Pregabalin (Monograph)
Brand name: Lyrica
Drug class:
Introduction
Anticonvulsant; structurally related to the inhibitory CNS neurotransmitter GABA; also possesses analgesic activity.
Uses for Pregabalin
Seizure Disorders
Management (in combination with other anticonvulsants) of partial seizures in adults and pediatric patients ≥1 month of age.
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.
Neuropathic Pain
Management of postherpetic neuralgia (PHN) in adults. 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.
Management of pain associated with diabetic peripheral neuropathy (DPN) in adults. 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.
Management of neuropathic pain associated with spinal cord injury in adults. Clinical studies establishing efficacy of pregabalin for this indication were conducted with conventional (immediate-release) preparations of the drug.
Fibromyalgia
Management of fibromyalgia in adults. Evidence suggests that the drug may be effective in a small proportion of patients.
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.
Pregabalin 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. (See Suicidality Risk under Cautions.)
-
If pregabalin is discontinued, gradually taper dosage over ≥1 week. (See Discontinuance of Therapy under Cautions.)
Administration
Oral Administration
Administer orally as conventional (immediate-release) capsules or oral solution. Also available as extended-release tablets for treatment of DPN or PHN.
Administer conventional capsules and oral solution orally without regard to food.
Administer extended-release tablets once daily after the evening meal. Swallow tablets whole; do not split, crush or chew.
Dosage
Pediatric Patients
Seizure Disorders
Partial Seizures
OralChildren 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). May increase dosage at approximately weekly intervals based on individual patient response and tolerability up to maximum of 14 mg/kg daily.
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). May increase dosage at approximately weekly intervals based on individual patient response and tolerability up to maximum of 14 mg/kg daily.
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). 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).
Adults
Seizure Disorders
Partial Seizures
OralInitially, 75 mg twice daily or 50 mg 3 times daily as conventional preparations. May increase dosage at approximately weekly intervals based on individual response and tolerability up to a maximum daily dosage of 600 mg.
Efficacy and adverse effects dose related; however, effect of dosage escalation rate on tolerability not studied.
Dosage recommendations for use of pregabalin in conjunction with gabapentin not available; such regimens were not evaluated in controlled clinical studies.
Dosage adjustments are required in patients with renal impairment. (See Renal Impairment under Dosage and Administration.)
Neuropathic Pain
Postherpetic Neuralgia
OralConventional 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. 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.
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. 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.
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. Perform appropriate dose conversion according to Table 1.
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. (See Renal Impairment under Dosage and Administration.)
Diabetic Neuropathy
OralConventional 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.
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.
Higher dosages (e.g., 600 mg daily) provide no additional benefit, but may increase risk of adverse effects.
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. Perform appropriate dose conversion according to Table 2.
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. (See Renal Impairment under Dosage and Administration.)
Neuropathic Pain Associated with Spinal Cord Injury
OralInitially, 150 mg daily (administered as 75 mg twice daily as conventional preparations). May increase dosage within 1 week up to 300 mg daily (150 mg twice daily) based on efficacy and tolerability. 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).
Dosage adjustments are required in patients with renal impairment. (See Renal Impairment under Dosage and Administration.)
Fibromyalgia
Oral
Initially, 150 mg daily (75 mg twice daily as conventional preparations). Increase dosage to 300 mg daily (150 mg twice daily) within 1 week based on efficacy and tolerability.
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.
Recommended maintenance dosage is 300–450 mg daily.
Higher dosages (e.g., 600 mg daily) provide no additional benefit, but may increase risk of adverse effects.
Dosage adjustments are required in patients with renal impairment. (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.
Children ≥1 month of age weighing ≥30 kg: Maximum 10 mg/kg daily (not to exceed 600 mg daily).
Adults
Seizure Disorders
Oral
Maximum daily dosage of 600 mg as conventional preparations.
Postherpetic Neuralgia
Oral
Maximum daily dosage of 600 mg as conventional preparations.
Maximum 660 mg daily (as extended-release tablet).
Diabetic Neuropathy
Oral
Maximum daily dosage of 300 mg as conventional preparations.
Maximum 330 mg daily (as extended-release tablet).
Neuropathic Pain Associated with Spinal Cord Injury
Oral
Maximum 600 mg daily (300 mg twice daily) as conventional preparations.
Fibromyalgia
Oral
Maximum 450 mg daily as conventional preparations; higher dosages not recommended because of dose-dependent adverse effects.
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). Not studied in pediatric patients with renal impairment.
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 |
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. 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. The extended-release preparation is not recommended in patients undergoing hemodialysis.
Geriatric Patients
Adjust dosage for geriatric patients with renal impairment. (See Renal Impairment under Dosage and Administration.)
Cautions for Pregabalin
Contraindications
-
Known hypersensitivity to pregabalin or any ingredient in the formulation.
Warnings/Precautions
Sensitivity Reactions
Angioedema
Angioedema, including life-threatening cases with respiratory compromise requiring emergency treatment, reported during postmarketing surveillance. Symptoms included swelling of the face, mouth (e.g., tongue, lips, gums), and neck (e.g., throat, larynx). Discontinue pregabalin immediately in patients with these symptoms.
Use with caution in patients with previous episode of angioedema.
Patients receiving concomitant drugs associated with angioedema (e.g., ACE inhibitors) may be at increased risk.
Hypersensitivity Reactions
Hypersensitivity reactions (i.e., skin redness, blisters, hives, rash, dyspnea, wheezing) reported during postmarketing surveillance. Discontinue pregabalin immediately if a hypersensitivity reaction occurs.
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%). 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. Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.
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.
Balance risk of suicidality with the risk of untreated illness. Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality. If suicidal thoughts or behavior emerge during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself. (See Advice to Patients.)
Respiratory Depression
Risk of respiratory depression, particularly when used concomitantly with opiates or other CNS depressants, or in patients with underlying respiratory impairment, or in geriatric patients.
Serious and sometimes fatal respiratory depression reported with gabapentinoids (i.e., gabapentin and pregabalin). In most cases, patients were receiving another CNS depressant concomitantly or had a respiratory risk factor, including older age. Although gabapentinoids may have an independent respiratory depressant effect, there is less evidence supporting the risk of serious respiratory complications when these drugs are administered alone in otherwise healthy individuals.
If pregabalin is used concomitantly with other CNS depressants or in the setting of underlying respiratory impairment, monitor patients and adjust dosage appropriately; considering initiating therapy with the lowest dosage and titrate carefully. (See Advice to Patients.)
If respiratory depression occurs, manage with supportive measures; reduction or withdrawal of CNS depressants, including pregabalin, may be necessary. If a decision is made to discontinue therapy, gradually reduce pregabalin dosage. (See Discontinuance of Therapy under Cautions.)
Dizziness and Somnolence
Risk of dizziness and somnolence. Occurs more frequently at higher doses and, in some cases, persists throughout therapy. (See Advice to Patients.)
Discontinuance of Therapy
Abrupt withdrawal may result in increased seizure frequency; withdraw therapy gradually and reduce dosage slowly over ≥1 week.
Following abrupt or rapid withdrawal, symptoms suggestive of physical dependence reported. (See Abuse Potential and Dependence under Cautions.)
Peripheral Edema
Risk of edema (mainly peripheral edema). Peripheral edema not associated with deterioration of renal or hepatic function.
No apparent association between peripheral edema and cardiovascular complications (e.g., hypertension, CHF) in patients without clinically important heart or peripheral vascular disease.
Concomitant use with a thiazolidinedione antidiabetic agent associated with a greater risk of weight gain and peripheral edema. (See Specific Drugs under Interactions.)
Use with caution in patients with NYHA class III or IV heart failure.
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.
Weight gain not associated with clinically important short-term changes in BP, but long-term cardiovascular effects not known.
Pregabalin therapy does not appear to be associated with loss of glycemic control.
Tumorigenic Potential
Carcinogenicity (e.g., hemangiosarcoma) demonstrated in animals.
New or worsening of preexisting tumors reported in humans; causal relationship not established.
Ocular Effects
Possible blurred vision, decreased visual acuity, visual field changes, and funduscopic changes. Clinical importance not known.
If visual disturbance persists, consider further or more frequent ophthalmologic assessment in those already monitored for ocular conditions.
Creatine Kinase Elevations
Possible increases in CPK concentrations (≥ 3 times the ULN) and rhabdomyolysis; causal relationship not established.
Discontinue pregabalin if myopathy is diagnosed or suspected or if markedly elevated CPK concentrations occur.
Thrombocytopenia
Risk of thrombocytopenia, although increased bleeding-related adverse effects not reported.
PR Interval Prolongation
Risk of prolongation of the PR interval (mean increase: 3–6 msec) with daily pregabalin dosages ≥300 mg. Patients with preexisting PR prolongation at baseline or those receiving drugs that prolong the PR interval do not appear to be at increased risk.
Abuse Potential and Dependence
Possible euphoria.
Abrupt or rapid discontinuance has resulted in withdrawal symptoms (e.g., insomnia, nausea, headache, diarrhea, anxiety, hyperhidrosis). (See Discontinuance of Therapy under Cautions.)
Pregabalin is not known to be active at receptor sites associated with drugs of abuse. However, the drug is subject to control as a schedule V (C-V) drug.
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).
Specific Populations
Pregnancy
North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or [Web].
May cause fetal harm. No adequate and well-controlled studies in pregnant women; in animal studies, developmental toxicity observed.
Lactation
Distributed into human milk. (See Extent under Pharmacokinetics.) Because of potential risk of tumorigenicity, breastfeeding not recommended. (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. 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.
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.
Safety and efficacy for treatment of fibromyalgia not established in pediatric patients.
Safety and efficacy of pregabalin extended-release tablets not established in pediatric patients.
Geriatric Use
Manufacturer states no substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out. 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.
FDA warns that geriatric patients receiving pregabalin are at increased risk of potentially serious, life-threatening, or fatal respiratory depression; initiate therapy with the lowest dosage and monitor for respiratory depression and sedation in these patients.
Substantially eliminated by kidneys; risk of adverse reactions may be increased in patients with impaired renal function.
Adjust dosage in geriatric patients with renal impairment. Monitoring renal function in geriatric patients may be helpful. (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).
Conventional preparation in pediatric patients: Somnolence, weight gain, increased appetite.
Extended-release preparation in adults: Dizziness, somnolence, headache, fatigue, peripheral edema, nausea, blurred vision, dry mouth, weight gain.
Drug Interactions
Does not appear to inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 or induce CYP1A2 or 3A4.
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.
Increased metabolism of concomitantly administered CYP1A2 substrates (e.g., caffeine, theophylline) or CYP3A4 substrates (e.g., midazolam, testosterone) not anticipated.
Protein-bound Drugs
Does not bind to plasma proteins; pharmacokinetic interactions unlikely with drugs that are highly protein bound.
Constipating Drugs
Increased risk of events related to decreased lower GI tract function (e.g., intestinal obstruction, paralytic ileus, constipation). (See Specific Drugs under Interactions.)
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
ACE inhibitors |
Potential increased risk of developing angioedema |
|
Alcohol |
Pharmacokinetic interaction not observed Additive effects on cognitive and gross motor functioning observed; no clinically important effects on respiration |
Avoid alcohol |
Anticonvulsants |
Pharmacokinetic interaction unlikely with carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, and valproate Possible slight decrease in rate of absorption of pregabalin when used concomitantly with gabapentin; gabapentin pharmacokinetics not affected Pharmacokinetics of pregabalin not affected by tiagabine |
|
Antidiabetic agents |
Pharmacokinetics of pregabalin not affected by glyburide, insulin, or metformin Potential increased risk of weight gain and peripheral edema with thiazolidinediones, possibly exacerbating or causing heart failure |
Use thiazolidinediones concomitantly with caution |
CNS depressants (e.g., opiates, benzodiazepines) |
Possible additive CNS and respiratory depressant effects; cases of serious and sometimes fatal respiratory depression reported with concomitant use |
Initiate pregabalin with the lowest dosage and titrate carefully Observe for signs of CNS or respiratory depression; reduce dosage of pregabalin or the CNS depressant if indicated |
Erythromycin |
Decreased systemic exposure of pregabalin (administered as the extended-release tablet) by 17% |
|
Furosemide |
Pharmacokinetics of pregabalin not affected |
|
Lorazepam |
Pharmacokinetic interaction not observed Additive effects on cognitive and gross motor functioning observed; no clinically important effects on respiration |
|
Opiate analgesics |
Possible additive CNS and respiratory depressant effects; cases of serious and sometimes fatal respiratory depression reported with concomitant use Events related to decreased lower GI tract function (e.g., intestinal obstruction, paralytic ileus, constipation) possible Oxycodone: Pharmacokinetic interaction not observed; additive effects on cognitive and gross motor functioning observed, but no clinically important effects on respiration |
Initiate pregabalin with the lowest dosage and titrate carefully Observe for signs of CNS or respiratory depression; reduce dosage of pregabalin or the opiate analgesic if indicated |
Oral contraceptives |
Pharmacokinetic interaction unlikely |
Pregabalin Pharmacokinetics
Absorption
Bioavailability
Well absorbed following oral administration and exhibits linear pharmacokinetics.
Peak plasma concentrations attained within 1.5 hours following oral administration of conventional preparations and within 12 hours following extended-release preparations. 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.
Oral bioavailability following administration of conventional preparation is ≥90% and independent of dose.
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.
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.
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.
Distribution
Extent
Distributed into human milk at concentrations approximately 76% of those in maternal plasma at steady state. Following maternal dosages of 300 mg daily, the estimated average dose in a nursing infant is 0.31 mg/kg daily.
Crosses the placenta in rats; not known whether crosses the placenta in humans.
Distributed into CSF in animals.
Elimination
Metabolism
Negligibly metabolized.
Elimination Route
Primarily excreted in urine, mainly as unchanged drug (90%). Clearance is nearly proportional to Clcr in adults and pediatric patients.
Half-life
Adults: 6.3 hours.
Children <6 years of age: 3–4 hours.
Children ≥7 years of age: 4–6 hours.
Special Populations
Pregabalin clearance tends to decrease with increasing age. (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.
Removed by hemodialysis; dosage adjustment is necessary. (See Renal Impairment under Dosage and Administration.)
Stability
Storage
Oral
Capsules
25°C (may be exposed to 15–30°C).
Extended-release Tablets
25°C (may be exposed to 15–30°C).
Oral Solution
25°C (may be exposed to 15–30°C).
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.
-
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.
-
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. In cultured neurons, prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport.
-
Does not block sodium channels; not active at opiate receptors; does not alter cyclooxygenase activity.
-
Inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
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.
-
Risk of suicidality (anticonvulsants, including pregabalin, may increase risk of suicidal thoughts or actions in about 1 in 500 people). 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).
-
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. Concomitant administration with an ACE inhibitor may increase such risk.
-
Importance of taking pregabalin only as prescribed. Importance of advising patients or caregivers to consult their clinician before changing the dosage of or abruptly discontinuing the drug. 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.
-
Risk of respiratory depression; concomitant use of CNS depressants (e.g., opiates) increases the risk. Risk also is increased in patients with underlying respiratory impairment and in geriatric patients. Importance of patients or caregivers seeking immediate medical attention if signs or symptoms of respiratory depression occur (e.g., slow, shallow, or difficult breathing; confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; bluish-colored or tinted skin, especially on the lips, fingers, and toes; unresponsiveness).
-
Risk of dizziness, somnolence, blurred vision, and other neuropsychiatric effects. Avoid driving or operating machinery or engaging in other hazardous activities while taking pregabalin until experienced with the drug’s effects.
-
Inform patients that concomitant use of CNS depressants and pregabalin (e.g., opiates or benzodiazepines) may result in additive CNS effects such as respiratory depression, somnolence, and dizziness.
-
Avoid alcohol-containing beverages or products; drug may potentiate impairment of motor skills and sedation associated with ingestion of alcohol.
-
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. Patients should not take 2 doses at the same time.
-
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. If they miss the dose prior to bedtime, then they should take their usual dose the next morning following breakfast. 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.
-
Risk of edema and weight gain; concomitant administration with a thiazolidinedione antidiabetic agent may increase such risk. In patients with preexisting cardiac conditions, risk of heart failure may be increased.
-
Risk of visual disturbances. Importance of informing clinician if changes in vision occur.
-
Importance of patients promptly informing clinicians of any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.
-
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.
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Importance of clinicians informing women about the existence of and encouraging enrollment in the NAAED Pregnancy Registry (see Pregnancy under Cautions). Women should be advised that breastfeeding is not recommended during treatment with pregabalin.
-
Advise patients of male-mediated teratogenicity. Importance of men informing clinicians if they plan to father a child.
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses. Potential for additive CNS effects if used concomitantly with other CNS depressants (e.g., opiates, benzodiazepines).
-
Importance of informing patients of other important precautionary information. (See Cautions.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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. (See Abuse Potential and Dependence under Cautions.)
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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 2024, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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