TASMAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TASMAR (TASMAR).
Selective and reversible inhibitor of catechol-O-methyltransferase (COMT), which increases the bioavailability of levodopa by reducing its peripheral metabolism.
| Metabolism | Metabolized primarily via glucuronidation; minor metabolism by CYP1A2, CYP2A6, CYP2C9, CYP2D6, and CYP3A4/5 |
| Excretion | Primarily hepatic metabolism (glucuronidation and methylation), with approximately 40% of the dose excreted in urine as metabolites and <0.5% as unchanged drug; about 50% is eliminated in feces via biliary excretion. |
| Half-life | Terminal elimination half-life is 2–3 hours in healthy volunteers; clinically, this short half-life necessitates three-times-daily dosing to maintain COMT inhibition, though peripheral COMT activity recovers within 4–6 hours. |
| Protein binding | >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.2–0.4 L/kg, indicating limited extravascular distribution consistent with high protein binding. |
| Bioavailability | Absolute bioavailability is approximately 60% after oral administration due to first-pass metabolism; food reduces bioavailability by 10–20%. |
| Onset of Action | Oral administration: clinical effect on motor fluctuations (reduction in OFF time) is typically observed within 1–2 hours after the first dose, corresponding to peak plasma concentrations at 2 hours. |
| Duration of Action | Duration of clinical efficacy (increased ON time) is approximately 6–8 hours per dose, consistent with the half-life and recovery of COMT activity; three-times-daily dosing provides coverage throughout the waking day. |
100 mg orally three times daily; maximum 200 mg three times daily.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl > 25 mL/min). Avoid use in severe renal impairment (CrCl < 25 mL/min) due to lack of data. |
| Liver impairment | Contraindicated in patients with clinically significant hepatic impairment (Child-Pugh class B or C). For mild hepatic impairment (Child-Pugh class A), use with caution and monitor liver enzymes; no specific dose adjustment established. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; use with caution due to potential increased risk of adverse effects (e.g., dizziness, orthostatic hypotension) and monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TASMAR (TASMAR).
| Breastfeeding | No human data on excretion in breast milk. Tolcapone is highly protein-bound (>99.9%) and theoretically minimal transfer; however, due to potential for serious adverse effects (hepatotoxicity), breastfeeding is not recommended. M/P ratio is unknown. |
| Teratogenic Risk | Tasmar (tolcapone) is contraindicated in pregnancy. Animal studies have shown fetal harm including reduced fetal weight and increased skeletal variations at doses comparable to human therapeutic levels. There are no adequate human studies; risk cannot be ruled out in all trimesters. |
■ FDA Black Box Warning
Not applicable
| Serious Effects |
["Hypersensitivity to tolcapone or any component","Liver disease or elevated liver enzymes (e.g., AST/ALT > 2x ULN)"]
| Precautions | ["Hepatotoxicity (elevated liver enzymes, hepatic failure)","May exacerbate levodopa-induced dyskinesias and hypotension","May cause diarrhea, which can be severe","Use with caution in patients with pre-existing liver disease"] |
Loading safety data…
| Fetal Monitoring |
| Monitor hepatic function (ALT/AST) at baseline and every 2-4 weeks for the first 6 months, then periodically. No specific fetal monitoring required if inadvertently used; consider prenatal ultrasound to assess fetal growth if exposure occurs. |
| Fertility Effects | In animal studies, no adverse effects on fertility were observed at clinically relevant doses. Human data are insufficient to determine impact on female or male fertility. |