|Labeler Name||Parke-Davis Div of Pfizer Inc|
|Dosage & Substance||capsule pregabalin|
|Date First Marketed||December 30, 2004|
LYRICA is indicated for:
- Management of neuropathic pain associated with diabetic peripheral neuropathy
- Management of postherpetic neuralgia
- Adjunctive therapy for adult patients with partial onset seizures
- Management of fibromyalgia
- Management of neuropathic pain associated with spinal cord injury
LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy.
6.1 Clinical Trials Experience
Because 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.
In premarketing controlled trials of all 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).
In premarketing controlled trials of all patient populations combined, 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 with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
In clinical trials in patients with neuropathic pain associated with diabetic peripheral neuropathy, 9% of patients treated with LYRICA and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (3%) and somnolence (2%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the LYRICA group than in the placebo group, were asthenia, confusion, and peripheral edema. Each of these events led to withdrawal in approximately 1% of patients.
Table 3 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with diabetic neuropathy in the combined LYRICA group for which the incidence was greater in this combined LYRICA group than in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate".
|Body system |
|75 mg/day |
|150 mg/day |
|300 mg/day |
|600 mg/day |
|Body as a whole|
|Metabolic and nutritional disorders|
Controlled Studies in Postherpetic Neuralgia
In clinical trials in patients with postherpetic neuralgia, 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 most common reasons for discontinuation due to adverse reactions were dizziness (4%) and somnolence (3%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring in greater frequency in the LYRICA group than in the placebo group, were confusion (2%), as well as peripheral edema, asthenia, ataxia, and abnormal gait (1% each).
Table 4 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with postherpetic neuralgia in the combined LYRICA group for which the incidence was greater in this combined LYRICA group than in the placebo group. In addition, an event is included, even if the incidence in the all LYRICA group is not greater than in the placebo group, if the incidence of the event in the 600 mg/day group is more than twice that in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate". Overall, 12.4% of all pregabalin-treated patients and 9.0% of all placebo-treated patients had at least one severe event while 8% of pregabalin-treated patients and 4.3% of placebo-treated patients had at least one severe treatment-related adverse event.
|Body system |
|75 mg/d |
|150 mg/d |
|300 mg/d |
|600 mg/d |
|All PGB* |
|Body as a whole|
|Metabolic and nutritional disorders|
Controlled Add-On Studies in Adjunctive Therapy for Adult Patients with Partial Onset Seizures
Approximately 15% of patients receiving LYRICA and 6% of patients receiving placebo in add-on epilepsy trials 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%). In comparison, less than 1% of patients in the placebo group withdrew due to each of these events. Other adverse reactions that led to discontinuation of at least 1% of patients in the LYRICA group and at least twice as frequently compared to the placebo group were asthenia, diplopia, blurred vision, thinking abnormal, nausea, tremor, vertigo, headache, and confusion (which each led to withdrawal in 2% or less of patients).
Table 5 lists all dose-related adverse reactions occurring in at least 2% of all LYRICA-treated patients. Dose-relatedness was defined as the incidence of the adverse event in the 600 mg/day group was at least 2% greater than the rate in both the placebo and 150 mg/day groups. In these studies, 758 patients received LYRICA and 294 patients received placebo for up to 12 weeks. Because patients were also treated with 1 to 3 other AEDs, it is not possible to determine whether the following adverse reactions can be ascribed to LYRICA alone, or the combination of LYRICA and other AEDs. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate".
|150 mg/d||300 mg/d||600 mg/d||All PGB*||Placebo|
|Body System |
|[N = 185]||[N = 90]||[N = 395]||[N = 670]†||[N = 294]|
|Body as a Whole|
|Metabolic and Nutritional Disorders|
Controlled Studies with Fibromyalgia
In clinical trials of patients with fibromyalgia, 19% of patients treated with pregabalin (150–600 mg/day) and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (6%) and somnolence (3%). In comparison, less than 1% of placebo-treated patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue, headache, balance disorder, and weight increased. Each of these adverse reactions led to withdrawal in approximately 1% of patients.
