DEMSER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEMSER (DEMSER).
Competitive inhibition of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, resulting in decreased production of dopamine, norepinephrine, and epinephrine.
| Metabolism | Primarily hepatic via glucuronidation and sulfation; minor metabolism by CYP2D6 and CYP1A2. Some metabolites are pharmacologically active (e.g., alpha-methyltyramine). |
| Excretion | Renal: 70-80% as unchanged drug within 24 hours; biliary/fecal: minor (<5%). |
| Half-life | Terminal elimination half-life: 9-11 hours in patients with normal renal function (CrCl >100 mL/min). In renal impairment (CrCl <30 mL/min), half-life is prolonged to 20-40 hours. |
| Protein binding | ~90% bound to albumin. |
| Volume of Distribution | 5.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability: 25-30% due to first-pass metabolism. |
| Onset of Action | Oral: Clinical effect (blood pressure reduction) begins within 1-2 hours; maximal effect at 4-6 hours. |
| Duration of Action | Duration of antihypertensive effect: 12-24 hours after single oral dose. Twice-daily dosing typically maintains effect throughout the day. |
Initial: 250 mg orally every 6 to 8 hours. Titrate to 2 g daily in divided doses. Maximum: 3 g/day.
| Dosage form | CAPSULE |
| Renal impairment | If GFR 30-59 mL/min: administer every 8 to 12 hours. If GFR 10-29 mL/min: administer every 24 to 48 hours. If GFR <10 mL/min: not recommended. |
| Liver impairment | Severe hepatic impairment (Child-Pugh C): contraindicated; moderate (Child-Pugh B): reduce dose by 25-50%. |
| Pediatric use | Children >12 years: 5 mg/kg/dose orally every 6-8 hours; maximum 2 g/day. |
| Geriatric use | Start at low end of dosing range; monitor for orthostatic hypotension; adjust according to renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEMSER (DEMSER).
| Breastfeeding | No human data available; M/P ratio unknown. Demser (metyrosine) may suppress prolactin via dopamine agonism. Discontinue breastfeeding or drug based on need. |
| Teratogenic Risk | Category C: Inadequate human data; animal studies show risk. First trimester: Potential for limb defects and neural tube closure delays based on animal models. Second/Third trimester: Risk of placental hypoperfusion due to alpha-receptor antagonism. Avoid use in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to metyrosine; concurrent use with antipsychotics (increased risk of extrapyramidal effects); severe renal impairment; untreated pheochromocytoma with catecholamine-induced cardiac dysfunction.
| Precautions | Crystalluria and urolithiasis (maintain high fluid intake), extrapyramidal symptoms, sedation/drowsiness, depression/suicidal ideation, diarrhea, and orthostatic hypotension. Monitor urine output and renal function. |
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| Monitor maternal blood pressure, heart rate, and catecholamine levels. Fetal ultrasound for growth and amniotic fluid volume; nonstress test after 24 weeks. |
| Fertility Effects | May impair fertility in females by disrupting hypothalamic-pituitary-ovarian axis; in males, reports of erectile dysfunction and reduced libido. |