Metyrosine (Demser) inhibits the enzyme tyrosine hydroxylase that is required for the synthesis of catecholamines (adrenaline, nor-adrenaline, and dopamine). It is used in patients with pheochromocytoma preoperatively and for long-term maintenance treatment in patients who are not fit to undergo surgery.

Metyrosine (Demser) Uses:

• Pheochromocytoma:

  • Pheochromocytoma should be treated temporarily before surgery as an adjuvant to other anti-hypertensive drugs such as alpha-blockers.
  • When surgery is not an option or there is a persistent malignant pheochromocytoma, long-term care for pheochromocytoma is necessary.

Note: Usually, simultaneous alpha- and beta-adrenergic inhibition is only used for those who cannot tolerate it.

Metyrosine Dose in Adults:

Metyrosine (Demser) Dose in the treatment of Pheochromocytoma:

• Oral: start with 250 mg four times per day, then increase by 250 to 500 mg per day up to 4 g per day in four evenly spaced dosages.
• In hypertensive patients titrate until blood pressure is controlled and symptoms resolve.
• For preoperative preparation, administer optimum effective dosage for 5 to 7 days.
• In patients without hypertension titrate to decrease catecholamines by ≥50%.
• The usual maintenance dose is: 2 to 3 g/day in 4 divided doses

Note:

• It may be given combined with alpha-adrenergic receptor inhibitors (eg, phenoxybenzamine) to increase intraoperative hemodynamic stability;
• Use 2 g/day, higher doses may potentially cause intraoperative hemodynamic instability.

Use in Children:

Refer to adults' dosing.

Pregnancy Risk Factor C

• No animal reproduction studies

Metyrosine use during breastfeeding:

• Use cautiously in lactating women.

Dose in Kidney Disease:

No dose adjustment is needed.

Dose in Liver disease:

No dose adjustment is needed.

Side Effects of Metyrosine (Demser):

• Cardiovascular:

  • Peripheral edema

• Central nervous system:

  • Hallucination
  • Headache
  • Extrapyramidal reactions
  • Parkinson’s disease
  • Sedation
  • Depression
  • Disorientation
  • Overstimulation (after withdrawal)
  • Anxiety
  • Confusion

• Dermatologic:

  • Urticaria

• Endocrine & metabolic:

  • Galactorrhea

• Hematologic & oncologic:

  • Anemia
  • Thrombocythemia
  • Thrombocytopenia
  • Eosinophilia

• Gastrointestinal:

  • Diarrhea
  • Abdominal pain
  • Nausea
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Dysuria
  • Hematuria
  • Breast swelling
  • Crystalluria
  • Impotence
  • Ejaculatory disorder

• Hepatic:

  • Increased serum AST

• Hypersensitivity:

  • Hypersensitivity reaction

• Respiratory:

  • Nasal congestion
  • Pharyngeal edema

Contraindication to Metyrosine (Demser):

Sensitivity to any ingredient in the mix, including metyrosine

Warnings and precautions

• CNS depression:

  • CNS depression
  • Reduced mental alertness

• Crystalluria

  • Crystalluria can be avoided by hydrating enough to produce urine output >=2L, especially if you take more than 2 g per day.
  • If crystalluria occurs, adjust the dosage or discontinue use

• Hepatic impairment

  • Patients with liver disease should be cautious.

• Renal impairment

  • Patients with impaired kidney function should be cautious.

Metyrosine: Drug Interaction

Risk Factor C (Monitor therapy)
Alcohol (Ethyl) Hair Removing Hard Beans Wax Painless Beauty Wax Beans For All Skins Wax Beans For Face Body Legs	May intensify metyrosine's sedative effects.
Antipsychotic Agents	The negative/toxic effects of antipsychotic agents may be amplified by metyroSINE.
CNS Depressants	May intensify metyrosine's sedative effects.
Droperidol	MetyroSINE may intensify Droperidol's harmful or hazardous effects.
Promethazine	Promethazine's negative/toxic effects may be exacerbated by metyroSINE.
Selective Serotonin Reuptake Inhibitors	Selective Serotonin Reuptake Inhibitors may have a negative or toxic impact that metyroSINE may amplify.
Tetrabenazine	Tetrabenazine's harmful or hazardous effects may be amplified by metyroSINE.
Tricyclic Antidepressants	Tricyclic antidepressants may have a worsened or more toxic effect when taken with metyroSINE.
Risk Factor D (Consider therapy modification)
Metoclopramide	The negative or hazardous effects of metoclopramide may be increased by metyroSINE. Management: When feasible, look for alternatives for this combination. Observe patients receiving metyrosine and metoclopramide for the emergence of extrapyramidal symptoms.
Risk Factor X (Avoid combination)
Bromopride	MetyroSINE may enhance the adverse/toxic effect of Bromopride.

Monitoring parameters:

• blood pressure
• ECG during surgery
• urinalysis
• urine output ≥2000 mL recommended especially with doses >2 g/day)

How to administer Metyrosine (Demser)?

Administer with or without food.

Mechanism of action of Metyrosine (Demser):

• Inhibits tyrosine hydroxylase required for conversion of tyrosine to dihydroxyphenylalanine, needed for catecholamine synthesis.
• Use the recommended dose to reduce catecholamine biosynthesis by between 35% and 80%

Half-life elimination:

• ~3-4 hours

Absorption:

• Well absorbed

Excretion:

• Primarily urine (53% to 88% as unchanged drug)

International Brand Names of Metyrosine:

• Demser

Metyrosine Brand Names in Pakistan:

No Brands Available in Pakistan.