Your activity: 347 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Pregabalin: Drug information

Pregabalin: Drug information
(For additional information see "Pregabalin: Patient drug information" and see "Pregabalin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Lyrica;
  • Lyrica CR
Brand Names: Canada
  • ACH-Pregabalin;
  • ACT Pregabalin [DSC];
  • AG-Pregabalin;
  • APO-Pregabalin;
  • Auro-Pregabalin;
  • DOM-Pregabalin;
  • JAMP-Pregabalin;
  • Lyrica;
  • M-Pregabalin;
  • Mar-Pregabalin;
  • MINT-Pregabalin;
  • NAT-Pregabalin;
  • NRA-Pregabalin;
  • PMS-Pregabalin;
  • RIVA-Pregabalin;
  • SANDOZ Pregabalin;
  • TARO-Pregabalin;
  • TEVA-Pregabalin
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous;
  • GABA Analog
Dosing: Adult

Note: For patients with respiratory disease, initiate therapy at the lowest dose (Ref).

Cough, chronic refractory

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

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

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 (Ref).

Neuropathic pain

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 (off-label use): Oral: Initial: 75 mg once or twice daily in combination with opioids; 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.

Pruritus, chronic

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

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 onset

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

Social 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: 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

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: In patients receiving pregabalin chronically, unless safety concerns require a more rapid withdrawal, pregabalin should be withdrawn gradually over ≥1 week 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) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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.

Pregabalin Dose Adjustments in Altered Kidney Functiona,b

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).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. However, no adjustment is expected since undergoes minimal hepatic metabolism.

Dosing: Pediatric

(For additional information see "Pregabalin: Pediatric drug information")

Note: When discontinuing, taper off gradually over at least 1 week.

Seizures, partial onset; adjunctive therapy

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

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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

Immediate release: There are no dosage adjustments provided in the manufacturer's labeling; however, no adjustment is expected since pregabalin undergoes minimal hepatic metabolism.

Dosing: Older Adult

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).

Dosage Forms: US

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

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Generic: 25 mg, 50 mg, 75 mg, 150 mg, 225 mg, 300 mg

Controlled Substance

C-V

Medication Guide and/or Vaccine Information Statement (VIS)

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/2019/021446s036,022488s014lbl.pdf#page=56

Lyrica CR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209501s000lbl.pdf#page=29

Administration: Adult

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 taken 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.

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.

Administration: Pediatric

Oral: Immediate release: May be administered with or without food.

Use: Labeled Indications

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

Use: Off-Label: Adult

Cancer-associated neuropathy; Cough, chronic refractory; Generalized anxiety disorder; Neuropathic pain, critically ill patients; Pruritus, neuropathic or malignancy related; Pruritus, uremic; Restless legs syndrome; Social anxiety disorder; Vasomotor symptoms associated with menopause

Medication Safety Issues
Sound-alike/look-alike issues:

Lyrica may be confused with Hydrea, Lopressor

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication (when used for neuropathic pain) among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

Other safety concerns:

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.

Adverse Reactions (Significant): Considerations
CNS and respiratory depression

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)

Hypersensitivity reactions (delayed)

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

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)

Suicidal ideation and tendencies

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)

Visual disturbances

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)

Weight gain

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

Adverse Reactions

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)

Pregabalin: Adverse Reaction: Peripheral Edema

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)

Pregabalin: Adverse Reaction: Weight Gain

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%)

Pregabalin: Adverse Reaction: Dizziness

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

Pregabalin: Adverse Reaction: Drowsiness

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)

Pregabalin: Adverse Reaction: Blurred Vision

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

Pregabalin: Adverse Reaction: Visual Field Loss

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%)

Pregabalin: Adverse Reaction: Decreased Visual Acuity

Drug (Pregabalin)

Placebo

Number of Patients (Pregabalin)

Number of Patients (Placebo)

7%

5%

N/A

N/A

Pregabalin: Adverse Reaction: Diplopia

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%)

Pregabalin: Adverse Reaction: Accidental Injury

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)

Contraindications

Hypersensitivity (eg, angioedema) to pregabalin or any component of the formulation

Warnings/Precautions

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 abuse: Use with caution in patients with a history of substance abuse; potential for behavioral dependence in this population exists (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).

