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Niaspan must not be replaced with other nicotinic acid preparations. When

switching from other nicotinic acid preparations to Niaspan, therapy with

Niaspan must be initiated with the recommended dose escalation schedule,

see section 4.2.

Liver

Nicotinic acid preparations have been associated with abnormal liver tests.

Severe hepatic toxicity, including fulminant hepatic necrosis, has occurred in

patients who have taken long-acting nicotinic acid products in place of

immediate-release nicotinic acid. Since the pharmacokinetics of Niaspan

are different to other nicotinic acid preparations, Niaspan must not be

replaced with other preparations. The prescribing information of the HMGCoA

reductase inhibitor should also be consulted for warnings and

precautions for use.

Caution is advised when Niaspan is used in patients who consume

substantial quantities of alcohol and/or have a past history of liver disease.

Elevated liver transaminases have been observed with Niaspan therapy.

However, transaminase elevations were reversible upon discontinuation of

Niaspan.

Liver tests including AST and ALT must be performed periodically in all

patients during therapy with Niaspan and prior to treatment in case of history

and/or symptoms of hepatic dysfunction (e.g. jaundice, nausea, fever,

and/or malaise). If the transaminase levels show evidence of progression,

particularly if they rise to three times the upper limit of normal, the drug must

be discontinued.

Skeletal muscle

4.8 Undesirable effects

Flush

In the placebo-controlled clinical trials, flushing episodes (i.e. warmth,

redness, itching and/or tingling) were the most common treatment-emergent

adverse events for Niaspan (reported by 88% of patients). In these studies

fewer than 6% of Niaspan patients discontinued due to flushing.

In comparisons of immediate-release (IR) nicotinic acid and Niaspan,

although the number of patients who flushed was similar, fewer flushing

episodes were reported by patients who received Niaspan. Following four

weeks of maintenance therapy with Niaspan at daily doses of 1500mg, the

frequency of flushing over the four week period averaged 1.88 events per

patient.

Flushing reactions generally occur during early treatment and the dose

titration phase. They are thought to be mediated by the release of

prostaglandin D2 and tolerance to flushing usually develops over the course

of several weeks.

Spontaneous reports suggest that in rare cases, flushing may be more

severe and accompanied by symptoms of dizziness, tachycardia,

palpitations, dyspnoea, sweating, chills and/or oedema which in rare cases

may lead to syncope. Medical treatment should be administered as

necessary.

Hypersensitivity reactions

Hypersensitivity reactions have been reported very rarely. These may be

characterised by symptoms such as generalised exanthema, flush, urticaria,

vesiculobullous rash, angioedema, laryngospasm, dyspnoea, hypotension,

and circulatory collapse. Medical treatment should be administered as

necessary.

The following adverse reactions have been observed in clinical studies or in

routine patient management, in patients receiving the recommended daily

maintenance doses (1000, 1500, and 2000mg) of Niaspan. They are

presented by system organ class and frequency grouping (very common

>1/10; common >1/100, <1/10; uncommon >1/1,000, <1/100; rare

>1/10,000, <1/1,000; very rare <1/10,000, including isolated reports). In

general, the incidence of adverse reactions was higher in women compared

to men. (Please refer to Table 2 below).

Table 2: Adverse reactions

ADR table amended