Xenical
Generic: ORLISTAT
Basic Information
Manufacturer
H2-Pharma LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
6240792b-9224-2d10-e053-2a91aa0a2c3e
Indications & Usage
1 INDICATIONS AND USAGE XENICAL is indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet.
XENICAL is also indicated to reduce the risk for weight regain after prior weight loss.
XENICAL is indicated for obese patients with an initial body mass index (BMI) ≥30 kg/m 2 or ≥27 kg/m 2 in the presence of other risk factors (e.g., hypertension, diabetes, dyslipidemia).
Table 1 illustrates body mass index (BMI) according to a variety of weights and heights.
The BMI is calculated by dividing weight in kilograms by height in meters squared.
For example, a person who weighs 180 lbs and is 5 ' 5 " would have a BMI of 30.
Table 1 Body Mass Index (BMI), kg/m 2 Conversion Factors: Weight in lbs ÷ 2.2 = weight in kilograms (kg) Height in inches × 0.0254 = height in meters (m) 1 foot = 12 inches XENICAL is a reversible inhibitor of gastrointestinal lipases indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet.
( 1 ) XENICAL is also indicated to reduce the risk for weight regain after prior weight loss.
( 1 ) Table 1
XENICAL is also indicated to reduce the risk for weight regain after prior weight loss.
XENICAL is indicated for obese patients with an initial body mass index (BMI) ≥30 kg/m 2 or ≥27 kg/m 2 in the presence of other risk factors (e.g., hypertension, diabetes, dyslipidemia).
Table 1 illustrates body mass index (BMI) according to a variety of weights and heights.
The BMI is calculated by dividing weight in kilograms by height in meters squared.
For example, a person who weighs 180 lbs and is 5 ' 5 " would have a BMI of 30.
Table 1 Body Mass Index (BMI), kg/m 2 Conversion Factors: Weight in lbs ÷ 2.2 = weight in kilograms (kg) Height in inches × 0.0254 = height in meters (m) 1 foot = 12 inches XENICAL is a reversible inhibitor of gastrointestinal lipases indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet.
( 1 ) XENICAL is also indicated to reduce the risk for weight regain after prior weight loss.
( 1 ) Table 1
Adverse Reactions
6 ADVERSE REACTIONS Most common treatment emergent adverse reactions (≥5% and at least twice that of placebo) include oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation and fecal incontinence.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact the Safety Call Center at 1-888-236-5445 or FDA at 1‑800‑FDA‑1088 (1-800-332-1088) or www.fda.gov/medwatch.
6.1 Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in patients.
Commonly Observed (based on first year and second year data) Gastrointestinal (GI) symptoms were the most commonly observed treatment-emergent adverse events associated with the use of XENICAL in the seven double-blind, placebo-controlled clinical trials and are primarily a manifestation of the mechanism of action.
(Commonly observed is defined as an incidence of ≥5% and an incidence in the XENICAL 120 mg group that is at least twice that of placebo.) Table 2 Commonly Observed Adverse Events Adverse Event Year 1 Year 2 XENICAL Treatment designates XENICAL three times a day plus diet or placebo plus diet % Patients (N=1913) Placebo % Patients (N=1466) XENICAL % Patients (N=613) Placebo % Patients (N=524) Oily Spotting Oily discharge may be clear or have a coloration such as orange or brown.
26.6 1.3 4.4 0.2 Flatus with Discharge 23.9 1.4 2.1 0.2 Fecal Urgency 22.1 6.7 2.8 1.7 Fatty/Oily Stool 20.0 2.9 5.5 0.6 Oily Evacuation 11.9 0.8 2.3 0.2 Increased Defecation 10.8 4.1 2.6 0.8 Fecal Incontinence 7.7 0.9 1.8 0.2 In general, the first occurrence of these events was within 3 months of starting therapy.
Overall, approximately 50% of all episodes of GI adverse events associated with XENICAL treatment lasted for less than 1 week, and a majority lasted for no more than 4 weeks.
However, GI adverse events may occur in some individuals over a period of 6 months or longer.
Discontinuation of Treatment In controlled clinical trials, 8.8% of patients treated with XENICAL discontinued treatment due to adverse events, compared with 5.0% of placebo-treated patients.
For XENICAL, the most common adverse events resulting in discontinuation of treatment were gastrointestinal.
Other Adverse Clinical Events The following table lists other treatment-emergent adverse events from seven multicenter, double-blind, placebo-controlled clinical trials that occurred at a frequency of ≥2% among patients treated with XENICAL 120 mg three times a day and with an incidence that was greater than placebo during year 1 and year 2, regardless of relationship to study medication.
Table 3 Other Treatment-Emergent Adverse Events From Seven Placebo-Controlled Clinical Trials Body System/Adverse Event Year 1 Year 2 XENICAL Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet % Patients (N=1913) Placebo % Patients (N=1466) XENICAL % Patients (N=613) Placebo % Patients (N=524) – None reported at a frequency ≥2% and greater than placebo Gastrointestinal System Abdominal Pain/Discomfort 25.5 21.4 – – Nausea 8.1 7.3 3.6 2.7 Infectious Diarrhea 5.3 4.4 – – Rectal Pain/Discomfort 5.2 4.0 3.3 1.9 Tooth Disorder 4.3 3.1 2.9 2.3 Gingival Disorder 4.1 2.9 2.0 1.5 Vomiting 3.8 3.5 – – Respiratory System Influenza 39.7 36.2 – – Upper Respiratory Infection 38.1 32.8 26.1 25.8 Lower Respiratory Infection 7.8 6.6 – – Ear, Nose & Throat Symptoms 2.0 1.6 – – Musculoskeletal System Back Pain 13.9 12.1 – – Pain Lower Extremities – – 10.8 10.3 Arthritis 5.4 4.8 – – Myalgia 4.2 3.3 – – Joint Disorder 2.3 2.2 – – Tendonitis – – 2.0 1.9 Central Nervous System Headache 30.6 27.6 – – Dizziness 5.2 5.0 – – Body as a Whole Fatigue 7.2 6.4 3.1 1.7 Sleep Disorder 3.9 3.3 – – Skin & Appendages Rash 4.3 4.0 – – Dry Skin 2.1 1.4 – – Reproductive, Female Menstrual Irregularity 9.8 7.5 – – Vaginitis 3.8 3.6 2.6 1.9 Urinary System Urinary Tract Infection 7.5 7.3 5.9 4.8 Psychiatric Disorder Psychiatric Anxiety 4.7 2.9 2.8 2.1 Depression – – 3.4 2.5 Hearing & Vestibular Disorders Otitis 4.3 3.4 2.9 2.5 Cardiovascular Disorders Pedal Edema – – 2.8 1.9 Table 4 illustrates the percentage of adult patients on XENICAL and placebo who developed a low vitamin level on two or more consecutive visits during 1 and 2 years of therapy in studies in which patients were not previously receiving vitamin supplementation.
Table 4 Incidence of Low Vitamin Values on Two or More Consecutive Visits (Nonsupplemented Adult Patients With Normal Baseline Values - First and Second Year) Placebo Treatment designates placebo plus diet or XENICAL plus diet XENICAL Vitamin A 1.0% 2.2% Vitamin D 6.6% 12.0% Vitamin E 1.0% 5.8% Beta-carotene 1.7% 6.1% Table 5 illustrates the percentage of adolescent patients on XENICAL and placebo who developed a low vitamin level on two or more consecutive visits during the 1-year study.
Table 5 Incidence of Low Vitamin Values on Two or More Consecutive Visits (Pediatric Patients With Normal Baseline Values All patients were treated with vitamin supplementation throughout the course of the study ) Placebo Treatment designates placebo plus diet or XENICAL plus diet XENICAL Vitamin A 0.0% 0.0% Vitamin D 0.7% 1.4% Vitamin E 0.0% 0.0% Beta-carotene 0.8% 1.5% In the 4-year XENDOS study, the general pattern of adverse events was similar to that reported for the 1- and 2-year studies with the total incidence of gastrointestinal-related adverse events occurring in year 1 decreasing each year over the 4-year period.
In clinical trials in obese diabetic patients, hypoglycemia and abdominal distension were also observed.
Pediatric Patients In clinical trials with XENICAL in adolescent patients ages 12 to 16 years, the profile of adverse reactions was generally similar to that observed in adults.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of XENICAL.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to XENICAL exposure.
