LYRICA in neuropathic pain (NeP) and fibromyalgia: proposed mechanism of action^1*

• LYRICA binds to the α2-δ subunit of the voltage-gated calcium channels in central nervous system tissues. In vitro, pregabalin reduces calcium influx at nerve terminals which may inhibit the release of excitatory neurochemicals such as glutamate
• Through this mechanism, LYRICA may modulate nerve impulses involved in the transmission of pain

* Clinical significance is unknown.

Powerful and sustained pain relief demonstrated in diabetic peripheral neuropathy (DPN) patients^2†

Mean weekly pain scores in patients with NeP due to DPN

Powerful and sustained pain relief demonstrated in postherpetic neuralgia (PHN) patients^3‡

Mean weekly pain scores in patients with NeP due to PHN

Powerful and sustained pain relief demonstrated in spinal cord injury patients suffering from NeP^4§

Mean weekly pain scores in patients with NeP due to spinal cord injury

† 5-week, double-blind, placebo-controlled, parallel-group study. 338 patients with DPN were randomized to receive LYRICA 75, 300 or 600 mg/day TID or placebo. Primary efficacy measurement was mean pain score at endpoint, derived from ratings recorded by patients in a daily diary on an 11-point numerical pain rating scale (0 = no pain, 10 = worst possible pain). Mean pain scores at baseline were 6.6 for placebo, 6.2 for LYRICA 300 mg/day and 6.2 for LYRICA 600 mg/day.

‡ 13-week, multicentre, double-blind, placebo-controlled trial. 368 patients with PHN were randomized to receive pregabalin 150 mg/day, 300 mg/day, 600 mg/day or placebo. In the 600 mg/day arm, patients with creatinine clearance (CLcr) >60 mL/min received 600 mg/day, while patients with CLcr ≤60 mL/min received 300 mg/day for an exposure equivalent to that in patients with CLcr >60 mL/min. The primary efficacy measurement was mean pain score at endpoint, derived from ratings recorded by patients in a daily diary on an 11-point numerical pain rating scale (0 = no pain, 10 = worst possible pain). Mean pain scores at baseline were 6.85 for placebo, 6.44 for LYRICA 150 mg/day, 6.72 for LYRICA 300 mg/day and 6.65 for LYRICA 600 mg/day.

§ Data based on a 12-week, parallel-group, double-blind, flexible-dose, placebo-controlled study. 137 patients with spinal cord injury for ≥1 year that had moderate-to-severe pain, i.e., mean baseline score (mean of the last 7 daily pain scores prior to study medication) of ≥4 were randomized to LYRICA 150 to 600 mg/day (n=70) or placebo (n=67) BID. In both the placebo and pregabalin groups, the majority of patients were taking concomitant analgesics, anti-inflammatories, and antidepressants for pain during the study. Pain scores rated on 11-point numerical scale from 0 (no pain) to 10 (worst possible pain) during the past 24 hours averaged over the last seven days. Percent of patients with mild (0-3), moderate (4-6) and severe (7-10) pain at baseline and endpoint was measured using average daily pain score from diary. Endpoint data were based upon last observation carried forward analysis.

References:

1. Upjohn Canada ULC. LYRICA Product Monograph. Available from: https://www.pfizer.ca/sites/default/files/202005/Lyrica_PM_E_237599_2020.05.11.pdf
2. Lesser H, et al. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004;63(11):2104-2110.
3. van Seventer R, et al. Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin. 2006;22(2):375-384.
4. Siddall PJ, et al. Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Neurology. 2006;67(10):1792-1800.

Safety profile

Adapted from Product Monograph¹

Most commonly reported treatment-emergent adverse events in NeP associated with PHN

Adapted from Product Monograph¹

Most commonly reported treatment-emergent adverse events in NeP associated with spinal cord injury

Adapted from Product Monograph¹

* Investigator term; summary level term is amblyopia.
† Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slow thinking.

Reference:

1. Upjohn Canada ULC. LYRICA Product Monograph. Available from:https://www.pfizer.ca/sites/default/files/202005/Lyrica_PM_E_237599_2020.05.11.pdf

Recommended dosing^1*

Adapted from Product Monograph¹

• Recommended starting dose for LYRICA is 75 mg BID or 50 mg TID in DPN and PHN

Dosing considerations for the renally impaired¹

• Dosage reduction is required in patients with renal impairment (creatinine clearance <60 mL/min) and in some elderly patients as LYRICA is primarily eliminated by renal excretion

LYRICA dosage adjustment based on renal function

BID = Two divided doses; QD = Single daily dose; TID = Three divided doses.

§ Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose.
¶ Based on individual patient response and tolerability.
** Supplementary dose is a single additional dose.

Available doses

Please refer to the Product Monograph for complete dosing instructions.

* Please consult Prescribing Information for complete Dosage and Administration instructions.

† Based upon individual response and tolerability.

‡ For patients who experience significant and ongoing pain and can tolerate 300 mg/day well, a maximum daily dose of 600 mg/day can be used. In clinical trials, the 600 mg/day dose did not provide additional significant efficacy and patients treated with this dose experienced markedly higher rates of adverse events and discontinued the trial more frequently. In fibromyalgia patients, the decision to treat with doses above 450 mg/day should be based upon the clinical judgement of the treating physician. Doses above 600 mg/day have not been studied and are not recommended.

Reference:

1. Upjohn Canada ULC. LYRICA Product Monograph. Available from:https://www.pfizer.ca/sites/default/files/202005/Lyrica_PM_E_237599_2020.05.11.pdf