Version November 2024
Dosage guidance:
Dosing: For patients with respiratory disease, initiate therapy at the lowest dose (Ref).
Cough, chronic refractory (alternative agent) (off-label use): Immediate release: Oral: Initial: 75 mg once daily; may increase gradually over the first week in increments of 75 mg/day based on response and tolerability up to a maximum of 300 mg/day in 3 divided doses (eg, 75 mg in morning and midday with 150 mg in the evening) (Ref).
Fibromyalgia (alternative agent): Note: For patients who do not respond to or tolerate preferred agents (Ref).
Immediate release: Oral: Initial: 75 mg twice daily; may increase to 150 mg twice daily within 1 week based on response and tolerability; maximum dose: 450 mg/day (Ref). Note: Some experts suggest lower initial doses of 25 to 50 mg at bedtime; some patients may respond to maintenance doses <300 mg/day (Ref).
Generalized anxiety disorder (alternative agent) (off-label use): Note: Monotherapy or adjunctive therapy for patients who do not tolerate or respond to preferred agents (Ref).
Immediate release: Oral: Initial: 150 mg/day in 2 to 3 divided doses; may increase based on response and tolerability at weekly intervals in increments of 150 mg/day up to a usual dose of 300 mg/day. May further increase up to 600 mg/day (Ref); however, additional benefit of doses >300 mg/day is uncertain (Ref). Note: Some experts suggest a lower initial dose of 50 mg/day, with an even lower starting dose of 25 mg/day for patients who are sensitive to side effects (Ref).
Neuropathic pain:
General dosing recommendations: Immediate release: Oral: Initial: 25 mg once daily or 50 to 150 mg/day in 2 to 3 divided doses; may increase in increments of 25 to 150 mg/day at weekly intervals based on response and tolerability up to a usual dose of 300 to 600 mg/day in 2 to 3 divided doses (Ref).
Cancer-associated neuropathy (monotherapy or combination therapy) (off-label use): Oral: Immediate release: Initial: 50 to 75 mg twice daily; increase over 1 to 2 weeks based on response and tolerability up to 300 mg twice daily (Ref).
Critically ill ICU patients (monotherapy or combination therapy) (off-label use):
Note: For critically ill patients with neuropathic pain, pregabalin may be a useful component of multimodal pain control (Ref).
Oral: Initial: 75 mg once or twice daily; maintenance dose: 150 to 300 mg twice daily (Ref).
Diabetic neuropathy:
Immediate release: Oral: Initial: 75 to 150 mg/day in 2 to 3 divided doses; may increase daily dose in 75 mg increments every ≥3 days based on response and tolerability up to a maximum dose of 300 to 450 mg/day (Ref). Higher doses up to 600 mg/day may have greater adverse effects without additional benefit (Ref).
Extended release: Oral: Initial: 165 mg once daily; may increase within 1 week based on response and tolerability up to maximum dose of 330 mg once daily.
Postherpetic neuralgia:
Immediate release: Oral: Initial: 150 mg/day in divided doses (75 mg twice daily or 50 mg 3 times daily); may increase to 300 mg/day within 1 week based on response and tolerability; after 2 to 4 weeks, may further increase up to the maximum dose of 600 mg/day.
Extended release: Oral: Initial: 165 mg once daily; may increase to 330 mg once daily within 1 week based on response and tolerability; after 2 to 4 weeks, may further increase up to the maximum dose of 660 mg/day.
Spinal cord injury-associated neuropathic pain: Immediate release: Oral: Initial: 75 mg twice daily; may increase within 1 week based on response and tolerability to 150 mg twice daily; after 2 to 3 weeks, may further increase up to a maximum of 600 mg/day.
Panic disorder (augmentation) (alternative agent):
Note: Reserve for augmentation of selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor in patients who need rapid symptom relief or who only experience partial relief of symptoms on antidepressant monotherapy (Ref).
Oral: Initial: 50 mg/day; increase daily dose based on response and tolerability in 75 mg increments to a total daily dose of 300 mg/day, in divided doses (Ref).
Pruritus, chronic (alternative agent) (off-label use): Note: For patients with pruritus resistant to preferred therapies (Ref).
Neuropathic (eg, brachioradial pruritus, notalgia paresthetica) or malignancy related: Based on limited data: Immediate release: Oral: Initial: 75 mg twice daily; may increase based on response and tolerability up to 150 to 300 mg/day in 2 to 3 divided doses (Ref). Higher doses up to 600 mg/day have been used in oncology populations (Ref).
Uremic: Immediate release: Oral: Variable dosing has been used and includes: 50 mg every other day given after dialysis on hemodialysis days (Ref) or 25 mg daily (Ref), each increased based on response and tolerability to 50 or 75 mg daily. 75 mg twice weekly given after dialysis on hemodialysis days also appears effective (Ref).
Restless legs syndrome (off-label use): Immediate release: Oral: Initial: 50 to 75 mg once daily, 1 to 3 hours before bedtime; gradually increase (eg, in increments of 75 to 150 mg) every 5 to 7 days based on response and tolerability to a usual effective dose of 150 to 450 mg/day (Ref).
Seizures , focal (partial) onset (adjunctive therapy with other antiseizure medications): Immediate release: Oral: Initial: 150 mg/day in 2 or 3 divided doses; may increase based on response and tolerability at weekly intervals up to a maximum dose of 600 mg/day.
Social anxiety disorder (alternative agent) (off-label use):
Note: Reserve for patients who do not tolerate or respond to preferred agents (Ref).
Immediate release: Oral: Initial: 100 mg 3 times daily; may increase over 1 week in increments of 150 mg/day based on response and tolerability up to 600 mg/day (Ref).
