LYRICA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYRICA (LYRICA).
Binds to the α2-δ subunit of voltage-gated calcium channels, reducing calcium influx and inhibiting release of excitatory neurotransmitters including glutamate, norepinephrine, and substance P.
| Metabolism | Negligible metabolism; excreted primarily unchanged in urine. Undergoes minimal hepatic metabolism (<2% of dose). |
| Excretion | Renal excretion of unchanged drug accounts for approximately 90% of elimination; less than 1% is secreted in feces or bile. Dose adjustment required in renal impairment (CrCl <60 mL/min). |
| Half-life | Terminal elimination half-life is 6.3 hours (range 5.5–6.7 hours) in patients with normal renal function. Half-life increases in renal impairment (up to 48 hours in anuria). |
| Protein binding | Pregabalin is not bound to plasma proteins (<1% bound); binding to albumin or α1-acid glycoprotein is negligible. |
| Volume of Distribution | Volume of distribution is approximately 0.5 L/kg (range 0.4–0.6 L/kg), indicating distribution into total body water. Low Vd suggests minimal tissue binding. |
| Bioavailability | Oral bioavailability is ≥90% following oral administration, independent of dose (up to 600 mg/day). Food does not affect the extent of absorption but may decrease peak concentration by 25–30% and delay Tmax by 2.5 hours. |
| Onset of Action | Oral: Onset of analgesic effect typically occurs within 1 week of therapeutic dosing; for adjunctive therapy in partial seizures, onset may be observed within 1–2 weeks. No parenteral route approved. |
| Duration of Action | Dosing interval is every 8 to 12 hours based on renal function. In patients with normal renal function, steady state is achieved within 24–48 hours. Duration of effect after a single dose is about 6–8 hours. |
| Action Class | Alpha 2 delta ligands (AED) |
| Brand Substitutes | Nervzone 75mg Capsule, Nova 75 Capsule, Pregabel 75 Capsule, Prosovit 75 Capsule, Pregalyv 75mg Capsule, Preglobin 150mg Capsule, Nuramed 150mg Capsule, Pregabanyl 150 Capsule, Recobal 150mg Capsule, Pregabin 150mg Capsule |
Oral: 75-150 mg twice daily or 50-100 mg three times daily; maximum 600 mg/day. Start at 75 mg twice daily.
| Dosage form | CAPSULE |
| Renal impairment | CrCl 30-59 mL/min: 75-300 mg/day in 2-3 divided doses; CrCl 15-29 mL/min: 25-150 mg/day once or twice daily; CrCl <15 mL/min: 25-75 mg once daily. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). For severe hepatic impairment (Child-Pugh C), reduce dose by 50%. |
| Pediatric use | For partial-onset seizures (4 years and older): 3.5 mg/kg/day in 3 divided doses, titrate up to 10.5 mg/kg/day based on response. For fibromyalgia (not approved in pediatric). |
| Geriatric use | Initiate at lower doses (e.g., 75 mg twice daily) due to reduced renal function; titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LYRICA (LYRICA).
| Breastfeeding | Pregabalin is excreted into human milk. The milk-to-plasma ratio (M/P) is approximately 0.76. Limited data suggest that infant exposure through breast milk is about 7% of the maternal weight-adjusted dose. Effects on the breastfed infant are unknown. Caution should be exercised when administered to a nursing woman. |
| Teratogenic Risk | Pregabalin (LYRICA) is classified as Pregnancy Category C. Animal studies have shown fetal developmental toxicity at clinically relevant doses. There are no adequate and well-controlled studies in pregnant women. First trimester exposure may be associated with an increased risk of major congenital malformations, particularly cardiac defects. Third trimester use may increase the risk for neonatal withdrawal symptoms, including respiratory distress, hypotonia, and feeding difficulties. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to pregabalin or any component of the formulation","Concomitant use with thiazolidinediones (TZDs) due to increased risk of edema and weight gain (relative contraindication)"]
| Precautions | ["Angioedema (can occur with or without history of angioedema, including laryngeal edema)","Hypersensitivity reactions (including skin lesions, eosinophilia, and drug reaction with eosinophilia and systemic symptoms [DRESS])","Suicidal behavior and ideation (antiepileptic drugs increase risk; monitor for depression/suicidality)","Respiratory depression (risk increased with concomitant CNS depressants or in patients with respiratory impairment)","Dizziness and somnolence (impair ability to drive or operate machinery)","Increased seizure frequency or status epilepticus (abrupt discontinuation may increase seizure frequency)","Peripheral edema (use with caution in patients with compromised cardiovascular function)","Weight gain (observed in clinical trials)"] |
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| Fetal Monitoring | For pregnant women exposed to pregabalin, consider serial fetal ultrasounds to detect congenital anomalies. Monitor for neonatal withdrawal symptoms after delivery, including respiratory depression, hypotonia, feeding difficulties, and irritability. For lactation, monitor infant for signs of sedation, poor feeding, or respiratory depression. |
| Fertility Effects | In animal studies, pregabalin did not impair fertility in male or female rats. Human data on fertility effects are lacking. No specific adverse effects on human reproduction or fertility have been reported. |