The effect of NIASPAN plus colestipol on cardiovascular morbidity and mortality is not known.

As an adjunct to diet when diet and non-pharmacological measures have been inadequate...

Additional Important Safety Information and Indications You Should Know About NIASPAN^® (niacin extended-release tablets)

IMPORTANT SAFETY INFORMATION

• NIASPAN preparations should not be substituted for equivalent doses of immediate-release (crystalline) niacin. For patients switching from immediate-release niacin to NIASPAN, therapy with NIASPAN should be initiated with low doses (i.e., 500 mg at bedtime) and the NIASPAN dose should then be titrated to the desired therapeutic response.
• Cases of severe hepatic toxicity, including fulminant hepatic necrosis, have occurred in patients who have substituted sustained-release (modified-release, timed-release) niacin products for immediate-release (crystalline) niacin at equivalent doses.
• NIASPAN should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of NIASPAN.
• Niacin is rapidly metabolized by the liver, and excreted through the kidneys. NIASPAN is contraindicated in patients with significant or unexplained hepatic impairment and should be used with caution in patients with renal impairment. Patients with a past history of jaundice, hepatobiliary disease, or peptic ulcer should be observed closely during NIASPAN therapy.
• Cases of rhabdomyolysis have been associated with concomitant administration of lipid altering doses (≥1 g/day) of niacin and statins. Patients on combined treatment with NIASPAN and statins should be monitored for muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Periodic serum creatine phosphokinase (CPK) and potassium determinations should be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy.
• The risk for myopathy and rhabdomyolysis are increased when lovastatin or simvastatin are coadministered with NIASPAN, particularly in elderly patients and patients with diabetes, renal failure, or uncontrolled hypothyroidism. Combination therapy with NIASPAN and lovastatin or NIASPAN and simvastatin should not exceed doses of 2000 mg NIASPAN and 40 mg lovastatin or simvastatin daily.
• Liver function tests should be performed on all patients before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (e.g., at approximately 6-month intervals). If the serum transaminase levels show evidence of progression, particularly if they rise to 3 times ULN and are persistent, or if they are associated with symptoms of nausea, fever, and/or malaise, the drug should be discontinued.
• Niacin treatment can increase fasting blood glucose. Frequent monitoring of blood glucose should be performed to ascertain that the drug is producing no adverse effects. Diabetic patients may experience a dose-related increase in glucose intolerance. Diabetic or potentially diabetic patients should be observed closely during treatment with NIASPAN, particularly during the first few months of use or dose adjustment; adjustment of diet and/or hypoglycemic therapy may be necessary.
• NIASPAN has been associated with decreases in platelet count and increases in prothrombin time; accordingly, patients undergoing surgery should be carefully evaluated. Caution should be observed when NIASPAN is administered concomitantly with anticoagulants; prothrombin time and platelet counts should be monitored closely in such patients.
• Elevated uric acid levels have occurred with niacin therapy, therefore use with caution in patients predisposed to gout. Transient decreases in serum phosphorus have been reported with the use of NIASPAN.
• The most commonly reported adverse reactions (incidence >5% and greater than placebo) in clinical trials with NIASPAN were flushing, diarrhea, nausea, vomiting, increased cough and pruritus.
• Bile acid sequestrants should be taken at least 4-6 hours apart from NIASPAN administration.
• The most common adverse event with NIASPAN is flushing (up to 88% in placebo-controlled trials; 6% of patients discontinued). Flushing is a redness, warmth, itching, and/or tingling sensation on the face, neck, chest, and/or back. Spontaneous reports suggest that flushing may also be accompanied by dizziness, tachycardia, palpitations, shortness of breath, sweating, chills, and/or edema, which in rare cases may lead to syncope. Flushing of the skin may be reduced in frequency or severity by pretreatment with aspirin (up to the recommended dose of 325 mg taken 30 minutes prior to NIASPAN dose).

INDICATIONS

• Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and other nonpharmacological measures alone has been inadequate.
• NIASPAN^® (niacin extended-release tablets) is indicated to reduce elevated TC, LDL-C, Apo B and TG levels, and to increase HDL-C in patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb).
• NIASPAN in combination with simvastatin or lovastatin is indicated for the treatment of primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb) when treatment with NIASPAN, simvastatin, or lovastatin monotherapy is considered inadequate.
• In patients with a history of myocardial infarction and hyperlipidemia, niacin is indicated to reduce the risk of recurrent nonfatal myocardial infarction.
• In patients with a history of coronary artery disease and hyperlipidemia, niacin, in combination with a bile acid binding resin, is indicated to slow progression or promote regression of atherosclerotic disease.
• Limitations of Use: No incremental benefit of NIASPAN coadministered with simvastatin or lovastatin on cardiovascular morbidity and mortality over and above that demonstrated for niacin, simvastatin, or lovastatin monotherapy has been established. NIASPAN has not been studied in Fredrickson Type I and III dyslipidemias.

References

1. NIASPAN^® [package insert]. North Chicago, IL; Abbott Laboratories.
2. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289-1298.
3. Blankenhorn DH, Nessim SA, Johnson RL, et al. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987;257:3233-3240.
4. The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA. 1975;231:360-381.

303-352108