Vasomotor symptoms associated with menopause (alternative agent) (off-label use): Note: Used as a nonhormonal alternative in patients unable or unwilling to take preferred agents (Ref). Some experts prefer gabapentin over pregabalin as an alternative agent because of greater available evidence (Ref).
Immediate release: Oral: Initial: 50 mg once daily at bedtime; may increase at weekly intervals based on response and tolerability to 50 mg twice daily, and then up to 75 mg twice daily; may further increase up to 150 mg twice daily (Ref).
Dosing conversion from immediate-release oral formulations to extended-release oral formulation: Note: On the day of the switch, administer morning dose of immediate-release product as prescribed, and initiate extended-release therapy after the evening meal.
Immediate-release total daily dose of 75 mg is equivalent to extended-release dose of 82.5 mg once daily
Immediate-release total daily dose of 150 mg is equivalent to extended-release dose of 165 mg once daily
Immediate-release total daily dose of 225 mg is equivalent to extended-release dose of 247.5 mg once daily
Immediate-release total daily dose of 300 mg is equivalent to extended-release dose of 330 mg once daily
Immediate-release total daily dose of 450 mg is equivalent to extended-release dose of 495 mg once daily
Immediate-release total daily dose of 600 mg is equivalent to extended-release dose of 660 mg once daily
Discontinuation of therapy: According to the manufacturer, in patients receiving pregabalin chronically, pregabalin should be withdrawn gradually over ≥1 week unless safety concerns require a more rapid withdrawal to minimize the potential of increased seizure frequency (in patients with epilepsy) or other withdrawal symptoms (eg, agitation, confusion, delirium, delusions, GI symptoms, mood changes, sweating, withdrawal seizures). For patients with epilepsy, some experts recommend discontinuing over 3 to 4 months (Ref).
Missed dose: Oral, extended release: If evening meal dose is missed, administer before bedtime following a snack. If missed before bedtime, administer in the morning with a meal. If missed in the morning, wait until the evening meal to take the next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
|
CrClc |
Immediate release |
Extended release | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
Usual indication-specific recommended dose |
Dosing frequency |
Usual indication-specific recommended dose |
Dosing frequency | |||||||
|
a Manufacturer’s labeling. | ||||||||||
|
b Choose usual dose based on indication (see "Dosing: Adult"), then choose the adjusted dose from the column corresponding to the patient's CrCl. | ||||||||||
|
c Estimated by Cockcroft-Gault equation. | ||||||||||
|
≥60 mL/minute (normal kidney function) |
150 mg/day |
300 mg/day |
450 mg/day |
600 mg/day |
2 to 3 divided doses |
165 mg/day |
330 mg/day |
495 mg/day |
660 mg/day |
Once daily |
|
30 to <60 mL/minute |
75 mg/day |
150 mg/day |
225 mg/day |
300 mg/day |
2 to 3 divided doses |
82.5 mg/day |
165 mg/day |
247.5 mg/day |
330 mg/day |
Once daily |
|
15 to <30 mL/minute |
25 to 50 mg/day |
75 mg/day |
100 to 150 mg/day |
150 mg/day |
1 to 2 divided doses |
Use not recommended (convert to pregabalin immediate release). | ||||
|
<15 mL/minute |
25 mg/day |
25 to 50 mg/day |
50 to 75 mg/day |
75 mg/day |
Single daily dose | |||||
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Immediate release: No dosage adjustment necessary; however, may consider increasing dose by 25% if poor response followed by a return to normal dosing as CrCl returns to baseline (Ref).
Extended release: Use not recommended (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (50% to 60%) (Ref):
Note: In a large observational cohort study, pregabalin use in hemodialysis was associated with up to a 51% and 68% higher risk of altered mental status and falls, respectively, compared to no use (Ref). This association was statistically significant, even in dose ranges of ≤100 mg/day. Use pregabalin cautiously in hemodialysis patients at the lowest effective dose with close monitoring (Ref).
Immediate release:
Daily dosing: Initial: 25 mg once daily, may titrate gradually based on tolerability and response to a maximum of 75 mg daily; administer after hemodialysis on dialysis days. A supplemental dose is not needed unless the usual daily dose is administered prior to the dialysis session; if this occurs, a supplementary posthemodialysis dose (50% to 100% of the usual daily dose) may be considered (Ref).
Three times weekly (posthemodialysis) dosing: 25 to 75 mg administered 3 times weekly after hemodialysis on dialysis days has been found to be effective for peripheral neuropathy and uremic pruritus (Ref).
Extended release: Use not recommended.
Peritoneal dialysis:
Immediate release: Initial: 25 mg once daily, may titrate gradually based on tolerability and response to a maximum of 75 mg once daily (Ref). Use cautiously at the lowest effective dose with close monitoring for adverse effects (Ref).
Extended release: Use not recommended (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of action is CNS) and indication (eg, antiseizure, analgesic). Close monitoring of response and adverse reactions (eg, confusion, myoclonus, altered mental status) due to drug accumulation is important.
Note: Although not studied in patients receiving CRRT, significant removal of pregabalin is expected based on pharmacokinetic properties (eg, small Vd, low protein binding) (Ref).
Immediate release: Initial: 50 to 75 mg/day in 1 to 2 divided doses; titrate gradually based on tolerability and response up to a maximum of 300 mg/day in 2 to 3 divided doses (Ref).
Extended release: Use not recommended (Ref).
PIRRT (eg, sustained low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of action is CNS) and indication (eg, antiseizure, analgesic). Close monitoring of response and adverse reactions (eg, confusion, myoclonus, altered mental status) due to drug accumulation is important.
