METYROSINE
| METYROSINE (me-tye'roe-seen) Demser Classifications: hormone; enzyme inhibitor; Therapeutic: enzyme inhibitor Pregnancy Category: C |
Availability
250 mg capsules
Action
Blocks the enzyme tyrosine hydroxylase inhibiting the conversion of tyrosine to DOPA, which is the initial and rate-setting step in synthesis of catecholamines (dopamine, epinephrine, norepinephrine).
Therapeutic Effect
In patients with pheochromocytoma, reduces catecholamine synthesis as much as 80%, ameliorating hypertensive attacks and associated symptoms.
Uses
Short-term management of pheochromocytoma until surgery is performed, in long-term control when surgery is contraindicated, and in patients with malignant pheochromocytoma.
Unlabeled Uses
Has been used in selected patients with schizophrenia to potentiate antipsychotic effects of phenothiazines.
Contraindications
Control of essential hypertension; dehydration; pregnancy (category C). Safe use in children <12 y is not established.
Cautious Use
Impaired liver or kidney function; Parkinson's disease; lactation.
Route & Dosage
| Pheochromocytoma Adult: PO 250 mg q.i.d., may increase to 2–3 g/d in divided doses (max: 4 g/d) |
Administration
Oral- Give each dose with a full glass of water and be consistent about time medication is to be taken.
- Store at 15°–30° C (59°–86° F).
Adverse Effects (≥1%)
CNS: Sedation, fatigue; extrapyramidal signs: drooling, difficulty in speaking (dysarthria), tremors, jaw stiffness (trismus); frank parkinsonism, psychic disturbances (anxiety, depression, hallucinations, disorientation, confusion), headache, muscle spasms. GI: Diarrhea, nausea, vomiting, abdominal pain, dry mouth. Skin: Rash, urticaria. Urogenital: Transient dysuria, crystalluria, hematuria, impotence, failure of ejaculation. Endocrine: Breast swelling, galactorrhea. Body as a Whole: Peripheral edema, nasal stuffiness, shortness of breath. Hematologic: Eosinophilia.Diagnostic Test Interference
False increases in urinary catecholamines may occur because of catechol metabolites of metyrosine.
Interactions
Drug: Alcohol and other cns depressants add to sedation and CNS depression; droperidol, haloperidol, phenothiazines potentiate extrapyramidal effects.Pharmacokinetics
Absorption: Readily absorbed from GI tract. Peak: 2–3 d. Duration: 3–4 d. Distribution: Crosses blood–brain barrier. Elimination: In urine. Half-Life: 3.4–7.2 h.Nursing Implications
Assessment & Drug Effects
- Monitor therapeutic effectiveness with frequent assessment of vital signs.
- Monitor I&O ratio and pattern. Fluid intake must be enough (e.g., 10–12 glasses or more) to maintain urinary output of 2000 mL or more to minimize risk of crystalluria.
- Perform routine urinalysis; if crystals occur, increase fluid intake further. If crystalluria persists, decrease drug dosage or discontinued.
- Lab tests: Obtain baseline and periodic measurements of urinary catecholamines and their metabolites (metanephrines and VMA). Metabolite excretion should decrease in patients with pheochromocytoma. Other baseline and regular determinations include kidney and liver function tests (in patients with dysfunction), and blood and urine glucose tests.
- Supervise ambulation. Sedative effects occur commonly within the first 24 h after drug is started. Maximal sedative effects in 2 or 3 d.
Patient & Family Education
- Notify physician if following adverse effects occur: Diarrhea, particularly if it is severe or persists, painful urination, jaw stiffness, drooling, difficult speech, tremors, disorientation. Dosage reduction or discontinuation of drug may be indicated.
- Avoid driving and potentially hazardous activities until response to drug is known.
- Be aware that abrupt withdrawal of metyrosine may result in psychic stimulation, feeling of increased energy, temporary changes in sleep pattern (usually insomnia). Symptoms may last for 2 or 3 d.
- Carry medical identification at all times if on prolonged therapy and notify all physicians and dentists involved in care about drug regimen.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug