ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Alirocumab: Drug information

Alirocumab: Drug information
(For additional information see "Alirocumab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Praluent
Brand Names: Canada
  • Praluent
Pharmacologic Category
  • Antilipemic Agent, PCSK9 Inhibitor;
  • Monoclonal Antibody
Dosing: Adult

Note: Use may be considered in patients who do not meet cholesterol treatment goals with dietary modification and other lipid-lowering therapies (ie, maximally tolerated statin plus ezetimibe) (Ref).

Homozygous familial hypercholesterolemia

Homozygous familial hypercholesterolemia: SUBQ: 150 mg once every 2 weeks.

Hyperlipidemia, primary

Hyperlipidemia, primary: SUBQ: Initial: 75 mg once every 2 weeks or 300 mg once every 4 weeks; for both regimens, if an adequate low-density lipoprotein cholesterol (LDL-C) response is not achieved, may increase or modify dosing regimen to a maximum of 150 mg every 2 weeks.

Heterozygous familial hypercholesterolemia undergoing LDL apheresis: SUBQ: 150 mg once every 2 weeks.

Secondary prevention of cardiovascular events

Secondary prevention of cardiovascular events: SUBQ: Initial: 75 mg once every 2 weeks or 300 mg once every 4 weeks; for both regimens, if an adequate LDL-C response is not achieved, may increase or modify dosing regimen to a maximum dose of 150 mg every 2 weeks.

Switching regimens: When switching from the monthly regimen to an every-2-week regimen, start the new dose on the next scheduled dosing date; reassess LDL-C 4 to 8 weeks after dosing change.

Missed dose: If a dose is missed ≤7 days from the usual day of administration, administer the dose as soon as possible and then resume the original schedule; otherwise, if beyond 7 days, skip the missed dose and resume the normal dosing schedule, or if dosage is monthly, start a new schedule based on this date.

Dosing: Kidney Impairment: Adult

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, dosage adjustment is unlikely to be required as monoclonal antibodies are not known to be renally eliminated.

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Local: Injection site reaction (4% to 17%, including erythema at injection site, injection site pruritus, pain at injection site, swelling at injection site, tenderness at injection site)

1% to 10%:

Gastrointestinal: Diarrhea (5%)

Hepatic: Increased serum transaminases (>3 x ULN: 2%), liver enzyme disorder (3%)

Hypersensitivity: Hypersensitivity reaction (9%, including nummular eczema and hypersensitivity angiitis)

Immunologic: Antibody development (6%; neutralizing: <1%)

Infection: Influenza (6%)

Neuromuscular & skeletal: Muscle spasm (3%), myalgia (4% to 6%)

Respiratory: Cough (3%)

Postmarketing:

Hypersensitivity: Angioedema

Respiratory: Flu-like symptoms

Contraindications

Serious hypersensitivity to alirocumab or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions, including some severe reactions requiring hospitalization (eg, hypersensitivity vasculitis, angioedema), have been reported. Discontinue treatment and initiate supportive treatment in patients who develop serious allergic reaction. Other hypersensitivity reactions, including pruritus, rash, and urticaria, have been reported.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Auto-injector, Subcutaneous:

Praluent: 75 mg/mL (1 mL); 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein]

Solution Auto-injector, Subcutaneous [preservative free]:

Praluent: 75 mg/mL (1 mL [DSC]); 150 mg/mL (1 mL [DSC]) [contains mouse (murine) and/or hamster protein]

Generic Equivalent Available: US

No

Pricing: US

Solution Auto-injector (Praluent Subcutaneous)

75 mg/mL (per mL): $303.89

150 mg/mL (per mL): $303.89

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Auto-injector, Subcutaneous:

Praluent: 75 mg/mL (1 mL); 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein]

Solution Prefilled Syringe, Subcutaneous:

Praluent: 75 mg/mL ([DSC]); 150 mg/mL ([DSC]) [contains mouse (murine) and/or hamster protein]

Prescribing and Access Restrictions

Only available via specialty pharmacies. Call 844-772-5836 or visit https://www.praluenthcp.com/support for additional information.

Administration: Adult

SUBQ: Allow solution to come to room temperature for 30 to 40 minutes prior to administration; do not warm in any other way. Do not shake. Administer by SUBQ injection into the thigh, abdomen (avoiding the 2-inch area around the navel), or upper arm; rotate injection site with each injection; may take up to 20 seconds for full dose to be injected. For the 300 mg dose, administer two 150 mg injections consecutively at 2 different injection sites. Do not inject into skin that is tender, bruised, hard, red hot or damaged, or has visible veins, scars, or stretch marks. Do not coadminister with other injectable drugs at the same injection site. Do not reuse prefilled pens/syringes; single use only. Do not administer if window on pen/syringe is solid yellow (indicates pen/syringe has been used). Do not use prefilled syringe if blue cap is missing or loose, if it has been dropped, or if damaged; avoid touching yellow safety cover. For patients undergoing LDL apheresis, may be administered without regard to the timing of apheresis.

Use: Labeled Indications

Homozygous familial hypercholesterolemia : Adjunct to other low-density lipoprotein cholesterol (LDL-C) lowering therapies in adults with homozygous familial hypercholesterolemia to reduce LDL-C.

Hyperlipidemia, primary: Adjunct to diet, alone or in combination with other LDL-C lowering therapies in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-C.

Secondary prevention of cardiovascular events: To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease (Schwartz 2018).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Pregnancy Considerations

Alirocumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Outcome data following maternal use of alirocumab during pregnancy are limited (Vuignier 2021).

