Gabatec

• Neuropathic Pain:
• Peripheral neuropathy associated with diabetes mellitus (diabetic peripheral neuropathy)
• Postherpetic neuralgia (pain following shingles)
• Peripheral neuropathy associated with spinal cord injury
• Epilepsy:
• Adjunctive therapy for partial-onset seizures with or without secondary generalization in adults and pediatric patients aged ≥4 years
• Generalized Anxiety Disorder (GAD):
• Management of generalized anxiety disorder in adults (approved in some countries)
• Fibromyalgia:
• Treatment of fibromyalgia to reduce pain and improve function
• Restless Legs Syndrome (RLS):
• Management of moderate-to-severe primary restless legs syndrome

Adults:

• Neuropathic Pain and Fibromyalgia:
• Initial dose: 75 mg twice daily (150 mg/day)
• May increase to 150 mg twice daily (300 mg/day) within 1 week based on response and tolerability
• Maximum dose: 300 mg twice daily (600 mg/day)
• Partial-Onset Seizures (Adjunctive):
• Starting dose: 75 mg twice daily
• Titrate to 150 mg twice daily after 1 week
• Further increases can be made up to 600 mg/day (divided doses)
• Generalized Anxiety Disorder (GAD):
• Typical starting dose: 150 mg/day in divided doses
• May increase to 300-600 mg/day as tolerated
• Restless Legs Syndrome:
• Recommended dose: 75 mg once daily at bedtime
• May be increased to 150 mg/day based on response

Pediatrics:

• Epilepsy (≥4 years):
• Starting dose: 2.5 mg/kg/day in two divided doses
• Maintenance dose: 5–10 mg/kg/day divided twice daily
• Maximum dose: 300 mg/day (for patients 10 to <18 years)
• Neuropathic pain, fibromyalgia, GAD, RLS: Safety and efficacy not established in children.

Elderly:

• Initiate at the lower end of dosing range (75 mg/day), titrate slowly; renal function monitoring advised.

Renal Impairment:

• Dosage adjustments required according to creatinine clearance:
• CrCl 30–60 mL/min: reduce dose by ~50%
• CrCl 15–30 mL/min: reduce dose by ~75%
• CrCl <15 mL/min or dialysis: further dose reduction required, typically 25–50 mg once or twice daily

Administration:

• Oral administration with or without food
• Capsules should be swallowed whole; oral solution available for those with swallowing difficulties

Pregabalin binds with high affinity to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system, particularly in presynaptic nerve terminals. By modulating calcium influx into nerve terminals, pregabalin reduces the release of several excitatory neurotransmitters, including glutamate, norepinephrine, substance P, and calcitonin gene-related peptide. This modulation decreases neuronal excitability and synaptic transmission, leading to analgesic, anticonvulsant, and anxiolytic effects.

• Absorption: Rapid and extensive oral absorption with peak plasma concentrations occurring within 1 hour; bioavailability >90%, independent of dose
• Distribution: Volume of distribution approximately 0.56 L/kg; low plasma protein binding (<1%)
• Metabolism: Negligible metabolism; >90% excreted unchanged in urine
• Half-life: Approximately 6.3 hours, allowing for twice-daily dosing
• Elimination: Primarily renal excretion via glomerular filtration; renal clearance proportional to creatinine clearance
• Onset of Action: Effects may begin within hours, but full therapeutic benefit often takes several days to weeks

• Pregnancy:
  FDA Pregnancy Category C
  Animal studies show adverse fetal effects at high doses; no adequate well-controlled human studies. Use only if benefits outweigh risks. Pregabalin crosses the placenta.
• Lactation:
  Pregabalin is excreted in breast milk; the potential effects on the nursing infant are unknown. Caution advised; consider alternative feeding options or discontinuation.

• Primary Class: Anticonvulsant and Neuropathic Pain Agent
• Subclass: Alpha-2-delta ligand; Gabapentinoid

• Known hypersensitivity to pregabalin or any excipients
• History of angioedema or severe allergic reaction to pregabalin

• Suicidal Thoughts and Behavior: Increased risk observed with antiepileptic drugs; monitor patients for mood changes, depression, or suicidal ideation
• Angioedema: Serious hypersensitivity reactions reported; discontinue immediately if swelling of face, lips, tongue, or throat occurs
• Dizziness and Somnolence: Common; caution patients regarding driving or operating machinery
• Peripheral Edema: Can occur, especially in elderly or patients with cardiac disease
• Withdrawal: Abrupt discontinuation may precipitate seizures or withdrawal symptoms; taper dose gradually
• Respiratory Depression: Risk increased in patients with respiratory impairment or concomitant CNS depressants
• Renal Impairment: Dose adjustments required to avoid toxicity

Common (≥10% incidence):

• Dizziness
• Somnolence
• Dry mouth
• Peripheral edema
• Blurred vision
• Weight gain
• Difficulty concentrating

Less Common / Serious:

• Ataxia
• Confusion
• Euphoria
• Myopathy
• Angioedema
• Hypersensitivity reactions
• Suicidal ideation or behavior

• Central Nervous System (CNS) Depressants (e.g., opioids, benzodiazepines, alcohol): Additive CNS depression and respiratory depression risk
• No significant interaction with CYP450 enzymes: Pregabalin is neither an inducer nor inhibitor of major CYP isoforms
• No significant interaction with warfarin or oral contraceptives

• Updated warnings on respiratory depression risk when combined with CNS depressants
• Recommendations for dose adjustments in renal impairment clarified in recent guidelines
• Emphasis on monitoring mood and behavioral changes due to risk of suicidal ideation
• Recognition of pregabalin’s role in managing fibromyalgia and RLS in expanded clinical guidelines

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Keep container tightly closed
• Do not freeze
• Keep out of reach of children