Olbetam Capsules 250

Red-brown/dark pink hard gelatin capsules, size no. 1, containing a white to cream powder.

Olbetam is indicated for the treatment of lipid disorders characterised, according to Fredrickson, by elevated plasma levels of triglycerides (type IV hyperlipo-proteinaemia), or cholesterol (type IIA hyperlipoproteinaemia) and triglycerides and cholesterol (type IIB hyperlipoproteinaemia).

To be given orally.

The daily dosage should be adjusted individually depending on plasma triglyceride and cholesterol levels.

The recommended dosage is one 250 mg capsule 2 or 3 times daily to be taken with or after meals. The lower dose is advised in type IV and the higher dose in types IIA and IIB hyperlipoproteinaemias.

Daily dosages of up to 1200 mg have been safely administered for long periods. Improvement in the plasma lipid's picture is usually seen within the first month of therapy.

In patients with slight renal impairment (creatinine clearance values > 60 ml/min) no dose reduction is required. For patients with moderate to severe renal impairment (creatinine clearance values between 60 and 30 ml/min) the dose needs to be reduced accordingly. Acipimox is eliminated entirely through the kidneys, therefore, accumulation can be expected and is related to the degree of renal impairment. It is advised that longer intervals are left between doses of the drug in patients with renal impairment.

Acipimox is contra-indicated in patients who are hypersensitive to the active substance or to any of the excipients and those with peptic ulceration.

Acipimox should not be given to patients with severe renal impairment (creatinine clearance < 30 ml/min)

Modification of hyperlipidaemia is recommended only for patients with hyperlipoproteinaemia of a degree and type considered appropriate for treatment.

Low cholesterol and low-fat diets, together with cessation of alcohol consumption, exercise and weight loss, in case of obesity are preferable therapeutic approaches to be tried before starting treatment with acipimox.

Since long term administration of acipimox is recommended, all baseline values, including lipid profile, should be measured before treatment and periodic determinations of serum lipids should be obtained to confirm that the desired therapeutic effect has been achieved.

Hepatic and renal functions should be monitored.

The absorption of acipimox is not affected by the concomitant administration of colestyramine

Evidence of clinical efficacy in the prevention of heart disease has not been established.

The possible beneficial and adverse, long-term consequences of some drugs used in the hyperlipidaemias are still the subject of scientific discussion.

No interaction has been shown with other lipid lowering agents. However, the combination with statins or fibrates should be used with caution due to reports of an increased risk of musculoskeletal events with nicotinic acid (a structural analogue of acipimox) when used in combination with such lipid-lowering agents.

No interaction has been shown with digoxin and warfarin.

There is no evidence from the animal studies that acipimox is teratogenic. However, a higher incidence of immature and underweight foetuses was seen in pregnant animals given higher doses of acipimox. This effect may be due to maternal toxicity.

There is only limited experience to date of administration of acipimox to humans therefore epidemiological data is not available. Taking into account the present experience of administration to humans of acipimox and that the safety of acipimox in human pregnancy has not yet been ascertained, it is recommended, therefore, that acipimox not be administered to women who are, or may be pregnant.

In the absence of animal data on the levels of acipimox excreted in milk, acipimox should not be administered to women who are breast-feeding.

The effect of acipimox on ability to drive or use machinery has not been studied, but based on its pharmacodynamic properties and overall safety profile it is unlikely to have an effect.

The following undesirable effects have been observed from the clinical and post-marketing experience and reported during treatment with acipimox with the following frequencies: 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); very rare (<1/10,000); Not Known (cannot be estimated from the available data).

* AE frequency estimated from post-marketing safety database

** AE frequency cannot be estimated from the available data

The drug may induce skin vasodilatation giving rise to a sensation of heat, flushing or itching, especially at the beginning of therapy and also rash and erythema. These reactions usually disappear rapidly during the first day of treatment.

If toxic effects are observed, supportive care and symptomatic treatment should be administered.

Acipimox inhibits the release of fatty acids from adipose tissue and reduces the blood concentrations of very low density lipoproteins (VLDL or Pre-beta) and low density lipoproteins (LDL or beta) with a subsequent overall reduction in triglyceride and cholesterol levels.

Acipimox also has a favourable effect on high density lipoproteins (HDL or alpha) which increase during treatment.

Acipimox is rapidly and completely absorbed orally, reaching peak plasma levels within two hours. The half-life is about two hours. It does not bind to plasma proteins; it is not significantly metabolised and is eliminated almost completely intact by the urinary route.

There is no evidence from the animal studies that acipimox is teratogenic. However, a higher incidence of immature and underweight foetuses was seen in pregnant animals given higher doses of acipimox. This effect may be due to maternal toxicity.

Physically modified corn starch (STA-RX 1500)

Hard gelatin capsules shell:

Titanium dioxide (E171)

Iron oxide red (E172)

Iron oxide yellow (E172)

None stated.

48 months

Store at a temperature below 30°C in a dry place.

Packed in blisters of 10 capsules per strip, inside cartons. Each carton contains 90 capsules.

None given.

Pharmacia Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

PL 00032/0322

2 May 2003

May 2011

Company Ref : OB4_1