Neurica

Neurica 75: White body red cap hard gelat in capsules size no. 4 with "B" marked on the cap and "75" on the body containing white powder.
Each capsule contains Pregabalin 75 mg.
Neurica 150: White opaque hard gelatin capsule size no. 2, with B marked on the cap and "150" on the body containing white powder.
Each capsule contains Pregabalin 150 mg.

Pharmacology: Mechanism of Action: Although the exact mechanism of action of pregabalin has not been elucidated, binding to the α₂-δ subunit may be involved in pregabalin's analgesic and anticonvulsant effects. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, including glutamate, norepinephrine, calcitonin gene-related peptide, and substance P, possibly by modulation of calcium channel function.
Pharmacodynamics: Pregabalin binds with high affinity to the α₂-δ site (an auxiliary subunit of voltage gated calcium channels) in CNS tissues.
Pharmacokinetics: Absorption: Pregabalin is well absorbed following oral administration and exhibits linear pharmacokinetics. Peak plasma concentrations are attained within 1.5 hour. Steady-state concentrations are achieved within 24-48 hours following repeated administration of conventional pregabalin. In pediatric patients receiving conventional pregabalin, peak plasma concentrations of the drug are achieved within 0.5-2 hours in the fasted state. The oral bioavailability of pregabalin administered as the conventional preparation) is at least 90% and is independent of dose. Administration of conventional preparations of pregabalin with food has been shown to delay the time to peak concentration and decrease peak plasma concentrations of the drug by approximately 25-30%, but does not affect the extent of absorption.
Distribution: Protein binding: 0%.
Metabolism: Negligible.
Excretion: Following administration of a single radiolabeled dose of pregabalin, approximately 90% of the administered dose was recovered in urine as unchanged drug. Clearance of pregabalin is nearly proportional to creatinine clearance in both adults and pediatric patients. In pediatric patients, the weight-normalized clearance of pregabalin is approximately 40% higher in those weighing less than 30 kg. The mean elimination half-life of pregabalin is 6.3 hours in adults with normal renal function, 3-4 hours in children up to 6 years of age, and 4-6 hours in children 7 years of age or older.

Neuropathic pain: Pregabalin is indicated for the treatment of central and peripheral neuropathic pain in adults which includes diabetic peripheral neuropathy and post herpetic neuralgia.
Epilepsy: Pregabalin is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalization.
Generalized anxiety disorder (GAD): Pregabalin is indicated for the treatment of generalized anxiety disorder in adults.
Fibromyalgia: Pregabalin is indicated for the management of fibromyalgia.

Recommended Doses: 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. Based on individual patient response and tolerability, the dosage 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. Based on individual patient response and tolerability, the dosage may be increased to 300 mg per day after 1 week. The maximum dosage of 600 mg per day may be achieved after an additional week.
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 dosage may be increased to 300 mg per day after 1 week.
Following an additional week the dosage may be increased to 450 mg per day. The maximum dosage of 600 mg per day may be achieved after an additional week.
Fibromyalgia: The usual dose range for most patients is 300 to 450 mg per day given in two divided doses. Some patients may derive additional benefit at 600 mg per day. Dosing should begin at 75 mg two times a day (150 mg/day) and 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). If needed, in some patients, based on individual response and tolerability, the dose may be increased to maximum dosage of 600 mg/day after an additional week.
Discontinuation of pregabalin: If pregabalin has to be discontinued, it is recommended this should be done gradually over a minimum of 1 week.
Patients with renal impairment: Dosage reduction in patients with compromised renal function must be individualized according to creatinine clearance (Clcr), as indicated in the table as follows determined using the following formula: See Equation.

Click on icon to see table/diagram/image

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 (see table).

Click on icon to see table/diagram/image

Use in patients with hepatic impairment: No dosage adjustment is required for patients with hepatic impairment.
Use in children and adolescents (12 to 17 years of age): The safety and effectiveness of pregabalin in pediatric patients below the age of 12 years and adolescents has not been established.
The use in children is not recommended.
Use in the elderly (over 65 years of age): Elderly patients may require a dose reduction of pregabalin due to decreased renal function.
Mode of Administration: Pregabalin is administered orally without regard to food.

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: Treatment of pregabalin overdose should include general supportive measures and may include haemodialysis if necessary.

Do not use pregabalin in patient with known hypersensitivity to pregabalin or any ingredient in the formulation.

