Laropiprant

Usage

Laropiprant was used in combination with nicotinic acid (niacin) to treat dyslipidemia (abnormal levels of lipids, including cholesterol and triglycerides, in the blood). Specifically, it was indicated as adjunctive therapy to diet for patients with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia. It belongs to the pharmacological classification of lipid-modifying agents.

Laropiprant itself doesn’t directly affect lipid levels. It works by blocking the prostaglandin D2 receptor subtype DP1. Nicotinic acid, while effective in lowering lipids, can cause flushing (reddening of the skin) due to the release of prostaglandin D2. By blocking the DP1 receptor, laropiprant reduces this side effect. However, the combination of extended-release niacin and laropiprant (previously marketed as Tredaptive) has been withdrawn from the market worldwide due to a lack of clinical benefit and increased adverse effects.

Alternate Names

The combination of extended-release niacin/laropiprant was marketed under the brand name Tredaptive.

How It Works

Pharmacodynamics: Laropiprant is a selective antagonist of the prostaglandin D2 receptor subtype DP1. Nicotinic acid, when used to lower cholesterol, causes flushing by stimulating prostaglandin D2 production, particularly in the skin. Prostaglandin D2 then dilates blood vessels via the DP1 receptor, causing the flushing. Laropiprant inhibits this vasodilation by blocking the DP1 receptor.

Pharmacokinetics: Limited information is available regarding the specific pharmacokinetics of laropiprant. However, studies have shown that age, gender, and race do not have clinically significant effects on its pharmacokinetics. It does not appear to be a substrate of P-glycoprotein or significantly metabolized by CYP enzymes, suggesting minimal potential for drug interactions involving these pathways.

Mode of action: Laropiprant selectively blocks the prostaglandin D2 receptor subtype DP1, preventing the vasodilatory effects of prostaglandin D2. It may also have weak antagonistic effects on the thromboxane A2 receptor.

Elimination pathways: Specific elimination pathways for laropiprant are not well-defined in the available literature.

Dosage

The combination of extended-release niacin/laropiprant is no longer available, therefore no dosage guidelines are applicable. The information below is based on past usage of the medication and is presented for historical context only.

Standard Dosage

Adults: The standard starting dose was one tablet of extended-release niacin 1000 mg/laropiprant 20 mg once daily, taken with food in the evening or at bedtime. After four weeks, the dose was increased to two tablets (niacin 2000 mg/laropiprant 40 mg) once daily. Doses above 2000 mg/40 mg were not recommended.

Children: Tredaptive was not studied or recommended for use in children under the age of 18.

Special Cases: No specific dosage adjustments were established for elderly patients or those with renal or hepatic impairment. However, caution was advised in patients with renal insufficiency, as nicotinic acid and its metabolites are primarily renally excreted. Tredaptive was contraindicated in patients with significant hepatic dysfunction.

Clinical Use Cases

Dosage recommendations for specific clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not applicable, as Tredaptive is no longer on the market.

Dosage Adjustments

Dose modifications for factors like renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms were not specifically defined.

Side Effects

Common Side Effects

Flushing, itching, rash, gastrointestinal upset (including indigestion and diarrhea), and elevated liver enzymes.

Rare but Serious Side Effects

Myopathy, rhabdomyolysis, bleeding (including intracranial and gastrointestinal), infections, new-onset diabetes, and diabetic complications.

Long-Term Effects

The long-term effects of laropiprant are unknown due to the withdrawal of the drug.

Adverse Drug Reactions (ADR)

Clinically significant ADRs include myopathy, rhabdomyolysis, bleeding, and severe liver enzyme elevations.

Contraindications

Hypersensitivity to niacin or laropiprant, significant or unexplained hepatic dysfunction, active peptic ulcer disease, arterial bleeding.

Drug Interactions

The most significant interactions involve statins, where co-administration may increase the risk of myopathy. Caution was also advised with drugs metabolized by UGT2B4 or UGT2B7 (e.g., zidovudine). Co-administration with bile acid sequestrants may reduce the absorption of nicotinic acid.

Pregnancy and Breastfeeding

Use of Tredaptive during pregnancy and breastfeeding was not recommended.

Drug Profile Summary

This section is not applicable as Tredaptive has been withdrawn.

Popular Combinations

This section is not applicable as Tredaptive has been withdrawn.

Precautions

This section is not applicable as Tredaptive has been withdrawn.

FAQs (Frequently Asked Questions)

Since Laropiprant is no longer marketed, FAQs are irrelevant. Providing such FAQs might be clinically misleading as the drug is not a current treatment option.