Adapted from Saldana M, et al. Rheumatol Int. 2010

The differences in pain reduction were significant from week 4 and maintained until the end of the study¹
The objective of this study was to evaluate the effect of Pregabalin in painful cervical or lumbosacral radiculopathy treated in Primary Care settings under routine clinical practice. An observational, prospective 12-week secondary analysis was carried-out. Male and female above 18 years, naïve to pregabalin, with refractory chronic pain secondary to cervical/lumbosacral radiculopathy were enrolled. SF-MPQ, Sheehan Disability Inventory, MOS Sleep Scale, Hospital Anxiety and Depression Scale and the EQ-5D were administered. A total of 490 (34%) patients were prescribed pregabalin-monotherapy, 702 (48%) received pregabalin add-on, and 159 (11%) were administered non-pregabalin drugs. After 12 weeks, significant improvements in pain, associated symptoms of anxiety, depression and sleep disturbances, general health; and level of disability were observed in the three groups, being significantly greater in pregabalin groups. In routine medical practice, monotherapy or add-on Pregabalin is associated with substantial pain alleviation and associated symptoms improvements in painful cervical or lumbosacral radiculopathy.
SF-MPQ: Short-form McGill Pain Questionnaire; MOS: The Medical Outcomes Study

LYRICA^® Provides a rapid Onset of Neuropathic Pain Reduction²
Pain relief on Day 1 or Day 2 versus placebo²

In your Chronic Low Back Pain patients with a Neuropathic Pain Component

In your CLBP patients with a Neuropathic Pain Component LYRICA^® is effective in the relief of the associated symptoms of Anxiety and Depression ¹

Adapted from Saldana M, et al. Rheumatol Int. 2010

The objective of this study was to evaluate the effect of Pregabalin in painful cervical or lumbosacral radiculopathy treated in Primary Care settings under routine clinical practice. An observational, prospective 12-week secondary analysis was carried-out. Male and female above 18 years, naïve to pregabalin, with refractory chronic pain secondary to cervical/lumbosacral radiculopathy were enrolled. SF-MPQ, Sheehan Disability Inventory, MOS Sleep Scale, Hospital Anxiety and Depression Scale and the EQ-5D were administered. A total of 490 (34%) patients were prescribed pregabalin-monotherapy, 702 (48%) received pregabalin add-on, and 159 (11%) were administered non-pregabalin drugs. After 12 weeks, significant improvements in pain, associated symptoms of anxiety, depression and sleep disturbances, general health; and level of disability were observed in the three groups, being significantly greater in pregabalin groups. In routine medical practice, monotherapy or add-on Pregabalin is associated with substantial pain alleviation and associated symptoms improvements in painful cervical or lumbosacral radiculopathy¹.

CLBP: Chronic low back pain; SF-MPQ: Short-form McGill pain Questionnaire; MOS: The Medical Outcomes Study
^*Hospital Anxiety and Depression Scale

DOSING

Take your Patients to the Effective Therapeutic Dose of LYRICA^{® 1,2}

*The dose range is 150 to 600 mg per day given in either two or three divided doses

CAPSULES NOT SHOWN IN ACTUAL SIZE

Evidence-Based Guidelines Recommend LYRICA^® for the
Treatment of Neuropathic Pain^1-10

International Guidelines Recommending Pregabalin as
First-line for Peripheral Neuropathic Pain^{3,4,5,6,7,8,10}

¶For focal neuropathy, such as post-herpetic neuropathy; *No differentiation between different types of neuropathic pain; **For painful diabetic peripheral neuropathy only †Population based on at least 2 consistent Class I studies (RCTs); Level B: probably effective, ineffective, or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population based on at least one Class l study (RCT)7 EFNS = European Federation of Neurological Societies; IASP = International Association for the Study of Pain; CPS = Canadian Pain Society: AAN = American Academy of Neurology; TCAs = Tricyclic Antidepressants; SNRIs = Serotonin-Norepinephrine Reuptake Inhibitors; RCT = Randomized Controlled Trial.

LYRICA^® Significantly Relieves Pain Associated with DPN¹

As early as week 1¹

Adapted from Freeman R et al., Diabetes Care, 2008

Objective: To evaluate the efficacy, safety, and tolerability of Pregabalin across the effective dosing range, to determine differences in the efficacy of three times daily (TID) versus twice daily (BID) dosage schedules, and to use time-to-event analysis to determine the time to onset of a sustained therapeutic effect using data from seven trials of Pregabalin in painful diabetic peripheral neuropathy (DPN).