Metabolism/Transport Effects

None known.

Drug Interactions

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 Lexicomp 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: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. 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

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

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

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

Food Interactions

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.

Reproductive Considerations

In a study conducted in males, 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.

Pregnancy Considerations

Pregabalin crosses the placenta (Ohman 2011). Studies which evaluated neonatal outcomes following pregabalin exposure during pregnancy are limited (Mostacci 2017; Patorno 2017; Veiby 2014; Winterfeld 2016). Pregabalin has been evaluated as an adjuvant pain medication following cesarean section and pregnancy termination (El Kenany 2016; Lavand'homme 2010).

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.

Breastfeeding Considerations

Pregabalin is present in breast milk.

The relative infant dose (RID) of pregabalin is ~7% when calculated using an average breast milk concentration compared to a weight-adjusted maternal dose of 300 mg/day.

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

The RID of pregabalin was calculated using an average milk concentration of 2.05 mcg/mL, providing an estimated daily infant dose via breast milk of 0.31 mg/kg/day. This milk concentration was obtained following maternal administration of pregabalin 150 mg orally twice daily for 4 doses. The study included 10 women who were ~37 weeks' postpartum (range: 15 to 81 weeks). Infants were not breastfed during the study period. Peak concentrations in breast milk were generally lower than those in the maternal plasma (Lockwood 2016). A slightly higher RID of ~8% was noted in a case report (Ohman 2011). Poor latching on, 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). Breastfeeding is not recommended by the manufacturer.

Monitoring Parameters

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)

Mechanism of Action

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.

Pharmacokinetics

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)

Pharmacokinetics: Additional Considerations

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.

Pricing: US

Capsules (Lyrica Oral)

25 mg (per each): $10.81

50 mg (per each): $10.81

75 mg (per each): $10.81

100 mg (per each): $10.81

150 mg (per each): $10.81

200 mg (per each): $10.81

225 mg (per each): $10.81

300 mg (per each): $10.81

Capsules (Pregabalin Oral)

25 mg (per each): $0.03 - $8.90

50 mg (per each): $0.04 - $8.90

75 mg (per each): $0.05 - $8.90

100 mg (per each): $0.05 - $8.90

150 mg (per each): $0.07 - $8.90

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): $2.88

Solution (Pregabalin Oral)

20 mg/mL (per mL): $2.12 - $2.24

Tablet, 24-hour (Lyrica CR Oral)

82.5 mg (per each): $18.57

165 mg (per each): $18.57

330 mg (per each): $18.57

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.