This drug may cause drowsiness, do not drive a motor vehicle or operate machinery, or drink alcoholic beverages while taking the drug.
This drug may cause hematologic disorder.
Using this drug in pregnant woman is contraindicated because it may cause teratogenesis.
Use this drug with caution in patients with liver and/or kidney disease.
Angioedema: Angioedema, including life-threatening cases with respiratory compromise requiring emergency treatment, has been reported during post marketing surveillance in patients receiving initial and chronic pregabalin therapy. Specific symptoms included swelling of the face, mouth (e.g., tongue, lips, gums), and neck (e.g., throat, larynx). Pregabalin should be immediately discontinued in patients with these symptoms. Caution is advised if the drug is used in patients who have had a previous episode of angioedema. Patients receiving concomitant drugs associated with angioedema (e.g., angiotensin converting enzyme ACE inhibitors) may be at increased risk of developing angioedema.
Hypersensitivity Reactions: Hypersensitivity reactions (i.e., skin redness, blisters, hives, rash, dyspnea, wheezing) have been reported during post-marketing surveillance in patients shortly after initiation of pregabalin therapy. Pregabalin should be immediately discontinued in patients with symptoms of hypersensitivity.
Suicidality Risk: An increased risk of suicidality (suicidal behavior or ideation) has been observed in an analysis of studies using various anticonvulsants, including pregabalin, compared with placebo. This increased suicidality risk was consistent among anticonvulsants with varying mechanisms of action and across a range of indications and was observed as early as 1 week after beginning therapy. Because most of these studies did not extend beyond 24 weeks, the suicidality risk beyond 24 weeks is not known. Although patients treated with an anticonvulsant for epilepsy, psychiatric disorders, and other conditions were all found to have an increased suicidality risk compared with those receiving placebo, the relative suicidality risk was higher for patients with epilepsy compared to those receiving anticonvulsants for other conditions.
Clinicians should inform patients, their families, and caregivers of the potential for an increased risk of suicidality with anticonvulsant therapy. All patients currently receiving or beginning therapy with any anticonvulsant should be closely monitored for notable changes that may indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Clinicians who prescribe pregabalin or any other anticonvulsant should balance the risk of suicidality with the risk of untreated illness. Epilepsy and many other illnesses for which anticonvulsants are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. If suicidal thoughts or behavior emerge during anticonvulsant therapy, the clinician should consider whether these symptoms may be related to the illness being treated.
Respiratory Depression: Serious, life threatening, or fatal respiratory depression has been reported in patients receiving gabapentinoids (i.e., gabapentin and pregabalin). In the majority of cases, the drugs were used in combination with an opiate analgesic (or other CNS depressant), in patients with pre-existing respiratory risk factors (e.g., COPD), or in geriatric patients.
Because of the risk of respiratory depression when gabapentinoids are used in combination with opiate analgesics or other CNS depressants (e.g., benzodiazepines) or in the setting of underlying respiratory impairment, patients should be monitored for respiratory depression and sedation in these situations. Consideration should be given to initiating pregabalin therapy at the lowest dosage and titrating the dosage carefully; appropriate dosage adjustments should be made in patients with renal impairment and those undergoing hemodialysis. Patients should be advised to seek immediate medical attention if signs or symptoms of respiratory depression occur. Management of respiratory depression may include supportive measures and reduction or withdrawal of CNS depressants, including pregabalin. If the decision is made to discontinue pregabalin, dosage should be reduced gradually.
Dizziness and Somnolence: Pregabalin may cause dizziness and somnolence. These adverse effects occurred more frequently at higher doses and, in some cases, persisted throughout therapy.
Discontinuance of Therapy: As with all anticonvulsant agents, there is a potential for increased seizure frequency when pregabalin therapy is withdrawn abruptly. When discontinuing pregabalin therapy, dosage should be reduced gradually over at least 1 week. Abrupt or rapid discontinuance of pregabalin has been associated with symptoms suggestive of physical dependence (e.g., insomnia, nausea, headache, anxiety, hyperhidrosis, diarrhea).
Peripheral Edema: Pregabalin may cause peripheral edema. In short term clinical trials of patients without clinically important cardiac or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications (e.g., hypertension, congestive heart failure). Peripheral edema was not associated with deterioration of renal or hepatic function.
Concomitant use of pregabalin with a thiazolidinedione antidiabetic agent has been associated with a greater risk of developing weight gain and peripheral edema than use of either drug alone.
Because there are limited data regarding use of pregabalin in patients with New York Heart Association (NYHA) class III or IV heart failure, the drug should be used with caution in these patients.
Weight Gain: Pregabalin may cause weight gain. Pregabalin-associated weight gain appeared to be related to dosage and duration of exposure; however, weight gain did not appear to be associated with baseline body mass index (BMI), gender, or age and 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 such weight gain have not been elucidated. In addition, while the effects of pregabalin-associated weight gain on glycemic control have not been systematically assessed in controlled and longer term open label clinical trials in diabetic patients, pregabalin therapy did not appear to be associated with loss of glycemic control.
Carcinogenicity: Possible carcinogenicity of pregabalin (e.g., hemangiosarcoma) has been demonstrated in animals.
In clinical studies across various patient populations, comprising 6396 patient years of exposure in those 12 years of age or older, new or worsening pre-existing tumors were reported in 57 patients; however, a causal relationship to the drug has not been established.
Ocular Effects: Patients receiving pregabalin should inform their clinician if any changes in vision occur. If visual disturbance persists, further ophthalmologic assessment should be considered, while more frequent assessment should be considered in patients who already are monitored for ocular conditions.
Creatine Kinase Elevations: In clinical trials in adults, increases in serum creatinine kinase (CK)), creatine phosphokinase, (CPK) concentrations at least 3 times the upper limit of normal have been reported in 1.5 or 0.7% of patients receiving pregabalin or placebo, respectively.
Rhabdomyolysis has been reported rarely in pre-marketing clinical trials. However, a definite causal relationship between these musculoskeletal effects and the drug has not been fully elucidated because the cases had documented factors that may have caused or contributed to these events.
Pregabalin treatment should be discontinued if myopathy is diagnosed or suspected or if markedly elevated CK (CPK) concentrations occur.
Thrombocytopenia: In controlled clinical trials in adults, potentially clinically important decreases in platelet count (thrombocytopenia; defined as 20% below baseline value and less than 150,000/mm³) have been reported in 3 or 2% of patients receiving pregabalin or placebo, respectively. Pregabalin treated patients experienced a mean maximal decrease in platelet count of 20,000/mm³ compared with 11,000/mm³ in placebo recipients. Severe thrombocytopenia with a platelet count less than 20,000/mm³ has been reported in at least one patient who received pregabalin. In randomized controlled trials, pregabalin was not associated with an increase in bleeding-related adverse effects.
PR Interval Prolongation: Prolongation of the PR interval (mean increase: 3-6 msec) has been reported in adults receiving pregabalin dosages of at least 300 mg daily. Subgroup analyses in a limited number of patients suggest that those with preexisting PR prolongation at baseline or those receiving drugs that prolong the PR interval do not appear to have an increased risk for developing prolongation of the PR interval.
Abuse Potential and Dependence: In controlled clinical studies using conventional pregabalin, 4 or 1% of patients receiving the drug or placebo, respectively, reported euphoria as an adverse event; in some patient populations studied, the rate of euphoria was higher and ranged from 1-12%. In clinical studies, abrupt or rapid discontinuance of pregabalin has resulted in withdrawal symptoms (e.g., insomnia, nausea, headache, diarrhea).
Pregabalin is not known to be active at receptor sites associated with drugs of abuse. However, the drug is subject to control as a dangerous drug.
As with any CNS active drug, clinicians should carefully evaluate patients for a history of drug abuse and observe them for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug seeking behavior).
This medicine contains lactose.
Patients with lactose intolerance should not take this medicine.

