Nevalin

Pregabalin.

Pregabalin 75 mg Capsule: Each capsule contains Pregabalin 75 mg.
Pregabalin 150 mg Capsule: Each capsule contains Pregabalin 150 mg.

Pharmacology: Mechanism of action: Pregabalin binds with affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues.

Neuropathic Pain: Pregabalin Capsule (Pregabalin) is indicated for the treatment of peripheral and central neuropathic pain in adults.
Epilepsy: Pregabalin Capsule is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalization.
Generalised Anxiety Disorder: Pregabalin Capsule is indicated for the treatment of Generalised Anxiety Disorder (GAD) in adults.
Fibromyalgia: Pregabalin is indicated to reduce pain in the management of fibromyalgia.

The dose range is 150 to 600 mg per day given in either two or three divided doses. Pregabalin Capsule (Pregabalin) is given with or without food.
Neuropathic Pain: The recommended starting dose for Pregabalin Capsule (Pregabalin) is 75 mg BID (150 mg/day), with or without food. Efficacy of Pregabalin was demonstrated in patients dosed in a range of 150 to 600 mg/day. For the majority of patients, 150 mg BID will be the optimal dose. Efficacy of Pregabalin has been demonstrated within the first week. However, based on individual patient response and tolerability, the dose may be increased to 150 mg BID after an interval of 3 to 7 days, and if needed, to a maximum dose of 300 mg BID after an additional week.
Epilepsy: The recommended effective starting dose for Pregabalin Capsule (Pregabalin) is 75 mg BID (150 mg/day), with or without food. Efficacy of pregabalin was demonstrated in patients dosed in a range of 150 to 600 mg/day. Efficacy of pregabalin has been demonstrated as early as 1 week. However, based on individual patient response and tolerability, the dose may be increased to 150 mg BID after 1 week and if needed, to a maximum dose of 300 mg BID after and additional week.
Generalised 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 and additional week the dosage may be increased to 450 per day. The maximum dosage 600 mg per day may be achieved after an additional week.
Fibromyalgia: The recommended dose of Pregabalin is 300 to 450 mg/day given in two divided doses. 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). Although Pregabalin was also studied at 600 mg/day, there is no view of the dose dependent adverse reactions, treatment which dose above 450 mg/day is not recommended. Because Pregabalin is eliminated primarily renal excretion, adjust the dose in patients with reduced renal function.
Discontinuation of Pregabalin: In accordance with current clinical practice, if Pregabalin Capsule (Pregabalin) has to be discontinued either in neuropathic pain or epilepsy, it is recommended this should be done gradually over a minimum of 1 week.
Patients with 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, dosage reduction in patients with compromised renal function must be individualized according to creatinine clearance (CLcr), as indicated in Table 1 determined using the following formula: see formula.


Click on icon to see table/diagram/image


For patients receiving haemodialysis, 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 haemodialysis 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.
Use in the Elderly (over 65 years of age): Elderly patients may require a dose reduction of Pregabalin due to decreased renal function.

There is limited experience with overdose of pregabalin. In overdose up to 15 g, no unexpected adverse reactions were reported. There is no specific antidote for overdose with pregabalin. Treatment of pregabalin overdose should include general supportive measures and may include haemodialysis if necessary.
The most commonly reported adverse events observed when pregabalin was taken in overdose included affective disorder, somnolence, confusional state, depression, agitation, restlessness and seizure.

Hypersensitivity to pregabalin or any of its components.

Patients with rare hereditary problems of galactose intolerance, the Lapp-Lactase deficiency or glucose-galactose malabsorption should not take this medicine.
In accordance with current clinical practice, some diabetic patients who gain weight on Pregabalin treatment may need to adjust hypoglycemic medications.
There have been reports of hypersensitivity reactions, including cases of angioedema. Pregalabin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.
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 post-marketing 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 medication.
Transient visual blurring and other changes in visual acuity have been reported in patients treated with pregabalin. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.
There are insufficient data for withdrawal of concomitant antiepileptic medicinal products, once seizures control with pregabalin in the add-on situation has been reached, in order to reach monotherapy on pregabalin.
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, diarrhea, hyperhidrosis, flu syndrome, nervousness, depression, pain, sweating, and dizziness. The patients should be informed about this at the start of treatments.
Pregabalin is not known to be active at receptor sites associated with drugs of abuse. Cases of misuse or abuse have been reported in the post-marketing database. As with any CNS active drug, carefully evaluate patients for history of drug misuse and abuse and observe them for signs of pregabalin abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).
Although the effects of discontinuation on the reversibility of renal failure have not been systematically studied, improved renal function following discontinuation or dose reduction of pregabalin has been reported.
Concerning discontinuation of long-term treatment of pregabalin there are no data of incidence and severity of withdrawal symptoms in relation to duration of use and dosage of pregabalin.
Although there has been no causal relationship identified between exposure to pregabalin and congestive heart failure, there have been reports of congestive heart failure in some patients receiving pregabalin. 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. Because there are limited data on congestive heart failure patients, pregabalin should be used with caution in these patients.
In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse events in general, CNS adverse events and especially somnolence was increased. This may be attributed to an additive effect due to concomitant medication (e.g., anti- spasticity agents) needed for this condition. This should be considered when prescribing pregabalin in this condition.
Effect on ability to drive and use machines: Pregabalin Capsule may have minor or moderate influence on the ability to drive and use machines. Pregabalin may cause dizziness and somnolence and therefore may influence the ability to drive or use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether this medication affects their ability to perform these activities.

