Xenical
Xenical
Generic Name
Xenical
Mechanism
- Orlistat is a *non‑selective* irreversible inhibitor of *pancreatic and gastric lipases*.
- It binds covalently to the catalytic serine (Ser 195) of lipase, preventing triglyceride hydrolysis in the lumen of the small intestine.
- Unhydrolyzed triglycerides, fatty acids, and mono‑/di‑acylglycerols are excreted in feces, resulting in a caloric loss (~30 kcal/day).
Pharmacokinetics
| Parameter | Value | Notes |
| Absorption | Minimal oral absorption (≤ 20 µg) | Orlistat remains largely intact in the gut. |
| Distribution | Negligible plasma distribution | No significant volume of distribution. |
| Metabolism | No systemic metabolism | Remains active in lumen; unabsorbed drug is excreted unchanged. |
| Excretion | Fecal (≈ 68 % of dose) | Small portion (≈ 32 %) excreted via bile or urine. |
| Half‑life | Approximately 2–4 h in the GI tract | Rapid clearance; dosing correlates with meal timing. |
*Key pharmacokinetic highlights*: Orlistat’s lack of systemic absorption limits systemic side‑effects and drug‑drug interactions, but necessitates strict adherence to meal‑timed administration.
Indications
- Obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one weight‑related comorbidity (e.g., hypertension, dyslipidemia, type 2 diabetes).
- Requires a combination with a reduced‑calorie diet (≈ 500 kcal/day deficit) and regular physical activity.
*Off‑label uses*: None formally approved; clinicians occasionally prescribe for weight reduction in patients not meeting strict BMI criteria but should exercise caution.
Contraindications
- Contraindications
- Acute or chronic cholestasis, biliary obstruction, or hepatic disease
- Severe chronic malabsorption syndromes (e.g., Crohn’s disease, celiac)
- Inflammatory bowel disease, ulcerative colitis, or chronic pancreatitis
- Known hypersensitivity to orlistat or any inactive ingredient
- Warnings
- Fat‑soluble vitamin malabsorption: May lead to deficiencies (A, D, E, K).
- Potential for decreased hepatic clearance of other drugs: Monitor if used with agents metabolized in liver (e.g., warfarin).
- Asthma and respiratory status: Rarely associated with intestinal inflammation.
Dosing
- Recommended dose: 120 mg orally three times daily with each main meal (breakfast, lunch, dinner) that contains fat.
- *Administration tips*:
- Take maintaining a minimum of 20 g fat per meal previously.
- Do not exceed 120 mg—the fixed dose capsule already contains 120 mg.
- If a meal is skipped, skip the dose; do not double dose.
- Duration: Long‑term use (≥ 12 months) is permissible if weight loss is achieved; periodic reassessment required.
Adverse Effects
| Common | Incidence | Notes |
| Bile‑stained diarrhea | 2–3 % | Co‑occurring with steatorrhea; often transient. |
| Flatulence with greasy or fatty substances | 1–2 % | May encourage a low‑fat diet. |
| Urgency and fecal incontinence | < 1 % | Usually mild. |
| Abdominal cramps/spasms | < 1 % | Advisable: take with sedation. |
| Elevated liver enzymes | < 0.5 % | Monitor AST/ALT at 3‑month intervals. |
| Serious | Incidence | Notes |
| Severe hypobetalipoproteinemia | Rare | Due to fat malabsorption. |
| Vitamin K deficiency bleeding | Rare | Monitor PT/INR in patients on warfarin. |
| Exacerbation of inflammatory bowel disease | Uncommon | Counsel patients with known IBD. |
Monitoring
- Baseline: Weight, BMI, waist circumference; fasting lipid profile; liver function tests (ALT, AST, bilirubin).
- Every 3–6 months: Repeat weight and BMI; serum lipids; liver enzymes; vitamin status (A, D) if deficiency suspected.
- Patients on anticoagulation: Monitor INR or aPTT weekly.
Clinical Pearls
- *“The fat‑stopping effect of Xenical is only as good as the dietary fat intake.”* Patients who drastically reduce fat consumption may experience reduced efficacy (“at the expense of symptom relief”).
- *Co‑administration with cholestyramine* can reduce orlistat’s efficacy; avoid within 12 h of each other.
- *Consider a vitamin‑supplement regimen*: 400 IU vitamin D, 400 µg vitamin K, 400 mg vitamin E, and 1 mg vitamin A daily in patients on orlistat ≥ 6 months.
- *Dosing schedule*: Take capsules with first spoonful of meal; for children/adolescent or surgical patients, adjust food fat content rather than dose.
- *High‑fat meal restriction*: Provide meal plans that maintain ≥ 20 g fat per main meal to prevent gastrointestinal side‑effects.
Key takeaway: Xenical’s unique local action offers a weight‑loss adjunct with minimal systemic adverse effects—provided patients adhere to meal‑timed dosing and maintain a low‑fat diet while monitoring for fat‑soluble vitamin deficiencies.