Flushing Profile of Extended-Release Niacin/Laropiprant Versus Gradually Titrated Niacin Extended-Release in Patients With Dyslipidemia With and Without Ischemic Cardiovascular Disease

A “Hot” Topic in Dyslipidemia Management—“How to Beat a Flush”: Optimizing Niacin Tolerability to Promote Long-term Treatment Adherence and Coronary Disease Prevention

“…57 Regimens of patients receiving the PGD 2 antagonist laropiprant along with extended-release niacin have consisted of a 2-step schedule: initiating niacin treatment at the relatively high daily dose of 1.0 g, which was maintained for 4 weeks, and then escalating to 2 g at treatment week 4 and maintaining this dose for 12 weeks. 142 In my practice, we use a combination of these 2 approaches, starting low (0.5 g/d) and going slowly (for a total of 8 weeks) until a stable dose of 1.0 g has been reached. At this juncture, the daily niacin dose is increased directly from 1.0 g to the maintenance daily dose of 2.0 g (if tolerated).…”

“…144 In a recent study (reported after the literature search had been conducted), frequencies of gastrointestinal adverse events were comparable in patients randomized to laropiprant and extended-release niacin (1.0 g for 4 weeks followed by 2.0 g for 12 weeks) or extended-release niacin monotherapy (0.5 g titrated to 2.0 g at 0.5-g monthly increments) when data were normalized by time of exposure to extended-release niacin at 2.0 g (1.7% vs 1.8%). 142 In this study, approximately 7% of patients in the laropiprant plus extended-release niacin group discontinued treatment because of flushing, compared with 12% in the extendedrelease niacin group (P=.002). 142 In contrast, patients receiving laropiprant and extendedrelease niacin may have increased frequencies of niacin-related, nonflushing adverse events (vs extended-release niacin monotherapy) because of dose inequities; recipients of laropiprant and extended-release niacin might experience a somewhat higher frequency of nonvasodilatory untoward effects because they are able to achieve higher niacin doses without flushing.…”

“…142 In this study, approximately 7% of patients in the laropiprant plus extended-release niacin group discontinued treatment because of flushing, compared with 12% in the extendedrelease niacin group (P=.002). 142 In contrast, patients receiving laropiprant and extendedrelease niacin may have increased frequencies of niacin-related, nonflushing adverse events (vs extended-release niacin monotherapy) because of dose inequities; recipients of laropiprant and extended-release niacin might experience a somewhat higher frequency of nonvasodilatory untoward effects because they are able to achieve higher niacin doses without flushing. Treatment adjuncts such as laropiprant and aspirin typically need to be used for a relatively For personal use.…”

HDL-C: Does it matter? An update on novel HDL-directed pharmaco-therapeutic strategies

“…However, the side effect of flushing of the face and upper body reduces compliance and leads to discontinuation of therapy in up to 25% to 40% of patients (44).The discovery of the niacin receptor GPR109A90 promised to usher in a new era in which the molecular mechanisms underlying the effects of niacin on lipids, and its adverse effects could be clearly defined (67). Co administration of the DP1 antagonist laropiprant reduces the incidence of the skin-related adverse effects of niacin (68). However, flushing still occurs in over half of the patients, and discontinuation of niacin treatment owing to severe skin-related symptoms remains a problem (69).…”

“…Co administration of the DP1 antagonist laropiprant reduces the incidence of the skin-related adverse effects of niacin (68). However, flushing still occurs in over half of the patients, and discontinuation of niacin treatment owing to severe skin-related symptoms remains a problem (69). A study in mice implicated keratinocyte-produced prostaglandin, PGE2 as a key mediator of niacin-induced skin flushing, suggesting that this molecule might be another potential target to minimize flushing (70, 71).…”