Pheochromocytomas are uncommon, catecholamine-releasing tumors arising from chromaffin cells in the adrenal
medulla.1 The majority of pheochromocytomas (about 75%) are benign; however, hypersecretion of
catecholamines can lead to hypertension, which may cause cardiovascular disease and death. Proper diagnosis and
treatment can reduce morbidity and mortality.2,3
Sporadic pheochromocytoma is mostly diagnosed between the ages of 40 and 50.4 A genetic susceptibility has
been identified and occurs in up to 40% of patients; this genetic component occurs at a higher incidence than for
any other solid tumor.2,5 The only cure for benign pheochromocytoma is surgery.6
Clinical manifestations and diagnostic considerations
Most of the signs and symptoms of pheochromocytomas result from the release of epinephrine, norepinephrine, and
dopamine.7,8 There are differences in biochemical patterns, and only about half of pheochromocytomas
secrete both epinephrine and norepinephrine.9 The most common signs and symptoms are persistent or
episodic hypertension, sweating, palpitations, and headache.2,5 Patients may also be
In the evaluation of pheochromocytoma, plasma or urine levels of normetanephrine, metanephrine, or 3-methoxytyramine
indicative of catecholamine overproduction provide good diagnostic sensitivity and specificity.2,8
A treatable disorder
It is important to treat a pheochromocytoma because of the potential cardiovascular risks.2,8 The mainstay
of treatment is the complete surgical removal of the lesion.6 Preoperative medical treatment is typically
recommended to reduce symptoms of catecholamine excess and the risk of perioperative cardiovascular
complications.10,11 Treatment generally starts with phenoxybenzamine to induce an alpha-adrenergic
blockade.6 DEMSER® (metyrosine) is a false catecholamine precursor that inhibits tyrosine
hydroxylase, the rate-limiting enzyme in catecholamine synthesis. DEMSER® reduces catecholamine synthesis
by up to 80%. The maximum biochemical effect usually occurs within 2 to 3 days, and the urinary concentration of
catecholamines and their metabolites usually returns to pretreatment levels within 3 to 4 days after
DEMSER® is discontinued. In some patients, the total excretion of catecholamines and catecholamine
metabolites may be lowered to normal or near normal levels (less than 10 mg/24 hours).12
DEMSER® (metyrosine) capsules are indicated in the treatment of patients with pheochromocytoma
for: preoperative preparation of patients for surgery, management of patients when surgery is contraindicated,
and/or chronic treatment of patients with malignant pheochromocytoma. DEMSER is not recommended for the control of
IMPORTANT SAFETY INFORMATION
- DEMSER is contraindicated in persons known to be hypersensitive to this compound.
- Maintain adequate intravascular volume intraoperatively (especially after tumor removal) and postoperatively to
avoid hypotension and decreased perfusion of vital organs resulting from vasodilatation and expanded volume
- Life-threatening arrhythmias may occur during anesthesia and surgery. Monitor blood pressure and
electrocardiogram continuously during surgery.
- DEMSER does not eliminate the danger of hypertensive crises or arrhythmias during manipulation of the tumor, and
the alpha-adrenergic blocking drug, phentolamine, may be needed.
- DEMSER may add to the sedative effects of alcohol and other CNS depressants, e.g., hypnotics, sedatives, and
- To minimize the risk of crystalluria, patients should be urged to maintain water intake sufficient to
achieve a daily urine volume of 2000 mL or more, particularly when doses greater than 2 g per day are given.
Routine examination of the urine should be carried out. If metyrosine crystalluria occurs, fluid intake
should be increased further. If crystalluria persists, the dosage should be reduced or the drug
- Observe caution in patients with impaired hepatic or renal function.
- Warn patients about engaging in activities requiring mental alertness and motor coordination, such as driving a
motor vehicle or operating machinery.
- Advise patients to maintain liberal fluid intake.
- Use caution in administering DEMSER to patients receiving phenothiazines or haloperidol because the
extrapyramidal effects of these drugs can be expected to be potentiated by inhibition of catecholamine
- The most common adverse reaction to DEMSER is moderate to severe sedation. Other commonly reported adverse
reactions are extrapyramidal signs such as drooling, speech difficulty and tremor in approximately 10 percent of
patients, occasionally accompanied by trismus and frank Parkinsonism. Anxiety and psychic disturbances such as
depression, hallucinations, disorientation, and confusion may occur. Diarrhea occurs in about 10 percent of
patients and may be severe.
To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health Customer Service at 1-800-321-4576 or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
CLICK HERE FOR
References: 1. Fang F, Ding L, He Q, Liu M. Preoperative management of
pheochromocytoma and paraganglioma. Front Endocrinol. 2020;11:586795. doi: 10.3389/fendo.2020.586795
2. Farrugia F-A, Charalampopoulos A. Pheochromocytoma. Endocrine Reg. 2019;53(3):191-212.
3. Prejbisz A, Lenders JW, Eisenhofer G, Januszewicz A. Cardiovascular manifestations of
phaeochromocytoma. J Hypertens. 2011;29(11):2049-2060. 4. Bihain F, Klein M, Nomine-Criqui
C, Brunaud L. Robotic adrenalectomy in patients with pheochromocytoma: a systematic review. Gland Surg.
2020;9(3):844-848. 5. Fishbein L. Pheochromocytoma and paraganglioma: Genetics, diagnosis, and
treatment. Hematol Oncol Clin North Am. 2016;30(1):135-150. 6. Aygun N, Uludag M.
Pheochromocytoma and paraganglioma: from treatment to follow-up. Med Bull Sisli Etfal Hosp.
2020;54(4):391-398. 7. Pappachan JM, Raskauskiene D, Sriraman R, Edavalath M, Hanna FW. Diagnosis
and management of pheochromocytoma: A practical guide to clinicians. Curr Hypertens Rep. 2014;16(7):442.
doi: 10.1007/s11906-014-0442-z 8. Berends AMA, Eisenhofer G, Fishbein L, et al. Intricacies of the
molecular machinery of catecholamine biosynthesis and secretion by chromaffin cells of the normal adrenal medulla
and in pheochromocytoma and paraganglioma. Cancers. 2019;11:1121. doi:10.3390/cancers11081121
9. Tsirlin A, Oo Y, Sharma R, Kansara A, Gliwa A, Banerji MA. Pheochromocytoma: A review.
Maturitas. 2014;77(3):229-238. 10. Mannelli M, Dralle H, Lenders JWM. Perioperative
management of pheochromocytoma/paraganglioma: Is there a state of the art? Horm Metab Res.
2012;44(5):373-378. 11. Wachtel H, Kennedy EH, Zaheer S, et al. Preoperative metyrosine improves
cardiovascular outcomes for patients undergoing surgery for pheochromocytoma and paraganglioma. Ann Surg
Oncol. 2015; 22(suppl 3):S646-S654. 12. Demser. Package insert. Bausch Health US, LLC;