Note: Although not studied in patients receiving PIRRT, significant removal of pregabalin is expected based on pharmacokinetic properties (eg, small Vd, low protein binding) (Ref).
Immediate release:
PIRRT days: Initial: 50 to 75 mg/day in 1 to 2 divided doses; titrate gradually based on tolerability and response up to a maximum of 300 mg/day in 2 to 3 divided doses (Ref).
Non-PIRRT days: 25 to 75 mg once daily (Ref).
Extended release: Use not recommended (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. However, no adjustment is expected since undergoes minimal hepatic metabolism.
Initiate therapy at the lowest dose (Ref). Refer to adult dosing; use with caution. In the management of restless legs syndrome, a starting dose of 50 mg once daily in patients >65 years has been recommended (Ref).
(For additional information see "Pregabalin: Pediatric drug information")
Dosage guidance:
Dosing: When discontinuing, taper off gradually over at least 1 week.
Seizures, partial onset; adjunctive therapy: Immediate release:
Infants and Children <4 years weighing <30 kg: Oral: Initial dose: 3.5 mg/kg/day in 3 divided doses; dose may be increased weekly based on clinical response and tolerability; maximum daily dose: 14 mg/kg/day.
Children ≥4 years and Adolescents <17 years:
<30 kg: Oral: Initial dose: 3.5 mg/kg/day in 2 or 3 divided doses; dose may be increased weekly based on clinical response and tolerability; maximum daily dose: 14 mg/kg/day.
≥30 kg: Oral: Initial dose: 2.5 mg/kg/day in 2 or 3 divided doses; dose may be increased weekly based on clinical response and tolerability; maximum daily dose: 10 mg/kg/day not to exceed 600 mg/day.
Adolescents ≥17 years: Oral: Initial dose: 150 mg daily in 2 or 3 divided doses; may be increased weekly based on tolerability and effect; maximum daily dose: 600 mg/day.
Fibromyalgia: Limited data available: Immediate release: Children ≥12 years and Adolescents: Oral: Initial: 37.5 mg twice daily for 1 week, then titrate based on clinical response and tolerability to 150 to 450 mg/day in 2 divided doses; maximum daily dose: 450 mg/day. Dosing based on a multi-center, double-blind, placebo-controlled trial (15 weeks) and secondary open-label continuation trial (6 months) (n=107; pregabalin n=54; age range: 12 to 17 years); total daily doses were titrated weekly to an individually optimized dose of 150 mg/day, 300 mg/day, or 450 mg/day; maximum daily dose: 450 mg/day; mean dose during maintenance phase of double-blind study was 244.5 mg/day and in the open label trial it was 254.3 mg/day. Although the primary endpoint of change in mean pain scores from baseline to week 15 was not statistically significant, there was a trend toward improvement in the pregabalin group. Change in weekly mean pain scores was significantly greater with pregabalin compared to placebo for 10 of the 15 weeks; the patient global impression of change was also significantly improved in patients receiving pregabalin (53.1%) compared to placebo (29.5%). The authors reported a large placebo effect, particularly at non-US study centers; however, significance of this is unknown (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Immediate release: There are no pediatric-specific dosage adjustments provided in manufacturer's labeling (has not been studied); based on experience in adult patients, dosing adjustment may be necessary.
Immediate release: There are no dosage adjustments provided in the manufacturer's labeling; however, no adjustment is expected since pregabalin undergoes minimal hepatic metabolism.
Dose-dependent CNS depression may occur and present as somnolence, dizziness, and/or drowsiness. In addition, serious, life-threatening, and fatal respiratory depression may occur; most cases occurred with concomitant use of CNS depressants (especially opioids) in the setting of underlying respiratory impairment or in the elderly (Ref). CNS depression may impair physical or mental abilities and result in accidental injury, including falls.
Mechanism: Dose-related; related to pharmacologic action (ie, structurally related to GABA).
Onset: Varied; timing impacted by concomitant use of medications known to cause CNS depression (eg, opioids) (Ref).
Risk factors:
• Concomitant use of alcohol or other CNS depressants (eg, opioids, benzodiazepines, antidepressants, antihistamines) (Ref)
• Patients with underlying respiratory impairment (Ref)
• Elderly patients (Ref)
Isolated cases of delayed hypersensitivity reactions have been reported ranging from maculopapular rashes to severe cutaneous adverse reactions (SCARs), namely drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Stevens-Johnson syndrome, and toxic epidermal necrolysis (Ref).
Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions are mediated by T-cells or antibodies other than IgE (eg, IgG-mediated, such as some cytopenias) (Ref). SCARs are delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref).
Onset: Varied. Type IV reactions are delayed hypersensitivity reactions that typically occur days to weeks after drug exposure, but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).
Risk factors:
• Prior history of delayed hypersensitivity reaction to pregabalin. Note: It is unknown whether cross-reactivity exists between gabapentin and pregabalin, given their similar structures. Gabapentinoids are usually considered safe agents for patients with a previous history of drug allergies to other antiseizure medications (Ref).
Peripheral edema may occur in patients with or without a prior history of heart failure (Ref). In patients with a prior history of heart failure, peripheral edema may result in acute decompensated heart failure (Ref).
Mechanism: Dose-related; related to pharmacologic action. Exact mechanism not fully established; a possible mechanism may be antagonism of the L-type calcium channels which results in vasodilation of mesenteric resistance arteries. The resultant increased intracapillary hydrostatic pressure leads to increased fluid in the interstitium and peripheral edema (Ref).
Onset: Varied. Onset of symptoms within days of initiation has been described (Ref); whereas, other reports describe onset of symptoms after months of therapy (Ref).
