Products
Nicotinic acid was commercially available in the form of modified-release tablets as a fixed combination with laropiprant (Tredaptive, 1000 mg/20 mg). The combination was approved in many countries in 2009, replacing earlier monopreparations such as Niaspan. The drug was withdrawn from the market on January 31, 2013.
Structure and properties
Nicotinic acid (C5H5NO2, Mr = 12.1 g/mol) is a 3-pyridine carboxylic acid. It exists as a white crystalline powder that is soluble in boiling water. Nicotinic acid is also known as niacin and is a vitamin belonging to the B complex.
Effects
Nicotinic acid (ATC C10AD02) is lipid-lowering. It lowers VLDL, LDL, and trigylcerides and increases HDL. Flushing is common during treatment (see below). This side effect is caused by prostaglandin D2 (PGD2), which causes vasodilation in the skin by binding to PGD2 receptor-1. Laropiprant blocks the binding of prostaglandin D2 to its receptor and reduces the frequency and intensity of the adverse effect. In January 2013, the European Medicines Agency assessed the drug’s benefit-risk ratio as negative. A multi-year study with 25,000 participants failed to confirm clinical efficacy when combined with statins. Nicotinic acid/laropiprant did not reduce the risk of serious cardiovascular diseases such as heart attack and stroke – but at the same time side effects, some of them severe, occurred. These findings do not relate to nicotinic acid as a vitamin. Most drugs containing vitamin B3 contain nicotinamide, which is given in much lower doses, is not lipid-lowering, and does not cause flushing.
Indications
For the treatment of disorders of lipid metabolism (combined dyslipidemia, primary hypercholesterolemia).
Dosage
According to the SmPC. Tablets are taken once daily in the evening after a meal or before bedtime after a low-fat snack. Nicotinic acid has often been given in combination with statins.
Contraindications
- Hypersensitivity
- Liver dysfunction
- Persistently elevated liver enzymes
- Active gastric ulcer
- Arterial bleeding
For complete precautions, see the drug label.
Interactions
Drug-drug interactions have been described with ion-exchange resins, antihypertensives, statins, acetylsalicylic acid, and clopidogrel. Laropiprant showed an interaction with midazolam.
Adverse effects
The most common potential adverse effect is flushing, which is a reddening of the skin that may be accompanied by a feeling of warmth, itching, and tingling. Other common side effects include diarrhea, dyspepsia, nausea, vomiting, skin rash, dizziness, headache, and paresthesias.
