home > drugs a-z list > niaspan (niacin) drug center > niaspan (niacin) drug - warnings and precautions

Included as part of the PRECAUTIONS section.

NIASPAN (niacin) preparations should not be substituted for equivalent doses of immediate-release (crystalline) niacin. For patients switching from immediate-release niacin to NIASPAN (niacin) , therapy with NIASPAN (niacin) should be initiated with low doses (i.e., 500 mg at bedtime) and the NIASPAN (niacin) dose should then be titrated to the desired therapeutic response [see DOSAGE AND ADMINISTRATION].

Caution should also be used when NIASPAN (niacin) is used in patients with unstable angina or in the acute phase of an MI, particularly when such patients are also receiving vasoactive drugs such as nitrates, calcium channel blockers, or adrenergic blocking agents.

Niacin is rapidly metabolized by the liver, and excreted through the kidneys. NIASPAN (niacin) is contraindicated in patients with significant or unexplained hepatic impairment [see CONTRAINDICATIONS] 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 (niacin) therapy.

Skeletal Muscle

Cases of rhabdomyolysis have been associated with concomitant administration of lipid-altering doses ( > 1 g/day) of niacin and statins. Physicians contemplating combined therapy with statins and NIASPAN (niacin) should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of 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 (niacin) , particularly in elderly patients and patients with diabetes, renal failure, or uncontrolled hypothyroidism.

Liver Dysfunction

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 (niacin) 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 preparations have been associated with abnormal liver tests. In three placebo-controlled clinical trials involving titration to final daily NIASPAN (niacin) doses ranging from 500 to 3000 mg, 245 patients received NIASPAN (niacin) for a mean duration of 17 weeks. No patient with normal serum transaminase levels (AST, ALT) at baseline experienced elevations to more than 3 times the upper limit of normal (ULN) during treatment with NIASPAN (niacin) . In these studies, fewer than 1% (2/245) of NIASPAN (niacin) patients discontinued due to transaminase elevations greater than 2 times the ULN.

In three safety and efficacy studies with a combination tablet of NIASPAN (niacin) and lovastatin involving titration to final daily doses (expressed as mg of niacin/ mg of lovastatin) 500 mg/10 mg to 2500 mg/40 mg, ten of 1028 patients (1.0%) experienced reversible elevations in AST/ALT to more than 3 times the ULN. Three of ten elevations occurred at doses outside the recommended dosing limit of 2000 mg/40 mg; no patient receiving 1000 mg/20 mg had 3-fold elevations in AST/ALT.

Niacin extended-release and simvastatin can cause abnormal liver tests. In a simvastatin-controlled, 24 week study with a fixed dose combination of NIASPAN (niacin) and simvastatin in 641 patients, there were no persistent increases (more than 3x the ULN) in serum transaminases. In three placebo-controlled clinical studies of extended-release niacin there were no patients with normal serum transaminase levels at baseline who experienced elevations to more than 3x the ULN. Persistent increases (more than 3x the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminases levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. There was no evidence of hypersensitivity.

In the placebo-controlled clinical trials and the long-term extension study, elevations in transaminases did not appear to be related to treatment duration; elevations in AST levels did appear to be dose related. Transaminase elevations were reversible upon discontinuation of NIASPAN (niacin) .

Liver function tests should be performed on all patients during therapy with NIASPAN (niacin) . Serum transaminase levels, including AST and ALT (SGOT and SGPT), should be monitored before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (e.g., at approximately 6-month intervals). Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently. If the 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.

Laboratory Abnormalities

Increase in Blood Glucose: 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 (niacin) , particularly during the first few months of use or dose adjustment; adjustment of diet and/or hypoglycemic therapy may be necessary.

Reduction in platelet count: NIASPAN (niacin) has been associated with small but statistically significant dose-related reductions in platelet count (mean of -11% with 2000 mg). Caution should be observed when NIASPAN (niacin) is administered concomitantly with anticoagulants; platelet counts should be monitored closely in such patients.

Increase in Prothrombin Time (PT): NIASPAN (niacin) has been associated with small but statistically significant increases in prothrombin time (mean of approximately +4%); accordingly, patients undergoing surgery should be carefully evaluated. Caution should be observed when NIASPAN (niacin) is administered concomitantly with -anticoagulants; r»mthrpmbin time should be monitored closely in such patients.

Increase in Uric Acid: Elevated uric acid levels have occurred with niacin therapy, therefore use with caution in patients predisposed to gout.

Decrease in Phosphorus: In placebo-controlled trials, NIASPAN (niacin) has been associated with small but statistically significant, dose-related reductions in phosphorus levels (mean of -13% with 2000 mg). Although these reductions were transient, phosphorus levels should be monitored periodically in patients at risk for hypophosphatemia.

