1. Clinical Overview
Cetilistat is a novel, peripherally acting lipase inhibitor used for the management of obesity in conjunction with a mildly hypocaloric diet. It acts locally in the gastrointestinal tract to inhibit dietary fat absorption. Approved in India in 2015, it offers an alternative to orlistat with a potentially different side effect profile, particularly regarding gastrointestinal adverse events.
| Onset | Duration | Bioavailability |
|---|---|---|
| Within 1-2 hours after oral administration. | Approximately 6-8 hours, primarily during the digestive phase following a meal. | <1% (Negligible systemic absorption). |
2. Mechanism of Action
Cetilistat is a potent and reversible inhibitor of gastrointestinal lipases, primarily pancreatic lipase. It forms a covalent bond with the active serine site of the lipase enzyme within the lumen of the stomach and small intestine. This inhibition prevents the hydrolysis of dietary triglycerides into absorbable free fatty acids and monoglycerides. As a result, undigested triglycerides are excreted in the feces, creating a caloric deficit.
3. Indications & Uses
- Management of obesity (Body Mass Index ≥ 30 kg/m²)
- Management of overweight (Body Mass Index ≥ 27 kg/m²) in the presence of associated risk factors (e.g., type 2 diabetes, dyslipidemia, hypertension)
4. Dosage & Administration
Adult Dosage: One 60mg capsule, taken three times daily (TDS) immediately before, during, or up to one hour after each main meal containing fat.
Administration: Must be taken with meals. If a meal is missed or contains no fat, the dose should be omitted. The capsule should be swallowed whole with a glass of water. A daily multivitamin supplement (containing fat-soluble vitamins A, D, E, K) is recommended, to be taken at least 2 hours before or after cetilistat (e.g., at bedtime).
5. Side Effects
Common side effects may include:
- Oily spotting from rectum
- Flatulence with discharge
- Fecal urgency
- Soft stools
- Oily/ fatty stools
- Increased defecation
- Abdominal pain/discomfort
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Cyclosporine | Reduced absorption of cyclosporine leading to subtherapeutic levels. Monitor levels closely. | Major |
| Amiodarone | Theoretical risk of reduced absorption. Monitor efficacy. | Moderate |
| Acarbose | Increased gastrointestinal side effects. Use with caution. | Moderate |
| Orlistat | Concomitant use not studied; likely additive GI effects and no added benefit. Contraindicated. | Major |
| Warfarin & other Anticoagulants | Potential reduced absorption of Vitamin K, potentially enhancing anticoagulant effect. Monitor INR closely. | Major |
| Antiepileptics (e.g., Phenytoin, Valproate) | Theoretical risk of reduced absorption. Monitor drug levels and clinical effect. | Moderate |
| Levothyroxine | Potential reduced absorption. Administer levothyroxine at least 4 hours apart from cetilistat. | Moderate |
| Fat-soluble Vitamin Supplements (A, D, E, K) | Reduced absorption of vitamins. Administer supplements at least 2 hours before or after cetilistat. | Moderate |
7. Patient Counselling
- DO take the capsule with each main meal containing fat.
- DO follow a balanced, reduced-calorie diet as advised by your doctor/dietitian.
- DO take a daily multivitamin supplement at bedtime (at least 2 hours after last dose).
- DO maintain adequate fluid intake.
- DO inform all your doctors and your surgeon (if scheduled for surgery) that you are taking this medicine.
- DON'T take the dose if you skip a meal or eat a fat-free meal.
- DON'T take it with a very high-fat meal as this will worsen side effects.
- DON'T take other medicines or supplements at the same time as cetilistat; space them by 2-4 hours.
8. Toxicology & Storage
Overdose: Expected to be an extension of its pharmacological effects: severe gastrointestinal effects including profuse oily stools, diarrhea, abdominal cramps, and potentially dehydration and hypovolemia.
Storage: Store below 30°C in a cool, dry place, protected from light and moisture. Keep the container tightly closed. Keep out of reach of children.