In a randomized, double-blind, placebo-controlled study with 31 healthy subjects, administration of aspirin (325 mg) prior to treatment with niacin (500 mg) significantly reduced the incidence of flushing associated with niacin (Whelan et al. 1992). However, concomitant administration of higher doses of aspirin (1 g) with niacin (0.075 to 0.100 mg/kg/min IV) reduced the clearance of niacin in six healthy volunteers (Ding et al. 1989). Administration of aspirin (325 mg) at least 30 minutes before niacin treatment may alleviate intolerance to cutaneous reactions associated with niacin therapy.

Lipid-lowering doses of nicotinic acid may cause hyperglycemia and lead to loss of glycemic control (PDR 2000). Patients taking niacin while on metformin should be monitored closely for glycemic control.

Niacin binds to these bile acid sequestrants and should be taken at different times of the day (Bays and Dujovne 1998).

Niacin combined with fluvastatin is more effective at lowering serum lipids than either substance administered alone (Jokubaitis 1996). A more recent study evaluating the combination of an extended-release form of niacin (1 to 2 g/day) with a statin drug in 269 hypercholesterolemic adult patients supported these findings (Guyton et al. 1998).

In a prospective, open-label trial, the combination of niacin with pravastatin produced favorable results on lipid profiles in 16 diabetic patients over 14 weeks (Gardner et al. 1997). The addition of niacin (up to 500 mg tid) to pravastatin (20 mg/day) significantly lowered LDL cholesterol levels. Only five patients required minor modifications to their hypoglycemic therapy to maintain glycemic control.

However, the risk of myopathy and/or rhabdomyolysis is increased when HMG- CoA reductase inhibitors are coadministered with niacin (Yee et al. 1998). The degree of risk may depend upon the type of drug administered because myotoxicity has been observed with lovastatin but not with fluvastatin (Hill and Bilbao 1999; Jokubaitis 1996). In addition, hepatic dysfunction may be associated with high dose niacin therapy; liver function tests should be performed periodically (PDR 2000).

Lipid-lowering doses of nicotinic acid may cause hyperglycemia and lead to loss of glycemic control (PDR 2000). However, nicotinamide has been used in conjunction with intensive insulin therapy to reduce beta-cell dysfunction in patients with recent-onset Type I diabetes (Visalli et al. 1999). In a randomized, blinded, multicenter trial with 74 patients on insulin therapy for the treatment of Type I diabetes, nicotinamide (25 mg/kg and 50 mg/kg) affected clinical remission and markers of metabolic control such as insulin dose, HbA(1c), and C-peptide. Lower doses of nicotinamide are preferable to avoid the development of insulin resistance. Patients taking both insulin and niacin should be monitored closely to maintain glycemic control.

Administration of neomycin sulfate (1 g bid) with niacin (maximum dose of 1 g tid) decreased levels of total cholesterol by 26%, LDL cholesterol by 32%, and lipoprotein by 45% (Gurakar, et al. 1985). Neomycin monotherapy only decreased levels by 18%, 23%, and 24%, respectively.

Repeated exposure to niacin (250 mg tid) and transdermal nicotine patches (21 mg/day) in a 60-year-old female patient resulted in flushing reactions within 30 minutes after taking niacin (Rockwell 1993).

Nicotinic acid may decrease the hypoglycemic effect of sulfonylureas (PDR 2000) and cause significant deterioration in glycemic control (Garg 1992).

In one study, the bioavailability of tetracycline hydrochloride was reduced significantly by concomitant administration of vitamin B complex to healthy subjects (Omray 1981). Patients should be cautioned to take vitamin B complex supplements at different times from tetracycline.

Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf. 1998;19(5):355-371.

Ding RW, Kolbe K, Merz B, de Vries J, Weber E, Benet Z. Pharmacokinetics of nicotinic acid-salicylic acid interaction. Clin Pharmacol Ther. 1989;46(6):642-647.

Gardner SF, Marx MA, White LM, et al. Combination of low-dose niacin and pravastatin improves the lipid profile in diabetic patients without compromising glycemic control. Ann Pharmacother. 1997;31(6):677-682.

Garg A. Lipid-lowering therapy and macrovascular disease in diabetes mellitus. Diabetes. 1992;41(Suppl 2):111-115.

Gurakar, A, Hoeg, J, Kostner, G, et al. Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment. Atheroscl. 1985;57:293-301.

Guyton JR, Goldberg AC, Kreisberg RA, et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholsterolemia. Am J Cardiol. 1998;82(6):737-743.

Hill MD, Bilbao JM. Case of the month: February 1999—54 year old man with severe muscle weakness. Brain Pathol. 1999;9(3):607-608.

Jokubaitis LA. Fluvastatin in combination with other lipid-lowering agents. Br J Clin Pract. 1996;Suppl. Jan;77A:28-32.

Omray A. Evaluation of pharmacokinetic parameters of tetracylcine hydrochloride upon oral administration with vitamin C and vitamin B complex. Hindustan Antibiot Bull. 1981;23(VI):33-37.

Physicians' Desk Reference, PDR. 54th ed. Montvale, NJ: Medical Economics Company; 2000.

Rockwell KA. Potential interaction between niacin and transdermal nicotine. Ann Pharmacother. 1993;27(10):1283-1288.

Visalli N, Cavallo MG, Signore A, et al. A multi-centre randomized trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes (the IMDIAB VI). Diabetes Metab Res Rev. 1999;15(3):181-185.

Whelan AM, Price SO, Fowler SF, et al. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract. 1992;34(2):165-168.

Yee HS, Fong NT, Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias. Ann Pharmacother. 1998 Oct;32(10):1030-1043.