LYRICA CR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LYRICA CR (LYRICA CR).

How it works

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).

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LYRICA CR (LYRICA CR).

Breastfeeding	Pregabalin is excreted into human milk; the milk-to-plasma ratio is estimated at 0.46 (range 0.26-0.76). Limited data suggest that infant exposure is approximately 0.3% of maternal weight-adjusted dose. Due to potential adverse effects (e.g., sedation, poor feeding), caution is advised. Consider breastfeeding only if clearly needed.
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.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to pregabalin or any component of the formulation","Concurrent use with other drugs known to cause angioedema (e.g., ACE inhibitors) due to additive risk"]

Clinical Precautions

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)"]

Clinical Tips & Counseling

Drug interactions

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LYRICA CR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LYRICA CR (LYRICA CR).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LYRICA CR (LYRICA CR).

Breastfeeding	Pregabalin is excreted into human milk; the milk-to-plasma ratio is estimated at 0.46 (range 0.26-0.76). Limited data suggest that infant exposure is approximately 0.3% of maternal weight-adjusted dose. Due to potential adverse effects (e.g., sedation, poor feeding), caution is advised. Consider breastfeeding only if clearly needed.
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.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to pregabalin or any component of the formulation","Concurrent use with other drugs known to cause angioedema (e.g., ACE inhibitors) due to additive risk"]