GABALYR-25 - Capsule: each capsule contains 25 mg Pregabalin.

GABALYR-50 - Capsule: each capsule contains 50 mg Pregabalin.

GABALYR-75 - Capsule: each capsule contains 75 mg Pregabalin.

GABALYR-100 - Capsule: each capsule contains 100 mg Pregabalin.

GABALYR-150 - Capsule: each capsule contains 150 mg Pregabalin.

GABALYR-200 - Capsule: each capsule contains 200 mg Pregabalin.

GABALYR-300 - Capsule: each capsule contains 300 mg Pregabalin.

lactose monohydrate, cornstarch, talc.

 

GABALYR (pregabalin) binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues, and inhibits excitatory neurotransmitter release . Although structurally related to GABA, it does not bind to GABA or benzodiazepine receptors. Pregabalin may also affect descending noradrenergic and serotonergic pain transmission pathways from the brainstem to the spinal cord.

Absorption and Distribution:

Following oral administration of  GABALYR capsules under fasting conditions, peak plasma concentrations occur within 1.5 hour following both single and multiple dose administration (3 hours with food).

Pregabalin oral bioavailability is ≥90% and is independent of dose. Pregabalin does not bind to plasma proteins.

Metabolism and Elimination:

 Pregabalin undergoes negligible metabolism in humans. Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug 90% with a mean elimination half-life of 6.3 hours in subjects with normal renal function.

 

GABALYR is indicated for:

-  Management of neuropathic pain associated with diabetic peripheral neuropathy or with spinal cord injury.

-  Management of postherpetic neuralgia.

-  Adjunctive therapy for adult patients with partial onset seizures.

 - Management of fibromyalgia.

 

- Neuropathic pain associated with diabetic peripheral neuropathy: Administer in 3 divided doses per day, Begin dosing at 150 mg/day, and may be increased to a maximum of 300 mg/day within 1 week.

- Neuropathic pain associated with spinal cord injury: Administer in 2 divided doses per day, Begin dosing at 150 mg/day, and may be increased to a maximum of 300 mg/day within 1 week. Maximum dose of 600 mg/day after 2-3 weeks.

- Postherpetic neuralgia: Administer in 2 or 3 divided doses per day, begin dosing at 150 mg/day, and may be increased to 300 mg/day within 1 week. Maximum dose of 600 mg/day after 2-4 weeks.

- Adjunctive Therapy for Adult Patients with Partial Onset Seizures:

Administer in 2 or 3 divided doses per day, begin dosing at 150 mg/day. Maximum dose of 600 mg/day after 2-4 weeks.

- Fibromyalgia: Administer in 2 divided doses per day. Begin dosing at 150 mg/day, and may be increased to 300 mg/day within 1 week. Maximum dose of 450 mg/day.

- Dose should be adjusted in patients with reduced renal function.

 

Supplementary dosage following hemodialysis (mg):

Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg.

Patients on the 25–50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg.

Patients on the 50–75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg.

Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg.

 

- GABALYR is contraindicated in patients hypersensitive to pregabalin or any of its other components. Cases of angioedema allergic have been reported in patients taking pregablin.

 

-  Angioedema (e.g. swelling of the face, mouth, Tongue, lips, gums, throat, larynx and neck) can occur during initial and chronic treatment with GABALYR so it should be taken with caution in patients taking other drugs which can cause edema concomitantly e.g., angiotensin converting enzyme inhibitors. There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. GABALYR should be discontinued immediately in patients with these symptoms.

- Suicidal behavior and Ideation:

Antiepileptic drugs (AEDs), inducing GABALYR, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Risk observed as early as 1 week after initiation.

- Hypersensitivity reactions (e.g. hives, dyspnea, and wheezing) can occur. In this case GABALYR should be discontinued immediately.

- Increased seizure frequency may occur in patients with seizure disorders if GABALYR is rapidly discontinued. So that GABALYR should be withdraw gradually over a minimum of 1 week.

 -GABALYR may cause peripheral edema. use with caution in patients with heart failure (NYHA Class III or IV) due to limited data in this patient population. In addition, effect on weight gain/edema may be additive with the thiazolidinedione class of antidiabetic agents, particularly in patients with prior cardiovascular disease.