Pregnancy: There are no adequate data on the use of Pregabalin in pregnant women. Pregabalin Capsule should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the fetus.
Lactation: Pregabalin is excreted in the milk of lactating women. As the safety of Pregabalin in infants is not known, breast-feeding is not recommended during treatment with pregabalin. A decision must be made whether to discontinue breast-feeding or to discontinue from pregabalin therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. The other adverse reactions listed as follows: Infection and Infestation: Nasopharyngitis.
Blood and lymphatic system disorder: Neutropenia.
Metabolism and nutrition disorder: Appetite Increased, Anorexia, hypoglycaemia.
Psychiatric disorder: Euphoric mood, confusion, irritability, depression, disorientation, insomnia, libido decreased, Hallucination, restlessness, agitation, depressed mood, elevated mood, mood swings, depersonalization, abnormal dreams, word finding difficulty, libido increased, anorgasmia.
Nervous system disorder: Panic attack, disinhibition, apathy, Dizziness somnolence, Ataxia, coordination abnormal, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoesthesia, sedation, balance disorder, lethargy, Syncope, myoclonus, psychomotor hyperactivity, dyskinesia, dizziness postural, intention tremor, nystagmus, cognitive disorder, speech disorder, hyporeflexia, hyperaesthesia, burning sensation, Stupor, parsmia, hypokinesia, ageusia, dysgraphia, mental impairment.
Eye disorder: Vision blurred, diplopia, Peripheral vision loss, visual disturbance, eye swelling, visual field defect, visual acuity reduced, eye pain, asthenopia, photopsia, dry eye lacrimation increased, eye irritation, Oscillopsia, altered visual depth perception, mydriasis, strabismus, visual brightness, keratitis.
Ear and labyrinth disorder: Vertigo, Hyperacusis.
Cardiac disorder: Tachycardia, atrioventricular block first degree, sinus bradycardia, Sinus tachycardia, sinus arrhythmia, congestive heart failure.
Vascular disorder: Hypotension, hypertension, hot flushes, flushing, peripheral coldness.
Respiratory, thoracic and mediastinal disorder: Dyspnea, epistaxis, cough, nasal congestion, rhinitis, snoring, Throat tightness, nasal dryness, pulmonary oedema.
Gastrointestinal disorder: Vomiting, constipation, flatulence, abdominal distension, dry mouth, Gastroesophageal reflux disease, salivary hypersecretion, hypoesthesia oral, Ascites, pancreatitis, dysphagia, nausea, diarrhoea, swollen tongue.
Skin and subcutaneous tissue disorder: Rash popular, urticarial, sweating, Cold sweat, Steven Johnson syndrome, pruritus, face swelling.
Musculoskeletal and connective tissue disorder: Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm, Joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness, Rhabdomyolysis.
Renal and urinary disorder: Urinary incontinence, dysuria, Renal failure, oliguria, urinary retention.
Reproductive system and breast disorder: Erectile dysfunction, sexual dysfunction, ejaculation delayed, dysmenorrhoea, Breast pain, amenorrhea, breast discharge, breast enlargement, gynecomastia.
General disorder and administration site conditions: Oedema peripheral, oedema, gait abnormal, fall, feeling drunk, feeling abnormal, fatigue, Generalized oedema, chest tightness, pain pyrexial, thirst, chill, asthenia, malaise.
Investigation: Weight increased, Blood creatine phosphokinase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood glucose increased, platelet count decreased, blood potassium decreased, weight decreased, White blood cell count decreased, blood creatinine increased.
Immune System Disorders: Hypersensitivity, angioedema, allergic reaction.
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: allergic reaction, hypersensitivity, pruritus, insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, nervousness, depression, pain, sweating, and dizziness. The patients should be informed about this at the start of treatments.
Concerning discontinuation of long-term treatment of pregabalin there are no data of incidence and severity of withdrawal symptoms in relation to duration of use and dosage of pregabalin.

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.
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 antibiotics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance.
Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl estradiol does not influence the steady-state pharmacokinetics of either agent. Pregabalin may potentiate the effects of ethanol and lorazepam. Multiple oral doses of pregabalin co-administered with oxycodone, lorazepam, or ethanol did not result in clinically important effects on respiration. Pregabalin appears to additive in the impairment of cognitive and gross motor function caused by oxycodone.
There are reports of respiratory failure and coma in patients taking pregabalin and CNS depressant medications. There are 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 analgesic.

Store at temperature below 30°C, protected from light.

Anticonvulsants

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

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