Pregnancy: Pregnancy category C: There are no adequate and well-controlled studies of pregabalin in pregnant women; however, based on animal studies, pregabalin may cause fetal harm.
The definition is one of the following. Animal studies have shown a harmful effect such as teratogenic, embrycidal or others. There are no well-controlled studies in pregnant women or both pregnant women studies and animal studies. Potential benefits may warrant use of the drug in pregnant women despite potential risks.
Lactation: Pregabalin is distributed into human milk at steady state concentrations approximately 76% of those in maternal plasma. Following administration of maternal dosages of 300 mg daily, the estimated average infant dose of pregabalin from breast milk is 0.31 mg/kg daily (approximately 7% of the maternal dose). Because of the potential for tumorigenicity, breastfeeding is not recommended during pregabalin therapy.

Very common: >10%.
Cardiovascular: Peripheral edema.
Endocrine & metabolic: Weight gain.
Gastrointestinal: Xerostomia.
Nervous system: Dizziness, drowsiness, fatigue, headache.
Ophthalmic: Blurred vision, visual field loss.
Common: 1-10%.
Cardiovascular: Chest pain, edema, facial edema, hypertension, hypotension.
Dermatologic: Contact dermatitis, ecchymoses, pressure ulcer.
Endocrine & metabolic: Decreased libido, fluid retention, hypoglycemia.
Gastrointestinal: Abdominal distension, abdominal pain, constipation, diarrhea, flatulence, gastroenteritis, increased appetite, nausea, sialorrhea, viral gastroenteritis, vomiting.
Genitourinary: Erectile dysfunction, impotence, urinary frequency, urinary incontinence, urinary tract infection.
Hematologic & oncologic: Thrombocytopenia (including severe thrombocytopenia).
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase.
Hypersensitivity: Hypersensitivity reaction.
Infection: Infection, viral infection.
Nervous system: Abnormal gait, abnormality in thinking, amnesia, anorgasmia, ataxia, balance impairment, confusion, depersonalization, disorientation, disturbance in attention, euphoria, feeling abnormal, hypertonia, hypoesthesia, insomnia, intoxicated feeling, lethargy, memory impairment, myasthenia, nervousness, neuropathy, pain, paresthesia, sedated state, speech disturbance, stupor, twitching (includes myokymia), vertigo.
Neuromuscular & skeletal: Arthralgia, asthenia, increased creatine phosphokinase in blood specimen, joint swelling, lower limb cramp, muscle spasm, tremor.
Ophthalmic: Conjunctivitis, decreased visual acuity, diplopia, eye disease, nystagmus disorder, visual disturbance.
Otic: Otitis media, tinnitus.
Respiratory: Bronchitis, dyspnea, flu-like symptoms, nasopharyngitis, pharyngolaryngeal pain, pneumonia, respiratory tract infection, sinusitis.
Miscellaneous: Accidental injury, fever.
Uncommon: <1%.
Cardiovascular: Cardiac failure, depression of ST segment on ECG, orthostatic hypotension, palpitations, retinal vascular disease, shock, syncope, tachycardia, thrombophlebitis, ventricular fibrillation.
Dermatologic: Alopecia, cellulitis, cutaneous nodule, dermal ulcer, eczema, erythema of skin, exfoliative dermatitis, lichenoid dermatitis, nail disease, pustular rash, skin atrophy, skin blister, skin necrosis, skin photosensitivity, skin rash, Stevens-Johnson syndrome, subcutaneous nodule, urticaria, vesiculobullous dermatitis, xeroderma.
Endocrine & metabolic: Albuminuria, decreased glucose tolerance, glycosuria, increased libido.
Gastrointestinal: Ageusia, aphthous stomatitis, cholecystitis, cholelithiasis, colitis, dry mucous membranes, dysgeusia, dysphagia, esophageal ulcer, esophagitis, gastritis, gastrointestinal hemorrhage, hiccups, increased serum lipase, melena, oral mucosa ulcer, oral paresthesia, pancreatitis, periodontal abscess.
Genitourinary: Ejaculatory disorder, oliguria, pelvic pain, proteinuria, retroperitoneal fibrosis, urate crystalluria, urinary retention, urine abnormality, uterine hemorrhage.
Hematologic & oncologic: Anemia, eosinophilia, granuloma, hemophthalmos, hypochromicanemia, hypoprothrombinemia, increased neutrophils, leukocytosis, leukopenia, lymphadenopathy, myelofibrosis, nonthrombocytopenic purpura, petechial rash, polycythemia, purpuric rash, rectal hemorrhage, thrombocythemia (rare).
Hepatic: Ascites.
Hypersensitivity: Angioedema.
Infection: Abscess.
Local: Local inflammation (coccygodynia).
Nervous system: Abnormal dreams, agitation, apathy, aphasia, cerebellar syndrome, chills, cognitive dysfunction, cogwheel rigidity, delirium, delusion, drug dependence, dysarthria, dysautonomia, dystonia, encephalopathy, extraocular palsy, extrapyramidal reaction, hallucination, hangover effect, hostility, hypoalgesia, hyperalgesia, hyperesthesia, hypotonia, impaired consciousness, irritability, malaise, myoclonus, neuralgia, psychomotor disturbance, sciatica, self-inflicted intentional injury, sleep disorder, trismus, yawning.
Neuromuscular & skeletal: Bradykinesia, dyskinesia, hyperkinetic muscle activity, hypokinesia, joint stiffness, neck stiffness.
Ophthalmic: Accommodation disturbance, blindness, iritis, miosis, mydriasis, night blindness, periorbital edema, photophobia.
Renal: Acute renal failure, glomerulonephritis, nephritis, nephrolithiasis, pyelonephritis.
Respiratory: Apnea, pulmonary edema.
Frequency not defined: Cardiovascular: Prolongation P-R interval on ECG.
Neuromuscular & skeletal: Rhabdomyolysis.
Post-marketing: Dermatologic: Maculopapular rash, toxic epidermal necrolysis (rare <1%).
Endocrine & metabolic: Gynecomastia.
Immunologic: Drug reaction with eosinophilia and systemic symptoms (rare <1%).
Respiratory: Respiratory depression.

Drugs affecting hepatic microsomal enzymes: Based on results of in vitro studies, pregabalin does not appear to inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 or induce CYP1A2 or CYP3A4.
Increased metabolism of concomitantly administered CYP1A2 substrates (e.g., caffeine, theophylline) or CYP3A4 substrates (e.g., midazolam, testosterone) is not anticipated.
Since pregabalin undergoes negligible metabolism in humans, pharmacokinetics of the drug are unlikely to be affected by other agents through metabolic interactions.
Drugs that cause constipation: Concomitant use of pregabalin and drugs that can cause constipation (e.g., opiate analgesics) has been associated with adverse events related to reduced lower gastrointestinal (GI) tract function (e.g., intestinal obstruction, paralytic ileus, constipation).
Protein bound Drugs: Because pregabalin does not bind to plasma proteins, pharmacokinetic interactions with drugs that are highly protein bound are unlikely.
Alcohol: Although a pharmacokinetic interaction has not been observed with pregabalin and alcohol, additive effects on cognitive and gross motor functioning have occurred; however, concomitant use of pregabalin and alcohol did not result in any clinically important effects on respiration. Use of alcohol should be avoided in patients receiving pregabalin.
Angiotensin converting enzyme inhibitors: Potential pharmacologic interaction with ACE inhibitors (e.g., increased risk of developing angioedema).
Anticonvulsants: Pharmacokinetic interactions have not been observed when pregabalin was used concomitantly with phenytoin, carbamazepine, valproate, lamotrigine, phenobarbital, or topiramate.
Concomitant administration of gabapentin with pregabalin did not alter pharmacokinetics of gabapentin, although the rate, but not extent, of absorption of pregabalin was decreased slightly.
Tiagabine does not appear to affect the pharmacokinetics of pregabalin.
Antidiabetic agents: Glyburide, insulin, and metformin do not appear to affect the pharmacokinetics of pregabalin.
Concomitant use of pregabalin and thiazolidinediones may increase the risk of weight gain and peripheral edema, possibly exacerbating or causing heart failure. Caution is advised when these drugs are used concomitantly.
CNS depressants: Additive CNS and respiratory depressant effects can occur with concurrent use of pregabalin and CNS depressants, including opiates and benzodiazepines. If pregabalin is used concomitantly with other CNS depressants, pregabalin should be initiated with the lowest dosage and titrated carefully.
Erythromycin: Concomitant administration of a single dose of pregabalin (as the extended-release tablet) and erythromycin resulted in a 17% decrease in systemic exposure of pregabalin.
Furosemide: Furosemide does not appear to affect the pharmacokinetics of pregabalin.
Lorazepam: Although a pharmacokinetic interaction has not been observed, additive effects on cognitive and gross motor functioning have occurred when pregabalin was administered concomitantly with lorazepam; concomitant use of these drugs did not result in any clinically important effects on respiration.
Opiates: Additive CNS and respiratory depressant effects can occur with concurrent use of pregabalin and opiates. If pregabalin is used concomitantly with opiates, pregabalin should be initiated with the lowest dosage and titrated carefully.
In addition, events related to reduced lower GI function (e.g., intestinal obstruction, paralytic ileus, constipation) have been reported during post marketing experience in patients taking pregabalin concomitantly with drugs that have the potential to produce constipation, such as opiates.
Oxycodone: Although a pharmacokinetic interaction has not been observed, additive effects on cognitive and gross motor functioning have occurred when pregabalin was administered concomitantly with oxycodone; concomitant use of these drugs did not result in any clinically important effects on respiration.
Oral contraceptives: Concomitant administration of pregabalin and an oral contraceptive containing norethindrone and ethinyl estradiol in healthy individuals did not affect the pharmacokinetics of either component of the oral contraceptive.

Store below 30°C.

Anticonvulsants / Anxiolytics / Drugs for Neuropathic Pain

N02BF02 - pregabalin ; Belongs to the class of gabapentinoids. Used to relieve pain and other conditions.

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