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  • CLASSES

    Peripherally-Acting Antiobesity Products

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Gastrointestinal lipase inhibitor; non-systemically blocks dietary fat absorption; causes weight loss and limits weight regain; significant GI side effects
    By prescription, indicated for obese adults and adolescents 12 years and older with a BMI 30 kg/m2 or more OR those with a BMI of 27 kg/m2 or more with 1 or more obesity-related risk factors
    Non-prescription product used to help promote weight loss in overweight adults

    COMMON BRAND NAMES

    alli, Xenical

    HOW SUPPLIED

    alli/Orlistat/Xenical Oral Cap: 60mg, 120mg

    DOSAGE & INDICATIONS

    For the treatment of obesity to promote weight loss and assist with weight maintenance in conjunction with a reduced-calorie diet.
    Oral dosage (prescription-only product, 120-mg capsules, e.g., Xenical)
    Adults

    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. If a meal is occasionally missed or contains no fat, the dose of orlistat can be omitted. INTENDED USE: Indicated for obese patients with a BMI 30 kg/m2 or more OR those with a BMI of 27 kg/m2 or more in the presence of at least 1 obesity-related risk factor (e.g., hypertension, diabetes mellitus, or dyslipidemia). Orlistat, when used under optimal conditions at prescription doses, can reduce BMI and weight, and reduces the risk for weight regain in chronic use. 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. The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat. The daily intake of fat, carbohydrate, and protein should be distributed over 3 main meals.

    Children and Adolescents 12 years and older

    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. If a meal is occasionally missed or contains no fat, the dose of orlistat can be omitted. INTENDED USE: Indicated for obese patients with a BMI 30 kg/m2 or more OR those with a BMI of 27 kg/m2 or more in the presence of at least 1 obesity-related risk factor (e.g., hypertension, diabetes mellitus, or dyslipidemia). Orlistat, when used under optimal conditions at prescription doses, can reduce BMI and weight, and reduces the risk for weight regain in chronic use; however, in pediatric patients, adherence may be problematic. 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. The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat. The daily intake of fat, carbohydrate, and protein should be distributed over 3 main meals. 

    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. If a meal is occasionally missed or contains no fat, the dose of orlistat can be omitted. Max: 180 mg (3 capsules) daily. INTENDED USE: To help with weight loss in overweight adults. 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.

    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

    360 mg/day PO (e.g., Xenical, Rx-only); OTC use (e.g., Alli) not recommended.

    Children

    12 years: 360 mg/day PO (Xenical, Rx-only); OTC use (i.e., Alli) not recommended.
    1 to 11 years: Safety and efficacy have not been established.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed. During treatment, if signs or symptoms of liver injury occur, discontinue treatment. Some guidelines suggest avoidance of orlistat and other weight-loss medications in patients with severe hepatic disease.

    Renal Impairment

    No dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Administer with each main meal containing fat; can be administered up to 1 hour after the meal. 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.
    May omit a dose when a meal is missed or if a meal contains no fat.
    Orlistat decreases the absorption of some fat-soluble vitamins (A, D, E, K) and beta-carotene. To ensure adequate nutrition, patients should take a daily multivitamin supplement that contains these fat-soluble vitamins. Administer the multivitamin at least 2 hours before or after the administration of orlistat. For example, have the patient take the multivitamin once per day at bedtime unless otherwise directed by the prescriber.

    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

    There have been rare postmarketing reports of severe liver injury or hepatotoxicity with hepatocellular necrosis or acute hepatic failure in patients treated with orlistat by prescription or non-prescription, with some of these cases resulting in liver transplant or death. Some of these cases involved patients with other potential risks for liver injury. Patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, dark urine, light-colored stools, or right upper quadrant pain) while taking orlistat. When these symptoms occur, orlistat and other suspect medications should be discontinued immediately and liver function tests and ALT and AST levels obtained. While no dosage adjustments are necessary in patients with pre-existing hepatic impairment, some guidelines recommend avoidance of orlistat and other drugs for weight loss in patients with severe hepatic disease. Orlistat may be best avoided in patients with hepatitis treated with antiretroviral drugs. Loss of virological control has been reported in non-hepatitis patients treated with antiretroviral drugs for human immunodeficiency virus (HIV) and some of these same medications may be used for patients infected with hepatitis or with co-infection with hepatitis.

