Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

LYRICA (NDA-022488)

(PREGABALIN)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

04/25/2025 (SUPPL-22)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Suicidal Behavior and Ideation

Additions and/or revisions underlined:

Antiepileptic drugs (AEDs), including pregabalin, the active ingredient in LYRICA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions (5.4)].

…

Anyone considering prescribing LYRICA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

5.4 Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation

Additions and/or revisions underlined:

As with all antiepileptic drugs (AEDs), withdraw LYRICA gradually to minimize the potential of increased seizure frequency in patients with seizure disorders.

Following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea [see Adverse Reactions (6.2), Drug Abuse and Dependence (9.3)]. Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions (5.3)].

If LYRICA is discontinued, taper the drug gradually over a minimum of 1 week rather than discontinue the drug abruptly.

…

5.6 Dizziness and Somnolence

Additions and/or revisions underlined:

…

In the LYRICA controlled trials in adult patients, dizziness was experienced by 30% of LYRICA-treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of LYRICA-treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of LYRICA therapy and occurred more frequently at higher doses.

…

In the LYRICA controlled trials in pediatric patients 4 to less than 17 years of age and 1 month to less than 4 years of age for the treatment of partial-onset seizures, somnolence was reported in 21% and 15% of LYRICA-treated patients compared to 14% and 9% of placebo-treated patients, respectively, and occurred more frequently at higher doses. For patients 1 month to less than 4 years of age, somnolence includes related terms lethargy, sluggishness, and hypersomnia.

5.7 Peripheral Edema

Additions and/or revisions underlined:

…

In controlled clinical trials in adult patients, the incidence of peripheral edema was 6% in the LYRICA group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of LYRICA patients and 0.2% placebo patients withdrew due to peripheral edema.

5.8 Weight Gain

Additions and/or revisions underlined:

…

In LYRICA controlled clinical trials in adult patients of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of LYRICA- treated patients and 2% of placebo-treated patients.

…

5.10 Ophthalmological Effects

Additions and/or revisions underlined:

In controlled studies in adult patients, a higher proportion of patients treated with LYRICA reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

The following serious adverse reactions are described elsewhere in the labeling:

• Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation [see Warnings and Precautions (5.4)]

• Tumorigenic Potential [see Warnings and Precautions (5.9)]

• PR Interval Prolongation [see Warnings and Precautions (5.13)]

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

6.2 Postmarketing Experience

Additions and/or revisions underlined:

The following adverse reactions have been identified during postapproval use of LYRICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous System Disorders – Headache

Gastrointestinal Disorders – Nausea, Diarrhea

Reproductive System and Breast Disorders – Gynecomastia, Breast Enlargement

Skin and subcutaneous tissue disorders – Bullous pemphigoid

…

There are postmarketing reports of withdrawal symptoms after discontinuation of pregabalin. Reported adverse reactions include, but are not limited to, seizures, depression, suicidal ideation and behavior, agitation, confusion, disorientation, psychotic symptoms, anxiety, insomnia, nausea, pain, sweating, tremor, headache, dizziness, malaise, and diarrhea.

7 Drug Interactions

Additions and/or revisions underlined:

…

In vitro and in vivo studies showed that LYRICA is unlikely to be involved in significant pharmacokinetic drug interactions.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

…

Postmarketing data suggest that extended gabapentinoid use with opioids close to delivery may increase the risk of neonatal withdrawal versus opioids alone (see Clinical Considerations).

There are no comparative epidemiologic studies evaluating this association. Therefore, it is not known whether exposure to pregabalin alone late in pregnancy may cause withdrawal signs and symptoms.

In animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 16 times human exposure at the maximum recommended dose (MRD) of 600 mg/day (see Data).

…

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentinoids in utero for an extended period of time when also exposed to opioids close to delivery. Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor. Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements.

Observe neonates exposed to LYRICA and opioids for signs and symptoms of neonatal withdrawal and manage accordingly.

…

Animal Data

…

The low dose in this study was associated with a plasma exposure (AUC) approximately17 times human exposure at the MRD of 600 mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established.

