TYZAVAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYZAVAN (TYZAVAN).
Levodopa is converted to dopamine in the brain, replenishing depleted dopamine levels in the striatum, improving motor function. Carbidopa inhibits peripheral decarboxylation of levodopa, increasing its central availability.
| Metabolism | Levodopa: metabolized by aromatic L-amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT). Carbidopa: not extensively metabolized. |
| Excretion | Renal excretion (70–80% unchanged); biliary/fecal excretion accounts for 15–20% as metabolites. |
| Half-life | Terminal elimination half-life is 12–15 hours in patients with normal renal function; prolonged to 30–50 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 85–90% bound primarily to albumin. |
| Volume of Distribution | Volume of distribution is 0.5–0.7 L/kg, indicating moderate tissue distribution. |
| Bioavailability | Oral bioavailability is 70–80% (tablet and capsule formulations); intravenous bioavailability is 100%. |
| Onset of Action | Oral: 1–2 hours; Intravenous: within 5–10 minutes. |
| Duration of Action | Oral: 12–24 hours; Intravenous: 6–12 hours. Clinical effect persists for the dosing interval; accumulation may occur with once-daily dosing. |
200 mg orally once daily, taken with food.
| Dosage form | SOLUTION |
| Renal impairment | eGFR >=30 mL/min/1.73 m^2: no adjustment; eGFR 15-29 mL/min/1.73 m^2: 100 mg once daily; eGFR <15 mL/min/1.73 m^2: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 100 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients; no established dosing. |
| Geriatric use | No specific dose adjustment required based on age alone; monitor renal function and adjust accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TYZAVAN (TYZAVAN).
| Breastfeeding | It is unknown whether TYZAVAN is excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 30 days after the last dose. The M/P ratio is not available. |
| Teratogenic Risk | TYZAVAN is contraindicated in pregnancy. Animal studies have shown teratogenic effects including fetal malformations and embryotoxicity. In humans, first trimester exposure is associated with major congenital anomalies; second and third trimester exposure may cause fetal growth restriction and oligohydramnios. |
■ FDA Black Box Warning
None.
| Common Effects | Application site reactions burning irritation itching and redness Skin peeling Headache Diarrhea Rash Indigestion Abnormal liver enzyme Itching Taste change Nausea Abdominal pain Flatulence |
| Serious Effects |
["Concurrent use with non-selective MAO inhibitors (except MAO-B inhibitors at recommended doses)","Narrow-angle glaucoma","Suspicious undiagnosed skin lesions or history of melanoma","Hypersensitivity to any component"]
| Precautions | ["May cause somnolence and sudden sleep onset","Risk of impulse control disorders","May cause dyskinesias","May cause hallucinations and psychosis","Abrupt withdrawal may cause neuroleptic malignant syndrome","May cause orthostatic hypotension","May cause melanoma (monitor skin lesions)"] |
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| Fetal Monitoring | Monitor pregnancy status before initiation and monthly during therapy. If pregnancy occurs, immediate discontinuation is required. Fetal ultrasound is recommended to assess for anomalies and amniotic fluid volume. Maternal liver function and blood counts should be monitored periodically. |
| Fertility Effects | TYZAVAN may impair fertility in females based on animal studies showing disruption of estrous cycles and reduced ovarian function. Reversibility in humans is unknown. Males may experience reduced sperm count and motility. |