Lyrica Information
Lyrica () Indications And Usage
Lyrica () is indicated for:
Lyrica () Dosage And Administration
Lyrica () is given orally with or without food.
When discontinuing Lyrica () , taper gradually over a minimum of 1 week.
Lyrica () Dosage Forms And Strengths
Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mgOral Solution: 20 mg/mL
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Lyrica () Contraindications
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.
Lyrica () Warnings And Precautions
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.
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.
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.
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.
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 31% of Lyrica () -treated patients compared to 9% of placebo-treated patients; somnolence was experienced by 22% of Lyrica () -treated patients compared to 7% 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.
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 HbA).
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 >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.
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 .
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 ≥300 mg/day. This mean change difference was not associated with an increased risk of PR increase ≥25% from baseline, an increased percentage of subjects with on-treatment PR >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.
Lyrica () Adverse Reactions
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.
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
Lyrica () Drug Interactions
Since Lyrica () is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (<2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. and studies showed that Lyrica () is unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between Lyrica () and commonly used antiepileptic drugs .
Lyrica () Use In Specific Populations
Pregnancy Category C. Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including lethality, growth retardation, and nervous and reproductive system functional impairment, were observed in the offspring of rats and rabbits given pregabalin during pregnancy, at doses that produced plasma pregabalin exposures (AUC) ≥5 times human exposure at the maximum recommended dose (MRD) of 600 mg/day.
When pregnant rats were given pregabalin (500, 1250, or 2500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at ≥1250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. Fetal body weights were decreased at the highest dose. The low dose in this study was associated with a plasma exposure (AUC) approximately 17 times human exposure at the MRD of 600 mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established.
When pregnant rabbits were given Lyrica () (250, 500, or 1250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. The no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 16 times human exposure at the MRD.
In a study in which female rats were dosed with Lyrica () (50, 100, 250, 1250, or 2500 mg/kg) throughout gestation and lactation, offspring growth was reduced at ≥ 100 mg/kg and offspring survival was decreased at ≥250 mg/kg. The effect on offspring survival was pronounced at doses ≥1250 mg/kg, with 100% mortality in high-dose litters. When offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at ≥250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg. The no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the MRD.
There are no adequate and well-controlled studies in pregnant women. Use Lyrica () during pregnancy only if the potential benefit justifies the potential risk to the fetus.
To provide information regarding the effects of in utero exposure to Lyrica () , physicians are advised to recommend that pregnant patients taking Lyrica () enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.
The safety and efficacy of pregabalin in pediatric patients have not been established.
In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses ≥50 mg/kg. The neurobehavioral changes of acoustic startle persisted at ≥250 mg/kg and locomotor activity and water maze performance at ≥500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long-term effects. The low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately equal to human exposure at the maximum recommended dose of 600 mg/day. A no-effect dose was not established.
In controlled clinical studies of Lyrica () in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older.
In controlled clinical studies of Lyrica () in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older.
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 .
Lyrica () Drug Abuse And Dependence
Lyrica () is a Schedule V controlled substance.
Lyrica () is not known to be active at receptor sites associated with drugs of abuse. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of Lyrica () misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).
Lyrica () Overdosage
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.
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 () Description
Pregabalin is described chemically as ()-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is CHNO and the molecular weight is 159.23. The chemical structure of pregabalin is:
Pregabalin is a white to off-white, crystalline solid with a pK of 4.2 and a pK 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.
Lyrica () Clinical Pharmacology
Lyrica () (pregabalin) binds with high affinity to the alpha-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha-delta subunit may be involved in pregabalin's antinociceptive and antiseizure effects in animal models. , pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.
While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA, GABA, or benzodiazepine receptors, does not augment GABA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Lyrica () Clinical Studies
The efficacy of the maximum recommended dose of Lyrica () for the management of neuropathic pain associated with diabetic peripheral neuropathy was established in three double-blind, placebo-controlled, multicenter studies with three times a day dosing, two of which studied the maximum recommended dose. Patients were enrolled with either Type 1 or Type 2 diabetes mellitus and a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for 1 to 5 years. A total of 89% of patients completed Studies DPN 1 and DPN 2. The patients had a minimum mean baseline pain score of ≥4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.1 to 6.7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.
Figure 1: Patients Achieving Various Levels of Pain Relief – Study DPN 1
Study DPN 2:
Figure 2: Patients Achieving Various Levels of Pain Relief – Study DPN 2
The efficacy of Lyrica () for the management of postherpetic neuralgia was established in three double-blind, placebo-controlled, multicenter studies. These studies enrolled patients with neuralgia persisting for at least 3 months following healing of herpes zoster rash and a minimum baseline score of ≥4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). Seventy-three percent of patients completed the studies. The baseline mean pain scores across the 3 studies ranged from 6 to 7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.
Study PHN 1:
Figure 3: Patients Achieving Various Levels of Pain Relief – Study PHN 1
Study PHN 2:
Figure 4: Patients Achieving Various Levels of Pain Relief – Study PHN 2
Study PHN 3:
Figure 5: Patients Achieving Various Levels of Pain Relief – Study PHN 3
The efficacy of Lyrica () as adjunctive therapy in partial onset seizures was established in three 12-week, randomized, double-blind, placebo-controlled, multicenter studies in adult patients. Patients were enrolled who had partial onset seizures with or without secondary generalization and were not adequately controlled with 1 to 3 concomitant antiepileptic drugs (AEDs). Patients taking gabapentin were required to discontinue gabapentin treatment 1 week prior to entering baseline. During an 8-week baseline period, patients had to experience at least 6 partial onset seizures with no seizure-free period exceeding 4 weeks. The mean duration of epilepsy was 25 years in these 3 studies and the mean and median baseline seizure frequencies were 22.5 and 10 seizures per month, respectively. Approximately half of the patients were taking 2 concurrent AEDs at baseline. Among the Lyrica () -treated patients, 80% completed the double-blind phase of the studies.