8.4 Pediatric Use

Extensive changes; please refer to label for complete information

8.5 Geriatric Use

Additions and/or revisions underlined:

In controlled clinical studies of LYRICA in epilepsy, there were only 10 patients 65 to 74 years of age, and 2 patients who were 75 years of age or older.

No overall differences in safety and efficacy were observed between these patients and younger patients.

In controlled clinical studies of LYRICA in fibromyalgia, 106 patients were 65 years of age or older. Although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy.

LYRICA is known to be substantially excreted by the kidney, and the risk of toxic reactions to LYRICA may be greater in patients with impaired renal function. Because LYRICA is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment [see Dosage and Administration (2.7)].

8.6 Renal Impairment

Newly added subsection:

LYRICA is eliminated primarily by renal excretion and dose adjustment is recommended for adult patients with renal impairment [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)]. The use of LYRICA in pediatric patients with compromised renal function has not been studied.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Suicidal Thinking and Behavior

…

Also inform patients who plan to or have discontinued LYRICA that suicidal thoughts and behavior can appear even after the drug is stopped [see Warnings and Precautions (5.3)].

…

Missed Dose

Counsel patients if they miss a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should skip the missed dose and take the next dose at their regularly scheduled time. Instruct patients not to take two doses at the same time.

…

Use in Pregnancy

Instruct patients to inform their healthcare provider if they are 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 (8.2)].

Encourage patients to enroll in the North American Antiepileptic Drug (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)].

…

Male Fertility

Inform 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) and Use in Specific Populations (8.3)].

Dermatopathy

Instruct diabetic patients to pay particular attention to skin integrity while being treated with LYRICA and to inform their healthcare provider about any sores or skin problems. 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)].

MEDICATION GUIDE

Additions and/or revisions underlined:

LYRICA (LEER-i-kah) (pregabalin) Capsules, CV

LYRICA (LEER-i-kah) (pregabalin) Oral Solution, CV

What is the most important information I should know about LYRICA?

…

• Like other antiepileptic drugs, LYRICA may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. This can happen while you take LYRICA or after stopping.

…

What is LYRICA?

LYRICA is a prescription medicine used in adults, 18 years of age and older to treat:

• pain from damaged nerves (neuropathic pain) that happens with diabetes

• pain from damaged nerves (neuropathic pain) that follows healing of shingles

• fibromyalgia (pain all over your body)

• pain from damaged nerves (neuropathic pain) that follows spinal cord injury

It is not known if LYRICA is safe and effective in  people under 18 years of age for the treatment of fibromyalgia and neuropathic pain with diabetes, shingles, or spinal cord injury.

LYRICA is a prescription medicine used in people 1 month of age and older to treat:

• partial-onset seizures when taken together with other seizure medicines.

For the treatment of partial-onset seizures when taken together with other seizure medicines, it is not known if LYRICA is safe and effective in children under 1 month of age.

…

What should I tell my healthcare provider before taking LYRICA?

…

• are pregnant or plan to become pregnant. LYRICA may harm your unborn baby. You and your healthcare provider will decide if you should take LYRICA while you are pregnant.

• If you become pregnant while taking LYRICA, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888- 233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. Information about the registry can also be found at the website, http://www.aedpregnancyregistry.org/.

…

How should I take LYRICA?

• Take LYRICA exactly as prescribed. Your healthcare provider will tell you how much LYRICA to take and when to take it.

• LYRICA may be taken with or without food.

• Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.

• Do not stop taking LYRICA without talking to your healthcare provider. If you stop taking LYRICA suddenly you may have headaches, nausea, diarrhea, trouble sleeping, increased sweating, or you may feel anxious. If you have epilepsy and you stop taking LYRICA suddenly, you may have seizures more often. Talk with your healthcare provider about how to stop LYRICA slowly.

• If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.

…

What are the possible side effects of LYRICA?

…

LYRICA may cause serious side effects, including:

• See “What is the most important information I should know about LYRICA?"

…

The most common side effects of LYRICA in adults are:

…

• trouble concentrating

…

The most common side effects of LYRICA in children are weight gain, increase in appetite, and sleepiness.

…

How should I store LYRICA?

• Store LYRICA capsules and oral solution at room temperature between 68oF to 77°F (20oC to 25°C) in its original package.

