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Lyrica

Generic Name: Pregabalin
Class: Anticonvulsants, Miscellaneous
VA Class: CN900
Chemical Name: (S)-3-(aminomethyl)-5-methylhexanoic acid
Molecular Formula: C8H17NO2
CAS Number: 148553-50-8

Medically reviewed by Drugs.com. Last updated on Mar 23, 2020.

Warning

Special Alerts:

[Posted 12-19-2019]

TOPIC: Neurontin, Gralise, Horizant (gabapentin) and Lyrica, Lyrica CR (pregabalin): Serious Breathing Problems

AUDIENCE: Patient, Neurology, Pain Management, Pulmonology, Pharmacy

BACKGROUND: Gabapentin and pregabalin are FDA-approved for a variety of conditions, including seizures, nerve pain, and restless legs syndrome.

ISSUE: FDA is warning that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors. These include the use of opioid pain medicines and other drugs that depress the central nervous system, and conditions such as chronic obstructive pulmonary disease that reduce lung function. The elderly are also at higher risk.

FDA is requiring new warnings about the risk of respiratory depression to be added to the prescribing information of the gabapentinoids. FDA has also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression.

RECOMMENDATION: Patients and caregivers should seek medical attention immediately if you or someone you are caring for experiences symptoms of respiratory problems, because these can be life-threatening. Symptoms to watch for include:

  • Confusion or disorientation

  • Unusual dizziness or lightheadedness

  • Extreme sleepiness or lethargy

  • Slowed, shallow, or difficult breathing

  • Unresponsiveness, which means a person doesn’t answer or react normally or you can’t wake them up

  • Bluish-colored or tinted skin, especially on the lips, fingers, and toes

Always inform your health care professional about all the drugs you are taking, including prescription and over-the-counter medicines and other substances such as alcohol.

Health care professionals should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when co-prescribing gabapentinoids with an opioid or other central nervous system depressant such as a benzodiazepine.

For more information visit the FDA website at: [Web] and [Web].

Introduction

Anticonvulsant; structurally related to the inhibitory CNS neurotransmitter GABA; also possesses analgesic activity.1 2 3 5 6 8 18

Uses for Lyrica

Seizure Disorders

Management (in combination with other anticonvulsants) of partial seizures in adults1 13 16 36 and pediatric patients ≥1 month of age.1 2 3 4 12 35

Clinical studies establishing efficacy of pregabalin for this indication were conducted with conventional (immediate-release) preparations; efficacy of extended-release pregabalin not established in patients with partial seizures.1 15 36

Neuropathic Pain

Management of postherpetic neuralgia (PHN) in adults.1 5 6 13 15 16 37 Considered one of several first-line therapies for PHN; more effective than placebo, but evidence suggests that only a small proportion of patients will derive a clinically meaningful benefit.27 67 89

Management of pain associated with diabetic peripheral neuropathy (DPN) in adults.1 7 8 13 15 16 Considered one of several first-line therapies for DPN; more effective than placebo, but evidence suggests that only a small proportion of patients will derive a clinically meaningful benefit.25 27 29 67 89 91 94 95 96

Management of neuropathic pain associated with spinal cord injury in adults.1 13 16 23 24 Clinical studies establishing efficacy of pregabalin for this indication were conducted with conventional (immediate-release) preparations of the drug.1

Fibromyalgia

Management of fibromyalgia in adults.1 13 16 17 18 19 20 34 Evidence suggests that the drug may be effective in a small proportion of patients.34

Clinical studies establishing efficacy of pregabalin for this indication were conducted with conventional (immediate-release) preparations; efficacy of extended-release pregabalin not established in patients with fibromyalgia.1 15

Lyrica Dosage and Administration

General

  • Closely monitor for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.1 14 21 (See Suicidality Risk under Cautions.)

  • If pregabalin is discontinued, gradually taper dosage over ≥1 week.1 15 (See Discontinuance of Therapy under Cautions.)

Administration

Oral Administration

Administer orally as conventional (immediate-release) capsules or oral solution.1 13 16 Also available as extended-release tablets for treatment of DPN or PHN.15

Administer conventional capsules and oral solution orally without regard to food.1

Administer extended-release tablets once daily after the evening meal.15 Swallow tablets whole; do not split, crush or chew.15

Dosage

Pediatric Patients

Seizure Disorders
Partial Seizures
Oral

Children 1 month to <4 years of age who weigh <30 kg: Initially, 3.5 mg/kg daily (administered in 3 divided doses as conventional preparations).1 May increase dosage at approximately weekly intervals based on individual patient response and tolerability up to maximum of 14 mg/kg daily.1

Children ≥4 years of age who weigh <30 kg: Initially, 3.5 mg/kg daily (administered in 2 or 3 divided doses as conventional preparations).1 May increase dosage at approximately weekly intervals based on individual patient response and tolerability up to maximum of 14 mg/kg daily.1

Children ≥1 month of age who weigh ≥30 kg: Initially, 2.5 mg/kg daily (administered in 2 or 3 divided doses as conventional preparations).1 May increase dosage at approximately weekly intervals based on individual patient response and tolerability up to 10 mg/kg daily (not to exceed 600 mg daily).1

