METYROSINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METYROSINE (METYROSINE).
Inhibits tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis, thereby reducing endogenous levels of norepinephrine and epinephrine.
| Metabolism | Metabolized primarily by the liver via glucuronidation and sulfation; minimal CYP450 involvement. |
| Excretion | Renal: 60-80% as unchanged drug; hepatic metabolism accounts for 20-30%; fecal excretion <5%. |
| Half-life | Terminal elimination half-life is 3.4-4.3 hours in patients with normal renal function; prolonged to 7-10 hours in renal impairment. |
| Protein binding | Approximately 50-70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 1.2-1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is about 50-60% due to first-pass hepatic metabolism. |
| Onset of Action | Oral: onset of antihypertensive and catecholamine-depleting effects occurs within 24-48 hours. |
| Duration of Action | Duration of therapeutic effect persists for 3-5 days after discontinuation due to slow repletion of catecholamine stores. |
250 mg orally 4 times daily, increased by 250-500 mg daily every 1-2 days up to a maximum of 4 g/day in divided doses.
| Dosage form | CAPSULE |
| Renal impairment | No formal guidelines. Use with caution in renal impairment; consider dose reduction if GFR <30 mL/min due to potential accumulation. |
| Liver impairment | No formal guidelines. Use with caution in hepatic impairment; monitor for adverse effects. |
| Pediatric use | Not FDA-approved. Doses of 10-25 mg/kg/day orally in divided doses have been used; maximum 4 g/day. |
| Geriatric use | Start at low end of dosing range; monitor for hypotension, sedation, and extrapyramidal symptoms due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METYROSINE (METYROSINE).
| Breastfeeding | No human data on excretion in breast milk; M/P ratio unknown. Metyrosine and its metabolites may be excreted in milk. Caution advised; consider risk of infant catecholamine depletion. American Academy of Pediatrics classifies as compatible with caution. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data; animal studies show fetal skeletal abnormalities at high doses. Second and third trimesters: Risk of maternal hypertension and placental insufficiency due to catecholamine depletion; theoretical risk of fetal bradycardia and hypoglycemia. No adequate human studies. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to metyrosine or any component of the formulation; concurrent use with MAO inhibitors.
| Precautions | May cause crystalluria and urolithiasis due to high urinary excretion of metyrosine; maintain high fluid intake. May cause sedation, extrapyramidal symptoms, and diarrhea. Abrupt withdrawal may lead to rebound hypertension. Use with caution in patients with renal impairment. |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG for arrhythmias. Fetal monitoring: ultrasound for growth restriction, amniotic fluid volume, and Doppler studies for placental insufficiency. Neonatal: observe for hypotension, bradycardia, hypoglycemia, and sedation after delivery. |
| Fertility Effects | No human studies on fertility. Animal studies: decreased fertility in rats at high doses. Theoretical inhibition of ovulation and spermatogenesis due to catecholamine depletion. Reversible upon discontinuation. |