    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 contraindicated for use during pregnancy, because weight loss offers no potential benefit to a pregnant woman and weight loss, coupled with reduced absorption of fat-soluble vitamins (A,D,E, K) may result in fetal harm. A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy and the need to provide appropriate nutrition to the developing fetus. No embryotoxicity or teratogenicity was seen in animals that received orlistat at doses much higher than the recommended human dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus. Pregnant women must avoid nonprescription use of the drug.

    Breast-feeding

    Use caution in administering orlistat to a breast-feeding woman. 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.It is not known if orlistat's effects on maternal availability of fat-soluble vitamins would affect breast milk quality or quantity. Women 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. Overall, the drug characteristics suggest that is does not represent a significant risk to the infant.

    Children, infants

    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; do not give to infants. Use of orlistat in adolescents 12 years and older should be in conjunction with a healthcare professionals approval and prescription. Monitor weight and growth, and, ensure the use of a properly selected multivitamin supplement daily. Nonprescription use is not advised in pediatric patients less than 18 years of age as the nonprescription product has been approved for use in adults only for self-care.

    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 / 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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Alogliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Alogliptin; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Alogliptin; Pioglitazone: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Alpha-glucosidase Inhibitors: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    Bictegravir; 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.
    Canagliflozin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Canagliflozin; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Dapagliflozin; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Dapagliflozin; Saxagliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    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.
    Dipeptidyl Peptidase-4 Inhibitors: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Dulaglutide: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    Efavirenz; Lamivudine; 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 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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Empagliflozin; Linagliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Empagliflozin; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    Ertugliflozin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Ertugliflozin; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Ertugliflozin; Sitagliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Glimepiride; Rosiglitazone: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Glipizide; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Glyburide; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Insulin Glargine; Lixisenatide: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Insulins: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of insulins or other medicines for diabetes may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    Lamivudine; 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.
    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.
    Levothyroxine; Liothyronine (Porcine): (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.
    Levothyroxine; Liothyronine (Synthetic): (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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Linagliptin; Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    Liraglutide: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Lixisenatide: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    Meglitinides: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Metformin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Metformin; Pioglitazone: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Metformin; Repaglinide: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Metformin; Rosiglitazone: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Metformin; Saxagliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Metformin; Sitagliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Pramlintide: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of pramlintide or other medicines for diabetes may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Semaglutide: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    SGLT2 Inhibitors: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Simvastatin; Sitagliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    Sitagliptin: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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.
    Thiazolidinediones: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
    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. Since vitamin K 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. 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 120 mg PO 3 times per day administered orally for 16 days in 12 normal-weight subjects did not appear to alter 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 warfarin in a placebo-controlled, randomized, third-party blind, 2-way crossover study. However, vitamin K levels decreased.
    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 contraindicated for use during pregnancy, because weight loss offers no potential benefit to a pregnant woman and weight loss, coupled with reduced absorption of fat-soluble vitamins (A,D,E, K) may result in fetal harm. A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy and the need to provide appropriate nutrition to the developing fetus. No embryotoxicity or teratogenicity was seen in animals that received orlistat at doses much higher than the recommended human dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus. Pregnant women must avoid nonprescription use of the drug.

    Use caution in administering orlistat to a breast-feeding woman. 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.It is not known if orlistat's effects on maternal availability of fat-soluble vitamins would affect breast milk quality or quantity. Women 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. Overall, the drug characteristics suggest that is does not represent a significant risk to the infant.

    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%. 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 during therapy, with the multivitamin supplement taken at least 2 hours before or after the administration orlistat.

    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.