Risk factors:
• Concomitant use of thiazolidinedione antidiabetic agents, particularly in patients with prior cardiovascular disease
• Concomitant use of drugs that may increase risk of peripheral edema
• Preexisting heart failure (NYHA Class III or IV) (cautious use recommended due to limited data in this patient population)
Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal ideation and suicidal tendencies.
Mechanism: Non-dose-related; exact mechanism is not established. Theories include lowering of the threshold for manifesting psychiatric symptoms in patients susceptible to psychiatric disorders or antiseizure-induced disinhibition and impulsiveness thereby influencing and promoting suicidal acts (Ref).
Onset: As early as 1 week after initiation of antiseizure drugs, including gabapentin
Risk factors:
• Preexisting risk factors for suicidal thoughts and behaviors (including epilepsy)
• Prior history of psychiatric disorders or aggressive behaviors (Ref)
Blurred vision, decreased visual acuity, amblyopia, diplopia, and visual field loss have been associated with therapy (Ref).
Mechanism: Unknown; likely involves vestibulocerebellar and/or brainstem structures (Ref).
Onset: Varied; effect is dose-dependent (Ref); therefore, timing may be impacted by high doses or accumulation.
Risk factors:
• Conditions which may lead to accumulation (eg, kidney impairment, elderly patients, drug interactions)
Use may cause weight gain. In clinical trials, as highlighted by the manufacturer, average weight gain was 5.2 kg for patients with diabetes receiving pregabalin for ≥2 years. The manufacturer reports that weight gain is not limited to patients with edema and does not appear to be associated with baseline BMI, gender, age, or loss of glycemic control in patients with diabetes.
Mechanism: Dose- and time-related; exact mechanism is unknown. Some observations from preclinical studies suggest that pregabalin may result in an increase in appetite and abdominal fat (Ref).
Onset: Delayed; a pooled analysis aimed at characterizing long-term weight change in pregabalin-treated patients found that 1 in 6 patients who gained ≥7% weight from baseline generally exceeded this level 2 to 12 months after the onset of treatment (Ref).
Risk factors:
• Longer duration of therapy
• Higher doses
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with adult patients, unless otherwise noted.
>10%:
Cardiovascular: Peripheral edema (≤16%) (table 1)
|
Drug (Pregabalin) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
9% |
2% |
Adults |
600 mg/day |
Fibromyalgia |
378 |
505 |
|
6% |
2% |
Adults |
450 mg/day |
Fibromyalgia |
505 |
505 |
|
5% |
2% |
Adults |
300 mg/day |
Fibromyalgia |
502 |
505 |
|
5% |
2% |
Adults |
150 mg/day |
Fibromyalgia |
132 |
505 |
|
12% |
2% |
Adults |
600 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
369 |
459 |
|
9% |
2% |
Adults |
300 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
321 |
459 |
|
6% |
2% |
Adults |
150 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
212 |
459 |
|
4% |
2% |
Adults |
75 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
77 |
459 |
|
16% |
4% |
Adults |
300 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
312 |
398 |
|
16% |
4% |
Adults |
600 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
154 |
398 |
|
8% |
4% |
Adults |
150 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
302 |
398 |
|
0% |
4% |
Adults |
75 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
84 |
398 |
|
10% |
5% |
Adults |
N/A |
Neuropathic pain associated with spinal cord injury |
182 |
174 |
Endocrine & metabolic: Weight gain (≤14%) (table 2)
|
Drug (Pregabalin) |
Placebo |
Population |
Dosage Form |
Dose |
Indication |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
13% |
4% |
Children and adolescents |
IR |
10 mg/kg/day |
Adjunctive therapy for partial-onset seizures |
97 |
94 |
|
4% |
4% |
Children and adolescents |
IR |
2.5 mg/kg/day |
Adjunctive therapy for partial-onset seizures |
104 |
94 |
|
14% |
2% |
Adults |
IR |
600 mg/day |
Fibromyalgia |
378 |
505 |
|
10% |
2% |
Adults |
IR |
450 mg/day |
Fibromyalgia |
505 |
505 |
|
10% |
2% |
Adults |
IR |
300 mg/day |
Fibromyalgia |
502 |
505 |
|
8% |
2% |
Adults |
IR |
150 mg/day |
Fibromyalgia |
132 |
505 |
|
6% |
0% |
Adults |
IR |
600 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
369 |
459 |
|
4% |
0% |
Adults |
IR |
300 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
321 |
459 |
|
4% |
0% |
Adults |
IR |
150 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
212 |
459 |
|
0% |
0% |
Adults |
IR |
75 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
77 |
459 |
|
7% |
0% |
Adults |
IR |
600 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
154 |
398 |
|
5% |
0% |
Adults |
IR |
300 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
312 |
398 |
|
2% |
0% |
Adults |
IR |
150 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
302 |
398 |
|
1% |
0% |
Adults |
IR |
75 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
84 |
398 |
|
3% |
1% |
Adults |
IR |
N/A |
Neuropathic pain associated with spinal cord injury |
182 |
174 |
|
4% |
1% |
Adults |
ER |
N/A |
Postherpetic neuralgia |
208 |
205 |
Gastrointestinal: Xerostomia (≤15%)
Nervous system: Dizziness (3% to 45%) (table 3), drowsiness (≤36%; infants, children, and adolescents: 13% to 26%) (table 4), fatigue (4% to 11%), headache (2% to 14%)