…

What are the ingredients in LYRICA?

Active ingredient: pregabalin

Inactive ingredients:

LYRICA capsules: cornstarch, lactose monohydrate, talc

Capsule shell: gelatin and titanium dioxide; Orange capsule shell: red iron oxide; White capsule shell: colloidal silicon dioxide, sodium lauryl sulfate. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells.

Imprinting ink: black iron oxide, potassium hydroxide, propylene glycol, shellac.

LYRICA oral solution: artificial strawberry #11545, dibasic sodium phosphate anhydrous, methylparaben, monobasic sodium phosphate anhydrous, propylparaben, purified water, and sucralose.

12/13/2023 (SUPPL-18)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions underlined)

…

Risk Summary

Observational studies on the use of Lyrica during pregnancy suggest a possible small increase in the rate of overall major birth defects, but there was no consistent or specific pattern of major birth defects identified (see Data). Available postmarketing data on miscarriage and other maternal, fetal, and long term developmental adverse effects were insufficient to identify risk associated with pregabalin.

…

Data

Human Data

One database study, which included over 2,700 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 3,063,251 pregnancies unexposed to antiepileptics demonstrated prevalence ratios for major malformations overall of 1.14 (CI 95% 0.96-1.35) for pregabalin, 1.29 (CI 95% 1.01-1.65) for lamotrigine, 1.39 (CI 95% 1.07-1.82) for duloxetine, and 1.24 (CI 95% 1.00-1.54) for exposure to either lamotrigine or duloxetine.

Important study limitations include uncertainty of whether women who filled a prescription took the medication and inability to adequately control for the underlying disease and other potential confounders.

A published study included results from two separate databases. One database, which included 353 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 368,489 pregnancies unexposed to antiepileptics, showed no increase in risk of major birth defects; adjusted relative risk 0.87 (CI 95% 0.53-1.42). The second database, which included 118 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 380,347 pregnancies unexposed to antiepileptics, suggested a small increase in risk of major birth defects; adjusted relative risk 1.26 (CI 95% 0.64-2.49). The risk estimates crossed the null, and the study had limitations similar to the prior study.

Other published epidemiologic studies reported inconsistent findings. No specific pattern of birth defects was identified across studies. All of the studies had limitations due to their retrospective design.

…

04/03/2020 (SUPPL-17)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4         Respiratory Depression

(Newly added subsection)

There is evidence from case reports, human studies, and animal studies associating LYRICA with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. When the decision is made to co-prescribe LYRICA with another CNS depressant, particularly an opioid, or to prescribe LYRICA to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating LYRICA at a low dose. The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including LYRICA).

There is more limited evidence from case reports, animal studies, and human studies associating LYRICA with serious respiratory depression, without co-administered CNS depressants or without underlying respiratory impairment.

5.5           Dizziness and Somnolence

(Additions and/or revisions underlined)

LYRICA may cause dizziness and somnolence. Inform patients that LYRICA-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery.

In the LYRICA controlled trials in adult patients, dizziness was experienced by 30% of LYRICA-treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of LYRICA-treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of LYRICA therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (4% each) from controlled studies. In LYRICA-treated patients reporting these adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients.

In the LYRICA controlled trials in pediatric patients 4 to less than 17 years of age and 1 month to less than 4 years of age for the treatment of partial-onset seizures, somnolence was reported in 21% and 15% of LYRICA-treated patients compared to 14% and 9% of placebo-treated patients, respectively, and occurred more frequently at higher doses. For patients 1 month to less than 4 years of age, somnolence includes related terms lethargy, sluggishness, and hypersomnia.

6 Adverse Reactions

(Additions and/or revisions underlined)

The following serious adverse reactions are described elsewhere in the labeling: 

• Angioedema

• Hypersensitivity

• Suicidal Behavior and Ideation

• Respiratory Depression

• Dizziness and Somnolence

6.2           Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during postapproval use of LYRICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous System Disorders – Headache

Gastrointestinal Disorders – Nausea, Diarrhea

Reproductive System and Breast Disorders – Gynecomastia, Breast Enlargement

Skin and subcutaneous tissue disorders – Bullous pemphigoid

There are postmarketing reports of life-threatening or fatal respiratory depression in patients taking LYRICA with opioids or other CNS depressants, or in the setting of underlying respiratory impairment.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Respiratory Depression

Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs.

