Usage
Laropiprant + Vitamin B3 (nicotinic acid) is primarily prescribed for dyslipidemia, particularly combined mixed dyslipidemia and primary hypercholesterolemia, in conjunction with lifestyle modifications like diet and exercise. Combined mixed dyslipidemia is characterized by high LDL cholesterol and triglycerides, and low HDL cholesterol. Primary hypercholesterolemia refers to high blood cholesterol without an identifiable cause. It is generally used alongside a statin or as monotherapy when statins are not tolerated. It may be used off-label for pellagra.
Its pharmacological classification is antihyperlipidemic or lipid-lowering agent.
Nicotinic acid reduces blood fat levels, but the exact mechanism is not fully understood. Laropiprant is added specifically to mitigate the flushing side effect caused by nicotinic acid.
Alternate Names
Vitamin B3 (nicotinic acid), Niacor, niacin. A combination of extended-release niacin and laropiprant is marketed under the brand name Tredaptive.
How It Works
Pharmacodynamics: Nicotinic acid reduces the production of very-low-density lipoprotein (VLDL) and its conversion to LDL. This, in turn, decreases LDL and triglyceride levels while increasing HDL. Laropiprant, a prostaglandin D2 receptor 1 antagonist, inhibits the vasodilatory effects of prostaglandin D2, thus reducing the flushing side effect of nicotinic acid.
Pharmacokinetics: Nicotinic acid is readily absorbed from the gastrointestinal tract. It is metabolized in the liver and excreted primarily in the urine. Laropiprant is also orally absorbed. It’s highly protein-bound, metabolized by CYP3A4, and eliminated through a combination of hepatic and renal pathways. Tredaptive is formulated as a modified-release tablet allowing for different release rates of the two active substances.
Mode of Action: Nicotinic acid’s lipid-lowering mechanism is not entirely clear, but it is thought to inhibit lipolysis in adipose tissue and decrease hepatic VLDL synthesis and secretion. It also reduces hepatic diacylglycerol acyltransferase 2 activity, suppressing triglyceride synthesis and VLDL secretion. Laropiprant specifically targets and blocks the prostaglandin D2 receptor 1 (DP1) receptor, preventing prostaglandin D2-mediated vasodilation responsible for flushing.
Elimination: Nicotinic acid is primarily excreted renally. Laropiprant is excreted via hepatic and renal routes.
Dosage
Standard Dosage
Adults:
The starting dose of Laropiprant + Vitamin B3 (Tredaptive) is one tablet (1000 mg nicotinic acid/20 mg laropiprant) once daily, taken orally with food in the evening. After four weeks, the dose is typically increased to two tablets (2000 mg nicotinic acid/40 mg laropiprant) once daily.
Children:
The safety and efficacy of Laropiprant + Vitamin B3 have not been established in children. Niacin (vitamin B3) is used in much lower doses for nutritional supplementation in children.
Special Cases:
- Elderly Patients: Similar dosing as adults, but initiate at the lower dose and monitor closely.
- Patients with Renal Impairment: Caution advised. Dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Contraindicated in moderate to severe hepatic impairment. Use cautiously in mild hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with diabetes, gout, peptic ulcer disease, or arterial bleeding.
Clinical Use Cases
The use of laropiprant + niacin is primarily indicated for dyslipidemia. Dosages mentioned above are applicable. The combination is not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments are primarily based on tolerability, especially the flushing side effect. Patients with renal or hepatic impairment may require dose reductions. Close monitoring of liver function tests and blood glucose is recommended.
Side Effects
Common Side Effects
Flushing (reduced by laropiprant), itching, headache, dizziness, nausea, vomiting, diarrhea, dyspepsia.
Rare but Serious Side Effects
Myopathy, rhabdomyolysis (especially when combined with statins), hepatotoxicity, severe hypotension, hyperglycemia, hyperuricemia, gastrointestinal bleeding.
Long-Term Effects
Potential long-term effects include liver damage, glucose intolerance, and gout.
Adverse Drug Reactions (ADR)
Severe hepatotoxicity, rhabdomyolysis, allergic reactions.
Contraindications
Active liver disease, severe hepatic impairment, arterial bleeding, hypersensitivity to nicotinic acid or laropiprant. Use with caution in patients with gout, diabetes, peptic ulcer disease, or a history of hypotension.
Drug Interactions
Statins (increased risk of myopathy and rhabdomyolysis), alcohol (additive vasodilation and increased risk of hepatotoxicity), antihypertensive medications (additive hypotensive effects), bile acid sequestrants, aspirin (325 mg may reduce flushing). Consult drug interaction databases for comprehensive information.
Pregnancy and Breastfeeding
The safety of Laropiprant + Vitamin B3 during pregnancy has not been well established. Higher doses of niacin have been associated with birth defects in animals. Consult a physician before use. Nicotinic acid is present in breast milk, but the amount is not sufficient to meet an infant’s nutritional needs. Consult a physician regarding use during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Nicotinic acid lowers LDL-C, triglycerides, and increases HDL-C. Laropiprant mitigates niacin-induced flushing.
- Side Effects: Flushing, itching, headache, dizziness, nausea, vomiting, diarrhea, dyspepsia, myopathy, hepatotoxicity.
- Contraindications: Active liver disease, severe hepatic impairment, arterial bleeding, hypersensitivity.
- Drug Interactions: Statins, alcohol, antihypertensives.
- Pregnancy & Breastfeeding: Consult a physician before use.
- Dosage: 1000/20 mg once daily initially, increasing to 2000/40 mg once daily.
- Monitoring Parameters: Liver function tests, blood glucose, uric acid, lipid profile.
Popular Combinations
Often combined with statins for enhanced lipid-lowering effects. However, this combination increases the risk of muscle-related side effects.
Precautions
Monitor liver function, blood glucose, and uric acid levels. Pre-screen for liver disease. Counsel patients about potential side effects, including flushing and gastrointestinal issues. Caution with alcohol and other medications that can affect the liver.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Laropiprant + Vitamin B3?
A: The starting dose is one tablet (1000 mg nicotinic acid/20 mg laropiprant) once daily. After four weeks, the dose can be increased to two tablets once daily.
Q2: What is the primary use of Laropiprant + Vitamin B3?
A: It is used to treat dyslipidemia, particularly in patients who haven’t responded well to other treatments.
Q3: What are the common side effects?
A: Flushing, itching, headache, dizziness, nausea, and gastrointestinal upset.
Q4: What is the role of laropiprant in this combination?
A: Laropiprant reduces the flushing side effect associated with nicotinic acid.
Q5: Are there any serious side effects to be aware of?
A: Yes, rare but serious side effects include myopathy, rhabdomyolysis, and liver damage.
Q6: Can this medication be taken during pregnancy or breastfeeding?
A: Consult with a doctor before using it during pregnancy or breastfeeding. The safety profile hasn’t been fully established.
Q7: How does this medication interact with statins?
A: Combining with statins can increase the risk of muscle-related side effects.
Q8: What should patients be monitored for during treatment?
A: Liver function, blood glucose levels, and uric acid levels.
Q9: What are the contraindications for Laropiprant + Vitamin B3?
A: Active liver disease, severe hepatic impairment, and arterial bleeding.