Adults

Seizure Disorders
Partial Seizures
Oral

Initially, 75 mg twice daily or 50 mg 3 times daily as conventional preparations.1 2 3 12 13 16 May increase dosage at approximately weekly intervals based on individual response and tolerability up to a maximum daily dosage of 600 mg.1 2 3 4 12 13 16

Efficacy and adverse effects dose related;1 2 3 however, effect of dosage escalation rate on tolerability not studied.1 10

Dosage recommendations for use of pregabalin in conjunction with gabapentin not available; such regimens were not evaluated in controlled clinical studies.1

Dosage adjustments are required in patients with renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Neuropathic Pain
Postherpetic Neuralgia
Oral

Conventional preparations: Initially, 150 mg daily (administered in 2 or 3 divided doses); may increase dosage to 300 mg daily (in 2 or 3 divided doses) within 1 week based on efficacy and tolerability.1 5 13 16 In patients who tolerate the drug but are not experiencing adequate pain relief following 2–4 weeks of treatment with a dosage of 300 mg daily, may increase up to 600 mg daily (administered in 2 or 3 divided doses); because of dose-dependent adverse reactions, reserve dosages >300 mg daily for those who have continuing pain and are tolerating the drug.1 5 13 16

Extended-release tablets: Initially, 165 mg once daily after the evening meal; may increase dosage within 1 week to 330 mg once daily based on individual patient response and tolerability.15 In patients who tolerate the drug but are not experiencing adequate pain relief following 2–4 weeks of treatment with a dosage of 330 mg daily, may increase dosage to maximum of 660 mg daily; because of dose-dependent adverse reactions, reserve dosages >330 mg daily for those who have continuing pain and are tolerating the drug.15

Transitioning from conventional preparations to extended-release tablets: Take usual morning dose of pregabalin capsules or oral solution and initiate therapy with the extended-release tablets after the evening meal.15 Perform appropriate dose conversion according to Table 1.15

Table 1. Dose Conversion from Conventional to Extended-release Pregabalin15

Conventional Pregabalin Total Daily Dose

Extended-release Pregabalin Dose

75 mg daily (given 2 or 3 times daily)

82.5 mg once daily

150 mg daily (given 2 or 3 times daily)

165 mg once daily

225 mg daily (given 2 or 3 times daily)

247.5 mg once daily

300 mg daily (given 2 or 3 times daily)

330 mg once daily

450 mg daily (given 2 or 3 times daily)

495 mg once daily

600 mg daily (given 2 or 3 times daily)

660 mg once daily

Dosage adjustments are required in patients with renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Diabetic Neuropathy
Oral

Conventional preparations: Initially, 150 mg daily (administered as 50 mg 3 times daily); may increase dosage within 1 week to a maximum of 300 mg daily (administered in 3 divided doses) based on efficacy and tolerability.1 7 8 13 16

Extended-release tablets: Initially, 165 mg once daily after the evening meal; may increase dosage within 1 week to maximum of 330 mg once daily based on individual patient response and tolerability.15

Higher dosages (e.g., 600 mg daily) provide no additional benefit, but may increase risk of adverse effects.1 7 15

Transitioning from conventional preparations to extended-release tablets: Take usual morning dose of pregabalin capsules or oral solution and initiate therapy with the extended-release tablets after the evening meal.15 Perform appropriate dose conversion according to Table 2.15

Table 2. Dose Conversion from Conventional to Extended-release Pregabalin15

Conventional Pregabalin Total Daily Dose

Extended-release Pregabalin Dose

75 mg daily (given 2 or 3 times daily)

82.5 mg once daily

150 mg daily (given 2 or 3 times daily)

165 mg once daily

225 mg daily (given 2 or 3 times daily)

247.5 mg once daily

300 mg daily (given 2 or 3 times daily)

330 mg once daily

450 mg daily (given 2 or 3 times daily)

495 mg once daily

600 mg daily (given 2 or 3 times daily)

660 mg once daily

Dosage adjustments are required in patients with renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Neuropathic Pain Associated with Spinal Cord Injury
Oral

Initially, 150 mg daily (administered as 75 mg twice daily as conventional preparations).1 13 16 May increase dosage within 1 week up to 300 mg daily (150 mg twice daily) based on efficacy and tolerability.1 13 16 In patients who tolerate the drug but do not experience adequate pain relief after 2–3 weeks of treatment with a dosage of 300 mg daily, may increase to 600 mg daily (300 mg twice daily).1 13 16

Dosage adjustments are required in patients with renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Fibromyalgia
Oral

Initially, 150 mg daily (75 mg twice daily as conventional preparations).1 13 16 Increase dosage to 300 mg daily (150 mg twice daily) within 1 week based on efficacy and tolerability.1 13 16

May increase dosage up to a maximum of 450 mg daily (225 mg twice daily) in patients who do not experience adequate benefit with a dosage of 300 mg daily.1 13 16

Recommended maintenance dosage is 300–450 mg daily.1 13 16

Higher dosages (e.g., 600 mg daily) provide no additional benefit, but may increase risk of adverse effects.1

Dosage adjustments are required in patients with renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Prescribing Limits

Pediatric Patients

Seizure Disorders
Oral

Children ≥1 month of age weighing <30 kg: Maximum 14 mg/kg daily.1

Children ≥1 month of age weighing ≥30 kg: Maximum 10 mg/kg daily (not to exceed 600 mg daily).1