Table 6 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients with fibromyalgia in the ‘all pregabalin’ treatment group for which the incidence was greater than in the placebo treatment group. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".
|System Organ Class |
|150 mg/d||300 mg/d||450 mg/d||600 mg/d||All PGB*||Placebo|
|Ear and Labyrinth Disorders|
|General Disorders and Administrative Site Conditions|
|Infections and Infestations|
|Metabolism and Nutrition Disorders|
|Musculoskeletal and Connective Tissue Disorders|
|Nervous System Disorders|
|Disturbance in attention||4||4||6||6||5||1|
|Respiratory, Thoracic and Mediastinal Disorders|
Controlled Studies in Neuropathic Pain Associated with Spinal Cord Injury
In clinical trials of patients with neuropathic pain associated with spinal cord injury, 13% of patients treated with pregabalin and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were somnolence (3%) and edema (2%). In comparison, none of the placebo-treated patients withdrew due to somnolence and edema. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue and balance disorder. Each of these adverse reactions led to withdrawal in less than 2% of patients.
Table 7 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients with neuropathic pain associated with spinal cord injury in the controlled trials. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".
|System Organ Class |
|PGB* (N=182)||Placebo (N=174)|
|Ear and labryrinth disorders|
|General disorders and administration site conditions|
|Infections and infestations|
|Blood creatine phosphokinase increased||2.7||0|
|Musculoskeletal and connective tissue disorders|
|Pain in extremity||3.3||2.3|
|Nervous system disorders|
|Disturbance in attention||3.8||0|
|Renal and urinary disorders|
|Skin and subcutaneous tissue disorders|
Other Adverse Reactions Observed During the Clinical Studies of LYRICA
Following is a list of treatment-emergent adverse reactions reported by patients treated with LYRICA during all clinical trials. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening.
Events are categorized by body system and listed in order of decreasing frequency according to the following definitions: adverse reactions are those occurring on one or more occasions in at least 1/100 patients; adverse reactions are those occurring in 1/100 to 1/1000 patients; reactions are those occurring in fewer than 1/1000 patients. Events of major clinical importance are described in the section (5).
Body as a Whole – Abdominal pain, Allergic reaction, Fever, Abscess, Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Photosensitivity reaction, Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional Injury, Retroperitoneal Fibrosis, Shock
Cardiovascular System – Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; ST Depressed, Ventricular Fibrillation
Digestive System – Gastroenteritis, Increased appetite; Cholecystitis, Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena, Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Aphthous stomatitis, Esophageal Ulcer, Periodontal abscess
Hemic and Lymphatic System – Ecchymosis; Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia
Metabolic and Nutritional Disorders – Glucose Tolerance Decreased, Urate Crystalluria
Musculoskeletal System – Arthralgia, Leg cramps, Myalgia, Myasthenia; Arthrosis; Chondrodystrophy, Generalized Spasm
Nervous System – Anxiety, Depersonalization, Hypertonia, Hypoesthesia, Libido decreased, Nystagmus, Paresthesia, Sedation, Stupor, Twitching; Abnormal dreams, Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia, Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Guillain-Barré syndrome, Hypalgesia, Intracranial hypertension, Manic reaction, Paranoid reaction, Peripheral neuritis, Personality disorder, Psychotic depression, Schizophrenic reaction, Sleep disorder, Torticollis, Trismus
Respiratory System – Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung edema, Lung fibrosis, Yawn
Skin and Appendages – Pruritus, Alopecia, Dry skin, Eczema, Hirsutism, Skin ulcer, Urticaria, Vesiculobullous rash; Angioedema, Exfoliative dermatitis, Lichenoid dermatitis, Melanosis, Nail Disorder, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy, Skin necrosis, Skin nodule, Stevens-Johnson syndrome, Subcutaneous nodule
Special senses – Conjunctivitis, Diplopia, Otitis media, Tinnitus; Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis, Photophobia, Retinal edema, Taste loss, Taste perversion; Anisocoria, Blindness, Corneal ulcer, Exophthalmos, Extraocular palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis, Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis
Urogenital System – Anorgasmia, Impotence, Urinary frequency, Urinary incontinence; Abnormal ejaculation, Albuminuria, Amenorrhea, Dysmenorrhea, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Menorrhagia, Metrorrhagia, Nephritis, Oliguria, Urinary retention, Urine abnormality; Acute kidney failure, Balanitis, Bladder Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis, Ovarian disorder, Pyelonephritis
Comparison of Gender and Race
The overall adverse event profile of pregabalin was similar between women and men. There are insufficient data to support a statement regarding the distribution of adverse experience reports by race.