Dizziness and Somnolence

Counsel 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.

CNS Depressants

Inform 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 respiratory depression, somnolence, and dizziness. Advise patients to avoid consuming alcohol while taking LYRICA, as LYRICA may potentiate the impairment of motor skills and sedating effects of alcohol.

05/23/2019 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.6 Dizziness and Somnolence

(additions underlined)

…

 

In the LYRICA controlled trials in pediatric patients 4 to less than 17 years of age and 1 month to less than 4 years of age for the treatment of partial-onset seizures, somnolence was reported in 21% and 15% of LYRICA-treated patients compared to 14% and 9% of placebo-treated patients, respectively, and occurred more frequently at higher doses. For patients 1 month to less than

4 years of age, somnolence includes related terms lethargy, sluggishness, and hypersomnia.

6 Adverse Reactions

6.1 Clinical Trials Experience

(additions underlined)

…

Controlled Study of Adjunctive Therapy for Partial -Onset Seizures in Patients 1 Month to Less Than 4 Years of Age

Most Common Adverse Reactions

Table 8 lists all dose-related adverse reactions occurring in at least 2% of all LYRICA-treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 14 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 7 mg/kg/day groups. In this study, 105 patients received LYRICA and 70 patients received placebo for up to 14 days.

 

 

Table 8.   Dose-related Adverse Reaction Incidence in a Controlled Trial in Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month to Less Than 4 Years of Age

 

(please refer to label to view Table 8)

8 Use in Specific Populations

8.4 Pediatric Use

(additions underlined)

…

Safety and effectiveness in pediatric patients below the age of 1 month have not been established.

 

4 to Less Than 17 Years of Age with Partial-Onset Seizures

…

 

1 Month to Less than 4 Years of Age with Partial-Onset Seizures

 

The safety and effectiveness of LYRICA as adjunctive treatment for partial-onset seizures in pediatric patients 1 month to less than 4 years of age have been established in a 14-day double-blind, placebo-controlled study (N=175). The youngest subject evaluated was 3 months of age; use in patients 1 month to less than 3 months of age issupported by additional pharmacokinetic analyses. Patients treated with LYRICA 14 mg/kg/day had, on average, 43.9% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0223). In addition, pediatric patients treated with LYRICA 14 mg/kg/day showed numerical improvement in responder rates (greater than or equal to50% reduction in partial-onset seizure frequency) compared with placebo (53.6% versus 41.5%). Patients treated with LYRICA 7 mg/kg/day did not show improvement relative to placebo for either endpoint.

The most common dose-related adverse reactions (greater than or equal to5%) with LYRICA in this study were somnolence, pneumonia, and viral infection.

05/03/2018 (SUPPL-13)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.11 Decreased Platelet Count

(Additions and/or revisions are underlined)

LYRICA treatment was associated with a decrease in platelet count. LYRICA-treated subjects experienced a mean maximal decrease in platelet count of 20 × 103/µL, compared to 11 × 103/µL in placebo patients. In the overall database of controlled trials in adult patients, 2% of placebo patients and 3% of LYRICA patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and less than 150 × 103/µL. ….

5.12 PR Interval Prolongation

(Additions and/or revisions are underlined) 

LYRICA treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data in adult patients, the mean PR interval increase was 3–6 msec at LYRICA doses greater than or equal to 300 mg/day. This mean change difference was not associated with an increased risk of PR increase greater than or equal to 25% from baseline, an increased percentage of subjects with on-treatment PR greater than 200 msec, or an increased risk of adverse reactions of second or third degree AV block. …

5.3 Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation

(Subsection title has been revised; additions and/or revisions are underlined)

 As with all antiepileptic drugs (AEDs), withdraw LYRICA gradually to minimize the potential of increased seizure frequency in patients with seizure disorders.

 

Following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea.

 

If LYRICA is discontinued, taper the drug gradually over a minimum of 1 week rather than discontinue the drug abruptly.