Brand Names: International
  • Algecia (DE, NL);
  • Algerica (RU);
  • Andogablin (EG);
  • Axual (AR);
  • Balinozar (EG);
  • Brieka (CZ, DK, IE);
  • Brillior (HK);
  • Dorene (BR);
  • Egzysta (PL, VN);
  • Funxion (PH);
  • Gabarol (BD);
  • Gabi (PH);
  • Gabica (PH, PK, VN);
  • Gablin (PH);
  • Gabrika (LB);
  • Galica (LB);
  • Gavin (AR);
  • Gloryca (VN);
  • Innikra (ZW);
  • Kemirica (EG);
  • Labalin (ID);
  • Lalaca (KR);
  • Lecaent (GB);
  • Leptica (ID);
  • Ligaba (PH);
  • Linefor (NL, PL);
  • Lingabat (NL);
  • Lipapyn (ZW);
  • Lirystad (VN);
  • Lybalin (TH);
  • Lygara (TW);
  • Lyraccord (AU);
  • Lyribastad (FI);
  • Lyrica (AE, AR, AT, AU, BB, BE, BG, BH, BR, CH, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EC, EE, EG, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, ID, IE, IL, IN, IS, IT, JO, JP, KR, KW, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, SV, TH, TR, TW, UA, UY, VE, VN, ZA, ZW);
  • Lyrigab (LK);
  • Lyzalon (AU);
  • Martesia (EC);
  • Neo Gaba (BH);
  • Neogabin (UA);
  • Nervax (BH, LB);
  • Nervica (TH);
  • Neufar (ID);
  • Neugalin (BD);
  • Neuroccord (AU);
  • Neurocover-PG (KR);
  • Neurovan (BD);
  • Neuroz (PH);
  • Neurum (CL, EC);
  • Nomathic (ID);
  • PGB (ID);
  • Plenica (LB);
  • Pobalin (TH);
  • Prapiola (CZ);
  • Prebarin (TH);
  • Prebictal (BR);
  • Prega 150 (ZW);
  • Pregaba (ZW);
  • Pregabadin (PY);
  • Pregadex (BH);
  • Pregalex (EC);
  • Pregalin (KR);
  • Pregaredi (SG);
  • Pregasafe-150 (TZ);
  • Pregasafe-75 (TZ);
  • Pregax (LK);
  • Pregeb (PH);
  • Prelica (CZ);
  • Preneurin (PH);
  • Prepentin (VN);
  • Prex (BH);
  • Probalin (TW);
  • Provelyn (ID);
  • Rabakir (PL);
  • Regab (BD);
  • Regalbax (IT);
  • Rewisca (GB, MY);
  • Silica (KR);
  • Syngexa (TW);
  • Tirica (TW);
  • Toprelin (TH);
  • Vexer (LK, PH);
  • Xablin (BD);
  • Zeegap (LK);
  • Zyzyx (PH)


