PREGABALIN
Clinical safety rating: safe
Animal studies have demonstrated safety
Binds to the alpha2-delta subunit of voltage-gated calcium channels, reducing calcium influx and decreasing release of excitatory neurotransmitters (e.g., glutamate, norepinephrine, substance P).
| Metabolism | Negligible hepatic metabolism; not metabolized by CYP450 enzymes; excreted primarily unchanged in urine (90-99%). |
| Excretion | Primarily renal excretion as unchanged drug (92-99% of dose). Approximately 0.1% is metabolized. No biliary or fecal elimination of significance. |
| Half-life | Terminal elimination half-life is approximately 6.3 hours. In patients with renal impairment, half-life is prolonged (up to 48 hours in anuria). Requires dose adjustment based on creatinine clearance. |
| Protein binding | Pregabalin does not bind to plasma proteins (<1%). |
| Volume of Distribution | Volume of distribution is approximately 0.5 L/kg (range 0.4-0.6). This suggests distribution into total body water, with negligible binding to plasma proteins. |
| Bioavailability | Oral: Fasted bioavailability is ≥90% and is dose-independent. Food delays absorption (Tmax increases by approximately 1 hour) but does not affect extent of absorption (AUC unchanged). |
| Onset of Action | Oral: Onset of pain relief in neuropathic pain occurs within 1 week; for fibromyalgia, improvement may be seen as early as 1 week. Maximal effect may require 4 weeks. |
| Duration of Action | Duration of analgesic effect is approximately 6-12 hours (supports three times daily dosing). For anticonvulsant use, dosing frequency is every 8-12 hours. |
Initial: 75 mg orally twice daily; may increase to 150 mg twice daily within 1 week; maximum: 600 mg/day in divided doses.
| Dosage form | CAPSULE |
| Renal impairment | GFR ≥60 mL/min: no adjustment; GFR 30-59 mL/min: 75-300 mg/day in 2-3 divided doses; GFR 15-29 mL/min: 25-150 mg/day once daily or in 2 divided doses; GFR <15 mL/min: 25-75 mg once daily. |
| Liver impairment | No specific adjustment recommended; use caution in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Children ≥1 month: 3.5-7 mg/kg/day in 3 divided doses; maximum 10 mg/kg/day or 600 mg/day. |
| Geriatric use | Initiate at lower dose (e.g., 75 mg once daily) due to decreased renal function; titrate slowly; monitor for dizziness and somnolence. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Can cause angioedema and withdrawal symptoms upon discontinuation.
| Breastfeeding | Pregabalin is excreted into human breast milk with an estimated milk-to-plasma (M/P) ratio of approximately 1.0. The relative infant dose is about 0.7% of the maternal weight-adjusted dose, which is considered low. However, because of potential adverse effects in nursing infants, including somnolence and poor feeding, caution is advised. The decision to breastfeed should consider the maternal need for pregabalin and the infant's developmental stage. |
| Teratogenic Risk | Pregabalin is classified as FDA Pregnancy Category C. Animal studies have shown developmental toxicity, including skeletal malformations and increased fetal mortality at clinically relevant doses. In humans, data are limited but suggest an increased risk of major congenital malformations, particularly neural tube defects and cardiac anomalies, when used during the first trimester. Exposure in the second and third trimesters may be associated with low birth weight, preterm birth, and neonatal withdrawal syndrome. Use is advised only if the potential benefit justifies the risk to the fetus. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Blurred vision Difficulty in paying attention Dizziness Dryness in mouth Edema swelling Sleepiness Weight gain |
| Serious Effects |
["Hypersensitivity to pregabalin or any component of the formulation"]
| Precautions | ["Angioedema (can occur with or without history of ACE inhibitor use)","Hypersensitivity reactions (including urticaria, dyspnea, and blistering)","Increased risk of suicidal thoughts or behavior","Dizziness and somnolence (especially in elderly, increased fall risk)","Respiratory depression (especially with concomitant CNS depressants or impaired respiratory function)","Abrupt discontinuation may cause withdrawal symptoms (insomnia, anxiety, nausea, pain)","Reduced platelet count in post-marketing reports"] |
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| Fetal Monitoring | Monitor maternal vital signs, particularly for hypotension and dizziness. Assess for signs of angioedema, thrombocytopenia, or myopathy. Perform fetal ultrasound for growth and anatomy if exposure occurs during pregnancy. Closely monitor neonatal adaptation after birth for symptoms of withdrawal, such as irritability, tremors, and poor feeding. |
| Fertility Effects | In animal studies, pregabalin did not impair fertility in male or female rats at exposures up to 5 times the maximum recommended human dose. Human data on fertility are lacking; however, no specific effects on spermatogenesis or ovarian function have been reported. Menstrual irregularities have been reported in some women. Use caution when prescribing to patients planning to conceive. |