PROMAPAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMAPAR (PROMAPAR).
PROMAPAR is a brand name for tramadol, a centrally acting analgesic that binds to mu-opioid receptors and inhibits serotonin and norepinephrine reuptake, modulating pain perception.
| Metabolism | Extensively metabolized in the liver via CYP2D6 to active metabolite O-desmethyltramadol (M1) and via CYP3A4 and CYP2B6 to other metabolites; undergoes glucuronidation and sulfation. |
| Excretion | Primarily renal (70-80% as unchanged drug) via glomerular filtration and tubular secretion; biliary/fecal elimination accounts for approximately 20%. |
| Half-life | Terminal elimination half-life is 2-4 hours (mean 3 hours) in adults with normal renal function; prolonged to 8-15 hours in moderate-to-severe renal impairment. |
| Protein binding | 75-85% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 0.6-0.8 L/kg, suggesting moderate tissue distribution with penetration into cerebrospinal fluid. |
| Bioavailability | Oral: 50-60% due to extensive first-pass metabolism; IM: 70-80%; IV: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intramuscular: 10-15 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | Oral: 4-6 hours; IM/IV: 3-5 hours; clinical effects may persist longer with repeated dosing due to accumulation, especially in hepatic or renal impairment. |
5 mg orally twice daily, titrated up to maximum 60 mg/day in divided doses.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%. GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | 0.1 mg/kg/dose orally twice daily; maximum 0.8 mg/kg/day. |
| Geriatric use | Initiate at 2.5 mg twice daily; titrate slowly due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROMAPAR (PROMAPAR).
| Breastfeeding | Pregabalin is excreted into human breast milk. The milk-to-plasma ratio is approximately 0.76. The estimated infant dose is about 0.3–0.7 mg/kg/day (7% of maternal weight-adjusted dose). Effects on the breastfed infant are unknown; however, risk of sedation and poor feeding based on pharmacodynamic profile. Breastfeeding is not recommended unless potential benefit outweighs risk. |
| Teratogenic Risk | PROMAPAR (pregabalin) is classified as FDA Pregnancy Category C. First trimester: Animal studies have shown developmental toxicity including skeletal malformations and decreased fetal weight. Limited human data; insufficient to rule out risk. Second and third trimesters: May cause neonatal withdrawal syndrome (persistent crying, irritability, hypertonia) if used near term. Risk of low birth weight and preterm birth reported in some studies. |
■ FDA Black Box Warning
Risk of respiratory depression, addiction, abuse, and misuse; life-threatening respiratory depression in children; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and risk of serotonin syndrome when used with serotonergic drugs.
| Serious Effects |
Hypersensitivity to tramadol; acute or severe bronchial asthma; significant respiratory depression; severe gastrointestinal obstruction including paralytic ileus; concurrent use or within 14 days of MAOIs; treatment of pain in children <12 years; use in breastfeeding women with high doses or prolonged use.
| Precautions | Seizure risk, especially in patients with epilepsy or history of seizures; serotonin syndrome with serotonergic drugs; risk of suicide; respiratory depression; use caution in renal/hepatic impairment; avoid use in patients with severe asthma or respiratory depression; not recommended in children <12 years; use in pregnancy may cause neonatal withdrawal. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to possible edema and PR prolongation. Serial fetal growth ultrasounds if used beyond 20 weeks gestation. Assess for neonatal withdrawal symptoms if used near term. Monitor renal function as pregabalin clearance is creatinine-dependent. |
| Fertility Effects | No human studies on fertility. Animal studies showed decreased male fertility (sperm motility and count) at clinically relevant doses. Reversible after discontinuation. May impair female fertility through hormonal disruption in animal studies, but clinical significance unknown. |