Table 7 shows median baseline seizure rates and median percent reduction in seizure frequency by dose.
In the first study (E1), there was evidence of a dose-response relationship for total daily doses of Lyrica () between 150 and 600 mg/day; a dose of 50 mg/day was not effective. In the first study (E1), each daily dose was divided into two equal doses (twice a day dosing). In the second study (E2), each daily dose was divided into three equal doses (three times a day dosing). In the third study (E3), the same total daily dose was divided into two equal doses for one group (twice a day dosing) and three equal doses for another group (three times a day dosing). While the three times a day dosing group in Study E3 performed numerically better than the twice a day dosing group, this difference was small and not statistically significant.
A secondary outcome measure included the responder rate (proportion of patients with ≥50% reduction from baseline in partial seizure frequency). The following figure displays responder rate by dose for two of the studies.
Figure 6. Responder rate by add-on epilepsy study
Figure 7. Seizure Reduction by Dose (All Partial Onset Seizures) for Studies E1, E2, and E3
Subset evaluations of the antiseizure efficacy of Lyrica () showed no clinically important differences as a function of age, gender, or race.
The efficacy of Lyrica () for management of fibromyalgia was established in one 14-week, double-blind, placebo-controlled, multicenter study (F1) and one six-month, randomized withdrawal study (F2). Studies F1 and F2 enrolled patients with a diagnosis of fibromyalgia using the American College of Rheumatology (ACR) criteria (history of widespread pain for 3 months, and pain present at 11 or more of the 18 specific tender point sites). The studies showed a reduction in pain by visual analog scale. In addition, improvement was demonstrated based on a patient global assessment (PGIC), and on the Fibromyalgia Impact Questionnaire (FIQ).
Study F1: This 14-week study compared Lyrica () total daily doses of 300 mg, 450 mg and 600 mg with placebo. Patients were enrolled with a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numeric pain rating scale and a score of greater than or equal to 40 mm on the 100 mm pain visual analog scale (VAS). The baseline mean pain score in this trial was 6.7. Responders to placebo in an initial one-week run-in phase were not randomized into subsequent phases of the study. A total of 64% of patients randomized to Lyrica () completed the study. There was no evidence of a greater effect on pain scores of the 600 mg daily dose than the 450 mg daily dose, but there was evidence of dose-dependent adverse reactions []. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study. The results are summarized in Figure 8 and Table 8.
For various degrees of improvement in pain from baseline to study endpoint, Figure 8 shows the fraction of patients achieving that degree of improvement. The figure is cumulative. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.
Figure 8: Patients Achieving Various Levels of Pain Relief – Fibromyalgia Study F1
Study F2: This randomized withdrawal study compared Lyrica () with placebo. Patients were titrated during a 6-week open-label dose optimization phase to a total daily dose of 300 mg, 450 mg, or 600 mg. Patients were considered to be responders if they had both: 1) at least a 50% reduction in pain (VAS) and, 2) rated their overall improvement on the PGIC as "much improved" or "very much improved." Those who responded to treatment were then randomized in the double-blind treatment phase to either the dose achieved in the open-label phase or to placebo. Patients were treated for up to 6 months following randomization. Efficacy was assessed by time to loss of therapeutic response, defined as 1) less than 30% reduction in pain (VAS) from open-label baseline during two consecutive visits of the double-blind phase, or 2) worsening of FM symptoms necessitating an alternative treatment. Fifty-four percent of patients were able to titrate to an effective and tolerable dose of Lyrica () during the 6-week open-label phase. Of the patients entering the randomized treatment phase assigned to remain on Lyrica () , 38% of patients completed 26 weeks of treatment versus 19% of placebo-treated patients.
When considering return of pain or withdrawal due to adverse events as loss of response (LTR), treatment with Lyrica () resulted in a longer time to loss of therapeutic response than treatment with placebo. Fifty-three percent of the pregabalin-treated subjects compared to 33% of placebo patients remained on study drug and maintained a therapeutic response to Week 26 of the study. Treatment with Lyrica () also resulted in a longer time to loss of response based on the FIQ, and longer time to loss of overall assessment of patient status, as measured by the PGIC.
Figure 9: Time to Loss of Therapeutic Response, Fibromyalgia Study F2 (Kaplan-Meier Analysis)
Lyrica () How Supplied/storage And Handling
White, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 25" on the body; available in:
White, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 50" and an ink band on the body, available in:
White/orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 75" on the body; available in:
Orange, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 100" on the body, available in:
White hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 150" on the body, available in:
Light orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 200" on the body, available in:
White/orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 300" on the body, available in:
Lyrica () Patient Counseling Information
Instruct 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
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 ].
Capsules manufactured by:Pfizer Pharmaceuticals LLCVega Baja, PR 00694
Oral Solution manufactured by:Pfizer IncKalamazoo, MI 49001
LAB-0294-16.0
Lyrica ()
Lyrica () Principal Display Panel
Lyrica () Principal Display Panel
Lyrica () Principal Display Panel
Lyrica () Principal Display Panel
Lyrica () Principal Display Panel
Lyrica () Principal Display Panel
