Zylin 75

Pregabalin.

ZYLIN 75: Each hard gelatin capsule contains Pregabalin 75 mg.

Pharmacology: Pharmacodynamics: Mechanism of action: Binds to alpha-2-delta subunit of voltage-gated calcium channels within the CNS and modulates calcium influx at the nerve terminals, thereby inhibiting excitatory neurotransmitter release including glutamate, norepinephrine (noradrenaline), serotonin, dopamine, substance P, and calcitonin gene-related peptide. Although structurally related to gamma aminobutyric acid (GABA), it does not bind to GABA or benzodiazepine receptors. Exerts antinociceptive and anticonvulsant activity. Pregabalin may also affect descending noradrenergic and serotonergic pain transmission pathways from the brainstem to the spinal cord.
Pharmacokinetics: Absorption: Onset of action: Pain management: Effects may be noted as early as the first week of therapy.
Bioavailability: ≥90%.
Time to peak plasma: Children ≥4 years and adolescents <17 years: 0.5 to 2 hours fasting; Median: 0.7 hours fasting (range: 0.7 to 1.5 hours), 3 hours with food.
Distribution: Volume of distribution: 0-5 L/ kg.
Protein binding: 0%.
Metabolism: Hepatic: Negligible.
Metabolite, N-methylated derivative (major): Activity not reported.
Excretion: Urine: 90% as unchanged drug; minor metabolites.
Renal clearance: 67 to 80.9 mL/min.
Dialyzable: Yes (hemodialysis), 50% removed after 4 hours dialysis treatment.
Elimination half life: Children 4 to 6 years: 3 to 4 hours.
Children ≥7 years and adolescents <17 years: 4 to 6 hours.
Adults: 6.3 hours.

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: Pregabalin is indicated for the treatment of Generalized Anxiety Disorder (GAD) in adults.
Fibromyalgia: Pregabalin is indicated for the management of fibromyalgia.

Recommended dose: The dose range is 150 to 600 mg per day given in either two or three divided doses. Pregabalin may be taken with or without food.
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 patient 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 (Cl_cr) as indicated in the table, 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 additional 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 elderly (over 65 years of age): Elderly patients may require a dose reduction of Pregabalin due to decreased renal function.
Mode of administration: Pregabalin capsules are administered orally without regard to food.
When switching from conventional preparations of pregabalin to the extended-release tablets, patients should take their usual morning dose of conventional capsules and initiate therapy with the extended-release tablets after the evening meal.
When discontinuing therapy, pregabalin should be withdrawn gradually by tapering the dosage over at least 1 week.
Patients currently receiving or beginning therapy with pregabalin and/or any other anticonvulsant for any indication should be closely monitored for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior.

Overdose and treatment: In overdose up to 15 g, no unexpected adverse reactions were reported.
In the post-marketing experience, the most commonly reported adverse events observed when Pregabalin was taken in overdose included affective disorder, somnolence, confusional state, depression, agitation, and restlessness. Seizures were also reported.
Treatment of pregabalin overdose should include general supportive measures and may include hemodialysis if necessary.
Management of mild to moderate toxicity: Treatment is symptomatic and supportive.
Management of severe toxicity: Treatment of pregabalin exposure is largely supportive in nature with careful attention to airway protection in severe cases. Hypotension is usually mild responding to intravenous fluid boluses. If hypotension persists, administer dopamine or norepinephrine. Admit all severely symptomatic patients. Treat seizures with IV benzodiazepines or barbiturates.