6.2 Postmarketing Experience
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
In addition, there are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when LYRICA was co-administered with medications that have the potential to produce constipation, such as opioid analgesics. There are also postmarketing reports of respiratory failure and coma in patients taking pregabalin and other CNS depressant medications.
There have been postmarketing reports of angioedema in patients during initial and chronic treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in patients with these symptoms.
Exercise caution when prescribing LYRICA to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema.
There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue LYRICA immediately in patients with these symptoms.
5.3 Withdrawal of Antiepileptic Drugs (AEDs)
As with all AEDs, withdraw LYRICA gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. If LYRICA is discontinued, taper the drug gradually over a minimum of 1 week.
5.4 Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including LYRICA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5–100 years) in the clinical trials analyzed.
Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
|Indication||Placebo Patients with Events Per 1000 Patients||Drug Patients with Events Per 1000 Patients||Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients||Risk Difference: Additional Drug Patients with Events Per 1000 Patients|
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
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.
Inform patients, their caregivers, and families that LYRICA and other AEDs increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of the signs and 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.
5.5 Peripheral Edema
LYRICA treatment may cause peripheral edema. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension or congestive heart failure. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function.
In controlled clinical trials 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.
Higher frequencies of weight gain and peripheral edema were observed in patients taking both LYRICA and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety database were participants in studies of pain associated with diabetic peripheral neuropathy. In this population, peripheral edema was reported in 3% (2/60) of patients who were using thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with LYRICA only, and 19% (23/120) of patients who were on both LYRICA and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on LYRICA only; and 7.5% (9/120) of patients on both drugs.
As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when co-administering LYRICA and these agents.
Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, exercise caution when using LYRICA in these patients.
5.6 Dizziness and Somnolence
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, 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.
5.7 Weight Gain
LYRICA treatment may cause weight gain. In LYRICA controlled clinical trials 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.
Although weight gain was not associated with clinically important changes in blood pressure in short-term controlled studies, the long-term cardiovascular effects of LYRICA-associated weight gain are unknown.
Among diabetic patients, LYRICA-treated patients gained an average of 1.6 kg (range: -16 to 16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a cohort of 333 diabetic patients who received LYRICA for at least 2 years, the average weight gain was 5.2 kg.
While the effects of LYRICA-associated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open label clinical trials with diabetic patients, LYRICA treatment did not appear to be associated with loss of glycemic control (as measured by HbA1C).
5.8 Abrupt or Rapid Discontinuation
Following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea. Taper LYRICA gradually over a minimum of 1 week rather than discontinuing the drug abruptly.
5.9 Tumorigenic Potential
In standard preclinical lifetime carcinogenicity studies of LYRICA, an unexpectedly high incidence of hemangiosarcoma was identified in two different strains of mice. The clinical significance of this finding is unknown. Clinical experience during LYRICA’s premarketing development provides no direct means to assess its potential for inducing tumors in humans.
In clinical studies across various patient populations, comprising 6396 patient-years of exposure in patients greater than 12 years of age, new or worsening-preexisting tumors were reported in 57 patients. Without knowledge of the background incidence and recurrence in similar populations not treated with LYRICA, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment.
5.10 Ophthalmological Effects
In controlled studies, 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).
Prospectively planned ophthalmologic testing, including visual acuity testing, formal visual field testing and dilated funduscopic examination, was performed in over 3600 patients. In these patients, visual acuity was reduced in 7% of patients treated with LYRICA, and 5% of placebo-treated patients. Visual field changes were detected in 13% of LYRICA-treated, and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of LYRICA-treated and 2% of placebo-treated patients.
Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions.