For country code abbreviations (show table)
  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767 [PubMed 30693946]
  2. Allen R, Chen C, Soaita A, et al. A randomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome. Sleep Med. 2010;11(6):512-519. [PubMed 20466589]
  3. Allen RP, Chen C, Garcia-Borreguero D, et al. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med. 2014;370(7):621-631. [PubMed 24521108]
  4. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. doi:10.1002/cpt.377 [PubMed 27060684]
  5. Arnold LM, McCarberg BH, Clair AG, et al. Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia. Postgrad Med. 2017;129(8):921-933. doi:10.1080/00325481.2017.1384691 [PubMed 28967801]
  6. Arnold LM, Schikler KN, Bateman L, et al. Safety and efficacy of pregabalin in adolescents with fibromyalgia: a randomized, double-blind, placebo-controlled trial and a 6-month open-label extension study. Pediatr Rheumatol Online J. 2016;14(1):46. [PubMed 27475753]
  7. Atıs G, Bilir Kaya B. Pregabalin treatment of three cases with brachioradial pruritus. Dermatol Ther. 2017;30(2). doi:10.1111/dth.12459 [PubMed 28168835]
  8. Baldwin D, Woods R, Lawson R, Taylor D. Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. BMJ. 2011;342:d1199. doi:10.1136/bmj.d1199 [PubMed 21398351]
  9. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28(5):403-439. doi:10.1177/0269881114525674 [PubMed 24713617]
  10. Bandelow B, Sher L, Bunevicius R, et al; WFSBP Task Force on Mental Disorders in Primary Care; WFSBP Task Force on Anxiety Disorders, OCD and PTSD. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract. 2012;16(2):77-84. [PubMed 22540422]
  11. Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ; WFSBP Task Force on Treatment Guidelines for Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision. World J Biol Psychiatry. 2008;9(4):248-312. doi:10.1080/15622970802465807 [PubMed 18949648]
  12. Based on expert opinion.
  13. Bellón T. Mechanisms of severe cutaneous adverse reactions: recent advances. Drug Saf. 2019;42(8):973-992. doi:10.1007/s40264-019-00825-2 [PubMed 31020549]
  14. Bilbao-Meseguer I, Rodríguez-Gascón A, Barrasa H, Isla A, Solinís MÁ. Augmented renal clearance in critically ill patients: a systematic review. ClinPharmacokinet. 2018;57(9):1107-1121. doi:10.1007/s40262-018-0636-7 [PubMed 29441476]
  15. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]
  16. Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol. 2017;27(12):1185-1215. doi:10.1016/j.euroneuro.2017.08.430 [PubMed 28988943]
  17. Boschen MJ. A meta-analysis of the efficacy of pregabalin in the treatment of generalized anxiety disorder. Can J Psychiatry. 2011;56(9):558-566. [PubMed 21959031]
  18. Bril V, England J, Franklin GM, et al. Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758-1765. [PubMed 21482920]
  19. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  20. Cabrera J, Emir B, Dills D, Murphy TK, Whalen E, Clair A. Characterizing and understanding body weight patterns in patients treated with pregabalin. Curr Med Res Opin. 2012;28(6):1027-1037. doi:10.1185/03007995.2012.684044 [PubMed 22494020]
  21. Cobin RH, Goodman NF; AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on menopause-2017 update. Endocr Pract. 2017;23(7):869-880. doi:10.4158/EP171828.PS [PubMed 28703650]
  22. Craske M, Bystritsky A. Generalized anxiety disorder in adults: Management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 3, 2021.
  23. Dalal S. Overview of pruritus in palliative care. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 29, 2021.
  24. De Smedt RH, Jaarsma T, van den Broek SA, Haaijer-Ruskamp FM. Decompensation of chronic heart failure associated with pregabalin in a 73-year-old patient with postherpetic neuralgia: a case report. Br J Clin Pharmacol. 2008;66(2):327-328. doi:10.1111/j.1365-2125.2008.03196.x [PubMed 18507657]
