Pregabalin

Pharmacokinetics

Pharmacokinetics

• Absorption: Fast and predictable; oral bioavailability 90%. It presents non-saturable **linear absorption kinetics** within its entire therapeutic dosage range (75 to 600 mg/day). The plasma peak is reached at the time of intake on an empty stomach.
• Distribution: Does not bind to plasma proteins (0%). Distribution volume: 0.5 L/kg. It quickly crosses the blood-brain barrier.
• Metabolism: Null. Less than 2% undergo transient inactive N-methylation.
• Excretion: Renal by glomerular filtration in unchanged form (>98%). Clearance linearly dependent on plasma creatinine clearance.
• Half-life (t_1/2): 6.3 hours; requires a dosage divided into two or three daily doses.

Indicators and dose

Indications

• Adjuvant therapy in focal seizures in adults (with or without secondary generalization).
• First-line treatment of Peripheral and Central Neuropathic Pain in adults.
• First-line treatment of Generalized Anxiety Disorder (GAD) in adults.
• Symptomatic treatment of primary fibromyalgia that is difficult to control.

Dosage and Settings

• Anxiety and Pain Disorder: Start with 75 mg twice a day (150 mg/day total). Rapid increase in 3-7 days to 150 mg twice daily (300 mg/day). Maximum dose: 600 mg/day in two or three doses.
• Analytical adjustment in Renal Failure:
  • Cl_Cr [30-60 ml/min]: Start with 75 mg/day as a single dose, limit of 300 mg/day.
  • Cl_Cr [15-30 ml/min]: Start with 25-50 mg/day, limit of 150 mg/day.
  • Cl_Cr < 15 ml/min (Anuria): Limit to 25-50 mg every other day or after each dialysis session.

Security

Contraindications

• Known hypersensitivity to the compound.
• Angioedema prior to or concomitant with ACE inhibitors (increased risk of airway obstruction).

Adverse Effects (ADR)

The Paradox of Weight Gain with Pregabalin

Weight gain is a very common adverse effect of pregabalin, affecting 12-15% of patients in a dose-dependent manner. It is due to a mixed mechanism: on the one hand, a notable peripheral hydrosaline retention (with the development of bilateral malleolar edema) and on the other, a direct increase in appetite mediated by the interaction with hypothalamic orexigenic peptides. Requires adequate nutritional education and weight control.

• Very common (>10%): Deep daytime sleepiness, dizziness, extreme fatigue, dry mouth, increased body weight.
• Frequent (1%-10%): Transient diplopia, blurred vision due to alteration of ocular accommodation, motor constipation, erectile dysfunction, mild paradoxical euphoria (origin of its potential for recreational abuse in multipurpose addictions).
• Rare (<0.1%): Decompensated congestive heart failure, reversible autoimmune thrombocytopenia, early-onset suicidal ideation.

Clinical Interactions

• CNS depressants: Pharmacodynamic synergy that multiplies the sedative and respiratory effects with benzodiazepines, alcohol and tricyclic antidepressants.
• Opioids: Coadministration with tramadol or fentanyl may exacerbate motor-induced constipation and cause severe respiratory depression.

Pregnancy and Breastfeeding

FDA Category: C. Recent epidemiological data associate a slight tendency to major malformations (cleft palate) if there is continued use in the first trimester. It is preferred to avoid its prescription unless there are no stable alternatives. Breastfeeding: Compatible. It is excreted in milk in reduced proportions; Relative childhood dose estimated at 7%. Monitor weight gain and sucking in the infant.