Adults

Seizure Disorders
Oral

Maximum daily dosage of 600 mg as conventional preparations.1 13 16

Postherpetic Neuralgia
Oral

Maximum daily dosage of 600 mg as conventional preparations.1 13 15 16

Maximum 660 mg daily (as extended-release tablet).15

Diabetic Neuropathy
Oral

Maximum daily dosage of 300 mg as conventional preparations.1 13 15 16

Maximum 330 mg daily (as extended-release tablet).15

Neuropathic Pain Associated with Spinal Cord Injury
Oral

Maximum 600 mg daily (300 mg twice daily) as conventional preparations.1 13 16

Fibromyalgia
Oral

Maximum 450 mg daily as conventional preparations; higher dosages not recommended because of dose-dependent adverse effects.1 13 16

Special Populations

Renal Impairment

Modify dosage of pregabalin in adults with renal impairment (Clcr <60 mL/minute) based on Clcr (see Tables 3 or 4 based on the preparation of drug used).1 13 15 16 Not studied in pediatric patients with renal impairment.1

Table 3: Dosage Adjustment of Pregabalin Conventional Preparations in Patients with Renal Impairment15101316

Usual Dosage Regimen (for Patients with Clcr of ≥60 mL/minute)

Clcr (mL/minute)

Adjusted Dosage Regimen

150 mg daily given in 2 or 3 divided doses

30–60

75 mg daily given in 2 or 3 divided doses

 

15–30

25–50 mg daily given as a single dose or in 2 divided doses

 

<15

25 mg once daily

300 mg daily given in 2 or 3 divided doses

30–60

150 mg daily given in 2 or 3 divided doses

 

15–30

75 mg daily given as a single dose or in 2 divided doses

 

<15

25–50 mg once daily

450 mg daily given in 2 or 3 divided doses

30–60

225 mg daily given in 2 or 3 divided doses

 

15–30

100–150 mg daily given as a single dose or in 2 divided doses

 

<15

50–75 mg once daily

600 mg daily given in 2 or 3 divided doses

30–60

300 mg daily given in 2 or 3 divided doses

 

15–30

150 mg daily given as a single dose or in 2 divided doses

 

<15

75 mg once daily

Table 4. Dosage Adjustment of Pregabalin Extended-release Tablets in Patients with Renal Impairment15

Usual Dosage Regimen (for Patients with Clcr ≥60 mL/minute)

Clcr (mL/minute)

Adjusted Dosage Regimen

165 mg daily

30–60

82.5 mg daily

<30 or receiving hemodialysis

Use conventional pregabalin preparations

330 mg daily

30–60

165 mg daily

<30 or receiving hemodialysis

Use conventional pregabalin preparations

495 mg daily

30–60

247.5 mg daily

<30 or receiving hemodialysis

Use conventional pregabalin preparations

660 mg daily

30–60

330 mg daily

<30 or receiving hemodialysis

Use conventional pregabalin preparations

Patients undergoing hemodialysis: Administer a supplemental dose (as conventional preparations) immediately following each 4-hour dialysis session.1 Individuals receiving the 25-mg once-daily dosage regimen should receive a supplemental dose of 25 or 50 mg, those receiving the 25- to 50-mg once-daily dosage regimen should receive a supplemental dose of 50 or 75 mg, those receiving the 50- to 75-mg once-daily dosage regimen should receive a supplemental dose of 75 or 100 mg, and those receiving the 75-mg once-daily dosage regimen should receive a supplemental dose of 100 or 150 mg.1 The extended-release preparation is not recommended in patients undergoing hemodialysis.15

Geriatric Patients

Adjust dosage for geriatric patients with renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Lyrica

Contraindications

  • Known hypersensitivity to pregabalin or any ingredient in the formulation.1 15

Warnings/Precautions

Sensitivity Reactions

Angioedema

Angioedema, including life-threatening cases with respiratory compromise requiring emergency treatment, reported during postmarketing surveillance.1 15 Symptoms included swelling of the face, mouth (e.g., tongue, lips, gums), and neck (e.g., throat, larynx).1 Discontinue pregabalin immediately in patients with these symptoms.1

Use with caution in patients with previous episode of angioedema.1

Patients receiving concomitant drugs associated with angioedema (e.g., ACE inhibitors) may be at increased risk.1

Hypersensitivity Reactions

Hypersensitivity reactions (i.e., skin redness, blisters, hives, rash, dyspnea, wheezing) reported during postmarketing surveillance.1 15 Discontinue pregabalin immediately if a hypersensitivity reaction occurs.1

Discontinuance of Therapy

Abrupt withdrawal may result in increased seizure frequency; withdraw therapy gradually and reduce dosage slowly over ≥1 week.1 15

Following abrupt or rapid withdrawal, symptoms suggestive of physical dependence reported.1 (See Abuse Potential and Dependence under Cautions.)

Suicidality Risk

Increased risk of suicidality (suicidal ideation or behavior) observed in an analysis of studies using various anticonvulsants, including pregabalin, in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).1 14 15 21 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy; because most studies were ≤24 weeks' duration, risk of suicidality beyond 24 weeks not known.1 14 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.1 14

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.1 14 21

Balance risk of suicidality with the risk of untreated illness.1 14 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.1 14 If suicidal thoughts or behavior emerge during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.1 21 (See Advice to Patients.)

