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

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.