- GABALYR may cause dizziness and somnolence and impair patients' ability to drive or operate machinery, it occurs shortly after initiation and occurs more frequently at higher doses.

- GABALYR treatment may cause weight gain; weight gain generally associated with dose and duration (average weight gain was 5.2 kg for patients receiving pregabalin for ≥2 years).

- Ophtalmological Effects: A higher proportion of patients treated with GABALYR reported blurred vision (7%), patients should be informed that if changes in vision occur, they should notify their physician.

- Creatine Kinase Elevations: GABALYR treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value 60U/L for GABALYR-treated patients and 28U/L for the placebo patients. The relationship between these myopathy events and GABALYR is not completely understood because the cases and documented factors that may have caused or contributed to these events. Prescribers should instruct patients to promptly report unexplained muscle pain,  tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. GABALYR treatment should be discontinued if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.

- Decreased Platelet Count: GABALYR treatment was associated with decrease in platelet count. GABALYR–treated subjects experienced a mean maximal decrease in platelet count of 20*103/µL, compared to 11*103/µL in placebo patients. GABALYR was not associated with an increase in bleeding-related adverse reactions.

- PR interval: May cause mild prolongation of PR interval. Clinical significance unknown.

- Cardiovascular disease: Use with caution in patients with severe cardiovascular disease, including heart failure; weight gain and/or peripheral edema may occur.

- Sedatives: Effects with other sedative drugs or ethanol may be potentiated.

 

Since GABALYR is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans, and does not bind to plasma proteins, its pharmacokinetics are unlikely to be

affected by other agents through metabolic interactions or protein binding displacement. GABALYR 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 GABALYR and commonly used antiepileptic drugs.

Antidiabetic Agents (Thiazolidinedione): Pregabalin may enhance the fluid-retaining effect of Antidiabetic Agents

CNS depressant  drugs: Pregabalin may enhance the CNS depressant effect of CNS Depressants drugs like Selective Serotonin Reuptake Inhibitors, and hydroxyzine.

 

The most common adverse reactions associated with GABALYR treatment are:

Increased appetite, weight increased, dizziness, somnolence, vertigo, euphoric mode, confusion, irritability, libido decreased, vision blurred, diplopia, vomiting, dry mouth, constipation, flatulence, erectile dysfunction, gait abnormal, feeling drunk, fatigue, edema and peripheral edema, tremor, Infection.

 

Increased incidence of fetal abnormalities, particularly skeletal malformations, were observed in animal studies.

Pregnancy: Category C.

GABALYR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

 

It is not known if pregabalin is excreted in human milk because many drugs are excreted in human milk, and because of the potential for tumorigenicity shown her.  Pregabalin in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

 

Men being treat with pregabalin ,who plant to be fathers should be informed about the potential risk of male- mediated teratogenicity.

preclinical studies in rats given pregabalin show an increase in the risk of teratogenic effect in male rats.

 

Pregabalin clearance is nearly proportional to creatinine clearance (CLcr). Dosage reduction in patients with renal dysfunction is necessary. Pregabalin is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%. For patients on hemodialysis, dosing must be modified.

 

The safety and efficacy of pregabalin in pediatric patients have not been established.

 

No overall differences in safety and efficacy were observed between these patients and younger patients.

 

Following abrupt or rapid discontinuation of GABALYR, some patients reported symptoms including insomnia, nausea, headache, or diarrhea.

 

Signs and Symptoms of Acute Overdosage in Humans:

The types of adverse reactions experienced by patients exposed to higher doses (≥900 mg) were not clinically different from those of patients administered recommended doses of GABALYR.

Treatment of Overdose:

There is no specific antidote for overdose with GABALYR. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage ,General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patients.

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.

 

GABALYR-25 - Capsule: Carton package of 10 capsules in blister.

GABALYR-50 - Capsule: Carton package of 10 capsules in blister.

GABALYR-75 - Capsule: Carton package of 10 capsules in blister.

GABALYR-100 - Capsule: Carton package of 10 capsules in blister.

GABALYR-150 - Capsule: Carton package of 10 capsules in blister.

GABALYR-200 - Capsule: Carton package of 10 capsules in blister.

GABALYR-300 - Capsule: Carton package of 10 capsules in blister.

 

Store GABALYR- Capsule at temperature between (15-30)°C away from light and moisture.