Usage
- Cetilistat is prescribed for the treatment of obesity, often in conjunction with a reduced-calorie diet and increased physical activity. It is particularly beneficial for patients with obesity associated with type 2 diabetes mellitus and dyslipidemia.
- Pharmacological classification: Anti-obesity agent, lipase inhibitor (specifically, a gastrointestinal lipase inhibitor).
- Mechanism of Action: Cetilistat inhibits pancreatic and gastric lipases, enzymes responsible for breaking down triglycerides in the digestive system. This action reduces the absorption of dietary fats, leading to increased fat excretion in the feces and contributing to weight loss.
Alternate Names
- ATL-962
- Brand Names: Cetislim, Kilfat, Checkwt, Slim Boost CTSTAT 60, Oblean
How It Works
- Pharmacodynamics: Cetilistat’s primary effect is the inhibition of dietary fat absorption. This leads to weight loss and may also positively impact blood lipid levels and glycemic control in patients with type 2 diabetes.
- Pharmacokinetics: Cetilistat is poorly absorbed orally, minimizing systemic exposure and potential for systemic side effects. The unabsorbed fat is excreted in the feces. It is primarily metabolized by carboxylesterases in the gastrointestinal tract. The small amount absorbed systemically is further metabolized by hepatic CYP3A4 enzymes. Elimination is primarily through feces, with minimal renal excretion.
- Mode of Action: Cetilistat binds directly to pancreatic and gastric lipases, preventing these enzymes from hydrolyzing triglycerides into absorbable free fatty acids and monoglycerides. This inhibition results in reduced fat absorption and increased fecal fat excretion.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Cetilistat primarily acts through the inhibition of pancreatic and gastric lipases in the gastrointestinal lumen. It does not significantly interact with receptors, other enzymes, or neurotransmitters.
- Elimination pathways: Primarily fecal excretion; negligible renal excretion. A small amount is metabolized by CYP3A4 enzymes.
Dosage
Standard Dosage
Adults:
- 120 mg taken orally three times a day with each main meal containing fat (during or up to 1 hour after the meal). Each meal should ideally contain approximately 30% of calories from fat.
Children:
- Cetilistat is not recommended for use in children under 18 years of age, as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Caution is advised due to potential age-related changes in organ function. Close monitoring for adverse effects is recommended. Dose adjustment may be considered on a case-by-case basis.
- Patients with Renal Impairment: Use with caution. Dose adjustments may be necessary depending on the severity of impairment. Consultation with a nephrologist is recommended.
- Patients with Hepatic Dysfunction: Use with caution. Dose adjustments may be necessary depending on the severity of impairment. Consultation with a hepatologist is recommended.
- Patients with Comorbid Conditions: Close monitoring is required, especially for patients with diabetes, cardiovascular disease, or other relevant conditions. Cetilistat may have positive effects on glycemic control in patients with type 2 diabetes, but dose adjustments of antidiabetic medication might be necessary.
Clinical Use Cases
Cetilistat is not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its sole indication is for chronic weight management in conjunction with lifestyle modifications.
Dosage Adjustments
Dose adjustments may be necessary for patients with renal or hepatic dysfunction, based on the severity of impairment. Consultation with a specialist is recommended. For patients with diabetes, careful monitoring of blood glucose levels is needed, and adjustments of antidiabetic medication might be necessary.
Side Effects
Common Side Effects
- Gastrointestinal issues: Oily or fatty stools (steatorrhea), increased frequency of bowel movements, fecal urgency, flatulence (with or without oily discharge), oily rectal leakage, abdominal pain/discomfort, stool incontinence. These side effects are generally mild and self-limiting, related to the mechanism of action (increased fat excretion). They tend to be more pronounced with a higher fat intake.
Rare but Serious Side Effects
- Severe allergic reactions (rare).
- Liver injury (rare).
- Kidney stones (particularly in those with a history of hyperoxaluria or calcium oxalate nephrolithiasis).
- Reduced absorption of fat-soluble vitamins (A, D, E, and K). Supplementation may be necessary.
Long-Term Effects
- Long-term effects are still being investigated. Potential concerns include nutritional deficiencies due to reduced fat-soluble vitamin absorption and the possible formation of kidney stones. Regular monitoring of vitamin levels and kidney function is advisable during long-term use.
Adverse Drug Reactions (ADR)
- Significant ADRs requiring immediate attention include severe allergic reactions (e.g., anaphylaxis) and signs of liver injury (e.g., jaundice, dark urine).
Contraindications
- Chronic malabsorption syndrome.
- Cholestasis.
- Hypersensitivity to cetilistat or any component of the formulation.