Data collection to monitor pregnancy and infant outcomes following exposure to alirocumab is ongoing. Health care providers are encouraged to report exposures of alirocumab during pregnancy (1-844-734-6643).

Breastfeeding Considerations

It is not known if alirocumab is present in breast milk.

Alirocumab is a humanized monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021). Serum concentrations to a breastfeeding infant are not expected to be substantial. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of exposure to the breastfed infant, and the benefits of treatment to the mother.

Monitoring Parameters

Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter (AHA/ACC [Grundy 2018]). For patients receiving 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose (LDL-C varies considerably between doses with this regimen). Monitor for hypersensitivity reactions.

Mechanism of Action

Alirocumab is a human monoclonal antibody (IgG1isotype) that binds to proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptors (LDLR) on hepatocyte surfaces to promote LDLR degradation within the liver. LDLR is the primary receptor that clears circulating LDL; therefore, the decrease in LDLR levels by PCSK9 results in higher blood levels of LDL-C. By inhibiting the binding of PCSK9 to LDLR, alirocumab increases the number of LDLRs available to clear LDL, thereby lowering LDL-C levels.

Pharmacokinetics (Adult Data Unless Noted)

Onset: Peak effect: Proprotein convertase subtilisin kexin type 9 (PCSK9) suppression: 4 to 8 hours.

Distribution: IV: Vd: ~0.04 to 0.05 L/kg.

Metabolism: Expected to undergo proteolysis and be degraded to small peptides and amino acids.

Bioavailability: SUBQ: ~85%.

Half-life elimination: SUBQ: Steady-state: 17 to 20 days; reduced to 12 days when administered with a statin.

Time to peak: SUBQ: 3 to 7 days.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Praluent;
  • (AR) Argentina: Praluent;
  • (AT) Austria: Praluent;
  • (AU) Australia: Praluent;
  • (BE) Belgium: Praluent;
  • (BR) Brazil: Praluent;
  • (CH) Switzerland: Praluent;
  • (CO) Colombia: Praluent;
  • (CZ) Czech Republic: Praluent;
  • (DE) Germany: Praluent;
  • (EE) Estonia: Praluent;
  • (EG) Egypt: Praluent;
  • (ES) Spain: Praluent;
  • (FI) Finland: Praluent;
  • (FR) France: Praluent;
  • (GB) United Kingdom: Praluent;
  • (GR) Greece: Praluent;
  • (HK) Hong Kong: Praluent;
  • (HR) Croatia: Praluent;
  • (HU) Hungary: Praluent;
  • (IE) Ireland: Praluent;
  • (IT) Italy: Praluent;
  • (JP) Japan: Praluent;
  • (KR) Korea, Republic of: Praluent;
  • (KW) Kuwait: Praluent;
  • (LB) Lebanon: Praluent;
  • (LT) Lithuania: Praluent;
  • (LU) Luxembourg: Praluent;
  • (LV) Latvia: Praluent;
  • (MX) Mexico: Praluent | Praluente;
  • (MY) Malaysia: Praluent;
  • (NL) Netherlands: Praluent;
  • (NO) Norway: Praluent;
  • (NZ) New Zealand: Praluent;
  • (PL) Poland: Praluent;
  • (PT) Portugal: Praluent;
  • (QA) Qatar: Praluent;
  • (RO) Romania: Praluent;
  • (RU) Russian Federation: Praluent;
  • (SA) Saudi Arabia: Praluent;
  • (SE) Sweden: Praluent;
  • (SG) Singapore: Praluent;
  • (SI) Slovenia: Praluent;
  • (SK) Slovakia: Praluent;
  • (TH) Thailand: Praluent;
  • (TR) Turkey: Praluent;
  • (TW) Taiwan: Praluent;
  • (ZA) South Africa: Praluent
  1. Anderson PO. Monoclonal antibodies during breastfeeding. Breastfeed Med. 2021;16(8):591-593. doi:10.1089/bfm.2021.0110 [PubMed 33956488]
  2. Clements T, Rice TF, Vamvakas G, et al. Update on transplacental transfer of IgG subclasses: impact of maternal and fetal factors. Front Immunol. 2020;11:1920. doi:10.3389/fimmu.2020.01920 [PubMed 33013843]
  3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol [published online November 10, 2018]. Circulation. 2018. doi: 10.1161/CIR.0000000000000625. [PubMed 30586774]
  4. Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol. 2015;9(2):129-169. doi: 10.1016/j.jacl.2015.02.003. [PubMed 25911072]
  5. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(suppl 2):1-87. doi: 10.4158/EP171764.APPGL. [PubMed 28437620]
  6. Kereiakes DJ, Robinson JG, Cannon CP, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015;169(6):906-915. [PubMed 26027630]
  7. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi:10.1155/2012/985646 [PubMed 22235228]
  8. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
  9. Praluent (alirocumab) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals Inc; April 2021.
  10. Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489-1499. [PubMed 25773378]
  11. Rosenson RS. Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 1, 2021.
  12. Roth EM, Taskinen MR, Ginsberg HN, et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int J Cardiol. 2014;176(1):55-61. [PubMed 25037695]
  13. Schwartz GG, Bessac L, Berdan LG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168(5):682-689. doi: 10.1016/j.ahj.2014.07.028. [PubMed 25440796]
  14. Schwartz GG, Steg PG, Szarek M, et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097-2107. doi: 10.1056/NEJMoa1801174. [PubMed 30403574]
  15. Vuignier Y, Beaud F, Kosinski C, et al. Exposure to alirocumab during the first trimester of pregnancy: a case report. Birth Defects Res. 2021;113(15):1156-1160. doi:10.1002/bdr2.1930 [PubMed 34105316]
Topic 103073 Version 162.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