  25. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. doi:10.1097/CCM.0000000000003299 [PubMed 30113379]
  26. El Kenany S, El Tahan MR. Effect of preoperative pregabalin on post-caesarean delivery analgesia: a dose-response study. Int J Obstet Anesth. 2016;26:24-31. [PubMed 26718698]
  27. Erdoğan G, Ceyhan D, Güleç S. Possible heart failure associated with pregabalin use: case report. Agri. 2011;23(2):80-83. [PubMed 21644108]
  28. Fazio SB, Yosipovitch G. Pruritus: therapies for localized pruritus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 29, 2021.
  29. FDA Safety Alert. MedWatch. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin. Published December 19, 2019. Accessed December 23, 2019.
  30. Feldman E. Management of diabetic neuropathy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2022.
  31. Feltner DE, Liu-Dumaw M, Schweizer E, Bielski R. Efficacy of pregabalin in generalized social anxiety disorder: results of a double-blind, placebo-controlled, fixed-dose study. Int Clin Psychopharmacol. 2011;26(4):213-220. doi:10.1097/YIC.0b013e32834519bd [PubMed 21368587]
  32. Fong T, Lee AJ. Pregabalin-associated heart failure decompensation in a patient with a history of stage I heart failure. Ann Pharmacother. 2014;48(8):1077-1081. doi:10.1177/1060028014530551 [PubMed 24769529]
  33. Foroutan N, Etminan A, Nikvarz N, Shojai Shahrokh Abadi M. Comparison of pregabalin with doxepin in the management of uremic pruritus: a randomized single blind clinical trial. Hemodial Int. 2017;21(1):63-71. doi:10.1111/hdi.12455 [PubMed 27397522]
  34. Foroutan N, Nikvarz N. Role of pregabalin in management of pruritus: a literature review. J Pharm Pharm Sci. 2016;19(4):465-474. doi:10.18433/J35K6N [PubMed 28057164]
  35. Frey N, Bodmer M, Bircher A, et al. The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs. Epilepsia. 2017;58(12):2178-2185. doi:10.1111/epi.13925 [PubMed 29027197]
  36. Gabapentin and pregabalin: abuse and addiction. Prescrire Int. 2012;21(128):152-154. [PubMed 22822593]
  37. Gajraj NM. Pregabalin: its pharmacology and use in pain management. Anesth Analg. 2007;105(6):1805-1815. [PubMed 18042886]
  38. Gallagher R, Apostle N. Peripheral edema with pregabalin. CMAJ. 2013;185(10):E506. doi:10.1503/cmaj.121232 [PubMed 23128284]
  39. Garassino MC, Piva S, La Verde N, et al. Randomised phase II trial (NCT00637975) evaluating activity and toxicity of two different escalating strategies for pregabalin and oxycodone combination therapy for neuropathic pain in cancer patients. PLoS One. 2013;8(4):e59981. doi:10.1371/journal.pone.0059981 [PubMed 23577077]
  40. Garcia-Borreguero D, Kohnen R, Silber MH, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Medicine. 2013;14(7):675-684. doi: 10.1016/j.sleep.2013.05.016. [PubMed 23859128]
  41. Garcia-Borreguero D, Patrick J, DuBrava S, et al. Pregabalin versus pramipexole: effects on sleep disturbance in restless legs syndrome. Sleep. 2014;37(4):635-643. doi:10.5665/sleep.3558 [PubMed 24899755]
  42. Garcia-Borreguero D, Silber MH, Winkelman JW, et al. Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-Foundation. Sleep Med. 2016;21:1-11. doi:10.1016/j.sleep.2016.01.017 [PubMed 27448465]
  43. Generoso MB, Trevizol AP, Kasper S, Cho HJ, Cordeiro Q, Shiozawa P. Pregabalin for generalized anxiety disorder: an updated systematic review and meta-analysis. Int Clin Psychopharmacol. 2017;32(1):49-55. [PubMed 27643884]
  44. Ghaly RF, Plesca A, Rana S, Candido KD, Knezevic NN. Gabapentin-related suicide: Myth or fact? Surg Neurol Int. 2018;9:210. doi:10.4103/sni.sni_420_17 [PubMed 30488008]
  45. Goldenberg DL. Treatment of fibromyalgia in adults not responsive to initial therapies. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2022.
  46. Greist JH, Liu-Dumaw M, Schweizer E, Feltner D. Efficacy of pregabalin in preventing relapse in patients with generalized social anxiety disorder: results of a double-blind, placebo-controlled 26-week study. Int Clin Psychopharmacol. 2011;26(5):243-251. doi:10.1097/YIC.0b013e3283491fd5 [PubMed 21734588]
  47. Gunathilake R, Boyce LE, Knight AT. Pregabalin-associated rhabdomyolysis. Med J Aust. 2013;199(9):624-625. doi:10.5694/mja13.10769 [PubMed 24182230]
  48. Guzelkucuk U, Duman I, Yılmaz B, Tan AK. Reversible post-pregabalin peripheral edema in a spinal cord injury patient. Spinal Cord. 2012;50(6):472-473. doi:10.1038/sc.2011.79 [PubMed 21747401]
  49. Hamer HM, Morris HH. Hypersensitivity syndrome to antiepileptic drugs: a review including new anticonvulsants. Cleve Clin J Med. 1999;66(4):239-245. doi:10.3949/ccjm.66.4.239 [PubMed 10199060]
  50. Inoue A, Sawada Y, Ohmori S, et al. Maculopapular type drug eruption caused by pregabalin: A case and literature review. Allergol Int. 2016;65(3):351-352. doi:10.1016/j.alit.2016.02.006 [PubMed 26976337]
  51. Ishida JH, McCulloch CE, Steinman MA, Grimes BA, Johansen KL. Gabapentin and pregabalin use and association with adverse outcomes among hemodialysis patients. J Am Soc Nephrol. 2018;29(7):1970-1978. doi:10.1681/ASN.2018010096 [PubMed 29871945]
  52. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  53. Khan TM, Aziz A, Suleiman AK. Effectiveness of posthemodialysis administration of pregabalin (75 mg) in treatment resistance uremia pruritus. J PharmBioalliedSci. 2016a;8(1):74-76. doi:10.4103/0975-7406.171736 [PubMed 26957874]
  54. Khan TM, Wu DB, Goh BH, Lee LH, Alhafez AA, Syed Sulaiman SA. An observational longitudinal study investigating the effectiveness of 75 mg pregabalin post-hemodialysis among uremic pruritus patients. Sci Rep. 2016b;6:36555. doi:10.1038/srep36555 [PubMed 27824127]
  55. Kanner AM. Are antiepileptic drugs used in the treatment of migraine associated with an increased risk of suicidality? Curr Pain Headache Rep. 2011;15(3):164-169. doi:10.1007/s11916-011-0199-x [PubMed 21479999]
  56. Kasper S, Brasser M, Schweizer E, Lyndon G, Prieto R. How well do randomized controlled trial data generalize to 'real-world' clinical practice settings? A comparison of two generalized anxiety disorder studies. Eur Neuropsychopharmacol. 2014;24(1):125-132. doi:10.1016/j.euroneuro.2013.10.015 [PubMed 24290532]
  57. Kato K, Iwasaki Y, Onodera K, et al. Pregabalin- and azithromycin-induced rhabdomyolysis with purpura: An unrecognized interaction: A case report. Int J Surg Case Rep. 2016;26:221-223. doi:10.1016/j.ijscr.2016.07.007 [PubMed 27521491]
  58. Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(suppl 1):S1. doi:10.1186/1471-244X-14-S1-S1 [PubMed 25081580]
  59. Kaufman MB, Choy M. Pregabalin and simvastatin: first report of a case of rhabdomyolysis. P T. 2012;37(10):579-595. [PubMed 23115467]
  60. Kobrin SM. Uremic pruritus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 6, 2021.
  61. Koncicki HM, Brennan F, Vinen K, Davison SN. An approach to pain management in end stage renal disease: considerations for general management and intradialytic symptoms. Semin Dial. 2015;28(4):384-391. doi:10.1111/sdi.12372 [PubMed 25864854]
  62. Lavand'homme PM, Roelants F. Evaluation of pregabalin as an adjuvant to patient-controlled epidural analgesia during late termination of pregnancy. Anesthesiology. 2010;113(5):1186-1191. [PubMed 20938333]
  63. Lockwood PA, Pauer L, Scavone JM, et al. The pharmacokinetics of pregabalin in breast milk, plasma, and urine of healthy postpartum women. J Hum Lact. 2016:0890334415626148. [PubMed 26961752]
  64. Loprinzi CL, Qin R, Balcueva EP, et al. Phase III, randomized, double-blind, placebo-controlled evaluation of pregabalin for alleviating hot flashes, N07C1. J Clin Oncol. 2010;28(4):641-647. [PubMed 19901102]
  65. Lydiard RB, Rickels K, Herman B, Feltner DE. Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol. 2010;13(2):229-241. doi:10.1017/S1461145709990460 [PubMed 19737439]
  66. Lyrica (pregabalin) [prescribing information]. New York, NY: Parke-Davis, Division of Pfizer Inc; April 2020.