Study design: Data were pooled across seven double-blind, randomized, placebo-controlled trials using Pregabalin to treat painful DPN with dosages of 150, 300, and 600 mg/day administered TID or BID. Only one trial included all three of these dosages, and TID dosing was used in four. All studies shared fundamental selection criteria, and treatment durations ranged from 5 to 13 weeks.

DPN: Diabetic Peripheral Neuropathy

[Lyrica] ^® abbreviated prescribing information

Presentation: Pregabalin 25, 50, 75, 150 & 300 mg hard capsules for oral use.

Indication(s): 1. Neuropathic pain, Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults. 2.Epilepsy, Lyrica is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalization. 3.Fibromyalgia, Lyrica is indicated for the management of fibromyalgia. 4.Generalized Anxiety Disorder, Lyrica is indicated for the treatment of Generalized Anxiety Disorder (GAD) in adults.

Dosage and Administration: Lyrica is for oral use only & may be taken with or without food. The dose range is 150 to 600 mg per day given in either two or three divided doses. Neuropathic pain: Pregabalin treatment can be started at a dose of 150 mg per day given as two or three divided doses. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after an interval of 3 to 7 days, and if needed, to a maximum dose of 600 mg per day after an additional 7-day interval. Epilepsy: Pregabalin treatment can be started with a dose of 150 mg per day given as two or three divided doses. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after 1 week. The maximum dose of 600 mg per day may be achieved after an additional week. Fibromyaglia: The recommended dose of LYRICA for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although LYRICA was also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended. Generalized anxiety disorder: The dose range is 150 to 600 mg per day given as two or three divided doses. The need for treatment should be reassessed regularly. Pregabalin treatment can be started with a dose of 150 mg per day. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after 1 week. Following an additional week the dose may be increased to 450 mg per day. The maximum dose of 600 mg per day may be achieved after an additional week. Discontinuation of pregabalin: In accordance with current clinical practice, if pregabalin has to be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication. Renal impairment: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As pregabalin clearance is directly proportional to creatinine clearance, dose reduction in patients with compromised renal function must be individualized according to creatinine clearance. Pregabalin is removed effectively from plasma by hemodialysis (50% of drug in 4 hours). For patients receiving hemodialysis, the pregabalin daily dose should be adjusted based on renal function. In addition to the daily dose, a supplementary dose should be given immediately following every 4 hour hemodialysis treatment. Hepatic impairment: No dose adjustment is required for patients with hepatic impairment. Pediatric population: The safety and efficacy of Lyrica in children below the age of 12 years and in adolescents (12-17 years of age) have not been established. Elderly: Elderly patients may require a dose reduction of pregabalin due to a decreased renal function. Pregnancy: There are no adequate data from the use of pregabalin in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Lyrica should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the fetus). Breast-feeding: Pregabalin is excreted into human milk. The effect of pregabalin on newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Contraindications: Hypersensitivity to the active substance or to any of the excipients.

