What are the potential drug interactions with Pregabalin (Lyrica)?

Drug Interactions with Pregabalin (Lyrica)

Pregabalin has minimal drug interactions due to its lack of hepatic metabolism and protein binding, making it a relatively safe option when combined with most medications. 1

Pharmacokinetic Properties Contributing to Low Interaction Risk

• Pregabalin is predominantly excreted unchanged in the urine (less than 2% metabolized), does not bind to plasma proteins, and does not affect the cytochrome P450 enzyme system, resulting in minimal pharmacokinetic drug interactions 1, 2
• Pregabalin has highly predictable and linear pharmacokinetics with high bioavailability and a mean elimination half-life of 6.3 hours 2
• Pregabalin does not induce or inhibit liver enzymes, further reducing the risk of pharmacokinetic interactions with other medications 2

Confirmed Lack of Pharmacokinetic Interactions

• No significant pharmacokinetic interactions have been observed with common antiepileptic drugs including carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate 1, 3
• Pregabalin does not affect the pharmacokinetics of oral contraceptives containing norethindrone and ethinyl estradiol 1
• No pharmacokinetic interactions have been observed with lorazepam, oxycodone, or ethanol 1
• Pregabalin does not interact pharmacokinetically with gabapentin, although there may be a small reduction in pregabalin absorption rate when co-administered 1
• No pharmacokinetic interactions have been observed with hypoglycemic agents (glyburide, insulin, metformin) or diuretics (furosemide) 1

Pharmacodynamic Interactions and Clinical Concerns

• Opioid combination risk: Co-administration of pregabalin with opioids requires caution due to additive effects on cognitive and gross motor functioning, although no significant effects on respiration were observed in controlled studies 1
• A population-based study found that concomitant use of gabapentin (a similar medication to pregabalin) with opioids was associated with a significantly increased risk of opioid-related death, suggesting potential similar concerns with pregabalin-opioid combinations 4
• Pregabalin may have additive central nervous system depressant effects when combined with other CNS depressants 5
• When used with benzodiazepines or other anxiolytics, pregabalin may enhance sedative effects 6

Special Populations and Dosing Considerations

• Dose adjustment is necessary in patients with renal impairment as pregabalin clearance is nearly proportional to creatinine clearance 1
• Pregabalin oral clearance tends to decrease with increasing age, potentially requiring dose adjustments in elderly patients 1
• In perioperative settings, pregabalin is often used as part of multimodal analgesia but should be used with caution due to potential sedative side effects, especially in elderly patients 5
• When used for neuropathic pain, pregabalin starting dose should be 50 mg three times daily or 75 mg twice daily, with gradual titration based on efficacy and tolerability 5

Adverse Effects to Monitor When Using with Other Medications

• Common adverse effects include dizziness, somnolence, peripheral edema, weight gain, blurred vision, and cognitive effects (confusion) 5
• Higher doses of pregabalin are associated with increased risk of withdrawal due to adverse events 5
• When used preoperatively, pregabalin may cause increased postoperative sedation, dizziness, and visual disturbances 5
• Pregabalin may have depressant effects when combined with certain antidepressants, potentially reversing their antidepressant effects 6

Clinical Recommendations

• When combining pregabalin with other medications, monitor for increased sedation, dizziness, and cognitive impairment, particularly with CNS depressants 5
• Use caution when combining pregabalin with opioids due to potential additive effects on sedation and possible increased risk of opioid-related adverse outcomes 1, 4
• Consider selective serotonin reuptake inhibitors (SSRIs) rather than tricyclic antidepressants when co-prescribing with pregabalin based on interaction profiles 6
• Start with lower doses and titrate slowly in elderly patients or those with renal impairment 5, 1
• Pregabalin dosing should be adjusted according to renal function, as it is primarily excreted unchanged by the kidneys 1