  67. Lyrica CR (pregabalin) [prescribing information]. New York, NY: Parke-Davis; June 2020.
  68. Lyseng-Williamson KA, Siddiqui MA. Pregabalin: a review of its use in fibromyalgia. Drugs. 2008;68(15):2205-2223. [PubMed 18840008]
  69. Málaga I, Sanmarti FX. Two cases of painful gynecomastia and lower extremity pain in association with pregabalin therapy. Epilepsia. 2006;47(9):1576-1579. doi:10.1111/j.1528-1167.2006.00713.x [PubMed 16981876]
  70. Matsuda KM, Sharma D, Schonfeld AR, Kwatra SG. Gabapentin and pregabalin for the treatment of chronic pruritus. J Am Acad Dermatol. 2016;75(3):619-625.e6. doi:10.1016/j.jaad.2016.02.1237 [PubMed 27206757]
  71. McKeage K, Keam SJ. Pregabalin: in the treatment of postherpetic neuralgia. Drugs Aging. 2009;26(10):883-892. [PubMed 19761281]
  72. Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP. A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study. Am J Hosp Palliat Care. 2012;29(3):177-182. doi:10.1177/1049909111412539 [PubMed 21745832]
  73. Mostacci B, Poluzzi E, D'Alessandro R, Cocchi G, Tinuper P; ESPEA Study Group. Adverse pregnancy outcomes in women exposed to gabapentin and pregabalin: data from a population-based study. J Neurol Neurosurg Psychiatry. 2018;89(2):223-224. doi:10.1136/jnnp-2017-31614 [PubMed 28716783]
  74. Moulin D, Boulanger A, Clark AJ, et al; Canadian Pain Society. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19(6):328-335. [PubMed 25479151]
  75. National Institute for Health and Care Excellence (NICE). Drug allergy: diagnosis and management. https://www.nice.org.uk/guidance/cg183. Published September 3, 2014. Accessed June 19, 2020.
  76. North American Menopause Society. Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause. 2015;22(11):1155-1172. [PubMed 26382310]
  77. Ohman I, De Flon P, Tomson T. Pregabalin kinetics in the neonatal period, and during lactation. Epilepsia. 2011;52 (suppl 6):249-250. Abstract p824.
  78. Ortega-Camarero MA, Avila R, Prados Castaño M, Piñero M, Quiralte J, Cimbollek S. Challenge-based pregabalin induced urticaria and angioedema. A case report. Allergol Immunopathol (Madr). 2012;40(5):323. doi:10.1016/j.aller.2011.09.012 [PubMed 22266144]
  79. Page RL 2nd, Cantu M, Lindenfeld J, Hergott LJ, Lowes BD. Possible heart failure exacerbation associated with pregabalin: case discussion and literature review. J Cardiovasc Med (Hagerstown). 2008;9(9):922-925. doi:10.2459/JCM.0b013e3282fb7629 [PubMed 18695430]
  80. Page RL 2nd, O'Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016;134(6):e32-e69. doi:10.1161/CIR.0000000000000426 [PubMed 27400984]
  81. Paice JA, Portenoy R, Lacchetti C, et al. Management of chronic pain in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34(27):3325-3345. doi:10.1200/JCO.2016.68.5206 [PubMed 27458286]
  82. Pande AC, Feltner DE, Jefferson JW, et al. Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study. J Clin Psychopharmacol. 2004;24(2):141-149. [PubMed 15206660]
  83. Patorno E, Bateman BT, Huybrechts KF, et al. Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology. 2017;88(21):2020-2025. [PubMed 28446648]
  84. Pop-Busui R, Boulton AJ, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-154. doi:10.2337/dc16-2042 [PubMed 27999003]
  85. Portenoy RK, Ahmed E, Keilson YY. Cancer pain management: role of adjuvant analgesics (coanalgesics). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2022.
  86. Qu C, Xie Y, Qin F, Liu W. Neuropsychiatric symptoms accompanying thrombocytopenia following pregabalin treatment for neuralgia: a case report. Int J Clin Pharm. 2014;36(6):1138-1140. doi:10.1007/s11096-014-0026-7 [PubMed 25297834]
  87. Ragucci MV, Cohen JM. Gabapentin-induced hypersensitivity syndrome. Clin Neuropharmacol. 2001;24(2):103-105. doi:10.1097/00002826-200103000-00007 [PubMed 11307046]