Warnings and Precautions: Diabetic patients: In accordance with current clinical practice, some diabetic patients who gain weight on Pregabalin treatment may need to adjust hypoglycaemic medicinal products. Hypersensitivity reactions: there have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur. Dizziness, somnolence, loss of consciousness, confusion and mental impairment: Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been postmarketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product. Vision-related effects: in controlled trials, a higher proportion of patients treated with Pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients .In the postmarketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of Pregabalin may result in resolution or improvement of these visual symptoms. Renal failure: Cases of renal failure have been reported and in some cases discontinuation of Pregabalin did show reversibility of this adverse reaction. Withdrawal of concomitant anti-epileptic medicinal products: there are insufficient data for the withdrawal of concomitant anti-epileptic medicinal products, once seizure control with Pregabalin in the add-on situation has been reached, in order to reach monotherapy on Pregabalin. Withdrawal symptoms: after discontinuation of short-term and long-term treatment with Pregabalin, withdrawal symptoms have been observed in some patients. The following events have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment. Convulsions, including status epilepticus and grand mal convulsions, may occur during pregabalin use or shortly after discontinuing pregabalin. Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related. Congestive heart failure: There have been postmarketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication. Pregabalin should be used with caution in these patients. Discontinuation of pregabalin may resolve the reaction. Treatment of central neuropathic pain due to spinal cord injury: In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, central nervous system adverse reactions and especially somnolence was increased. This may be attributed to an additive effect due to concomitant medicinal products (e.g. anti-spasticity agents) needed for this condition. This should be considered when prescribing pregabalin in this condition. Suicidal ideation and behavior: Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled studies of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for pregabalin. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Reduced lower gastrointestinal tract function: There are post marketing reports of events related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics. When pregabalin and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and elderly). Concomitant use with opioids: Caution is advised when prescribing pregabalin concomitantly with opioids due to risk of CNS depression (see section 4.5). In a case-control study of opioid users, those patients who took pregabalin concomitantly with an opioid had an increased risk for opioid-related death compared to opioid use alone (adjusted odds ratio [aOR], 1.68 [95% CI, 1.19 – 2.36]). This increased risk was observed at low doses of pregabalin (≤ 300 mg, aOR 1.52 [95% CI, 1.04 – 2.22]) and there was a trend for a greater risk at high doses of pregabalin (> 300 mg, aOR 2.51 [95% CI 1.24 – 5.06]). Misuse, abuse potential or dependence: Cases of misuse, abuse and dependence have been reported. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of pregabalin misuse, abuse or dependence (development of tolerance, dose escalation, drug-seeking behaviour have been reported). Encephalopathy: Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy. Lactose intolerance: Lyrica contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Geriatric 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. Respiratory Depression: 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. Sodium content: Lyrica contains less than 1 mmol sodium (23 mg) per hard capsule. Patients on low sodium diets can be informed that this medicinal product is essentially ‘sodium-free’.

Interactions: Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (< 2% of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions. In vivo studies and population pharmacokinetic analysis: Accordingly, in in vivo studies no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance. Oral contraceptives, norethisterone and/or ethinyl oestradiol: Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl oestradiol does not influence the steady-state pharmacokinetics of either substance. Central nervous system influencing medical products: Pregabalin may potentiate the effects of ethanol and lorazepam. In controlled clinical trials, multiple oral doses of pregabalin co-administered with oxycodone, lorazepam, or ethanol did not result in clinically important effects on respiration. In the postmarketing experience, there are reports of respiratory failure and coma in patients taking pregabalin and other central nervous system (CNS) depressant medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone. Interactions and the elderly: No specific pharmacodynamic interaction studies were conducted in elderly volunteers. Interaction studies have only been performed in adults.

Overdose: In the post marketing experience, the most commonly reported adverse reactions observed when Pregabalin was taken in overdose included somnolence, confusional state, agitation, and restlessness. Seizures were also reported. In rare occasions, cases of coma have been reported. Treatment of Pregabalin overdose should include general supportive measures and may include haemodialysis if necessary.

Adverse Reaction: The Pregabalin clinical programme involved over 8,900 patients exposed to Pregabalin, of whom over 5,600 were in double-blind placebo-controlled trials. The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse reactions was 12% for patients receiving Pregabalin and 5% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from Pregabalin treatment groups were dizziness and somnolence. The very common adverse reactions (≥ 1/10) are; Dizziness, somnolence & headache. Common adverse reactions (≥ 1/100 to < 1/10) are; Nasopharyngitis, Appetite increased, Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased, Ataxia, coordination abnormal, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoaesthesia, sedation, balance disorder, lethargy, Vision blurred, diplopia, Vertigo, Vomiting, nausea, constipation, diarrhea, flatulence, abdominal distension, dry mouth, Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm, Erectile dysfunction, Edema peripheral, edema, gait abnormal, fall, feeling drunk, feeling abnormal, fatigue, & Weight increased. After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed in some patients. The following reactions have been mentioned: insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment. Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related. Pediatric population: The pregabalin safety profile observed in five paediatric studies in patients with partial seizures with or without secondary generalisation was similar to that observed in the adult studies of patients with epilepsy. The most common adverse events observed in the 12 week study with pregabalin treatment were somnolence, pyrexia, upper respiratory tract infection, increased appetite, weight increased, and nasopharyngitis. The most common adverse events observed in the 14 day study with pregabalin treatment were somnolence, upper respiratory tract infection, and pyrexia. Fibromyalgia: Safety and effectiveness in pediatric patients have not been established. 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.

Pharmaceutical Precautions: Do not store above 25°C.