LYRICA CR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYRICA CR (LYRICA CR).
Binds to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system, reducing calcium influx and inhibiting excitatory neurotransmitter release (e.g., glutamate, norepinephrine, substance P).
| Metabolism | Negligible metabolism in humans; eliminated primarily unchanged via renal excretion. <1% metabolized by CYP enzymes (minor N-methylation). |
| Excretion | Primarily renal excretion as unchanged drug (98-99% of absorbed dose); <0.1% biliary/fecal. |
| Half-life | 6.3 hours (mean terminal elimination half-life); correlates with creatinine clearance, prolonged in renal impairment. |
| Protein binding | Negligible (<1% bound to plasma proteins). |
| Volume of Distribution | 0.56 L/kg (apparent volume); consistent with distribution into total body water, minimal tissue binding. |
| Bioavailability | 90% (oral); absorption rate-limited by extended-release formulation, dose-proportional exposure. |
| Onset of Action | Steady-state within 24-48 hours with twice-daily dosing; analgesic effect onset within 1 week for neuropathic pain. |
| Duration of Action | Approximately 12 hours with twice-daily dosing; sustained relief over 24 hours with extended-release formulation. |
| Molecular Weight | 159.23 |
Initial 75 mg orally twice daily (150 mg/day), or 50 mg three times daily (150 mg/day). Based on efficacy and tolerability, may increase to 150 mg twice daily (300 mg/day) after 1 week, then to 225 mg twice daily (450 mg/day) if needed. Maximum dose 450 mg/day. Take with food. Administer whole; do not split, crush, or chew.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For CrCl ≥60 mL/min: no adjustment. CrCl 30-59: 75 mg twice daily, max 300 mg/day. CrCl 15-29: 25-50 mg twice daily, max 150 mg/day. CrCl <15: 25 mg once daily, max 75 mg/day. Post-hemodialysis: supplemental dose of 25-50 mg after each 4-hour session. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Severe hepatic impairment (Child-Pugh C): not studied; use with caution. |
| Pediatric use | Not approved for pediatric use (<18 years). Safety and efficacy not established. |
| Geriatric use | Start at low end of dosing range (75 mg twice daily). Monitor renal function closely; adjust dose per CrCl. Increased risk of dizziness and somnolence. |
| 1st trimester | Pregabalin is associated with increased risk of major congenital malformations, particularly neural tube defects, when used in the first trimester. Use is not recommended unless benefit outweighs risk. |
| 2nd trimester | Limited data; potential for fetal harm. Use only if clearly needed and potential benefits justify potential risks to fetus. |
| 3rd trimester | Pregabalin may cause neonatal withdrawal symptoms if used near term. Use with caution and monitor neonate for sedation, respiratory depression, and withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for LYRICA CR (LYRICA CR).
| Placental transfer | Pregabalin crosses the placenta. In animal studies, it was detected in fetal plasma at concentrations similar to maternal plasma. Human data are limited but suggest transfer. |
| Breastfeeding | Pregabalin is excreted in human milk in moderate amounts. In a study, the average infant dose was 0.31 mg/kg/day (about 7% of maternal weight-adjusted dose). Monitor infant for sedation, poor feeding, and respiratory depression. Consider alternative therapies, especially when breastfeeding a preterm or ill infant. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to pregabalin or any component of the formulation
| Precautions | Angioedema (including life-threatening cases) – discontinue immediately if symptoms occur, Hypersensitivity reactions (e.g., skin redness, blisters, urticaria, dyspnea, wheezing), Suicidal behavior and ideation (antiepileptic drug class effect), Dizziness and somnolence (increased risk of accidental injury, especially in elderly), Reduced renal clearance (dose adjustment required for CrCl <60 mL/min), Increased risk of respiratory depression when used with CNS depressants or in patients with respiratory compromise, Abrupt discontinuation may precipitate withdrawal symptoms (insomnia, nausea, anxiety, hyperhidrosis) or increase seizure frequency, Peripheral edema (use with caution with other agents associated with edema), Visual effects (blurred vision, diplopia, reduced visual acuity) |
| Food/Dietary | Take with or without food, but avoid high-fat meals (>600 calories, 50% fat) as they may affect absorption. No specific food interactions; however, alcohol should be avoided due to additive CNS depression. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - Limited data, potential for adverse effects. Use with caution and monitor infant. |
| Teratogenic Risk | Pregabalin is classified as Pregnancy Category C. Animal studies have shown fetal developmental toxicity at clinically relevant doses. There is insufficient human data to establish risk; however, potential risks include major malformations (particularly neural tube defects) and fetal growth restriction. Use during pregnancy only if potential benefit justifies risk. |
| Fetal Monitoring | Monitor fetal growth via ultrasound due to risk of intrauterine growth restriction. Assess for maternal sedation, dizziness, and central nervous system depression. Evaluate infant for signs of withdrawal or sedation after delivery. Consider therapeutic drug monitoring of pregabalin levels during pregnancy as clearance may increase. |
| Fertility Effects | In female animal studies, pregabalin has been associated with decreased fertility and increased embryofetal death. In male animals, fertility was reduced with increased sperm abnormalities and decreased sperm motility. Human data are lacking; advise caution in patients planning conception. |
| Clinical Pearls | LYRICA CR is an extended-release formulation of pregabalin, suitable for once-daily dosing. It must be swallowed whole without crushing, chewing, or splitting. Use is limited to neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia; not for fibromyalgia due to lack of evidence for CR formulation. Dose adjustments required for renal impairment (CrCl <60 mL/min). Abrupt discontinuation may cause withdrawal symptoms; taper over at least 1 week. Monitor for dizziness, somnolence, and peripheral edema. Concomitant use with CNS depressants increases risk of respiratory depression. |
| Patient Advice | Take exactly as prescribed, once daily, preferably at the same time each day. · Swallow the tablet whole; do not crush, chew, or break it. If a dose is missed, skip it and take the next dose at the regular time. · Do not stop taking this medication suddenly; sudden stoppage can cause insomnia, headache, nausea, or anxiety. · Avoid driving or operating heavy machinery until you know how this medication affects you, as it may cause dizziness or drowsiness. · Report any new or worsening symptoms such as muscle pain, tenderness, or weakness, as this could indicate a serious muscle problem. · Contact your doctor if you experience swelling in your hands, legs, or feet, or if you have suicidal thoughts. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) while taking this medication. · For diabetic neuropathy: pain relief may take several weeks to become noticeable. · Keep out of reach of children; dispose of unused medication via a take-back program. |