SEARCH

SEARCH BY CITATION

Reduced Absorption of Lipophilic Anti-Epileptic Medications When Used Concomitantly with the Anti-Obesity Drug Orlistat

  1. Top of page
  2. Reduced Absorption of Lipophilic Anti-Epileptic Medications When Used Concomitantly with the Anti-Obesity Drug Orlistat
  3. REFERENCES

Dear Editors:

We suggest a reduced absorption of lipophilic anti-epileptic medications when used concomitantly with the anti-obesity drug orlistat (Xenical). An 18 year old epileptic woman presented with increased frequency of seizures. Her normal anti-epileptic medication was lamotrigine 200 mg daily. Her drug compliance and epileptic control was good. She had recently started orlistat therapy, 120 mg three times a day, for obesity. Since starting orlistat her seizure frequency had increased from one per month to more than one per week, sufficient for her to be admitted to hospital for further investigation. On her admission to hospital, her plasma lamotrigine level was 8 mmol/l (normal 0–15), although she had not previously had her levels measured.

Weight gain is a commonly reported side effect of anti-epileptic drugs. It has been observed with the lipophilic medications: valproic acid, carbamazepine, vigabatrin and gabapentin (Jallon and Picard, 2001). Orlistat is a chemically synthesised derivative of lipstatin, a natural product of streptomyces toxytricini, and is a potent selective inhibitor of pancreatic and gastric lipases (the principal enzymes responsible for the hydrolysis and subsequent absorption of dietary fat) (Melia A et al., 1996). Thus, orlistat inhibits absorption of dietary fat and is designed for the treatment of obesity. In March 2001, the National Institute for Health and Clinical Excellence (NICE) recommended the use of orlistat in obese patients, if they had lost at least 2.5 kg through dietary control and had a body mass index of greater than 30 kg/m2 or greater than 27 kg/m2 with risk factors (for instance diabetes, ischaemic heart disease, hypertension or obstructive sleep apnoea) (NICE guidelines, 2001).

Orlistat reduces the dietary absorption of fat and therefore can potentially alter the absorption of lipophilic drugs. There are no studies measuring lamotrigine's lipophilicity, nor the effect of lipophilicity on absorption. However it is considered to be a highly lipophilic drug (Personal communication, GST Drugs information, 2006).

Case reports show altered absorption between orlistat and other lipophilic drugs. For instance, sub-therapeutic levels of serum cyclosporine after treatment with orlistat in renal transplant patients (Evans S et al., 2003) and reduced absorption of amiodarone by approximately one quarter in cardiac patients. Fluoxetine, simvastatin, atenolol, furosemide, captopril and nifedipine absorption are not affected (Wber C et al., 1996). Chronic use of orlistat can lead to reduced absorption of fat soluble vitamins A, D, E, and K and interfere with warfarin dosage (MacWalter RS et al., 2003).

Antiepileptic medications therapeutic levels require monitoring because alterations can lead to deterioration in epileptic control. Closer monitoring of drug levels may be required during concomitant use of orlistat. We feel clarification of this possible interaction would be beneficial in this group of patients.

REFERENCES

  1. Top of page
  2. Reduced Absorption of Lipophilic Anti-Epileptic Medications When Used Concomitantly with the Anti-Obesity Drug Orlistat
  3. REFERENCES