Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• Orlistat is a pancreatic lipase inhibitor that inhibits triglyceride digestion and reduces fat absorption by approximately 30%.

• Orlistat is licensed in conjunction with a mildly hypocaloric diet for adults aged between 18 and 75 years who meet one of the following criteria:
• Body mass index (BMI) greater than or equal to 30 kg/m², or
• BMI greater than or equal to 28 kg/m² with associated risk factors.

[ABPI Medicines Compendium, 2006]

• Because it reduces the absorption of dietary fat, orlistat should not be prescribed for anyone with a chronic malabsorption syndrome or cholestasis, as dietary absorption of fat is already impaired [ABPI Medicines Compendium, 2006; Micromedex, 2007].

• Gastrointestinal adverse effects are common (e.g. oily spotting, abdominal discomfort, faecal urgency, fatty stools). These usually reduce with continued use of orlistat and can often be reduced by limiting fat intake [ABPI Medicines Compendium, 2006].
• Malabsorption of fat-soluble vitamins (A, D, E, K, and beta-carotene) is a theoretical concern, but this is not an issue for most people treated in primary care [National Obesity Forum, 2005]. Routine vitamin supplementation is not necessary.
• Very rarely (< 1/10,000) hepatitis and cholelithiasis have been reported [MHRA, 2010].

• Treatment with orlistat should only continue beyond 3 months if the person has lost at least 5% of their body weight, as measured at the start of drug treatment [ABPI Medicines Compendium, 2006; NICE, 2006b].
• There is no restriction on how long orlistat may be prescribed [ABPI Medicines Compendium, 2006]. Expert opinion is that, after 12 months, a decision to continue treatment should be taken on an individual basis, weighing up the benefits, costs, and risks for that person. This should be reviewed at regular intervals.

• Rates of weight loss may be slower in people with type 2 diabetes, so less strict goals may be appropriate. These goals should be agreed with the person and reviewed regularly [NICE, 2006b].

• If fat-soluble vitamins or multivitamin supplements are taken, they should be given at least 2 hours after a dose of orlistat or at bedtime.
• Orlistat reduces plasma levels of ciclosporin. If concomitant use is unavoidable, ciclosporin levels should be monitored frequently, both after initiation of orlistat and on discontinuation [Baxter, 2006].
• Orlistat may reduce the absorption of levothyroxine, leading to reduced control of hypothyroidism [MHRA, 2010]. Consider taking levothyroxine at a different time to orlistat to reduce the interaction (such as 2 hours after a dose of orlistat or at bedtime).
• Orlistat may also reduce the absorption of antiepileptic drugs. Loss of seizure control has been reported during concomitant treatment with orlistat and sodium valproate or lamotrigine [MHRA, 2010]. Consider taking antiepileptic drugs at a different time to orlistat to reduce the interaction (such as 2 hours after a dose of orlistat or at bedtime).
• Orlistat may reduce the absorption of fat-soluble vitamin K, with the result that a lower dose of warfarin is required. In people taking warfarin, the international normalized ratio (INR) should be monitored closely, especially when starting or stopping treatment with orlistat [Micromedex, 2007].
• No direct interaction between oral contraceptives and orlistat has been demonstrated in specific drug-drug interaction studies. However, orlistat may indirectly reduce the availability of oral contraceptives through its action on the gastrointestinal tract. If a woman experiences severe diarrhoea whilst taking orlistat an additional contraceptive method is recommended [ABPI Medicines Compendium, 2006].

• Orlistat 120 mg should be taken immediately before, during, or up to 1 hour after each main meal (up to a maximum of three times a day).
• The dose of orlistat should be omitted if a meal is missed, or if the meal contains little or no fat.

[ABPI Medicines Compendium, 2006]

• Roche provide a support service for people who have been prescribed orlistat. Details for registration are provided with the drug packaging.

• Orlistat is not recommended for use during pregnancy.
• Orlistat is contraindicated during breastfeeding.

• The use of weight-loss medications during pregnancy is not recommended because they may interfere with adequate nutrition for both the woman and the fetus.
• No clinical data on pregnancies exposed to orlistat are available. The potential effects on the fetus are unknown. Studies in animals do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition, or postnatal development.
• It is not known whether orlistat is secreted into human milk.

[ABPI Medicines Compendium, 2006; Micromedex, 2007]