Patient Counseling Information

Patient Counseling

Patients should be advised to adhere to their National Cholesterol Education Program (NCEP) recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel.

Patients should be advised to inform other healthcare professionals prescribing a new medication that they are taking NIASPAN (niacin) .

The patient should be informed of the following:

Dosing Time

NIASPAN (niacin) tablets should be taken at bedtime, after a low-fat snack. Administration on an empty stomach is not recommended.

Tablet Integrity

NIASPAN (niacin) tablets should not be broken, crushed or chewed, but should be swallowed whole.

Dosing Interruption

If dosing is interrupted for any length of time, their physician should be contacted prior to restarting therapy; re-titration is recommended.

Muscle Pain

Notify their physician of any unexplained muscle pain, tenderness, or weakness promptly. They should discuss all medication, both prescription and over the counter, with their physician.

Flushing

Flushing (warmth, redness, itching and/or tingling of the skin) is a common side effect of niacin therapy that may subside after several weeks of consistent NIASPAN (niacin) use. Flushing may vary in severity and is more likely to occur with initiation of therapy, or during dose increases. By dosing at bedtime, flushing will most likely occur during sleep. However, if awakened by flushing at night, the patient should get up slowly, especially if feeling dizzy, feeling faint, or taking blood pressure medications. Advise patients of the symptoms of flushing and how they differ from the symptoms of a myocardial infarction.

Use of Aspirin Medication

Taking aspirin (up to the recommended dose of 325 mg) approximately 30 minutes before dosing can minimize flushing.

Diet

Avoid ingestion of alcohol, hot beverages and spicy foods around the time of taking NIASPAN (niacin) to minimize flushing.

Supplements

Notify their physician if they are taking vitamins or other nutritional supplements containing niacin or nicotinamide.

Dizziness

Notify their physician if symptoms of dizziness occur.

Diabetics

If diabetic, to notify their physician of changes in blood glucose.

Pregnancy

Discuss future pregnancy plans with your patients, and discuss when to stop NIASPAN (niacin) if they are trying to conceive. Patients should be advised that if they become pregnant, they should stop taking NIASPAN (niacin) and call their healthcare professional.

Breastfeeding

Women who are breastfeeding should be advised to not use NIASPAN (niacin) . Patients, who have a lipid disorder and are breastfeeding, should be advised to discuss the options with their healthcare professional.

Nonclinical Toxicology

Carcinogenesis and Mutagenesis and Impairment of Fertility

Niacin administered to mice for a lifetime as a 1% solution in drinking water was not carcinogenic. The mice in this study received approximately 6 to 8 times a human dose of 3000 mg/day as determined on a mg/m² basis. Niacin was negative for mutagenicity in the Ames test. No studies on impairment of fertility have been performed. No studies have been conducted with NIASPAN (niacin) regarding carcinogenesis, mutagenesis, or impairment of fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with niacin or with NIASPAN. It is also not known whether niacin at doses typically used for lipid disorders can cause fetal harm when administered to pregnant women or whether it can affect reproductive capacity. If a woman receiving niacin for primary hyperlipidemia becomes pregnant, the drug should be discontinued. If a woman being treated with niacin for hypertriglyceridemia conceives, the benefits and risks of continued therapy should be assessed on an individual basis.

All statins are contraindicated in pregnant and nursing women. When NIASPAN (niacin) is administered with a statin in a woman of childbearing potential, refer to the pregnancy category and product labeling for the statin.

Nursing Mothers

Niacin is excreted into human milk but the actual infant dose or infant dose as a percent of the maternal dose is not known. Because of the potential for serious adverse reactions in nursing infants from lipid-altering doses of nicotinic acid, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. No studies have been conducted with NIASPAN (niacin) in nursing mothers.

Pediatric Use

Safety and effectiveness of niacin therapy in pediatric patients ( ≤ 16 years) have not been established.

Geriatric Use

Of 979 patients in clinical studies of NIASPAN (niacin) , 21% of the patients were age 65 and over. No overall differences in safety and effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

No studies have been performed in this population. NIASPAN (niacin) should be used with caution in patients with renal impairment [see WARNINGS AND PRECAUTIONS].

Hepatic Impairment

No studies have been performed in this population. NIASPAN (niacin) should be used with caution in patients with a past history of liver disease and/or who consume substantial quantities of alcohol. Active liver disease, unexplained transaminase elevations and significant or unexplained hepatic dysfunction are contraindications to the use of NIASPAN [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Gender

Data from the clinical trials suggest that women have a greater hypolipidemic response than men at equivalent doses of NIASPAN (niacin) .

Last reviewed on RxList: 12/13/2010
This monograph has been modified to include the generic and brand name in many instances.