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

Beers Criteria: Avoid use in older adults with a history of falls or fractures (unless used for seizure or mood disorders) as syncope, impaired psychomotor function or ataxia may occur. Reduce dose in older adults with CrCl less than 60 mL/min due to increased risk of adverse CNS effects. Avoid concomitant use of 3 or more CNS-active agents in any combination as this may increase the risk of falls. Avoid concomitant use of opioids due to increased risk of severe sedation-related adverse events including respiratory depression and death (except when transitioning from opioids to gabapentin or when using gabapentin to reduce opioid dose; caution is advised).
Cardiovascular: New York Heart Association Class III and IV congestive heart failure; increased risk of peripheral edema; monitoring recommended.
Cardiovascular: Peripheral edema has been reported; increased frequency of weight gain and peripheral edema with concomitant thiazolidinedione use; monitoring recommended during concomitant thiazolidinedione use.
Cardiovascular: PR interval prolongation has been reported.
Endocrine and Metabolic: Weight gain has been reported.
Hematologic: Thrombocytopenia has been reported.
Immunologic: Angioedema, including life-threatening cases, has been reported, especially in patients with prior episode of angioedema or concurrently taking medications associated with angioedema (eg, ACE inhibitors); discontinue immediately if symptoms develop.
Immunologic: Hypersensitivity reactions, including skin redness, blisters, hives, rash, dyspnea, and wheezing, have been reported; discontinue immediately if symptoms develop.
Musculoskeletal: Creatine kinase elevations have been reported; discontinue if marked elevations occur, or if myopathy is suspected or diagnosed.
Neurologic: Significant dizziness and somnolence or sedation have been reported, including lethargy, sluggishness, and hypersomnia in patients less than 4 years old.
Ophthalmic: Vision-related events, including reduced visual acuity, visual field changes, and blurred vision have been reported.
Psychiatric: Suicidal ideation and behavior, worsening of depression, and unusual changes in mood or behavior may occur as early as 1 week following initiation; monitoring recommended.
Renal: Renal impairment (ie, CrCl less than 60 mL/min); dosage adjustment recommended.
Respiratory: Serious, life-threatening, or fatal respiratory depression has been reported both with and without coadministration of CNS depressants (eg, opioids) or in patients with underlying respiratory impairment; monitoring required for these patients, and dosage adjustment or discontinuation of pregabalin or coadministered CNS depressants may be recommended.
Withdrawal: Withdrawal seizure and other adverse effects (eg, insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea) may be precipitated by abrupt discontinuation; tapering over minimum of 1 week recommended.

Pregnancy: There are no adequate data on the use of Pregabalin in pregnant women.
Studies in animals have shown reproductive toxicity. The potential risk to humans is unknown. Therefore, Pregabalin should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the fetus. Effective contraception must be used in women of child-bearing potential.
Lactation: Pregabalin is excreted in milk or 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.

Common: Cardiovascular: Peripheral edema (3.8% to 12%).
Endocrine metabolic: Increased appetite (Adult, 5%; pediatric, 8%), Weight gain (Adult, 2.5% to 12%; pediatric, 8%).
Gastrointestinal: Constipation (4% to 8.2%), Nausea (3% to 4.9%), Xerostomia (Up to l1 %).
Neurologic: Asthenia (5% to 10%), Ataxia (3% to 15%), Dizziness (17.1% to 32%), Headache (1.9% to 7%), Incoordination (2% to 10.1%), Somnolence (Adult, 11.4% to 35.7%; pediatric, 21%), Tremor (1% to 11.2%).
Ophthalmic: Diplopia (2% to 9%).
Psychiatric: Disturbance in thinking (2% to 8%), Euphoria (2% to 6%).
Respiratory: Nasopharyngitis (8.2%).
Other: Fatigue (3.9% to 11%).
Serious: Hepatic: Jaundice.
Immunologic: Hypersensitivity reaction.
Musculoskeletal: Increased creatine kinase level (1.5% to 2.7%).
Ophthalmic: Blurred vision (Up to 10%).
Psychiatric: Suicidal thoughts.
Respiratory: Respiratory depression.
Other: Angioedema.

Metabolism/Transport effects substrate: None known.
Avoid concomitant use: Avoid concomitant use of Pregabalin with any of the following: Azelastine (Nasal); Bromperidol; Orphenadrine; Oxomemazine; Paraldehyde; Thalidomide.
Increased effect/toxicity: Pregabalin may increase the levels/effects of: Alcohol (Ethyl); Azelastine (Nasal); Blonanserin; Buprenorphine; CNS Depressants; Flunitrazepam; Hydrocodone; Methotrimeprazine; Metyrosine; Mirtazapine; Opioid Analgesics; Orphenadrine; Oxycodone; Paraldehyde; Piribedil; Pramipexole; Ropinirole; Rotigotine; Selective Serotonin Reuptake Inhibitors; Suvorexant; Thalidomide; Thiazolidinediones; Zolpidem.
The levels/effects of Pregabalin may be increased by: Alizapride; Angiotensin-Converting Enzyme Inhibitors; Brimonidine (Topical); Bromopride; Bromperidol; Cannabidiol; Cannabis; Chlormethiazole; Chlorphenesin Carbamate; Dimethindene (Topical); Doxylamine; Dronabinol; Droperidol; Hydroxyzine; Kava Kava; Lofexidine; Magnesium Sulfate; Methotrimeprazine; Minocycline; Nabilone; Oxomemazine; Perampanel; Rufinamide; Sodium Oxybate; Tapentadol; Tetrahydrocannabinol; Tetrahydrocannabinol and Cannabidiol; Trimeprazine.
Decreased effect: The levels/effects of Pregabalin may be decreased by: Mefloquine; Mianserin; Orlistat.

Store below 30°C.

Anxiolytics / Drugs for Neuropathic Pain / Anticonvulsants

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

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