 60%. Patients should be advised to take adaily multiple vitamin supplement that contains vitamin E while receiving orlistat.
    Vitamin E: (Moderate) Orlistat has been shown to inhibit the absorption of a vitamin E acetate supplement by 60%. Patients should be advised to take adaily multiple vitamin supplement that contains vitamin E while receiving orlistat.
    Warfarin: (Moderate) Warfarin therapy can be affected by changes in dietary intake of vitamin K. Reports of decreased prothrombin, increased INR and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants. Orlistat doses of 120 mg three times per day administered orally for 16 days in 12 normal-weight subjects did not appear to alter undercarboxylated osteocalcin, a marker of vitamin K nutritional status. No changes in the pharmacokinetics or pharmacodynamics (PT and serum Factor VII) of warfarin were noted following a single 30 mg dose of Coumadin in a placebo-controlled, randomized, third-party blind, two-way crossover study. However, vitamin K levels tended to decrease in patients taking orlistat. Since vitamin K1 (phytonadione, vitamin K1) absorption may be affected by orlistat, patients on chronic stable doses of warfarin should be monitored closely for changes in coagulation parameters when orlistat is prescribed; some experts recommend that the INR be monitored weekly during the first month of orlistat therapy.
    Zalcitabine, ddC: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Zidovudine, ZDV: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Zonisamide: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.

    PREGNANCY AND LACTATION

    Pregnancy

    Orlistat is a FDA pregnancy risk category X drug and is therefore contraindicated in pregnancy. Because weight loss offers no potential benefit to a pregnant woman and this coupled with reduced absorption of fat-soluble vitamins (vitamins A, D, E, K) may result in fetal harm, orlistat should not be used in pregnancy. Patients who are pregnant should consult a qualified health care provider during pregnancy; patients should not self-treat with orlistat. 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. No data are available on the use of orlistat during human pregnancy; however, animal studies at doses up to 800 mg/kg/day of orlistat show no teratogenicity or embryotoxicity. In general weight loss during pregnancy would not be encouraged in most women, due to the need to provide appropriate nutrition to the developing fetus.

    The minimal systemic bioavailability of orlistat suggests that the drug is not expressed in breast milk; however, it is not known, with certainty, if orlistat is secreted into human milk, or if the effects of orlistat on maternal availability of fat-soluble vitamins would affect breast milk quality. Overall, the drug characteristics suggest that is does not represent a significant risk to the infant and the benefits of breast-feeding outweigh any risk this drug might pose to the baby. Mothers who are breast-feeding should be encouraged to take proper vitamin supplementation as suggested by orlistat product labeling to avoid deficiencies of fat-soluble vitamins.

    MECHANISM OF ACTION

    Mechanism of Action: Orlistat produces weight loss through inhibition of nutrient absorption. A covalent bond is formed with the active serine residue site of gastric and pancreatic lipases within the lumen of the stomach and the small intestine. As these enzymes become unavailable to hydrolyze dietary triglycerides into free fatty acids and monoglycerides, less fat is absorbed by the body. This results in decreased caloric intake that may result in negative energy balance and weight loss. Therefore, systemic absorption of the drug is not needed to produce a weight-lowering effect. At the recommended therapeutic dose of 120 mg orlistat PO three times per day, dietary fat absorption is inhibited by approximately 30%.

    PHARMACOKINETICS

    Orlistat is administered orally and has minimal systemic absorption. Sporadic intact amounts of orlistat, low plasma concentration levels (<10 ng/ml), and no evidence of accumulation were observed during therapeutic studies. In vitro, orlistat was > 99% bound to plasma proteins (primarily lipoproteins and albumin) with minimal partitioning into erythrocytes. Metabolism of orlistat to weakly active and inactive metabolites is believed to occur mainly within the gastrointestinal wall. Approximately 83% of a single oral dose of orlistat was excreted unchanged in the feces. Renal excretion was < 2% of the dose. Complete excretion of both urinary and fecal orlistat was reached in 3 to 5 days. The estimated half-life of the absorbed portion of orlistat was approximately 1 to 2 hours.

    Oral Route

    Peak plasma concentrations of orlistat (<5 ng/ml) occurred approximately 8 hours after a 360 mg dose. Based on fecal fat measurements, the effect of orlistat may be seen within 24 to 48 hours.