|
Drug (Pregabalin) |
Placebo |
Population |
Dosage Form |
Dose |
Indication |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
45% |
9% |
Adults |
IR |
600 mg/day |
Fibromyalgia |
378 |
505 |
|
43% |
9% |
Adults |
IR |
450 mg/day |
Fibromyalgia |
505 |
505 |
|
31% |
9% |
Adults |
IR |
300 mg/day |
Fibromyalgia |
502 |
505 |
|
23% |
9% |
Adults |
IR |
150 mg/day |
Fibromyalgia |
132 |
505 |
|
29% |
5% |
Adults |
IR |
600 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
369 |
459 |
|
23% |
5% |
Adults |
IR |
300 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
321 |
459 |
|
9% |
5% |
Adults |
IR |
150 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
212 |
459 |
|
8% |
5% |
Adults |
IR |
75 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
77 |
459 |
|
37% |
9% |
Adults |
IR |
600 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
154 |
398 |
|
31% |
9% |
Adults |
IR |
300 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
312 |
398 |
|
18% |
9% |
Adults |
IR |
150 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
302 |
398 |
|
11% |
9% |
Adults |
IR |
75 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
84 |
398 |
|
21% |
7% |
Adults |
IR |
N/A |
Neuropathic pain associated with spinal cord injury |
182 |
174 |
|
3% |
0.5% |
Adults |
ER |
N/A |
Postherpetic neuralgia |
208 |
205 |
|
Drug (Pregabalin) |
Placebo |
Population |
Dosage Form |
Dose |
Indication |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
21% |
9% |
Infants and children |
IR |
14 mg/kg/day |
Adjunctive therapy for partial-onset seizures |
34 |
70 |
|
13% |
9% |
Infants and children |
IR |
7 mg/kg/day |
Adjunctive therapy for partial-onset seizures |
71 |
70 |
|
26% |
14% |
Children and adolescents |
IR |
10 mg/kg/day |
Adjunctive therapy for partial-onset seizures |
97 |
94 |
|
17% |
14% |
Children and adolescents |
IR |
2.5 mg/kg/day |
Adjunctive therapy for partial-onset seizures |
104 |
94 |
|
22% |
4% |
Adults |
IR |
600 mg/day |
Fibromyalgia |
378 |
505 |
|
22% |
4% |
Adults |
IR |
450 mg/day |
Fibromyalgia |
505 |
505 |
|
18% |
4% |
Adults |
IR |
300 mg/day |
Fibromyalgia |
502 |
505 |
|
13% |
4% |
Adults |
IR |
150 mg/day |
Fibromyalgia |
132 |
505 |
|
16% |
3% |
Adults |
IR |
600 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
369 |
459 |
|
13% |
3% |
Adults |
IR |
300 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
321 |
459 |
|
6% |
3% |
Adults |
IR |
150 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
212 |
459 |
|
4% |
3% |
Adults |
IR |
75 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
77 |
459 |
|
25% |
5% |
Adults |
IR |
600 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
154 |
398 |
|
18% |
5% |
Adults |
IR |
300 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
312 |
398 |
|
12% |
5% |
Adults |
IR |
150 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
302 |
398 |
|
8% |
5% |
Adults |
IR |
75 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
84 |
398 |
|
36% |
12% |
Adults |
IR |
N/A |
Neuropathic pain associated with spinal cord injury |
182 |
174 |
|
0.5% |
0% |
Adults |
ER |
N/A |
Postherpetic neuralgia |
208 |
205 |
Ophthalmic: Blurred vision (1% to 12%) (table 5), visual field loss (13%) (table 6)
|
Drug (Pregabalin) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
12% |
1% |
Adults |
600 mg/day |
Fibromyalgia |
378 |
505 |
|
8% |
1% |
Adults |
150 mg/day |
Fibromyalgia |
132 |
505 |
|
7% |
1% |
Adults |
300 mg/day |
Fibromyalgia |
502 |
505 |
|
7% |
1% |
Adults |
450 mg/day |
Fibromyalgia |
505 |
505 |
|
6% |
2% |
Adults |
600 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
369 |
459 |
|
3% |
2% |
Adults |
75 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
77 |
459 |
|
3% |
2% |
Adults |
300 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
321 |
459 |
|
1% |
2% |
Adults |
150 mg/day |
Neuropathic pain associated with diabetic peripheral neuropathy |
212 |
459 |
|
9% |
3% |
Adults |
600 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
154 |
398 |
|
5% |
3% |
Adults |
150 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
302 |
398 |
|
5% |
3% |
Adults |
300 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
312 |
398 |
|
1% |
3% |
Adults |
75 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
84 |
398 |
|
7% |
1% |
Adults |
N/A |
Neuropathic pain associated with spinal cord injury |
182 |
174 |
|
Drug (Pregabalin) |
Placebo |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|
|
13% |
12% |
N/A |
N/A |
1% to 10%:
Cardiovascular: Chest pain (2%), edema (≤8%), facial edema (1% to 3%), hypertension (2%), hypotension (2%)
Dermatologic: Contact dermatitis (1%), ecchymoses (≥1%), pressure ulcer (3%)
Endocrine & metabolic: Decreased libido (≥1%), fluid retention (2% to 3%), hypoglycemia (2% to 3%)
Gastrointestinal: Abdominal distension (2%), abdominal pain (≥1%), constipation (3% to 10%), diarrhea (1%), flatulence (2% to 3%), gastroenteritis (≥1%), increased appetite (3% to 10%), nausea (3% to 5%), sialorrhea (children and adolescents: 1% to 4%), viral gastroenteritis (≤1%), vomiting (1% to 3%)
Genitourinary: Erectile dysfunction (≤1%), impotence (≥1%), urinary frequency (≥1%), urinary incontinence (1% to 3%), urinary tract infection (1%)
Hematologic & oncologic: Thrombocytopenia (3%, including severe thrombocytopenia)
