antiobesity preparations, excl. diet products, peripherally acting antiobesity products - ATC code A08AB01

orlistat

Alli 60 mg hard capsules

Hard capsule The capsule has a dark blue centre band, and a turquoise cap and body bearing the imprint of “alli”.

alli is indicated for weight loss in adults who are overweight (body mass index, BMI, 28 kg/m²) and should be taken in conjunction with a mildly hypocaloric, lower-fat diet.

Posology

Adults

The recommended dose of alli is one 60 mg capsule to be taken three times daily. No more than three 60 mg capsules should be taken in 24 hours.

Diet and exercise are important parts of a weight loss programme. It is recommended that a diet and exercise programme is started before beginning treatment with alli.

While taking orlistat, the patient should be on a nutritionally balanced, mildly hypocaloric diet that contains approximately 30% of calories from fat (e.g. in a 2,000 kcal/day diet, this equates to <67 g of fat). The daily intake of fat, carbohydrate and protein should be distributed over three main meals.

The diet and exercise programme should continue to be followed when treatment with alli is stopped.

Treatment should not exceed 6 months.

If patients have been unable to lose weight after 12 weeks of treatment with alli, they should consult their doctor or a pharmacist. It may be necessary to discontinue treatment.

Special populations

Hepatic and renal impairment

The effect of orlistat in individuals with hepatic and/or renal impairment has not been studied.

However, as orlistat is minimally absorbed, no dose adjustment is necessary in individuals with hepatic and/or renal impairment.

Method of administration

The capsule should be taken with water immediately before, during or up to 1 hour after each main meal. If a meal is missed or contains no fat, the dose of orlistat should be omitted.

The safety and efficacy of alli in children below 18 years of age has not been established. No data are available.

There are limited data on the use of orlistat in the elderly. However, as orlistat is minimally absorbed, no dose adjustment is necessary in the elderly.

• Hypersensitivity to the active substance or to any of the excipients

• Concurrent treatment with ciclosporin

• Chronic malabsorption syndrome

• Cholestasis

• Pregnancy

• Breast-feeding

• Concurrent treatment with warfarin or other oral anticoagulants

Patients should be advised to adhere to the dietary recommendations they are given. The possibility of experiencing gastrointestinal symptoms may increase when orlistat is taken with an individual meal or a diet high in fat.

Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K). For this reason, a multivitamin supplement should be taken at bedtime.

As weight loss may be accompanied by improved metabolic control in diabetes, patients who are taking a medicinal product for diabetes should consult a doctor before starting treatment with alli, in case it is necessary to adjust the dose of the antidiabetic medicinal product.

Weight loss may be accompanied by an improvement in blood pressure and cholesterol levels. Patients who are taking a medicinal product for hypertension or hypercholesterolaemia should consult a doctor or pharmacist when taking alli, in case it is necessary to adjust the dose of these medicinal products.

Patients who are taking amiodarone should consult a doctor before starting treatment with alli.

Cases of rectal bleeding have been reported in patients taking orlistat. If this occurs, the patient should consult a doctor.

The use of an additional contraceptive method is recommended to prevent possible failure of oral contraception that could occur in case of severe diarrhoea.

Patients with kidney disease should consult a doctor before starting treatment with alli, as the use of orlistat may rarely be associated with hyperoxaluria and oxalate nephropathy.

Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine are co-administered. Patients taking levothyroxine should consult a doctor before starting treatment with alli, as orlistat and levothyroxine may need to be taken at different times and the dose of levothyroxine may need to be adjusted.

Patients taking an antiepileptic medicinal product should consult a doctor before starting treatment with alli, as they should be monitored for possible changes in the frequency and severity of convulsions. If this occurs, consideration could be given to administering orlistat and antiepileptic medicinal products at different times.

Ciclosporin

A decrease in ciclosporin plasma levels has been observed in a drug-drug interaction study and also reported in several cases, when orlistat was administered concomitantly. This could potentially lead to a decrease of immunosuppressive efficacy. Concurrent use of alli and ciclosporin is contraindicated.

Oral anticoagulants

When warfarin or other oral anticoagulants are given in combination with orlistat, international normalised ratio (INR) values could be affected. Concurrent use of alli and warfarin or other oral anticoagulants is contraindicated.

Oral contraceptives

The absence of an 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 and lead to unexpected pregnancies in some individual cases. An additional contraceptive method is recommended in case of severe diarrhoea.

Levothyroxine

Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine are taken at the same time. This could be due to a decreased absorption of iodine salts and/or levothyroxine.

Antiepileptic medicinal products

Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic medicinal products e.g. valproate, lamotrigine, for which a causal relationship to an interaction cannot be excluded. Orlistat may decrease the absorption of antiepileptic medicinal products, leading to convulsions.

Fat soluble vitamins

Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K).

The vast majority of subjects receiving up to 4 full years of treatment with orlistat in clinical studies had vitamin A, D, E and K and beta-carotene levels that stayed within normal range. However, patients should be advised to use a multivitamin supplement at bedtime to help ensure adequate vitamin intake.

Acarbose

In the absence of pharmacokinetic interaction studies, alli is not recommended to be used by patients receiving acarbose.

Amiodarone

A decrease in plasma levels of amiodarone, when given as a single dose, has been observed in a limited number of healthy volunteers who received orlistat concomitantly. The clinical relevance of this effect in patients receiving amiodarone treatment remains unknown. Patients who are taking amiodarone should consult a doctor before starting treatment with alli. The dose of amiodarone may need to be adjusted during treatment with alli.

Adverse reactions to orlistat are largely gastrointestinal in nature and related to the pharmacologic effect of the medicinal product on preventing the absorption of ingested fat.

The gastrointestinal adverse reactions identified from clinical trials with orlistat 60 mg of 18 months to 2 years duration were generally mild and transient. They generally occurred early in treatment (within 3 months) and most patients experienced only one episode. Consumption of a diet low in fat will decrease the likelihood of experiencing adverse gastrointestinal reactions.

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (1/10), common (1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).

The frequencies of adverse reactions identified during post-marketing use of orlistat are not known as these reactions were reported voluntarily from a population of uncertain size.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

†It is plausible that treatment with orlistat can lead to anxiety in anticipation of or secondary to gastrointestinal adverse reactions.

GlaxoSmithKline Consumer Healthcare

P

28 March 2012