Nervica

Pregabalin.

Each capsule contains Pregabalin 25 mg, 50 mg, 75 mg and 150 mg, respectively.

PHARMACOLOGY: PHARMACODYNAMICS: Pregabalin is a gamma-aminobutyric acid (GABA) analog that strongly binds to the alpha₂-delta site (α₂-δ; a subunit of voltage-gated calcium channels) in CNS tissues. The exact mechanism of action is not fully understood.
Binding to the alpha₂-delta subunit may be involved in pregabalin's effects on neuropathic pain and seizure control. Pregabalin reduces the calcium-dependent release of pro-nociceptive neurotransmitters, possibly by modulation of calcium channel function. Pregabalin may also interact with descending noradrenergic and serotonergic pathways in the brainstem that modulate pain transmission in the spinal cord.
PHARMACOKINETICS: Absorption: Tmax, adults: 0.7 to 1.5 hours.
Tmax, pediatrics: 0.5 to 2 hours (fasted state).
Bioavailability: 90% or greater.
Effect of food: No clinically relevant effect on total absorption, increase Tmax to 3 hours.
Onset of action: Pain management: Effects may be noted as early as the first week of therapy.
Distribution: Protein binding: 0%.
Volume of distribution (Vd): 0.5 L/kg.
Metabolism: Hepatic: Negligible.
Metabolite, N-methylated derivative (major): Activity not reported.
Excretion: Renal clearance: 67 to 80.9 mL/min.
Renal: 90% unchanged in the urine.
Dialyzable: approximately 50% removed after a 4-hour dialysis treatment.
Elimination Half Life: Adults: 6.3 hours.
Pediatrics: 3 to 4 hours (up to 6 years); 4 to 6 hours (7 years or older).

Neuropathic pain: Treatment of central and peripheral neuropathic pain in adults; Treatment of neuropathic pain associated with diabetic peripheral neuropathy; Treatment of neuropathic pain associated with spinal cord injury; Treatment of postherpetic neuralgia.
Epilepsy: Adjunctive therapy in patients with partial-onset seizures with or without secondary generalization.
Generalized anxiety disorder: Treatment of generalized anxiety disorder (GAD) in adults.
Fibromyalgia: Management of fibromyalgia.

Neuropathic pain: Initial: 150 mg/day. Based on individual response and tolerability, dosage may be increased to 300 mg/day after an interval of 3 to 7 days, and if needed, to a maximum dose of 600 mg/day after an additional 7-day interval.
Diabetic peripheral neuropathy: Initial 150 mg/day in 3 divided dose; may increase to maximum dose of 300 mg/day in 3 divided doses within 1 week based on efficacy and tolerability.
Neuropathic pain associated with spinal cord injury: Initial 75 mg twice daily; may increase within 1 week based on response and tolerability to 150 mg twice daily; after 2 to 3 weeks, may further increase up to a maximum of 600 mg/day (300 mg twice daily).
Postherpetic neuralgia: Initial 150 mg/day in divided doses (75 mg twice daily or 50 mg 3 times daily); may increase to 300 mg/day within 1 week based on response and tolerability; after 2 to 4 weeks, may further increase up to the maximum dose of 600 mg/day in divided doses (300 mg twice daily or 200 mg 3 times daily).
Epilepsy: Initial 150 mg/day in 2 to 3 divided doses, may increase based on response and tolerability at weekly intervals up to a maximum dose of 600 mg/day.
Generalized anxiety disorder: Initial 150 mg/day in 2 to 3 divided doses; may increase based on response and tolerability at weekly intervals in increments of 150 mg/day up to a usual dose of 300 mg/day. May further increase up to 600 mg/day.
Fibromyalgia: Initial 75 mg twice daily; may increase to 150 mg twice daily within 1 week based on response and tolerability; maximum dose 450 mg/day.
Dosage adjustment in renal impairment: See table.

Click on icon to see table/diagram/image

Supplementary dosage post-hemodialysis (as a single additional dose): 25 mg/day schedule: Single supplementary dose of 25 mg or 50 mg.
25 to 50 mg/day schedule: Single supplementary dose of 50 mg or 75 mg.
50 to 75 mg/day schedule: Single supplementary dose of 75 mg or 100 mg.
75 mg/day schedule: Single supplementary dose of 100 mg or 150 mg.
Dosage adjustment in Hepatic impairment: No dosage adjustment necessary.
Discontinuation: In patients receiving pregabalin chronically, unless safety concerns require a more rapid withdrawal, pregabalin should be withdrawn gradually over ≥ 1 week to minimize the potential of increased seizure frequency or other withdrawal symptoms.
Administration: May be administered with or without food.

OVERDOSE AND TREATMENT: Overdose effects are expected to be extensions of adverse effects at therapeutic doses. In patients receiving greater than or equal to 900 mg, the clinical events reported were similar to those at the recommended doses. An adult ingested an estimated 1.5 g; mild drowsiness was the only symptom observed. An adult intentionally ingested 8.4 g of pregabalin and developed CNS depression and coma approximately 3 hours after exposure. The patient required intubation and mechanical ventilation for 26 hours. No permanent sequelae occurred.
Treatment is symptomatic and supportive. 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 pregabalin or any other component of the product.

(Based on the notification of the Ministry of Public Health): 1. This drug may cause drowsiness, do not drive a car or operate machinery, or drink alcoholic beverages while taking this drug.
2. This drug may cause hematologic disorder.
3. Do not use this drug while pregnant because it may cause teratogenesis.
4. Use this drug with caution in patients with liver and kidney disease.

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.
Cardiovascular: New York Heart Association Class III and IV congestive heart failure; increased risk of peripheral edema; monitoring recommended.
Peripheral edema has been reported; increased frequency of weight gain and peripheral edema with concomitant thiazolidinedione use; monitoring recommended during concomitant thiazolidinedione use.
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.
Hypersensitivity reactions, including skin redness, blisters, hives, rash, dyspnea, and wheezing, have been reported; discontinue immediately if symptoms develop.
Musculoskeletal: Creatinine 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 considerations: Pregabalin crosses the human placenta. Outcome data following maternal use of pregabalin during pregnancy is limited.
Breast-feeding considerations: Pregabalin is excreted in breast milk. Breastfeeding is not recommended.

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 11%).
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.

Pregabalin may potentiate the effects of ethanol and lorazepam. Pregabalin appears to be 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 other CNS depressant medication.
There are reports of event related to reduce 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 analgesics.

Store at below 30°C.

Anticonvulsants / Drugs for Neuropathic Pain / Anxiolytics

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

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