5.11 Creatine Kinase Elevations
LYRICA treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for LYRICA-treated patients and 28 U/L for the placebo patients. In all controlled trials across multiple patient populations, 1.5% of patients on LYRICA and 0.7% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three LYRICA treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and LYRICA is not completely understood because the cases had documented factors that may have caused or contributed to these events. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with LYRICA if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.
5.12 Decreased Platelet Count
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, 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. A single LYRICA treated subject developed severe thrombocytopenia with a platelet count less than 20 × 103/ µL. In randomized controlled trials, LYRICA was not associated with an increase in bleeding-related adverse reactions.
5.13 PR Interval Prolongation
LYRICA treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data, 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.
Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline PR prolongation or in patients taking other PR prolonging medications. However, these analyses cannot be considered definitive because of the limited number of patients in these categories.
|This Medication Guide has been approved by the U.S. Food and Drug Administration.||December 2016|
|LYRICA (LEER-i-kah) |
|LYRICA (LEER-i-kah) |
Oral Solution, CV
|Read this Medication Guide before you start taking LYRICA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about LYRICA, ask your healthcare provider or pharmacist.|
|What is the most important information I should know about LYRICA? |
LYRICA may cause serious side effects including:
| || |
|These serious side effects are described below: |
| || |
|What is LYRICA? |
LYRICA is a prescription medicine used in adults, 18 years and older, to treat:
| || |
|It is not known if LYRICA is safe and effective in children.|
|Who should not take LYRICA? |
Do not take LYRICA if you are allergic to pregabalin or any of the ingredients in LYRICA.
See "What is the most important information I should know about LYRICA?" for the signs of an allergic reaction.
See the end of this leaflet for a complete list of ingredients in LYRICA.
|What should I tell my healthcare provider before taking LYRICA? |
Before taking LYRICA, tell your healthcare provider about all your medical conditions, including if you:
|Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins or herbal supplements. LYRICA and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take: |
|Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider.|
|How should I take LYRICA? |
|What should I avoid while taking LYRICA? |
|What are the possible side effects of LYRICA? |
LYRICA may cause serious side effects, including:
|The most common side effects of LYRICA are:|
| || |
|LYRICA caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking LYRICA and tell your healthcare provider about any sores or skin problems. |
Tell your healthcare provider about any side effect that bothers you or that does not go away.
These are not all the possible side effects of LYRICA. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
|How should I store LYRICA? |
|Keep LYRICA and all medicines out of the reach of 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. Do not use LYRICA for a condition for which it was not prescribed. Do not give LYRICA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about LYRICA that is written for health professionals.
You can also visit the LYRICA website at www.LYRICA.com or call 1-866-459-7422 (1-866-4LYRICA).
|What are the ingredients in LYRICA? |
Active ingredient: pregabalin
LYRICA capsules: lactose monohydrate, cornstarch, talc
Capsule shell: gelatin and titanium dioxide; Orange capsule shell: red iron oxide; White capsule shell: sodium lauryl sulfate, colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells.
Imprinting ink: shellac, black iron oxide, propylene glycol, potassium hydroxide.
LYRICA oral solution: methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water.
Signs, 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. In the postmarketing experience, the most commonly reported adverse events observed when LYRICA was taken in overdose included affective disorder, somnolence, confusional state, depression, agitation, and restlessness. Seizures were also reported.
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).
Pregabalin is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C8H17NO2 and the molecular weight is 159.23. The chemical structure of pregabalin is:
Pregabalin is a white to off-white, crystalline solid with a pKa1 of 4.2 and a pKa2 of 10.6. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is – 1.35.
LYRICA (pregabalin) Capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose monohydrate, cornstarch, and talc as inactive ingredients. The capsule shells contain gelatin and titanium dioxide. In addition, the orange capsule shells contain red iron oxide and the white capsule shells contain sodium lauryl sulfate and colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells. The imprinting ink contains shellac, black iron oxide, propylene glycol, and potassium hydroxide.
LYRICA (pregabalin) oral solution, 20 mg/mL, is administered orally and is supplied as a clear, colorless solution contained in a 16 fluid ounce white HDPE bottle with a polyethylene-lined closure. The oral solution contains 20 mg/mL of pregabalin, along with methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water as inactive ingredients.