Peripheral Edema

Risk of edema (mainly peripheral edema).1 15 Peripheral edema not associated with deterioration of renal or hepatic function.1

No apparent association between peripheral edema and cardiovascular complications (e.g., hypertension, CHF) in patients without clinically important heart or peripheral vascular disease.1

Concomitant use with a thiazolidinedione antidiabetic agent associated with a greater risk of weight gain and peripheral edema.1 (See Specific Drugs under Interactions.)

Use with caution in patients with NYHA class III or IV heart failure.1

Dizziness and Somnolence

Risk of dizziness and somnolence.1 15 Occurs more frequently at higher doses and, in some cases, persists throughout therapy.1 15 (See Advice to Patients.)

Weight Gain

Possible weight gain related to dosage and duration of exposure to pregabalin, but not related to baseline body mass index (BMI), gender, age, or existing edema.1 15

Weight gain not associated with clinically important short-term changes in BP, but long-term cardiovascular effects not known.1

Pregabalin therapy does not appear to be associated with loss of glycemic control.1

Tumorigenic Potential

Carcinogenicity (e.g., hemangiosarcoma) demonstrated in animals.1 15

New or worsening of preexisting tumors reported in humans; causal relationship not established.1

Ocular Effects

Possible blurred vision, decreased visual acuity, visual field changes, and funduscopic changes.1 15 Clinical importance not known.1

If visual disturbance persists, consider further or more frequent ophthalmologic assessment in those already monitored for ocular conditions.1

Creatine Kinase Elevations

Possible increases in CPK concentrations (≥ 3 times the ULN) and rhabdomyolysis; causal relationship not established.1 15

Discontinue pregabalin if myopathy is diagnosed or suspected or if markedly elevated CPK concentrations occur.1

Thrombocytopenia

Risk of thrombocytopenia, although increased bleeding-related adverse effects not reported.1 15

PR Interval Prolongation

Risk of prolongation of the PR interval (mean increase: 3–6 msec) with daily pregabalin dosages ≥300 mg.1 15 Patients with preexisting PR prolongation at baseline or those receiving drugs that prolong the PR interval do not appear to be at increased risk.1

Concomitant Use with Opiates

Increased risk of opiate-related death observed in opiate users who used pregabalin and an opiate concomitantly.1 15 Use caution when pregabalin is prescribed concomitantly with opiates.1 (See Specific Drugs under Interactions.)

Abuse Potential and Dependence

Possible euphoria.1 12 15

Abrupt or rapid discontinuance has resulted in withdrawal symptoms (e.g., insomnia, nausea, headache, diarrhea, anxiety, hyperhidrosis).1 (See Discontinuance of Therapy under Cautions.)

Pregabalin is not known to be active at receptor sites associated with drugs of abuse.1 However, the drug is subject to control as a schedule V (C-V) drug.9 12

Carefully evaluate patients for history of drug abuse and observe for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).1

Specific Populations

Pregnancy

North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or [Web].1

May cause fetal harm.1 No adequate and well-controlled studies in pregnant women; in animal studies, developmental toxicity observed.1

Lactation

Distributed into human milk.1 (See Extent under Pharmacokinetics.) Because of potential risk of tumorigenicity, breastfeeding not recommended.1 (See Tumorigenic Potential under Cautions.)

Pediatric Use

Safety and efficacy for adjunctive treatment of partial seizures not established in pediatric patients <1 month of age.1 Although the youngest patient evaluated in principal efficacy studies was 3 months of age, use of pregabalin in infants 1–3 months of age can be supported by additional pharmacokinetic data.1

Safety and efficacy for treatment of neuropathic pain conditions (i.e., DPN, PHN, neuropathic pain associated with spinal cord injury) not established in pediatric patients.1

Safety and efficacy for treatment of fibromyalgia not established in pediatric patients.1

Safety and efficacy of pregabalin extended-release tablets not established in pediatric patients.15

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1 15 Neurologic adverse reactions including dizziness, blurred vision, balance disorder, tremor, confusional state, abnormal coordination, and lethargy occurred more frequently in patients ≥65 years of age than in younger adults in controlled clinical studies of patients with fibromyalgia.1

Substantially eliminated by kidneys; risk of adverse reactions may be increased in patients with impaired renal function.1

Adjust dosage in geriatric patients with renal impairment.1 Monitoring renal function in geriatric patients may be helpful.15 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Conventional preparation in adults: Dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, abnormal thinking (primarily difficulty with concentration/attention).1

Conventional preparation in pediatric patients: Somnolence, weight gain, increased appetite.1

Extended-release preparation in adults: Dizziness, somnolence, headache, fatigue, peripheral edema, nausea, blurred vision, dry mouth, weight gain.15

Interactions for Lyrica

Does not appear to inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 or induce CYP1A2 or 3A4.1 10

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Since pregabalin undergoes negligible metabolism in humans, pharmacokinetics unlikely to be affected by other agents through metabolic interactions.1

Increased metabolism of concomitantly administered CYP1A2 substrates (e.g., caffeine, theophylline) or CYP3A4 substrates (e.g., midazolam, testosterone) not anticipated.1

Protein-bound Drugs

Does not bind to plasma proteins; pharmacokinetic interactions unlikely with drugs that are highly protein bound.1

Constipating Drugs

Increased risk of events related to decreased lower GI tract function (e.g., intestinal obstruction, paralytic ileus, constipation).1 (See Specific Drugs under Interactions.)

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Potential increased risk of developing angioedema1

Alcohol

Pharmacokinetic interaction not observed1

Additive effects on cognitive and gross motor functioning observed; no clinically important effects on respiration1

Avoid alcohol1

Anticonvulsants

Pharmacokinetic interaction unlikely with carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, and valproate1

Possible slight decrease in rate of absorption of pregabalin when used concomitantly with gabapentin; gabapentin pharmacokinetics not affected1

Pharmacokinetics of pregabalin not affected by tiagabine 1

 

Antidiabetic agents

Pharmacokinetics of pregabalin not affected by glyburide, insulin, or metformin1

Potential increased risk of weight gain and peripheral edema with thiazolidinediones, possibly exacerbating or causing heart failure1

Use thiazolidinediones concomitantly with caution1

CNS depressants (e.g., opiates, benzodiazepines)

Possible additive CNS depressant effects (e.g., somnolence)1

Respiratory failure, coma, and death reported with concomitant use1

Erythromycin

Decreased systemic exposure of pregabalin (administered as the extended-release tablet) by 17%15

Furosemide

Pharmacokinetics of pregabalin not affected1

 

Lorazepam

Pharmacokinetic interaction not observed1

Additive effects on cognitive and gross motor functioning observed; no clinically important effects on respiration1

 

Opiates

Possible additive CNS depressant effects1

Increased risk of opiate-related death1

Events related to decreased lower GI tract function (e.g., intestinal obstruction, paralytic ileus, constipation) possible1

Oxycodone: Pharmacokinetic interaction not observed; additive effects on cognitive and gross motor functioning observed, but no clinically important effects on respiration1

Use concomitantly with caution1

Oral contraceptives

Pharmacokinetic interaction unlikely1

 

Lyrica Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration and exhibits linear pharmacokinetics.1 15

Peak plasma concentrations attained within 1.5 hours following oral administration of conventional preparations and within 12 hours following extended-release preparations.1 15 Steady-state concentrations are achieved within 24–48 hours following repeated administration of conventional pregabalin and within 48–72 hours following repeated administration of extended-release pregabalin.1 15

Oral bioavailability following administration of conventional preparation is ≥90% and independent of dose.1

Bioavailability of the extended-release tablets administered once daily following an evening meal is equivalent to that of comparable doses of the conventional preparation administered without food twice daily.15

Food

Food reduces peak plasma concentration of conventional preparations by about 25–30% and delays time to peak plasma concentration, but does not affect extent of absorption.1

Administration of the extended-release tablets in the fasted state reduces systemic exposure of pregabalin by approximately 30% compared with administration following an evening meal.15

Distribution

Extent

Distributed into human milk at concentrations approximately 76% of those in maternal plasma at steady state.1 Following maternal dosages of 300 mg daily, the estimated average dose in a nursing infant is 0.31 mg/kg daily.1

Crosses the placenta in rats; not known whether crosses the placenta in humans.1

Distributed into CSF in animals.1

Elimination

Metabolism

Negligibly metabolized.1 18

Elimination Route

Primarily excreted in urine, mainly as unchanged drug (90%).1 18 Clearance is nearly proportional to Clcr in adults and pediatric patients.1

Half-life

Adults: 6.3 hours.1

Children <6 years of age: 3–4 hours.1

Children ≥7 years of age: 4–6 hours.1

Special Populations

Pregabalin clearance tends to decrease with increasing age.1 (See Geriatric Use under Cautions and see Renal Impairment under Dosage and Administration.)

Weight-normalized clearance is approximately 40% higher in pediatric patients weighing <30 kg than in those weighing ≥30 kg.1 22

Removed by hemodialysis; dosage adjustment is necessary.1 (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Extended-release Tablets

25°C (may be exposed to 15–30°C).15

Oral Solution

25°C (may be exposed to 15–30°C).1

Actions

  • Exact mechanism of anticonvulsant and analgesic action unknown; may be related to binding with high affinity to the α2-δ subunit (an auxiliary subunit of voltage-gated calcium channels) in CNS tissues.1 2 3 5 6 7 8 18

  • In vitro, reduces calcium-dependent release of several neurotransmitters, including glutamate, norepinephrine, calcitonin gene-related peptide, and substance P, possibly by modulation of calcium channel function.1 2 3 4 6 7 8 18

  • Does not bind directly to GABAA, GABAB, or benzodiazepine receptors; does not augment GABAA responses in cultured neurons; and does not alter brain concentrations of GABA in rats or affect GABA uptake or degradation.1 2 18 In cultured neurons, prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport.1 18

  • Does not block sodium channels; not active at opiate receptors; does not alter cyclooxygenase activity.1

  • Inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.1

Advice to Patients

  • Importance of advising patients or caregivers to read the manufacturer's patient information (medication guide) before the start of therapy and each time the prescription is refilled.1

  • Risk of suicidality (anticonvulsants, including pregabalin, may increase risk of suicidal thoughts or actions in about 1 in 500 people).1 14 21 Importance of patients, family, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one’s life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).1 14

  • Risk of angioedema (e.g., swelling of the face, mouth [e.g., tongue, lips, gums], and neck [e.g., throat, larynx] with or without life-threatening respiratory compromise) and other hypersensitivity reactions (e.g., wheezing, dyspnea, rash, hives, blisters); importance of discontinuing the drug and seeking immediate medical attention if such reactions occur.1 Concomitant administration with an ACE inhibitor may increase such risk.1