Rare cases of increase in transaminases and in alkaline phosphatase and hepatitis that may be serious have been reported.
There have been reports of hepatic failure observed with the use of XENICAL in postmarketing surveillance, with some of these cases resulting in liver transplant or death [see Warnings and Precautions (5.2) ] .
Rare cases of hypersensitivity have been reported with the use of XENICAL.
Signs and symptoms have included pruritus, rash, urticaria, angioedema, bronchospasm and anaphylaxis.
Very rare cases of bullous eruption have been reported.
Rare cases of leukocytoclastic vasculitis have been reported.
Clinical signs include palpable purpura, maculopapular lesions, or bullous eruption.
Acute oxalate nephropathy after treatment with XENICAL has been reported in patients with or at risk for renal disease [see Warnings and Precautions (5.3) ] .
Pancreatitis has been reported with the use of XENICAL in postmarketing surveillance.
No causal relationship or physiopathological mechanism between pancreatitis and obesity therapy has been definitively established.
Lower gastrointestinal bleeding has been reported in patients treated with XENICAL.
Most reports are nonserious; severe or persistent cases should be investigated further.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact the Safety Call Center at 1-888-236-5445 or FDA at 1‑800‑FDA‑1088 (1-800-332-1088) or www.fda.gov/medwatch.
6.1 Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in patients.
Commonly Observed (based on first year and second year data) Gastrointestinal (GI) symptoms were the most commonly observed treatment-emergent adverse events associated with the use of XENICAL in the seven double-blind, placebo-controlled clinical trials and are primarily a manifestation of the mechanism of action.
(Commonly observed is defined as an incidence of ≥5% and an incidence in the XENICAL 120 mg group that is at least twice that of placebo.) Table 2 Commonly Observed Adverse Events Adverse Event Year 1 Year 2 XENICAL Treatment designates XENICAL three times a day plus diet or placebo plus diet % Patients (N=1913) Placebo % Patients (N=1466) XENICAL % Patients (N=613) Placebo % Patients (N=524) Oily Spotting Oily discharge may be clear or have a coloration such as orange or brown.
26.6 1.3 4.4 0.2 Flatus with Discharge 23.9 1.4 2.1 0.2 Fecal Urgency 22.1 6.7 2.8 1.7 Fatty/Oily Stool 20.0 2.9 5.5 0.6 Oily Evacuation 11.9 0.8 2.3 0.2 Increased Defecation 10.8 4.1 2.6 0.8 Fecal Incontinence 7.7 0.9 1.8 0.2 In general, the first occurrence of these events was within 3 months of starting therapy.
Overall, approximately 50% of all episodes of GI adverse events associated with XENICAL treatment lasted for less than 1 week, and a majority lasted for no more than 4 weeks.
However, GI adverse events may occur in some individuals over a period of 6 months or longer.
Discontinuation of Treatment In controlled clinical trials, 8.8% of patients treated with XENICAL discontinued treatment due to adverse events, compared with 5.0% of placebo-treated patients.
For XENICAL, the most common adverse events resulting in discontinuation of treatment were gastrointestinal.
Other Adverse Clinical Events The following table lists other treatment-emergent adverse events from seven multicenter, double-blind, placebo-controlled clinical trials that occurred at a frequency of ≥2% among patients treated with XENICAL 120 mg three times a day and with an incidence that was greater than placebo during year 1 and year 2, regardless of relationship to study medication.
