alirocumab (Praluent)
Jump to navigation
Jump to search
Indications
- coronary artery disease
- lowers risk major adverse cardiovascular events (1.7% vs 3.3%) RR=0.52
- lowers risk of cardiovascular mortality or cardiovascular event within 3 years of acute coronary syndrome (15%)[9][10]*
- familial hypercholesterolemia (FDA approved July 2015)[4][5]
- secondary prevention of cardiovascular events[12] FDA-approved April 2019
- statin intolerant, LDL cholesterol above goal, taking ezetimibe
* addition to high-intensity statin[9][10]
Dosage
- 75 or 150 mg SQ biweekly
Adverse effects
- itching, swelling, pain, bruising at the injection site
- nasopharyngitis
- flu-like syndreom
- hypersensitivity reactions requiring hospitalization
- reportedly, no increased risk of peripheral neuropathy, cognitive impairment, or diabetes complications with LDL cholesterol levels < 25 mg/dL[7]
- cataracts[7]
- antidrug antibodies (5.1% vs 1.0% for placebo)
- patients with antidrug antibodies still with lowering of LDL cholesterol & without apparent adverse reactions other then more frequent injection site reactions[8]
- increased risk of new onset diabetes mellitus type 2 (absolute risk 0.9%)[13]
- drug adverse effects of anti-hyperlipidemic agents
- drug adverse effects of PCSK9 inhibitor(s)
- drug adverse effects of pharmaceutical monoclonal antibodies
Drug interactions
- in combination with statin[2]
- increases risk of myalgia (5.4% vs 2.9%)
- increases risk of neurocognitive events (1.2% vs 0.5%)
- increases risk of ophthalmologic events (2.9% vs 1.9%)
Mechanism of action
- PCSK9 inhibitor
- average reduction in LDL cholesterol ranging 36-59 mg/dL vs placebo[5]
- lowers LDL cholesterol in patients taking statin
- lowers Lp(a)[13]
Clinical trials
- post-hoc analysis of Odyssey long-term
- alirocumab reduces cardiac death, myocardial infarction, & unstable angina requiring hospitalization (1.4 vs 3% for placebo)[1]
- no established differences in health outcomes relative to statins alone[3]
Notes
- available at list price of $5850 a year for the 75 mg & 150 mg doses beginning in early March 2019[11]
More general terms
References
- ↑ 1.0 1.1 Physician's First Watch, Sept 2, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief News from the European Society of Cardiology Congress. Massachusetts Medical Society http://www.jwatch.org
- ↑ 2.0 2.1 Robinson JG et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015 Mar 15; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25773378 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1501031
- ↑ 3.0 3.1 Husten L, Di Francesco S Success of Two New Cholesterol Drugs May Come Down to Convenience, Dosing, and Cost. Physician's First Watch, May 27, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
- ↑ 4.0 4.1 Young K, Saitz R FDA Advisers Recommend First-in-Class Cholesterol-Lowering Meds Physician's First Watch, June 11, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
FDA Briefing Document BLA 125559. June 9, 2015 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM449865.pdf - ↑ 5.0 5.1 5.2 5.3 Brauser D FDA Approves New LDL-Lowering Agent Alirocumab (Praluent). Medscape Oncology. July 24, 2015 http://www.medscape.com/viewarticle/848535
FDA News Release. July 24, 2015 FDA approves Praluent to treat certain patients with high cholesterol. First in a new class of injectable cholesterol- lowering drugs http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455883.htm - ↑ Prescriber's Letter 22(8): 2015 PCSK9 Inhibitors for High Cholesterol Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=310813&pb=PRL http://www.prescribersletter.com (subscription needed)
- ↑ 7.0 7.1 7.2 Robinson JG, Rosenson RS, Farnier M Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab. Pooled Data From Randomized Trials. J Am Coll Cardiol 69(5) Feb 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28153102 Free Article <Internet> http://www.onlinejacc.org/content/69/5/471
Everett BM Low-Density Lipoprotein Cholesterol and the On-Target Effects of Therapy. How Low Is Too Low? J Am Coll Cardiol 69(5) Feb 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28153103 - ↑ 8.0 8.1 Roth EM, Goldberg AC, Catapano A et al. Antidrug antibodies in patients treated with alirocumab. N Engl J Med 2017 Mar 17 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28304229
- ↑ 9.0 9.1 9.2 Wendling P ODYSSEY Outcomes: Alirocumab Cuts CV Events, All-Cause Death Post-ACS. Medscape - Mar 10, 2018. https://www.medscape.com/viewarticle/893754
ClinicalTrials.gov ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab. https://clinicaltrials.gov/ct2/show/NCT01663402 - ↑ 10.0 10.1 10.2 Schwartz GG, Steg G, Szarek M et al Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. Nov 7, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30403574 Free full text https://www.nejm.org/doi/full/10.1056/NEJMoa1801174
- ↑ 11.0 11.1 Wendling P Second Price Cut for PCSK9 Inhibitor Alirocumab (Praluent). Medscape - Feb 12, 2019. https://www.medscape.com/viewarticle/908990
- ↑ 12.0 12.1 Regeneron News Release. April 26, 2019 FDA Approves Praluent<TM> (alirocumab) to Prevent Heart Attack, Stroke and Unstable Angina Requiring Hospitalization. https://investor.regeneron.com/news-releases/news-release-details/fda-approves-praluentr-alirocumab-prevent-heart-attack-stroke
- ↑ 13.0 13.1 13.2 Brooks M Lp(a) Lowering With Alirocumab Tied to Small Increase in Risk of Type 2 Diabetes. Medscape - Apr 01, 2021 https://www.medscape.com/viewarticle/948542
Schwartz GG, Szarek M, Bittner VA Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment. Diabetes Care 2021 Mar; dc202842. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33722880 https://care.diabetesjournals.org/content/early/2021/03/10/dc20-2842