  • Importance of taking pregabalin only as prescribed.1 Importance of advising patients or caregivers to consult their clinician before changing the dosage of or abruptly discontinuing the drug.1 Patients or caregivers should be informed that abrupt or rapid discontinuance of pregabalin can result in increased risk of seizures in patients with epilepsy or withdrawal symptoms such as insomnia, nausea, headache, anxiety, hyperhidrosis, or diarrhea.1

  • Risk of dizziness, somnolence, blurred vision, and other neuropsychiatric effects.1 Avoid driving or operating machinery or engaging in other hazardous activities while taking pregabalin until experienced with the drug’s effects.1

  • Risk of edema and weight gain; concomitant administration with a thiazolidinedione antidiabetic agent may increase such risk.1 In patients with preexisting cardiac conditions, risk of heart failure may be increased.1

  • Risk of visual disturbances.1 Importance of informing clinician if changes in vision occur.1

  • Importance of patients promptly informing clinicians of any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.1

  • Inform patients that concomitant use of CNS depressants and pregabalin (e.g., opiates or benzodiazepines) may result in additive CNS effects such as somnolence.1

  • Avoid alcohol-containing beverages or products; drug may potentiate impairment of motor skills and sedation associated with ingestion of alcohol.1

  • Advise patients that if a dose of pregabalin (as conventional preparations) is missed, the missed dose should be taken as soon as possible; if it is almost time for the next dose, the missed dose should be skipped and the next dose should be taken at the regularly scheduled time.1 Patients should not take 2 doses at the same time.1

  • Advise patients that if a dose of pregabalin (as extended-release tablets) is missed after an evening meal, the dose should be taken prior to bedtime following a snack.15 If they miss the dose prior to bedtime, then they should take their usual dose the next morning following breakfast.15 If they miss taking the dose following the morning meal, they should take their usual dose at the regularly scheduled time after the evening meal.15

  • Advise diabetic patients to watch for skin damage while receiving pregabalin therapy, since increased risk of skin ulcerations associated with pregabalin therapy has been observed in animal studies.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of clinicians informing women about the existence of and encouraging enrollment in the NAAED Pregnancy Registry (see Pregnancy under Cautions).1 Women should be advised that breastfeeding is not recommended during treatment with pregabalin.1

  • Advise patients of male-mediated teratogenicity.1 Importance of men informing clinicians if they plan to father a child.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 Potential for additive CNS effects if used concomitantly with other CNS depressants (e.g., opiates, benzodiazepines).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule V (C-V) drug.1 9 12 (See Abuse Potential and Dependence under Cautions.)

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pregabalin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

25 mg

Lyrica (C-V)

Pfizer

50 mg

Lyrica (C-V)

Pfizer

75 mg*

Lyrica (C-V)

Pfizer

Pregabalin Capsules

100 mg*

Lyrica (C-V)

Pfizer

Pregabalin Capsules

150 mg*

Lyrica (C-V)

Pfizer

Pregabalin Capsules

200 mg*

Lyrica (C-V)

Pfizer

Pregabalin Capsules

225 mg*

Lyrica (C-V)

Pfizer

Pregabalin Capsules

300 mg*

Lyrica (C-V)

Pfizer

Pregabalin Capsules

Solution

20 mg/mL*

Lyrica (C-V)

Pfizer

Pregabalin Oral Solution

Tablets, extended-release

82.5 mg

Lyrica CR (C-V)

Pfizer

165 mg

Lyrica CR (C-V)

Pfizer

330 mg

Lyrica CR (C-V)

Pfizer

AHFS DI Essentials™. © Copyright 2020, Selected Revisions March 23, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Pfizer, Inc. Lyrica (pregabalin) capsules prescribing information. New York, NY; 2019 Jun.

2. French JA, Kugler AR, Robbins JL et al. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology. 2003; 60:1631-7. http://www.ncbi.nlm.nih.gov/pubmed/12771254?dopt=AbstractPlus

3. Arroyo S, Anhut H, Kugler AR et al. Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures. Epilepsia. 2004; 45:20-7. http://www.ncbi.nlm.nih.gov/pubmed/14692903?dopt=AbstractPlus

4. Beydoun A, Uthman BM, Kugler AR et al. Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology. 2005; 64:475-80. http://www.ncbi.nlm.nih.gov/pubmed/15699378?dopt=AbstractPlus

5. Dworkin RH, Corbin AE, Young JP et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2003; 60:1274-83. http://www.ncbi.nlm.nih.gov/pubmed/12707429?dopt=AbstractPlus

6. Sabatowski R, Gálvez R, Cherry DA et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain. 2004; 109:26-35. http://www.ncbi.nlm.nih.gov/pubmed/15082123?dopt=AbstractPlus

7. Lesser H, Sharma U, LaMoreaux L et al. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004; 63:2104-10. http://www.ncbi.nlm.nih.gov/pubmed/15596757?dopt=AbstractPlus

8. Rosenstock J, Tuchman M, LaMoreaux L et al. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain. 2004; 110:628-38. http://www.ncbi.nlm.nih.gov/pubmed/15288403?dopt=AbstractPlus