- Pregnancy and breastfeeding.
Drug Interactions
- Ciclosporin: Cetilistat can reduce ciclosporin absorption. Administer ciclosporin at least 3 hours after cetilistat.
- Warfarin: Cetilistat may potentiate the effects of warfarin. Close monitoring of INR is recommended.
- Levothyroxine: Cetilistat may reduce levothyroxine absorption. Monitor thyroid function tests and adjust levothyroxine dose as needed.
- Fat-soluble vitamins (A, D, E, and K): Cetilistat can impair absorption. Supplement these vitamins, ideally at bedtime or separated from cetilistat administration by at least 2 hours.
- Antidiabetic medications: Cetilistat may enhance the blood glucose-lowering effects of antidiabetic drugs, potentially leading to hypoglycemia. Careful monitoring and adjustment of antidiabetic medication may be necessary.
- Other potential interactions: Amiodarone, lamotrigine, atazanavir, acarbose. Consult drug interaction resources for the most up-to-date information.
- Food: Avoid high-fat meals as they can exacerbate gastrointestinal side effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated during pregnancy due to potential fetal harm.
- Cetilistat is contraindicated in breastfeeding women. Although it is poorly absorbed orally, it can interfere with fat-soluble vitamin absorption, potentially impacting breast milk quality.
Drug Profile Summary
- Mechanism of Action: Inhibits pancreatic and gastric lipases, reducing dietary fat absorption.
- Side Effects: Primarily gastrointestinal (steatorrhea, increased bowel movements, flatulence, abdominal pain); rarely, allergic reactions or liver injury.
- Contraindications: Chronic malabsorption syndrome, cholestasis, pregnancy, breastfeeding.
- Drug Interactions: Ciclosporin, warfarin, levothyroxine, fat-soluble vitamins, antidiabetic drugs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 120 mg orally three times a day with meals.
- Monitoring Parameters: Weight, waist circumference, blood lipid profile, liver function tests, kidney function tests (especially in those with a history of kidney stones), fat-soluble vitamin levels, HbA1c (in diabetics), INR (if on warfarin).
Popular Combinations
Cetilistat is typically used as monotherapy. However, it might be used alongside other anti-obesity medications under specialist supervision if the patient has not achieved sufficient weight loss with lifestyle modifications and cetilistat alone. Combining with other weight loss drugs may increase the risk of side effects and requires careful monitoring.
Precautions
- General Precautions: Assess for pre-existing liver or kidney disease, malabsorption syndromes, and allergies. Monitor liver and kidney function, especially during long-term use. Supplement with fat-soluble vitamins.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Not recommended for children. Use with caution in the elderly.
- Lifestyle Considerations: Advise patients to adhere to a reduced-calorie diet and regular exercise program. Limit high-fat meals to minimize gastrointestinal side effects. Alcohol consumption is generally not advised, as it may exacerbate side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cetilistat?
A: The recommended dose is 120 mg orally three times a day with each main meal containing fat.
Q2: How does Cetilistat differ from Orlistat?
A: Both are lipase inhibitors, but Cetilistat has a different chemical structure and is associated with fewer gastrointestinal side effects, particularly steatorrhea.
Q3: What are the most common side effects of Cetilistat?
A: The most common side effects are gastrointestinal: oily or fatty stools, increased bowel movements, flatulence, abdominal pain.
Q4: Is Cetilistat safe for patients with diabetes?
A: It can be used in patients with type 2 diabetes, but close monitoring of blood glucose levels and possible adjustment of antidiabetic medication is essential. It may improve glycemic control.
Q5: Can Cetilistat be used during pregnancy or breastfeeding?
A: No, Cetilistat is contraindicated during pregnancy and breastfeeding.
Q6: Does Cetilistat interact with other medications?
A: Yes, it can interact with medications like ciclosporin, warfarin, levothyroxine, and fat-soluble vitamins. Check for potential interactions with all concomitant medications.
Q7: How long should Cetilistat be taken?
A: The duration of treatment should be determined by a healthcare professional based on the individual patient’s response and needs. Weight loss medications are usually part of a long-term weight management strategy.
Q8: What should patients do if they experience side effects?
A: Patients should report any side effects to their physician. Most GI side effects are mild and resolve over time. Adjusting dietary fat intake can help manage these side effects.
Q9: How should Cetilistat be stored?
A: Store Cetilistat at room temperature below 30°C (86°F), protected from light and moisture.
Q10: Is there a risk of vitamin deficiency with Cetilistat?
A: Due to reduced fat absorption, there is a risk of fat-soluble vitamin (A, D, E, K) deficiency. Supplementation is often recommended to prevent this.