Table 3 Other Treatment-Emergent Adverse Events From Seven Placebo-Controlled Clinical Trials Body System/Adverse Event Year 1 Year 2 XENICAL Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet % Patients (N=1913) Placebo % Patients (N=1466) XENICAL % Patients (N=613) Placebo % Patients (N=524) – None reported at a frequency ≥2% and greater than placebo Gastrointestinal System Abdominal Pain/Discomfort 25.5 21.4 – – Nausea 8.1 7.3 3.6 2.7 Infectious Diarrhea 5.3 4.4 – – Rectal Pain/Discomfort 5.2 4.0 3.3 1.9 Tooth Disorder 4.3 3.1 2.9 2.3 Gingival Disorder 4.1 2.9 2.0 1.5 Vomiting 3.8 3.5 – – Respiratory System Influenza 39.7 36.2 – – Upper Respiratory Infection 38.1 32.8 26.1 25.8 Lower Respiratory Infection 7.8 6.6 – – Ear, Nose & Throat Symptoms 2.0 1.6 – – Musculoskeletal System Back Pain 13.9 12.1 – – Pain Lower Extremities – – 10.8 10.3 Arthritis 5.4 4.8 – – Myalgia 4.2 3.3 – – Joint Disorder 2.3 2.2 – – Tendonitis – – 2.0 1.9 Central Nervous System Headache 30.6 27.6 – – Dizziness 5.2 5.0 – – Body as a Whole Fatigue 7.2 6.4 3.1 1.7 Sleep Disorder 3.9 3.3 – – Skin & Appendages Rash 4.3 4.0 – – Dry Skin 2.1 1.4 – – Reproductive, Female Menstrual Irregularity 9.8 7.5 – – Vaginitis 3.8 3.6 2.6 1.9 Urinary System Urinary Tract Infection 7.5 7.3 5.9 4.8 Psychiatric Disorder Psychiatric Anxiety 4.7 2.9 2.8 2.1 Depression – – 3.4 2.5 Hearing & Vestibular Disorders Otitis 4.3 3.4 2.9 2.5 Cardiovascular Disorders Pedal Edema – – 2.8 1.9 Table 4 illustrates the percentage of adult patients on XENICAL and placebo who developed a low vitamin level on two or more consecutive visits during 1 and 2 years of therapy in studies in which patients were not previously receiving vitamin supplementation.
Table 4 Incidence of Low Vitamin Values on Two or More Consecutive Visits (Nonsupplemented Adult Patients With Normal Baseline Values - First and Second Year) Placebo Treatment designates placebo plus diet or XENICAL plus diet XENICAL Vitamin A 1.0% 2.2% Vitamin D 6.6% 12.0% Vitamin E 1.0% 5.8% Beta-carotene 1.7% 6.1% Table 5 illustrates the percentage of adolescent patients on XENICAL and placebo who developed a low vitamin level on two or more consecutive visits during the 1-year study.
Table 5 Incidence of Low Vitamin Values on Two or More Consecutive Visits (Pediatric Patients With Normal Baseline Values All patients were treated with vitamin supplementation throughout the course of the study ) Placebo Treatment designates placebo plus diet or XENICAL plus diet XENICAL Vitamin A 0.0% 0.0% Vitamin D 0.7% 1.4% Vitamin E 0.0% 0.0% Beta-carotene 0.8% 1.5% In the 4-year XENDOS study, the general pattern of adverse events was similar to that reported for the 1- and 2-year studies with the total incidence of gastrointestinal-related adverse events occurring in year 1 decreasing each year over the 4-year period.
In clinical trials in obese diabetic patients, hypoglycemia and abdominal distension were also observed.
Pediatric Patients In clinical trials with XENICAL in adolescent patients ages 12 to 16 years, the profile of adverse reactions was generally similar to that observed in adults.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of XENICAL.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to XENICAL exposure.
Rare cases of increase in transaminases and in alkaline phosphatase and hepatitis that may be serious have been reported.
There have been reports of hepatic failure observed with the use of XENICAL in postmarketing surveillance, with some of these cases resulting in liver transplant or death [see Warnings and Precautions (5.2) ] .
Rare cases of hypersensitivity have been reported with the use of XENICAL.
Signs and symptoms have included pruritus, rash, urticaria, angioedema, bronchospasm and anaphylaxis.
Very rare cases of bullous eruption have been reported.
Rare cases of leukocytoclastic vasculitis have been reported.
Clinical signs include palpable purpura, maculopapular lesions, or bullous eruption.
Acute oxalate nephropathy after treatment with XENICAL has been reported in patients with or at risk for renal disease [see Warnings and Precautions (5.3) ] .
Pancreatitis has been reported with the use of XENICAL in postmarketing surveillance.
No causal relationship or physiopathological mechanism between pancreatitis and obesity therapy has been definitively established.
Lower gastrointestinal bleeding has been reported in patients treated with XENICAL.
Most reports are nonserious; severe or persistent cases should be investigated further.