PRALUENT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRALUENT (PRALUENT).
Praluent (alirocumab) is a human monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9). By inhibiting PCSK9 binding to the low-density lipoprotein receptor (LDLR), it prevents PCSK9-mediated LDLR degradation, thereby increasing the number of LDLRs available on hepatocyte surfaces to clear LDL-C from the blood.
| Metabolism | Alirocumab is a monoclonal antibody; it is degraded into small peptides and amino acids via general protein catabolism. No specific metabolic enzymes (e.g., CYP450) are involved. |
| Excretion | Degraded into small peptides and amino acids via proteolytic catabolism; no significant renal or biliary excretion of intact drug. |
| Half-life | Terminal half-life: 17–20 days. Supports every 2-week or every 4-week subcutaneous dosing. |
| Protein binding | Binds to PCSK9 with high affinity; no significant binding to plasma proteins. |
| Volume of Distribution | Approximately 0.04–0.05 L/kg, consistent with limited distribution in the vascular space. |
| Bioavailability | Subcutaneous: 85–90% absolute bioavailability. |
| Onset of Action | Subcutaneous: LDL-C reduction observed within 4 weeks of initiation. |
| Duration of Action | Pharmacodynamic effect persists for up to 4 weeks after a single subcutaneous dose. Maximal LDL-C reduction sustained with continuous dosing. |
Praluent (alirocumab) is administered subcutaneously at a dose of 75 mg every 2 weeks. If additional LDL-C lowering is needed, the dose may be increased to 150 mg every 2 weeks or 300 mg every 4 weeks. The starting dose is 75 mg every 2 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment is required for patients with renal impairment, including those with end-stage renal disease (ESRD), as alirocumab pharmacokinetics are not significantly affected by renal function. |
| Liver impairment | No dose adjustment is required for patients with mild or moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution. |
| Pediatric use | The safety and efficacy of Praluent in pediatric patients have not been established; therefore, no specific dosing guidelines are available for children. |
| Geriatric use | No specific dose adjustment is recommended for elderly patients (age ≥65 years). Clinical studies included elderly patients and no overall differences in safety or efficacy were observed. However, greater sensitivity of some older individuals cannot be ruled out. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRALUENT (PRALUENT).
| Breastfeeding | Unknown if excreted in human milk. Human IgG is present in milk but published data suggest that breast milk IgG does not enter neonatal and infant circulations in substantial amounts. Because many drugs are excreted in human milk, caution should be exercised when Praluent is administered to a nursing woman. M/P ratio not available. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproductive studies, there was no evidence of fetal harm at doses up to 5-8 times the maximum recommended human dose (MRHD) based on AUC. However, because animal reproduction studies are not always predictive of human response, Praluent should be used during pregnancy only if clearly needed. Monoclonal antibodies are transported across the placenta linearly as pregnancy progresses; therefore, potential exposure to a fetus increases with gestational age. Risk of congenital anomalies and miscarriage cannot be reliably estimated. |
■ FDA Black Box Warning
No boxed warning.
| Serious Effects |
["History of serious hypersensitivity reaction to alirocumab or any excipients"]
| Precautions | ["Hypersensitivity reactions (e.g., pruritus, rash, urticaria) including serious allergic reactions (e.g., angioedema) have been reported; discontinue if signs of serious allergic reaction occur","Increased risk of myalgia and possibly myopathy when used with statins; monitor for muscle symptoms","Hepatic effects: increases in transaminases were infrequent but have been observed; monitor liver enzymes as clinically indicated","Immunogenicity: anti-drug antibodies may develop; clinical significance unknown"] |
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| Fetal Monitoring | No specific maternal or fetal monitoring required beyond standard pregnancy care. Monitor for adverse events, particularly hypersensitivity reactions (angioedema, urticaria) and injection site reactions. Consider monitoring lipid profiles as clinically indicated. |
| Fertility Effects | No human data on fertility. In animal studies, there were no effects on mating or fertility indices in male or female rats at doses up to 150 mg/kg (approximately 5-8 times the MRHD based on AUC). Praluent may impair fertility in females of reproductive potential due to potential effects on ovulation based on animal studies (reduced corpora lutea observed in some studies). |