9. Department of Justice, Drug Enforcement Administration. Schedules of controlled substances: placement of pregabalin into schedule V. Final rule. Fed Regist. 2005; 70:43633-5. http://www.ncbi.nlm.nih.gov/pubmed/16050051?dopt=AbstractPlus

10. Pfizer, Morris Plains, NJ: Personal communication.

11. Huppertz HJ, Feuerstein TJ, Schulze-Bonhage A. Myoclonus in epilepsy patients with anticonvulsive add-on therapy with pregabalin. Epilepsia. 2001; 42:790-2. http://www.ncbi.nlm.nih.gov/pubmed/11422338?dopt=AbstractPlus

12. Anon. Drugs for epilepsy. Med Lett Treat Guid. 2005; 3:75-82.

13. Ascend. Pregabalin oral solution prescribing information. Parsipanny, NJ; 2019 July.

14. Food and Drug Administration. FDA Alert: Information for healthcare professionals: suicidality and antiepileptic drugs. Rockville, MD; 2008 Jan 31. From the FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100192.htm

15. Pfizer. Lyrica CR (pregabalin) extended-release tablets prescribing information. New York, NY; 2019 Jun.

16. Teva. Pregabalin capsules prescribing information. North Wales, PA; 2019 May.

17. Crofford LJ, Mease PJ, Simpson SL et al. Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. Pain. 2008; 136:419-31. http://www.ncbi.nlm.nih.gov/pubmed/18400400?dopt=AbstractPlus

18. Lyseng-Williamson KA, Siddiqui MA. Pregabalin : a review of its use in fibromyalgia. Drugs. 2008; 68:2205-23. http://www.ncbi.nlm.nih.gov/pubmed/18840008?dopt=AbstractPlus

19. . Pregabalin (Lyrica) for fibromyalgia. Med Lett Drugs Ther. 2007; 49:77-8. http://www.ncbi.nlm.nih.gov/pubmed/17878888?dopt=AbstractPlus

20. Arnold LM, Russell IJ, Diri EW et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain. 2008; 9:792-805. http://www.ncbi.nlm.nih.gov/pubmed/18524684?dopt=AbstractPlus

21. Food and Drug Administration. Suicidal behavior and ideation and antiepileptic drugs: update 5/5/2009. Rockville, MD; 2009 May 5. From the FDA website. Accessed 2009 Oct 21. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100190.htm

22. Mann D, Liu J, Chew ML et al. Safety, tolerability, and pharmacokinetics of pregabalin in children with refractory partial seizures: a phase 1, randomized controlled study. Epilepsia. 2014; 55:1934-43. http://www.ncbi.nlm.nih.gov/pubmed/25377429?dopt=AbstractPlus

23. Siddall PJ, Cousins MJ, Otte A et al. Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Neurology. 2006; 67:1792-800. http://www.ncbi.nlm.nih.gov/pubmed/17130411?dopt=AbstractPlus

24. Cardenas DD, Nieshoff EC, Suda K et al. A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury. Neurology. 2013; 80:533-9. http://www.ncbi.nlm.nih.gov/pubmed/23345639?dopt=AbstractPlus

25. Freeman R, Durso-Decruz E, Emir B. Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized, controlled trials across a range of doses. Diabetes Care. 2008; 31:1448-54. http://www.ncbi.nlm.nih.gov/pubmed/18356405?dopt=AbstractPlus

26. Freynhagen R, Strojek K, Griesing T et al. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain. 2005; 115:254-63. http://www.ncbi.nlm.nih.gov/pubmed/15911152?dopt=AbstractPlus

27. Derry S, Bell RF, Straube S et al. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev. 2019; 1:CD007076. http://www.ncbi.nlm.nih.gov/pubmed/30673120?dopt=AbstractPlus

28. Richter RW, Portenoy R, Sharma U et al. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. J Pain. 2005; 6:253-60. http://www.ncbi.nlm.nih.gov/pubmed/15820913?dopt=AbstractPlus

29. Raskin P, Huffman C, Toth C et al. Pregabalin in patients with inadequately treated painful diabetic peripheral neuropathy: a randomized withdrawal trial. Clin J Pain. 2014; 30:379-90. http://www.ncbi.nlm.nih.gov/pubmed/23887339?dopt=AbstractPlus

30. Kim JS, Bashford G, Murphy TK et al. Safety and efficacy of pregabalin in patients with central post-stroke pain. Pain. 2011; 152:1018-23. http://www.ncbi.nlm.nih.gov/pubmed/21316855?dopt=AbstractPlus

31. Simpson DM, Schifitto G, Clifford DB et al. Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology. 2010; 74:413-20. http://www.ncbi.nlm.nih.gov/pubmed/20124207?dopt=AbstractPlus

32. Simpson DM, Rice AS, Emir B et al. A randomized, double-blind, placebo-controlled trial and open-label extension study to evaluate the efficacy and safety of pregabalin in the treatment of neuropathic pain associated with human immunodeficiency virus neuropathy. Pain. 2014; 155:1943-54. http://www.ncbi.nlm.nih.gov/pubmed/24907403?dopt=AbstractPlus

33. Matsuoka H, Iwase S, Miyaji T et al. Additive Duloxetine for Cancer-Related Neuropathic Pain Nonresponsive or Intolerant to Opioid-Pregabalin Therapy: A Randomized Controlled Trial (JORTC-PAL08). J Pain Symptom Manage. 2019; 58:645-653. http://www.ncbi.nlm.nih.gov/pubmed/31254640?dopt=AbstractPlus