Hepatic: Increased serum alanine aminotransferase (≤1%), increased serum aspartate aminotransferase (≤1%)
Hypersensitivity: Hypersensitivity reaction (≥1%)
Infection: Infection (6% to 8%), viral infection (infants and children: 6%)
Nervous system: Abnormal gait (1% to 8%), abnormality in thinking (1% to 6%), amnesia (1% to 4%), anorgasmia (≥1%), ataxia (2% to 9%), balance impairment (2% to 9%), confusion (1% to 7%), depersonalization (≥1%), disorientation (1% to 2%), disturbance in attention (4% to 6%), euphoria (2% to 7%), feeling abnormal (1% to 3%), hypertonia (≥1%), hypoesthesia (2% to 3%), insomnia (4%), intoxicated feeling (1% to 2%), lethargy (1% to 2%), memory impairment (1% to 4%), myasthenia (1% to 5%), nervousness (1%), neuropathy (5%), pain (3% to 5%), paresthesia (2%), sedated state (≥1%), speech disturbance (1% to 3%), stupor (≥1%), twitching (≥1%; includes myokymia), vertigo (1% to 4%)
Neuromuscular & skeletal: Arthralgia (1% to 6%), asthenia (4% to 7%), increased creatine phosphokinase in blood specimen (2% to 3%), joint swelling (≤2%), lower limb cramp (≥1%), muscle spasm (4%), tremor (1% to 3%)
Ophthalmic: Conjunctivitis (≥1%), decreased visual acuity (7%) (table 7), diplopia (≤4%) (table 8), eye disease (1% to 2%), nystagmus disorder (≥1%), visual disturbance (1% to 5%)
|
Drug (Pregabalin) |
Placebo |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|
|
7% |
5% |
N/A |
N/A |
|
Drug (Pregabalin) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
4% |
0% |
Adults |
600 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
154 |
398 |
|
2% |
0% |
Adults |
150 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
302 |
398 |
|
2% |
0% |
Adults |
300 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
312 |
398 |
|
0% |
0% |
Adults |
75 mg/day |
Neuropathic pain associated with postherpetic neuralgia |
84 |
398 |
Otic: Otitis media (≥1%), tinnitus (≥1%)
Respiratory: Bronchitis (3%), dyspnea (2%), flu-like symptoms (2%), nasopharyngitis (1% to 8%), pharyngolaryngeal pain (3%), pneumonia (infants and children: 1% to 9%; adults: <1%), respiratory tract infection (1%), sinusitis (≤7%)
Miscellaneous: Accidental injury (2% to 6%) (table 9), fever (≥1%)
|
Drug (Pregabalin) |
Placebo |
Dose |
Population |
Indication |
Number of Patients (Pregabalin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
6% |
3% |
600 mg/day |
Adults |
Neuropathic pain associated with diabetic peripheral neuropathy |
369 |
459 |
|
2% |
3% |
300 mg/day |
Adults |
Neuropathic pain associated with diabetic peripheral neuropathy |
321 |
459 |
|
5% |
3% |
75 mg/day |
Adults |
Neuropathic pain associated with diabetic peripheral neuropathy |
77 |
459 |
|
2% |
3% |
150 mg/day |
Adults |
Neuropathic pain associated with diabetic peripheral neuropathy |
212 |
459 |
|
5% |
2% |
600 mg/day |
Adults |
Neuropathic pain associated with postherpetic neuralgia |
154 |
398 |
|
4% |
2% |
75 mg/day |
Adults |
Neuropathic pain associated with postherpetic neuralgia |
84 |
398 |
|
3% |
2% |
150 mg/day |
Adults |
Neuropathic pain associated with postherpetic neuralgia |
302 |
398 |
|
3% |
2% |
300 mg/day |
Adults |
Neuropathic pain associated with postherpetic neuralgia |
312 |
398 |
<1%:
Cardiovascular: Cardiac failure, depression of ST segment on ECG, orthostatic hypotension, palpitations, retinal vascular disease, shock, syncope, tachycardia, thrombophlebitis, ventricular fibrillation
Dermatologic: Alopecia, cellulitis, cutaneous nodule, dermal ulcer, eczema, erythema of skin, exfoliative dermatitis, lichenoid dermatitis, nail disease, pustular rash, skin atrophy, skin blister, skin necrosis, skin photosensitivity, skin rash, Stevens-Johnson syndrome (Frey 2017), subcutaneous nodule, urticaria, vesiculobullous dermatitis, xeroderma
Endocrine & metabolic: Albuminuria, decreased glucose tolerance, glycosuria, increased libido
Gastrointestinal: Ageusia, aphthous stomatitis, cholecystitis, cholelithiasis, colitis, dry mucous membranes, dysgeusia, dysphagia, esophageal ulcer, esophagitis, gastritis, gastrointestinal hemorrhage, hiccups, increased serum lipase, melena, oral mucosa ulcer, oral paresthesia, pancreatitis, periodontal abscess
Genitourinary: Ejaculatory disorder, oliguria, pelvic pain, proteinuria, retroperitoneal fibrosis, urate crystalluria, urinary retention, urine abnormality, uterine hemorrhage
Hematologic & oncologic: Anemia, eosinophilia, granuloma, hemophthalmos, hypochromic anemia, hypoprothrombinemia, increased neutrophils, leukocytosis, leukopenia, lymphadenopathy, myelofibrosis, nonthrombocytopenic purpura, petechial rash, polycythemia, purpuric rash, rectal hemorrhage, thrombocythemia (rare) (Qu 2014)
Hepatic: Ascites
Hypersensitivity: Angioedema (Ortega-Camarero 2012)
Infection: Abscess
Local: Local inflammation (coccydynia)
Nervous system: Abnormal dreams, agitation, apathy, aphasia, cerebellar syndrome, chills, cognitive dysfunction, cogwheel rigidity, delirium, delusion, drug dependence, dysarthria, dysautonomia, dystonia, encephalopathy, extraocular palsy, extrapyramidal reaction, hallucination, hangover effect, hostility, hypalgesia, hyperalgesia, hyperesthesia, hypotonia, impaired consciousness, irritability, malaise, myoclonus, neuralgia, psychomotor disturbance, sciatica, self-inflicted intentional injury, sleep disorder, trismus, yawning
Neuromuscular & skeletal: Bradykinesia, dyskinesia, hyperkinetic muscle activity, hypokinesia, joint stiffness, neck stiffness
Ophthalmic: Accommodation disturbance, blindness, iritis, miosis, mydriasis, night blindness, periorbital edema, photophobia
Renal: Acute renal failure, glomerulonephritis, nephritis, nephrolithiasis, pyelonephritis
Respiratory: Apnea, pulmonary edema
Frequency not defined:
Cardiovascular: Prolongation P-R interval on ECG (Schiavo 2017)
Neuromuscular & skeletal: Rhabdomyolysis (Gunathilake 2013; Kato 2016; Kaufman 2012)
Postmarketing:
Dermatologic: Maculopapular rash (Inoue 2016), toxic epidermal necrolysis (rare: <1%) (Frey 2017)
Endocrine & metabolic: Gynecomastia (Málaga 2006)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (rare: <1%) (Thein 2019)
Respiratory: Respiratory depression (FDA Safety Alert, Dec 19, 2019)
Hypersensitivity (eg, angioedema) to pregabalin or any component of the formulation
Concerns related to adverse effects:
• Angioedema: Angioedema has been reported during initial and chronic treatment. Use with caution in patients with a history of angioedema episodes. Concurrent use with other drugs known to cause angioedema (eg, ACE inhibitors) may increase risk. Discontinue treatment immediately if angioedema occurs.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.
• Substance misuse: Use with caution in patients with a history of substance misuse (Bonnet 2017).
Other warnings/precautions:
• Tumorigenic potential: Increased incidence of hemangiosarcoma noted in animal studies; significance of these findings in humans is unknown.
• Withdrawal: In patients receiving pregabalin chronically, unless safety concerns require a more rapid withdrawal, pregabalin should be withdrawn gradually over ≥1 week (Bonnet 2017; "Gabapentin and Pregabalin" 2012).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Lyrica: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg [contains corn starch]
Generic: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg
Solution, Oral:
Lyrica: 20 mg/mL (473 mL) [contains methylparaben, propylparaben]
Generic: 20 mg/mL (473 mL)
Tablet Extended Release 24 Hour, Oral:
Lyrica CR: 82.5 mg, 165 mg, 330 mg
Generic: 82.5 mg, 165 mg, 330 mg
Yes
Capsules (Lyrica Oral)
25 mg (per each): $12.14
50 mg (per each): $12.14
75 mg (per each): $12.14
100 mg (per each): $12.14
150 mg (per each): $12.14
200 mg (per each): $12.14
225 mg (per each): $12.14
300 mg (per each): $12.14
Capsules (Pregabalin Oral)
25 mg (per each): $0.03 - $8.90
50 mg (per each): $0.04 - $9.60
75 mg (per each): $0.05 - $9.90
100 mg (per each): $0.05 - $10.20
150 mg (per each): $0.07 - $10.50
200 mg (per each): $0.08 - $8.90
225 mg (per each): $0.08 - $8.90
300 mg (per each): $0.10 - $8.90
Solution (Lyrica Oral)
20 mg/mL (per mL): $3.08
Solution (Pregabalin Oral)
20 mg/mL (per mL): $2.12 - $2.24
Tablet, 24-hour (Lyrica CR Oral)
82.5 mg (per each): $20.87
165 mg (per each): $20.87
330 mg (per each): $20.87
Tablet, 24-hour (Pregabalin ER Oral)
82.5 mg (per each): $10.62 - $20.66
165 mg (per each): $10.62 - $20.66
330 mg (per each): $10.62 - $20.66
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Lyrica: 25 mg, 50 mg, 75 mg, 150 mg, 225 mg, 300 mg [contains corn starch]
Generic: 25 mg, 50 mg, 75 mg, 150 mg, 225 mg, 300 mg
C-V
Oral:
Immediate release: May be administered with or without food.
Extended release: Administer once daily after an evening meal; swallow whole, do not split, crush, or chew. A missed dose should be administered before bedtime following a snack. If missed before bedtime, administer in the morning with a meal. If missed in the morning, wait until the evening meal to administer the next scheduled dose.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR capsule and solution formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of IR capsule or solution should be strongly considered for postherpetic neuralgia and seizures indications.
Oral: Immediate release: May be administered with or without food.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Lyrica: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021446s041,022488s018lbl.pdf#page=57
Lyrica CR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209501s005lbl.pdf#page=31
Fibromyalgia (immediate release only): Management of fibromyalgia
Neuropathic pain associated with diabetic peripheral neuropathy (immediate release and extended release): Management of neuropathic pain associated with diabetic peripheral neuropathy
Neuropathic pain associated with spinal cord injury (immediate release only): Management of neuropathic pain associated with spinal cord injury
Postherpetic neuralgia (immediate release and extended release): Management of postherpetic neuralgia
Seizures, focal (partial) onset (immediate release only): Adjunctive therapy in patients ≥1 month of age with focal onset (partial-onset) seizures
Cancer-associated neuropathy; Cough, chronic refractory; Generalized anxiety disorder; Neuropathic pain, critically ill patients; Panic disorder; Pruritus, neuropathic or malignancy related; Pruritus, uremic; Restless legs syndrome; Social anxiety disorder; Vasomotor symptoms associated with menopause
Lyrica may be confused with Hydrea, Lopressor
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (GABA analog) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Long-Term Care Settings).
