Effects of Aspirin When Added to the Prostaglandin D₂ Receptor Antagonist Laropiprant on Niacin‐Induced Flushing Symptoms

Abstract

Niacin is an effective lipid-modifying therapy whose use has been limited by suboptimal tolerability. The adverse effect of flushing is due to prostaglandin D2 (PGD2)-mediated cutaneous vasodilation. Adjunctive treatment with the PGD2 receptor antagonist laropiprant significantly reduces the incidence and severity of niacin-induced flushing. The objective of this study was to assess the effect of aspirin pretreatment on flushing symptoms with extended-release (ER) niacin/laropiprant in healthy volunteers. A randomized, double-blind, placebo-controlled crossover study compared patient-rated flushing following pretreatment with aspirin 325 mg versus placebo administered 30 minutes before ER niacin 2 g/laropiprant 40 mg. Flushing responses were assessed using participant-reported overall symptom severity score (OSSS), including individual characteristics of redness, warmth, tingling, or itching. The overall incidence and severity of flushing were comparable for participants receiving aspirin or placebo before ER niacin 2 g/laropiprant 40 mg. The difference in 3-day average OSSS between treatments was 0.2 (P=.180). Profiles of flushing severity, frequency, and bothersomeness were comparable for the aspirin/ER niacin/laropiprant and ER niacin/laropiprant regimens. All treatments were safe and well tolerated. Coadministration of aspirin 325 mg daily with ER niacin 2 g/laropiprant 40 mg does not further reduce residual flushing symptoms associated with ER niacin 2 g/laropiprant 40 mg alone.

Nicotinic acid– and monomethyl fumarate–induced flushing involves GPR109A expressed by keratinocytes and COX-2–dependent prostanoid formation in mice

“…The involvement of PGE 2 in the keratinocyte-dependent late phase of flushing explains the remaining flush response seen in animals and humans after blockade of DP 1 (18,19). The fact that oral administration of 325 mg aspirin is not able to reduce the residual flushing seen when nicotinic acid is combined with the DP 1 receptor antagonist laropiprant (46) does not contradict the role of PGE 2 mainly produced via COX-2 in the flushing reaction, since 325 mg aspirin given orally may not lead to systemic aspirin concentrations sufficiently high to block COX-2 in keratinocytes and therefore block the second phase of flushing (47)(48)(49).…”

Effect of Citalopram and Aspirin on Hot Flashes and Quality of Life in Premenopausal Women with Breast Cancer: A Randomized Double-blind Clinical Trial

“…Studies have also pointed to the positive impact of aspirin on reducing hot flashes. Patients who experienced hot flashes arising from niacin were treated with aspirins, in order to control the prostaglandin it was taken 30 minutes before using niacin [15,16]. Kalay et al (2007) studied 254 menopausal women with breast cancer histories that had avoided HRT.…”

“…Aspirin was employed in this study to alleviate vascular kinetic symptoms, in order to assess both its effect on other menopausal symptoms and its promoting influence on citalopram. The effect of aspirin has previously been studied in a number of researches, and has been confirmed to be positive [15,16]. Considering the importance of premature menopause resulting from chemotherapy, reported in over 70% of women with breast cancer, this study focused on the efficacy of a drug regimen of citalopram plus aspirin, compared to citalopram plus a placebo on cancerous women with CIA symptoms.…”

Extended-release niacin with laropiprant: a review on efficacy, clinical effectiveness and safety

“…As with niacin alone, ERN/ LRPT is associated with a slight increase in fasting blood glucose and HbA1c; however, benefits from favorable lipoprotein changes are likely to outweigh any possible detrimental effect associated with this mild increase in glycemic parameters. Adding 325 mg aspirin to ERN/LRPT (2 g/40 mg) does not reduce the residual flushing any further [123]. Safety and tolerability of ERN and LRPT has been discussed in more detail by Yadav et al [55].…”