34. Derry S, Cording M, Wiffen PJ et al. Pregabalin for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 2016; 9:CD011790. http://www.ncbi.nlm.nih.gov/pubmed/27684492?dopt=AbstractPlus

35. Antinew J, Pitrosky B, Knapp L et al. Pregabalin as Adjunctive Treatment for Focal Onset Seizures in Pediatric Patients: A Randomized Controlled Trial. J Child Neurol. 2019; 34:248-255. http://www.ncbi.nlm.nih.gov/pubmed/30688135?dopt=AbstractPlus

36. Kanner AM, Ashman E, Gloss D et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018; 91:82-90. http://www.ncbi.nlm.nih.gov/pubmed/29898974?dopt=AbstractPlus

37. Huffman CL, Goldenberg JN, Weintraub J et al. Efficacy and Safety of Once-Daily Controlled-Release Pregabalin for the Treatment of Patients With Postherpetic Neuralgia: A Double-Blind, Enriched Enrollment Randomized Withdrawal, Placebo-Controlled Trial. Clin J Pain. 2017; 33:569-578. http://www.ncbi.nlm.nih.gov/pubmed/27753650?dopt=AbstractPlus

66. Dubinsky RM, Kabbani H, El-Chami Z et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004; 63:959-65. http://www.ncbi.nlm.nih.gov/pubmed/15452284?dopt=AbstractPlus

67. Attal N, Cruccu G, Baron R et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010; 17:1113-e88. http://www.ncbi.nlm.nih.gov/pubmed/20402746?dopt=AbstractPlus

68. Edelsberg JS, Lord C, Oster G. Systematic review and meta-analysis of efficacy, safety, and tolerability data from randomized controlled trials of drugs used to treat postherpetic neuralgia. Ann Pharmacother. 2011; 45:1483-90. http://www.ncbi.nlm.nih.gov/pubmed/22085778?dopt=AbstractPlus

87. Goodman CW, Brett AS. A Clinical Overview of Off-label Use of Gabapentinoid Drugs. JAMA Intern Med. 2019; http://www.ncbi.nlm.nih.gov/pubmed/30907944?dopt=AbstractPlus

88. Bates D, Schultheis BC, Hanes MC et al. A Comprehensive Algorithm for Management of Neuropathic Pain. Pain Med. 2019; 20:S2-S12. http://www.ncbi.nlm.nih.gov/pubmed/31152178?dopt=AbstractPlus

89. Cruccu G, Truini A. A review of Neuropathic Pain: From Guidelines to Clinical Practice. Pain Ther. 2017; 6:35-42. http://www.ncbi.nlm.nih.gov/pubmed/29178033?dopt=AbstractPlus

90. Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015; 14:162-73. http://www.ncbi.nlm.nih.gov/pubmed/25575710?dopt=AbstractPlus

91. Diabetes Canada Clinical Practice Guidelines Expert Committee, Bril V, Breiner A et al. Neuropathy. Can J Diabetes. 2018; 42 Suppl 1:S217-S221. http://www.ncbi.nlm.nih.gov/pubmed/29650100?dopt=AbstractPlus

92. National Institute for Health and Care Excellence, Centre for Clinical Practice. Neuropathic pain: The pharmacological management of neuropathic pain in adults in non-specialist settings [Internet]. London, United Kingdom; 2013 Nov.

93. Moore A, Derry S, Wiffen P. Gabapentin for Chronic Neuropathic Pain. JAMA. 2018; 319:818-819. http://www.ncbi.nlm.nih.gov/pubmed/29486015?dopt=AbstractPlus

94. Pop-Busui R, Boulton AJ, Feldman EL et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017; 40:136-154. http://www.ncbi.nlm.nih.gov/pubmed/27999003?dopt=AbstractPlus

95. 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; 76:1758-65 National Institute for Health and Care Excellence. http://www.ncbi.nlm.nih.gov/pubmed/21482920?dopt=AbstractPlus

96. Snyder MJ, Gibbs LM, Lindsay TJ. Treating Painful Diabetic Peripheral Neuropathy: An Update. Am Fam Physician. 2016; 94:227-34. http://www.ncbi.nlm.nih.gov/pubmed/27479625?dopt=AbstractPlus

97. Hagen EM, Rekand T. Management of Neuropathic Pain Associated with Spinal Cord Injury. Pain Ther. 2015; 4:51-65. http://www.ncbi.nlm.nih.gov/pubmed/25744501?dopt=AbstractPlus

99. Stubblefield MD, Burstein HJ, Burton AW. National Comprehensive Cancer Network. NCCN Task Force Reprt: Management of neuropathy in cancer. J Natl Comp Canc Netw. 2009; 8(Suppl 5): S1-26.

100. Moulin D, Boulanger A, Clark AJ et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014 Nov-Dec; 19:328-35. http://www.ncbi.nlm.nih.gov/pubmed/25479151?dopt=AbstractPlus

101. Deng Y, Luo L, Hu Y et al. Clinical practice guidelines for the management of neuropathic pain: a systematic review. BMC Anesthesiol. 2016; 16:12. http://www.ncbi.nlm.nih.gov/pubmed/26892406?dopt=AbstractPlus

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