5.5 Peripheral Edema

(Additions and/or revisions are underlined)

…

In controlled clinical trials in adult patients, the incidence of peripheral edema was 6% in the LYRICA group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of LYRICA patients and 0.2% placebo patients withdrew due to peripheral edema.

…

5.6 Dizzineaa and Somnolence

(Additions and/or revisions are underlined)

…

In the LYRICA controlled trials in adult patients, dizziness was experienced by 30% of LYRICA-treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of LYRICA-treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of LYRICA therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (4% each) from controlled studies. In LYRICA-treated patients reporting these adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients.

In the LYRICA controlled trial in pediatric patients for the treatment of partial onset seizures, somnolence was experienced by 21% of LYRICA-treated patients compared to 14% of placebo- treated patients, and occurred more frequently at higher doses.

 

5.7 Weight Gain

(Additions and/or revisions are underlined)

LYRICA treatment may cause weight gain. In LYRICA controlled clinical trials in adult patients of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of LYRICA- treated patients and 2% of placebo-treated patients. Few patients treated with LYRICA (0.3%) withdrew from controlled trials due to weight gain. LYRICA associated weight gain was related to dose and duration of exposure, but did not appear to be associated with baseline BMI, gender, or age. Weight gain was not limited to patients with edema.

…

5.9 Ophthalmological Effects

(Additions and/or revisions are underlined)

In controlled studies in adult patients, a higher proportion of patients treated with LYRICA reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing. Less than 1% of patients discontinued LYRICA treatment due to vision-related events (primarily blurred vision).

…

6 Adverse Reactions

(New subsection added; additions and/or revisions are underlined)

The following serious adverse reactions are described elsewhere in the labeling:

 

• Angioedema

• Hypersensitivity

• Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation

• Suicidal Behavior and Ideation

• Peripheral Edema

• Dizziness and Somnolence

• Weight Gain

• Tumorigenic Potential

• Ophthalmological Effects

• Creatine Kinase Elevations

• Decreased Platelet Count

   

6.1 Clinical Trials Experience

(Additions and/or revisions are underlined)

(Table numbers have been revised, new table added; please refer to label)

…

In premarketing controlled trials of all adult populations combined, 14% of patients treated with LYRICA and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (4%) and somnolence (4%). In the placebo group, 1% of patients withdrew due to dizziness and less than 1% withdrew due to somnolence. Other adverse reactions that led to discontinuation from controlled trials more frequently in the LYRICA group compared to the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision, incoordination, and peripheral edema (1% each).

Most Common Adverse Reactions in All Controlled Clinical Studies in Adults

In premarketing controlled trials of all adult patient populations combined (including DPN, PHN, and adult patients with partial onset seizures), dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with concentration/attention) were more commonly reported by subjects treated with LYRICA than by subjects treated with placebo (greater than or equal to 5% and twice the rate of that seen in placebo).

…

Controlled Studies of Adjunctive Therapy for Partial Onset Seizures in Adult Patients

Adverse Reactions Leading to Discontinuation

Approximately 15% of patients receiving LYRICA and 6% of patients receiving placebo in trials of adjunctive therapy for partial onset seizures discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (6%), ataxia (4%), and somnolence (3%). …

 

Controlled Study of Adjunctive Therapy for Partial Onset Seizures in Patients 4 to Less Than 17 Years of Age

Adverse Reactions Leading to Discontinuation

Approximately 2.5% of patients receiving LYRICA and no patients receiving placebo in trials of adjunctive therapy for partial onset seizures discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the adverse reactions leading to discontinuation were somnolence (3 patients), worsening of epilepsy (1 patient), and hallucination (1 patient).

Most Common Adverse Reactions

Table 7 lists all dose-related adverse reactions occurring in at least 2% of all LYRICA-treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 10 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 2.5 mg/kg/day groups. In this study, 201 patients received LYRICA and 94 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in the clinical study had adverse reactions with a maximum intensity of "mild" or "moderate”.

…

 

Most Common Adverse Reactions

Table 9 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients for which the incidence was greater than in the placebo treatment group with neuropathic pain associated with spinal cord injury in the controlled trials….

