GABAFIX

Gabafix contains Pregabalin IP 50 mg/ 75 mg.

Pack Size: 10*10 Blisters

• Neuropathic pain: GABAFIX is indicated for the treatment of peripheral and central neuropathic pain in adults.
  
• Epilepsy: GABAFIX is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalization.
  
• Generalized Anxiety Disorder: GABAFIX is indicated for the treatment of Generalized Anxiety Disorder (GAD) in adults.

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

• Neuropathic Pain: GABAFIX 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: GABAFIX 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.
  
• 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. GABAFIX 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.
  
• Patients with Renal Impairment: GABAFIX is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As pregabalin clearance is directly proportional to creatinine, dose 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:

GABAFIX is removed effectively from plasma by hemodialysis (50% of drug in 4 hours). For patients receiving hemodialysis, the GABAFIX 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.

Table 1. Pregabalin Dose Adjustment Based On Renal Function

Creatinine clearance (CLcr)

(mL/min)

Total pregabalin daily dose *

Dose regimen

Starting dose

(mg/day)

Maximum dose

(mg/day)

≥ 60

150

600

BID or TID

≥30- <60

75

300

BID or TID

≥15 - <30

25 – 50

150

Once Daily or BID

< 15

25

75

Once Daily

Supplementary dosage following hemodialysis (mg)

25

100

Single dose+

Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose

+ Supplementary dose is a single additional dose

• Patients with Hepatic Impairment: No dose adjustment is required for patients with hepatic impairment.
• Elderly (Over 65 Years of Age) Population: Elderly patients may require a dose reduction of pregabalin due to a decreased renal function.

• GABAFIX may be taken with or without food. Pregabalin is for oral use only.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Diabetic Patients: In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycemic medicinal products.
• Hypersensitivity Reactions: Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.
• Renal failure: Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse 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.
• Reduced Lower Gastrointestinal Tract Function: When pregabalin and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and elderly).
• 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 behavior have been reported).
• Encephalopathy: Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.

• 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. Pregabalin 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.

Since GABAFIX 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.
• 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 post marketing experience, there are reports of respiratory failure and coma in patients taking pregabalin and other 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 pharmacodynamics interaction studies were conducted in elderly volunteers. Interaction studies have only been performed in adults.
• Effects on Ability to Drive and Use Machines: Pregabalin 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 medicinal product affects their ability to perform these activities.

In the table below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed by class and frequency (very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System Organ Class

Adverse Drug Reactions

infections and infestations

Common

Nasopharyngitis

Blood and lymphatic system disorders

Uncommon

Neutropenia

Immune system disorders

Uncommon

Hypersensitivity

Rare

Angioedema, allergic reaction

Metabolism and nutrition disorders

Common

Appetite increased

Uncommon

Anorexia, hypoglycaemia

Psychiatric disorders

Common

Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased

Uncommon

Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalization, word finding difficulty, abnormal dreams, libido increased, anorgasmia, apathy

Rare

Disinhibition

Nervous system disorders

Very Common

Dizziness, somnolence, headache

Common

Ataxia, coordination abnormal, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paresthesia, hypo aesthesia, sedation, balance disorder, lethargy

Uncommon

Syncope, stupor, myoclonus, loss of consciousness, psychomotor hyperactivity, dyskinesia, dizziness postural, intention tremor, nystagmus, cognitive disorder, mental impairment, speech disorder, hyporeflexia, hyperaesthesia, burning sensation, ageusia, malaise

Rare

Convulsions, parosmia, hypokinesia, dysgraphia

Eye disorders

Common

Vision blurred, diplopia

Uncommon

Peripheral vision loss, visual disturbance, eye swelling, visual field defect, visual acuity reduced, eye pain, asthenopia, photopsia, dry eye, lacrimation increased, eye irritation

Rare

Vision loss, keratitis, oscillopsia, altered visual depth perception, mydriasis, strabismus, visual brightness

Ear and labyrinth disorders

Common

Vertigo

Uncommon

Hyperacusis

Cardiac disorders

Uncommon

Tachycardia, atrioventricular block first degree, sinus bradycardia, congestive heart failure

Rare

QT prolongation, sinus tachycardia, sinus arrhythmia

Vascular disorders

Uncommon

Hypotension, hypertension, hot flushes, flushing, peripheral coldness

Respiratory, thoracic and mediastinal disorders

Uncommon

Dyspnoea, epistaxis, cough, nasal congestion, rhinitis, snoring, nasal dryness

Rare

Pulmonary edema, throat tightness

Gastrointestinal disorders

Common

Vomiting, nausea, constipation, diarrhoea, flatulence, abdominal distension, dry mouth

Uncommon

Gastro esophageal reflux disease, salivary hyper secretion, hypo aesthesia oral

Rare

Ascites, pancreatitis, swollen tongue, dysphagia

Skin and subcutaneous tissue disorders

Uncommon

Rash popular, urticaria, hyperhidrosis, pruritus

Rare

Stevens Johnson syndrome, cold sweat

Musculoskeletal and connective tissue disorders

Common

Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm

Uncommon

Joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness

Rare

Rhabdomyolysis

Renal and urinary disorders

Uncommon

Urinary incontinence, dysuria

Rare

Renal failure, oliguria, urinary retention

Reproductive system and breast disorders

Common

Erectile dysfunction

Uncommon

Sexual dysfunction, ejaculation delayed, dysmenorrhea, breast pain

Rare

Amenorrhea, breast discharge, breast enlargement, gynaecomastia

General disorders and administration site conditions

Common

Edema peripheral, edema, gait abnormal, fall, feeling drunk, feeling abnormal, fatigue

Uncommon

Generalized edema, face edema, chest tightness, pain, pyrexia, thirst, chills, asthenia

Investigations

Common

Weight increased

Uncommon

Blood creatine phosphokinase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood glucose increased, platelet count decreased, blood creatinine increased, blood potassium decreased, weight decreased

Rare

White blood cell count decreased

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, diarrhoea, 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.

Pharmacodynamics Properties

Pharmacokinetic Properties

Pregabalin steady-state pharmacokinetics are similar in healthy volunteers, patients with epilepsy receiving anti-epileptic drugs and patients with chronic pain.

• Pharmacotherapeutic Group: Antiepileptic, other antiepileptic.
• calcium channels in the central nervous system.
• Absorption: Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations occurring within 1 hour following both single and multiple dose administration. Pregabalin oral bioavailability is estimated to be ≥ 90% and is independent of dose. Following repeated administration, steady state is achieved within 24 to 48 hours. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25-30% and a delay in tmax to approximately 2.5 hours. However, administration of pregabalin with food has no clinically significant effect on the extent of pregabalin absorption.
  
• Distribution: In preclinical studies, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the apparent volume of distribution of pregabalin following oral administration is approximately 0.56 l/kg. Pregabalin is not bound to plasma proteins.
  
• Biotransformation: Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabelled pregabalin, approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, there was no indication of racemization of pregabalin S -enantiomer to the R-enantiomer.
  
• Elimination: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Pregabalin mean elimination half-life is 6.3 hours. Pregabalin plasma clearance and renal clearance are directly proportional to creatinine clearance (see section 5.2 Renal impairment). Dose adjustment in patients with reduced renal function or undergoing hemodialysis is necessary.

This medicinal product does not require any special storage conditions