Version July 2025
Focal (partial) onset seizures, adjunctive therapy:
Infants and Children <4 years weighing <30 kg: Immediate release: Oral: Initial: 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: Immediate release: Oral: Initial: 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: Immediate release: Oral: Initial: 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: Immediate release: Oral: Initial: 150 mg/day in 2 or 3 divided doses; may be increased weekly based on tolerability and effect; maximum daily dose: 600 mg/day.
Neuropathic pain: Limited data available: Children and Adolescents: Immediate release: Oral: Initial: 1 mg/kg/dose on days 1 to 3 (3 doses), maximum initial dose: 50 mg/dose; then 1 mg/kg/dose twice daily; continue to titrate in 3 mg/kg/dose increments administered 2 or 3 times daily at 2- to 4-day intervals up to maximum dose of 6 mg/kg/dose; maximum daily dose: 600 mg/day (Ref).
Discontinuation of therapy: Discontinuation of treatment for seizures is dependent on several factors to minimize chance of seizure relapse. Favorable factors include: childhood onset, normal EEG at time of discontinuation, idiopathic generalized epilepsy, low seizure frequency before and during treatment, seizure type, normal neurologic exam, and normal intellectual development. Withdrawal of therapy is typically evaluated if patient has been seizure free for 2 years. Abrupt discontinuation is not recommended. Gradual tapers of pregabalin over at least 1 week suggested; the slow discontinuation should be tailored to the patient's preference and needs. Other considerations include the drug pharmacokinetic properties, dosage at the start of withdrawal, dosage forms, and need for follow-up serum concentration monitoring (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.
(For additional information see "Pregabalin: Drug information")
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.
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 (Ref), 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) (Ref)
Hepatic: Ascites
Hypersensitivity: Angioedema (Ref)
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 (Ref)
Neuromuscular & skeletal: Rhabdomyolysis (Ref)
Postmarketing:
Dermatologic: Maculopapular rash (Ref), toxic epidermal necrolysis (rare: <1%) (Ref)
Endocrine & metabolic: Gynecomastia (Ref)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (rare: <1%) (Ref)
Respiratory: Respiratory depression (Ref)
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): $0.04 - $9.90
100 mg (per each): $0.05 - $10.20
150 mg (per each): $0.05 - $10.50
200 mg (per each): $0.05 - $8.90
225 mg (per each): $0.05 - $8.90
300 mg (per each): $0.06 - $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): $15.78 - $20.66
165 mg (per each): $19.76 - $20.66
330 mg (per each): $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 capsule, oral solution: May be administered with or without food.
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.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
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
Immediate release: Adjunctive therapy for focal (partial)-onset seizure disorder (FDA approved in ages ≥1 month and adults); management of neuropathic pain associated with diabetic peripheral neuropathy (FDA approved in adults); management of neuropathic pain associated with spinal cord injury (FDA approved in adults); management of postherpetic neuralgia (FDA approved in adults); management of fibromyalgia (FDA approved in adults).
Extended release: Management of neuropathic pain associated with diabetic peripheral neuropathy (FDA approved in adults); management of postherpetic neuralgia (FDA approved in adults).
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 is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with recurrent falls or for the treatment of non-neuropathic pain (O’Mahony 2023).
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.
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
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: May increase adverse/toxic effects of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects 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
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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 increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects 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 increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects 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
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects 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 increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects 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
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease 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
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects 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
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects 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
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects 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
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects 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 increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thiazolidinediones: Pregabalin may increase fluid-retaining effects of Thiazolidinediones. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects 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.
Manage epilepsy in patients who could become pregnant based on a shared decision-making process that optimizes seizure control and considers the possibility of pregnancy during treatment (Pack 2024). Regularly discuss age-specific and developmental needs, including pregnancy planning and contraceptive options during the patient’s reproductive lifespan (ACOG 2020; NICE 2022).
Evaluate pregnancy status prior to initiating treatment for mental health conditions in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of treatment response (ACOG 2023). Pregabalin is not a first line medication for use prior to conception when treating anxiety disorders in patients who are treatment naïve or who do not have a history of effective treatment with another medication (ACOG 2023; BAP [McAllister-Williams 2017]). Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]). Manage mental health conditions in patients who could become pregnant based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]).
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 limited. Available data are insufficient to evaluate the risk of specific major congenital malformations or the risk of neurodevelopmental outcomes (IQ scores or autism spectrum disorder) in children following in utero exposure to pregabalin (Pack 2024). Screen for major congenital malformations and monitor fetal growth when antiseizure medications are used during pregnancy. Conduct age-appropriate developmental screening in children who had in utero exposure to antiseizure medications (Pack 2024).
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 (Tomson 2013).
Epilepsy is associated with adverse maternal and fetal outcomes (Kuang 2024; Mazzone 2023). Convulsive seizures should be minimized to reduce risks to the fetus and pregnant patient. Use caution if removing or replacing an effective seizure medication in patients who become pregnant during therapy. Folic acid supplementation prior to and during pregnancy minimizes the risk of congenital malformations and poor neurodevelopment (Pack 2024).
Patients effectively treated for mental health conditions prepregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]). Treatment should not be withheld or discontinued based only on pregnancy status. Agents other than pregabalin may be preferred when treatment for anxiety is initiated for the first time during pregnancy. When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Monthly monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects, as needed (ACOG 2023).
Untreated fibromyalgia may be associated with adverse pregnancy outcomes, including placental abruption, venous thrombosis, premature rupture of membranes, preterm birth, and intrauterine growth restriction/small for gestational age. It is not known if these outcomes are due specifically to fibromyalgia or comorbid conditions. Due to limited data, use of pregabalin for the treatment of fibromyalgia syndrome (FMS) in pregnancy should be reserved for patients with severe forms of FMS complicated by depressive symptoms which worsen during pregnancy. Close monitoring is recommended (Gentile 2019). Nonmedication therapies should be maximized in pregnant patients treated for fibromyalgia (Marcus 2011).
Pregabalin is used off label for the treatment of restless leg syndrome; however, current guidelines note there is insufficient evidence to recommend its use in pregnant patients for this indication. Avoid use of pregabalin for restless leg syndrome during pregnancy (Garcia-Borreguero 2016; Picchietti 2015).
Data collection to monitor pregnancy outcomes following exposure to antiepileptic drugs is ongoing. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or https://www.aedpregnancyregistry.org).
Seizure frequency, duration, and severity; pain intensity; degree of sedation; respiratory rate; symptoms of myopathy (eg, unexplained muscle pain, tenderness, weakness accompanied by fever and malaise); creatine kinase (as clinically indicated); symptoms of ocular disturbance (eg, blurred vision, visual field change); weight gain, edema; skin integrity (in diabetic patients); 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.