  88. Randinitis EJ, Posvar EL, Alvey CW, Sedman AJ, Cook JA, Bockbrader HN. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol. 2003;43(3):277-283. doi:10.1177/0091270003251119 [PubMed 12638396]
  89. Refer to manufacturer's labeling.
  90. Reid R, Abramson BL, Blake J, et al; Menopause and Osteoporosis Working Group; Society of Obstetricians and Gynaecologists of Canada. Managing menopause. J Obstet Gynaecol Can. 2014;36(9):830-838. [PubMed 25222364]
  91. Santen R, Loprinzi C, Casper R. Menopausal hot flashes. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 10, 2019.
  92. Schiavo A, Stagnaro FM, Salzano A, et al. Pregabalin-induced first degree atrioventricular block in a young patient treated for pain from extrapulmonary tuberculosis. Monaldi Arch Chest Dis. 2017;87(3):838. doi:10.4081/monaldi.2017.838 [PubMed 29424197]
  93. Smetana KS, Cook AM, Bastin ML, Oyler DR. Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. J Crit Care. 2016;36:116-124. doi:10.1016/j.jcrc.2016.06.023 [PubMed 27546759]
  94. Solak Y, Biyik Z, Atalay H, et al. Pregabalin versus gabapentin in the treatment of neuropathic pruritus in maintenance haemodialysis patients: a prospective, crossover study. Nephrology (Carlton). 2012;17(8):710-717. doi:10.1111/j.1440-1797.2012.01655.x [PubMed 22909343]
  95. Stein M. Pharmacotherapy for social anxiety disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 5, 2018.
  96. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011. doi:10.1210/jc.2015-2236 [PubMed 26444994]
  97. Thein OS, Sutton B, Thickett DR, Parekh D. Mepolizumab rescue therapy for acute pneumonitis secondary to DRESS. BMJ Case Rep. 2019;12(10):e231355. doi:10.1136/bcr-2019-231355 [PubMed 31604720]
  98. Tietze KJ. Sedative-analgesic medications in critically ill adults: properties, dosage regimens, and adverse effects. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 14, 2019.
  99. Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. ClinPharmacokinet. 2010;49(1):1-16. doi:10.2165/11318140-000000000-00000 [PubMed 20000886]
  100. Veiby G, Daltveit AK, Engelsen BA, Gilhus NE. Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol. 2014;261(3):579-588. doi:10.1007/s00415-013-7239-x [PubMed 24449062]
  101. Vertigan AE, Kapela SL, Ryan NM, Birring SS, McElduff P, Gibson PG. Pregabalin and speech pathology combination therapy for refractory chronic cough: a randomized controlled trial. Chest. 2016;149(3):639-648. doi:10.1378/chest.15-1271 [PubMed 26447687]
  102. Vestita M, Cerbone L, Calista D. Brachioradial pruritus in a 47-year-old woman treated with pregabalin. G Ital Dermatol Venereol. 2016;151(6):727-728. [PubMed 27824228]
  103. Weisshaar E, Szepietowski JC, Dalgard F, et al; European Dermatology Forum; European Academy of Dermatology and Venereology. European guideline on chronic pruritus. https://www.edf.one/dam/jcr:9c925c23-fa0f-4765-8592-a86a75ce0ec3/GL_Chronic_pruritus.pdf. Published 2019. Accessed January 19, 2022.
  104. Weisshaar E, Szepietowski JC, Darsow U, et al. European guideline on chronic pruritus. Acta Derm Venereol. 2012;92(5):563-581. doi: 10.2340/00015555-1400. [PubMed 22790094]
  105. Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: treatment of restless legs syndrome in adults. Neurology. 2016;87(24):2585-2593. doi:10.1212/WNL.0000000000003388 [PubMed 27856776]
  106. Winterfeld U, Merlob P, Baud D, et al. Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology 2016;86(24):2251-2257 [PubMed 27194385]
  107. Yue J, Jiao S, Xiao Y, Ren W, Zhao T, Meng J. Comparison of pregabalin with ondansetron in treatment of uraemic pruritus in dialysis patients: a prospective, randomized, double-blind study. Int Urol Nephrol. 2015;47(1):161-167. doi:10.1007/s11255-014-0795-x [PubMed 25099523]
  108. Zaccara G, Gangemi P, Perucca P, Specchio L. The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials. Epilepsia. 2011;52(4):826-836. doi:10.1111/j.1528-1167.2010.02966.x [PubMed 21320112]
Topic 9473 Version 540.0