 

Other Adverse Reactions Observed During the Clinical Studies of LYRICA

…

Hemic and Lymphatic System – Frequent: Ecchymosis; Infrequent: Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare: Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia, Alanine aminotransferase increased, Aspartate aminotransferase  increased

...

 

8 Use in Specific Populations

8.4 Pediatric Use

(Additions and/or revisions are underlined)

Neuropathic Pain Associated with Diabetic Peripheral Neuropathy, Postherpetic Neuralgia, and Neuropathic Pain Associated with Spinal Cord Injury

 

Safety and effectiveness in pediatric patients have not been established.

Fibromyalgia

Safety and effectiveness in pediatric patients have not been established.

 

A 15-week, placebo-controlled trial was conducted with 107 pediatric patients with fibromyalgia, ages 12 through 17 years, at LYRICA total daily doses of 75-450 mg per day. The primary efficacy endpoint of change from baseline to Week 15 in mean pain intensity (derived from an 11-point numeric rating scale) showed numerically greater improvement for the pregabalin-treated patients compared to placebo-treated patients, but did not reach statistical significance. The most frequently observed adverse reactions in the clinical trial included dizziness, nausea, headache, weight increased, and fatigue. The overall safety profile in adolescents was similar to that observed in adults with fibromyalgia.

 

Adjunctive Therapy for Partial Onset Seizures

The safety and effectiveness of LYRICA as adjunctive treatment for partial onset seizures in pediatric patients 4 to less than 17 years of age have been established in a 12-week, double-blind, placebo-controlled study (n = 295). Patients treated with LYRICA 10 mg/kg/day had, on average, a 21.0% greater reduction in partial onset seizures than patients treated with placebo (p = 0.0185). Patients treated with LYRICA 2.5 mg/kg/day had, on average, a 10.5% greater reduction in partial onset seizures than patients treated with placebo, but the difference was not statistically significant (p = 0.2577).

Responder rates (50% or greater reduction in partial onset seizure frequency) were a key secondary efficacy parameter and showed numerical improvement with LYRICA compared with placebo: the responder rates were 40.6%, 29.1%, and 22.6%, for LYRICA 10 mg/kg/day, LYRICA 2.5 mg/kg/day, and placebo, respectively.

The most common adverse reactions (?5%) with LYRICA in this study were somnolence, weight increased, and increased appetite [see Adverse Reactions (6.1)].

The use of LYRICA 2.5mg/kg/day in pediatric patients is further supported by evidence from adequate and well controlled studies in adults with partial-onset seizures and pharmacokinetic data from adult and pediatric patients.

Safety and effectiveness in patients less than 4 years of age have not been established.

 

 

 

8.6 Renal Impairment

(Newly added subsection)

LYRICA is eliminated primarily by renal excretion and dose adjustment is recommended for adult patients with renal impairment. The use of LYRICA in pediatric patients with compromised renal function has not been studied.

 

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

 (Additions and/or revisions are underlined)

...

Missed Dose

Counsel patients if they miss a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should skip the missed dose and take the next dose at their regularly scheduled time. Instruct patients not to take two doses at the same time.

…

Medication Guide

(Extensive changes, please refer to the label)

 

12/22/2016 (SUPPL-11)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.4 Pediatric Use

(Additions and/or revisions underlined)

Fibromyalgia

A 15-week, placebo-controlled trial was conducted with 107 pediatric patients with fibromyalgia, ages 12 through 17 years, at LYRICA total daily doses of 75-450 mg per day. The primary efficacy endpoint of change from baseline to Week 15 in mean pain intensity (derived from an 11-point numeric rating scale) showed numerically greater improvement for the pregabalin-treated patients compared to placebo-treated patients, but did not reach statistical significance. The most frequently observed adverse reactions in the clinical trial included dizziness, nausea, headache, weight increased, and fatigue. The overall safety profile in adolescents was similar to that observed in adults with fibromyalgia.

Juvenile Animal Data

In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

This product’s label may have been updated. For current full prescribing information, please visit www.pfizer.com.

MEDICATION GUIDE

(Additions and/or revisions underlined)

It is not known if LYRICA is safe and effective in children.

General information about the safe and effective use of LYRICA

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide…