LYRICA
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pregabalin capsule
Lake Erie Medical DBA Quality Care Products LLC
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LYRICA 200 mg 11 DESCRIPTIONPediatric Pharmacokinetics
Pharmacokinetics of pregabalin have not been adequately studied in pediatric patients.
Drug Interactions
In Vitro Studies
Pregabalin, at concentrations that were, in general, 10-times those attained in clinical trials, does not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzyme systems. In vitro drug interaction studies demonstrate that pregabalin does not induce CYP1A2 or CYP3A4 activity. Therefore, an increase in the metabolism of coadministered CYP1A2 substrates (e.g. theophylline, caffeine) or CYP 3A4 substrates (e.g. midazolam, testosterone) is not anticipated.
In Vivo Studies
The drug interaction studies described in this section were conducted in healthy adults, and across various patient populations.
Gabapentin
The pharmacokinetic interactions of pregabalin and gabapentin were investigated in 12 healthy subjects following concomitant single-dose administration of 100-mg pregabalin and 300-mg gabapentin and in 18 healthy subjects following concomitant multiple-dose administration of 200-mg pregabalin every 8 hours and 400-mg gabapentin every 8 hours. Gabapentin pharmacokinetics following single- and multiple-dose administration were unaltered by pregabalin coadministration. The extent of pregabalin absorption was unaffected by gabapentin coadministration, although there was a small reduction in rate of absorption.
Oral Contraceptive
Pregabalin coadministration (200 mg three times a day) had no effect on the steady-state pharmacokinetics of norethindrone and ethinyl estradiol (1 mg/35 µg, respectively) in healthy subjects.
Lorazepam
Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of lorazepam single-dose pharmacokinetics and single-dose administration of lorazepam (1 mg) had no effect on the steady-state pharmacokinetics of pregabalin.
Oxycodone
Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of oxycodone single-dose pharmacokinetics. Single-dose administration of oxycodone (10 mg) had no effect on the steady-state pharmacokinetics of pregabalin.
Ethanol
Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of ethanol single-dose pharmacokinetics and single-dose administration of ethanol (0.7 g/kg) had no effect on the steady-state pharmacokinetics of pregabalin.
Phenytoin, carbamazepine, valproic acid, and lamotrigine
Steady-state trough plasma concentrations of phenytoin, carbamazepine and carbamazepine 10,11 epoxide, valproic acid, and lamotrigine were not affected by concomitant pregabalin (200 mg three times a day) administration.
Population pharmacokinetic analyses in patients treated with pregabalin and various concomitant medications suggest the following:
1 INDICATIONS AND USAGE
LYRICA is indicated for:
1.1 Management of neuropathic pain associated with diabetic peripheral neuropathy1.2 Management of postherpetic neuralgia1.3 Adjunctive therapy for adult patients with partial onset seizures1.4 Management of fibromyalgia 4 CONTRAINDICATIONSBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In all controlled and uncontrolled trials across various patient populations during the premarketing development of LYRICA, more than 10,000 patients have received LYRICA. Approximately 5000 patients were treated for 6 months or more, over 3100 patients were treated for 1 year or longer, and over 1400 patients were treated for at least 2 years 10 OVERDOSAGESigns, Symptoms and Laboratory Findings of Acute Overdosage in Humans
There is limited experience with overdose of LYRICA. The highest reported accidental overdose of LYRICA during the clinical development program was 8000 mg, and there were no notable clinical consequences.
Treatment or Management of Overdose
There is no specific antidote for overdose with LYRICA. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with LYRICA.
Although hemodialysis has not been performed in the few known cases of overdose, it may be indicated by the patient's clinical state or in patients with significant renal impairment. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours).
LYRICA is given orally with or without food.
When discontinuing LYRICA, taper gradually over a minimum of 1 week.
2.1 Neuropathic pain associated with diabetic peripheral neuropathyThe maximum recommended dose of LYRICA is 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability. Because LYRICA is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function [see Dosage and Administration (2.5)].
Although LYRICA was also studied at 600 mg/day, there is no evidence that this dose confers additional significant benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 300 mg/day is not recommended [see Adverse Reactions (6.1)].
2.2 Postherpetic neuralgiaThe recommended dose of LYRICA is 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability. Because LYRICA is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function [see Dosage and Administration (2.5)].
Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 300 mg/day, and who are able to tolerate LYRICA, may be treated with up to 300 mg two times a day, or 200 mg three times a day (600 mg/day). In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, reserve dosing above 300 mg/day for those patients who have on-going pain and are tolerating 300 mg daily [see Adverse Reactions (6.1)].
2.3 Adjunctive therapy for adult patients with partial onset seizuresLYRICA at doses of 150 to 600 mg/day has been shown to be effective as adjunctive therapy in the treatment of partial onset seizures in adults. Both the efficacy and adverse event profiles of LYRICA have been shown to be dose-related. Administer the total daily dose in two or three divided doses. In general, it is recommended that patients be started on a total daily dose no greater than 150 mg/day (75 mg two times a day, or 50 mg three times a day). Based on individual patient response and tolerability, the dose may be increased to a maximum dose of 600 mg/day.
Because LYRICA is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function [see Dosage and Administration (2.5)].
The effect of dose escalation rate on the tolerability of LYRICA has not been formally studied.
The efficacy of add-on LYRICA in patients taking gabapentin has not been evaluated in controlled trials. Consequently, dosing recommendations for the use of LYRICA with gabapentin cannot be offered.
2.4 Management of FibromyalgiaThe recommended dose of LYRICA for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although LYRICA was also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended [see Adverse Reactions (6.1)]. Because LYRICA is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function [see Dosage and Administration (2.5)].
2.5 Patients with Renal ImpairmentIn view of dose-dependent adverse reactions and since LYRICA is
eliminated primarily by renal excretion, adjust the dose in patients with
reduced renal function. Base the dose adjustment in patients with renal
impairment on creatinine clearance (CLcr), as indicated in Table 1. To use this
dosing table, an estimate of the patient's CLcr in mL/min is needed. CLcr in
mL/min may be estimated from serum creatinine (mg/dL) determination using the
Cockcroft and Gault equation
Next, refer to the Dosage and Administration section to determine the recommended total daily dose based on indication, for a patient with normal renal function (CLcr ≥60 mL/min). Then refer to Table 1 to determine the corresponding renal adjusted dose.
(For example: A patient initiating LYRICA therapy for postherpetic neuralgia with normal renal function (CLcr ≥60 mL/min), receives a total daily dose of 150 mg/day pregabalin. Therefore, a renal impaired patient with a CLcr of 50 mL/min would receive a total daily dose of 75 mg/day pregabalin administered in two or three divided doses.)
2.6 Oral Solution Concentration and DispensingThe oral solution is 20 mg pregabalin per milliliter (mL) and prescriptions should be written in milligrams (mg). The pharmacist will calculate the applicable dose in mL for dispensing (e.g., 150 mg equals 7.5 mL oral solution).
300 mg capsules:
White/orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 300" on the body
Storage and Handling
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature). For the oral solution, use within 45 days of first opening the bottle.
17 PATIENT COUNSELING INFORMATION17.1 Medication GuideInform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking LYRICA. Instruct patients to take LYRICA only as prescribed.
17.2 AngioedemaAdvise patients that LYRICA may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue LYRICA and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.1)].
17.3 HypersensitivityAdvise patients that LYRICA has been associated with hypersensitivity reactions such as wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue LYRICA and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.2)].
17.4 Suicidal Thinking and BehaviorPatients, their caregivers, and families should be counseled that AEDs, including LYRICA, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.4)].
17.5 Dizziness and SomnolenceCounsel patients that LYRICA may cause dizziness, somnolence, blurred vision and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on LYRICA to gauge whether or not it affects their mental, visual, and/or motor performance adversely. [see Warnings and Precautions (5.6)].
17.6 Weight Gain and EdemaCounsel patients that LYRICA may cause edema and weight gain. Advise patients that concomitant treatment with LYRICA and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this may increase the risk of heart failure. [see Warnings and Precautions (5.5 and 5.7)].
17.7 Abrupt or Rapid DiscontinuationAdvise patients to take LYRICA as prescribed. Abrupt or rapid discontinuation may result in insomnia, nausea, headache, or diarrhea. [see Warnings and Precautions (5.8)].
17.8 Ophthalmological EffectsCounsel patients that LYRICA may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician [see Warnings and Precautions (5.10)].
17.9 Creatine Kinase ElevationsInstruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. [see Warnings and Precautions (5.11)].
17.10 CNS DepressantsInform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as somnolence.
17.11 AlcoholTell patients to avoid consuming alcohol while taking LYRICA, as LYRICA may potentiate the impairment of motor skills and sedating effects of alcohol.
17.12 Use in PregnancyInstruct patients to notify their physician if they become pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use In Specific Populations (8.1) and (8.3)].
Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 [see Use In Specific Populations (8.1)].
17.13 Male FertilityInform men being treated with LYRICA who plan to father a child of the potential risk of male-mediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an increased risk of male-mediated teratogenicity. The clinical significance of this finding is uncertain [see Nonclinical Toxicology (13.1)].
17.14 DermatopathyInstruct diabetic patients to pay particular attention to skin integrity while being treated with LYRICA. Some animals treated with pregabalin developed skin ulcerations, although no increased incidence of skin lesions associated with LYRICA was observed in clinical trials [see Nonclinical Toxicology (13.2)].
Capsules manufactured by:
Pfizer Pharmaceuticals LLC
Vega
Baja, PR 00694
Oral Solution manufactured by:
Pfizer Inc
Kalamazoo, MI 49001
Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking LYRICA. Instruct patients to take LYRICA only as prescribed.
17.2 AngioedemaAdvise patients that LYRICA may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue LYRICA and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.1)].
17.3 HypersensitivityAdvise patients that LYRICA has been associated with hypersensitivity reactions such as wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue LYRICA and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.2)].
17.4 Suicidal Thinking and BehaviorPatients, their caregivers, and families should be counseled that AEDs, including LYRICA, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.4)].
17.5 Dizziness and SomnolenceCounsel patients that LYRICA may cause dizziness, somnolence, blurred vision and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on LYRICA to gauge whether or not it affects their mental, visual, and/or motor performance adversely. [see Warnings and Precautions (5.6)].
17.6 Weight Gain and EdemaCounsel patients that LYRICA may cause edema and weight gain. Advise patients that concomitant treatment with LYRICA and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this may increase the risk of heart failure. [see Warnings and Precautions (5.5 and 5.7)].
17.7 Abrupt or Rapid DiscontinuationAdvise patients to take LYRICA as prescribed. Abrupt or rapid discontinuation may result in insomnia, nausea, headache, or diarrhea. [see Warnings and Precautions (5.8)].
17.8 Ophthalmological EffectsCounsel patients that LYRICA may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician [see Warnings and Precautions (5.10)].
17.9 Creatine Kinase ElevationsInstruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. [see Warnings and Precautions (5.11)].
17.10 CNS DepressantsInform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as somnolence.
17.11 AlcoholTell patients to avoid consuming alcohol while taking LYRICA, as LYRICA may potentiate the impairment of motor skills and sedating effects of alcohol.
17.12 Use in PregnancyInstruct patients to notify their physician if they become pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use In Specific Populations (8.1) and (8.3)].
Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 [see Use In Specific Populations (8.1)].
17.13 Male FertilityInform men being treated with LYRICA who plan to father a child of the potential risk of male-mediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an increased risk of male-mediated teratogenicity. The clinical significance of this finding is uncertain [see Nonclinical Toxicology (13.1)].
17.14 DermatopathyInstruct diabetic patients to pay particular attention to skin integrity while being treated with LYRICA. Some animals treated with pregabalin developed skin ulcerations, although no increased incidence of skin lesions associated with LYRICA was observed in clinical trials [see Nonclinical Toxicology (13.2)].
Capsules manufactured by:
Pfizer Pharmaceuticals LLC
Vega
Baja, PR 00694
Oral Solution manufactured by:
Pfizer Inc
Kalamazoo, MI 49001
Image of label
LYRICA
pregabalin capsule |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
NDA | NDA021724 | 09/27/2010 |
Labeler - Lake Erie Medical DBA Quality Care Products LLC (831276758) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Lake Erie Medical DBA Quality Care Products LLC | 831276758 | repack |
Establishment | |||
Name | Address | ID/FEI | Operations |
Pfizer Pharmaceuticals LLC | 829084552 | manufacture |