Pregabalin (Lyrica) oral solution (20 mg/mL): Prescriptions should be written in terms of mg. The pharmacist will calculate the appropriate dose in mL for dispensing.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazolidinediones: Pregabalin may enhance the fluid-retaining effect of Thiazolidinediones. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Extended release: Bioavailability is reduced if taken on an empty stomach. The AUC is approximately 30% lower when fasting relative to following an evening meal. Management: Administer after evening meal.
Pregabalin was found to temporarily decrease mean sperm concentrations; no effects on sperm morphology or motility were observed. Concentrations increased after pregabalin was discontinued. The clinical relevance of this is not known.
Pregabalin crosses the placenta (Ohman 2011).
Outcome data following maternal use of pregabalin during pregnancy are available (Dudukina 2023; Nucera 2022; Richardson 2023).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of pregabalin may be altered. Theoretically, the increase in renal clearance that occurs during pregnancy may decrease plasma concentrations of pregabalin (Nucera 2022).
Data collection to monitor pregnancy and infant outcomes following exposure to pregabalin is ongoing. Patients exposed to pregabalin during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Pregabalin is present in breast milk.
Multiple reports summarize data related to the presence of pregabalin in breast milk:
• Breast milk and maternal plasma were sampled in 10 lactating patients following administration of pregabalin 150 mg every 12 hours for 3 days. Sampling occurred in all patients prior to the first dose on days 1 and 3, then at specified intervals for 24 hours (n = 10) and for 40 to 48 hours (n = 5) following dosing on day 3. Patients did not breastfeed during the study period. Median maximum concentrations of pregabalin were 2.47 mcg/mL (breast milk) and 4.67 mcg/mL (maternal plasm). Maximum concentrations occurred at 4.63 hours (breast milk) and 2.01 hours (maternal plasma). The median half-life of pregabalin was 8.12 and 5.62 hours in breast milk and maternal plasma, respectively. Authors of the study calculated the estimated daily infant dose of pregabalin via breast milk to be 0.379 mg/kg/day (range 0.202 to 0.458 mcg/kg/day) providing a relative infant dose (RID) of 7.18% (range 4.4% to 9.8%) compared to the weight adjusted maternal dose (Lockwood 2016). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
• Limited data are available following pregabalin use in one patient treated for epilepsy during pregnancy. Pregabalin was detected in the serum of the breastfed infant at ~8% of concentration in the maternal plasma. Adverse events were not observed in the infant (Ohman 2011).
• Poor latch, lasting ~8 hours, was observed in three infants immediately postpartum following a single maternal dose of pregabalin for pain during cesarean delivery (El Kenany 2016).
A case series presented in abstract describes the use of pregabalin to treat persistent severe nipple pain in 4 lactating patients that was presumed to be neuropathic. Patients had an average Visual Analog Scale (VAS) score of 8 and neuropathic pain as evaluated using a neuropathic pain diagnostic questionnaire. Three of the four patients had complete resolution of pain following use of pregabalin and continued exclusive breastfeeding. Adverse events were not observed in the infants. All babies in the study also required interventions to correct sucking (Faraoni 2023).
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Measures of efficacy (pain intensity/seizure frequency); degree of sedation; mental alertness; symptoms of respiratory depression and sedation in patients with underlying respiratory disease (FDA 2019); symptoms of myopathy; creatine kinase (as clinically indicated); symptoms of ocular disturbance; weight gain/edema; skin integrity (in patients with diabetes); signs and symptoms of suicidality (eg, suicidal thoughts, anxiety, depression, behavioral changes); platelet count (as clinically indicated)
Binds to alpha-2-delta subunit of voltage-gated calcium channels within the CNS and modulates calcium influx at the nerve terminals, thereby inhibiting excitatory neurotransmitter release including glutamate, norepinephrine (noradrenaline), serotonin, dopamine, substance P, and calcitonin gene-related peptide (Gajraj 2007; McKeage 2009). Although structurally related to GABA, it does not bind to GABA or benzodiazepine receptors. Exerts antinociceptive and antiseizure activity. Pregabalin may also affect descending noradrenergic and serotonergic pain transmission pathways from the brainstem to the spinal cord.
Onset of action: Pain management: Effects may be noted as early as the first week of therapy.
Absorption: Extended release: AUC is approximately 30% lower when administered while fasting
Distribution: Vd: 0.5 L/kg
Protein binding: 0%
Metabolism: Negligible
Bioavailability: ≥90%
Half-life elimination:
Children ≤6 years: 3 to 4 hours
Children 7 to <17 years: 4 to 6 hours
Adult: 6.3 hours
Time to peak, plasma:
Extended release: Median: 8 hours with food (range: 5 to 12 hours)
Immediate release:
Infants ≥3 months, Children, and Adolescents <17 years: 0.5 to 2 hours fasting
Adults: Within 1.5 hours fasting; ~3 hours with food
Excretion: Urine (90% as unchanged drug; minor metabolites)
Pediatric: Clearance in pediatric patients weighing <30 kg has been observed to be 40% higher than those weighing ≥30 kg.
Older adult: Oral clearance tends to decrease with increasing age.
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