Urea May Offer Cheaper Option for Long-Term SIADH Treatment
Researchers present results from the first long-term study of Urea USP in the United States.
CHICAGO—The first long-term results of a US study of urea as a treatment for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) suggest it is safe and effective and could be an inexpensive alternative to other medications, researchers concluded in a poster presentation at the American Society of Nephrology's Kidney Week 2016 meeting.
Urea may provide another option for patients who are intolerant of demeclocycline (a mainstay of SIADH therapy in the United States) or who cannot afford this drug or tolvaptan, according to investigators led by Gregory Braden, MD, of the University of Massachusetts Medical School-Baystate Medical Center in Springfield.
For more than 35 years, urea has been used for the long-term treatment of SIADH in Europe, where it is the treatment of choice for the syndrome, Dr Braden said.
Urea USP is made by Merck in Germany and is available in the United States from MEDISCA, a Canadian compounding company, through the wholesale distributor Cardinal Health, Dr Braden noted.
In a 6-month trial, Dr Braden and his colleagues examined the effects of Urea USP in 6 SIADH patients, all of whom had hypouricemia (uric acid levels below 4 mg/dL). The patients took Urea USP—which was mixed in fruit syrup or juice—at a dose of 10–15 grams orally twice daily. For the first week, patients were instructed to limit oral fluid intake to 1000 mL daily.
Prior to urea treatment, patients had a mean serum sodium level of 126 mEq/L. This rose to 132 mEq/L after 1 week of treatment and 136 mEq/L after 6 months of therapy. The mean plasma osmolality increased from 266 mOsm/kg H2O at baseline to 287 mOsm/kg H2O after 6 months. Mean serum uric acid levels increased from 2.7 mg/dL before urea therapy to 3.8 mg/dL after 1 week of urea therapy (normalized) and 4.7 mg/dL after 6 months. Additionally, the fractional excretion of uric acid was elevated at the time of SIADH diagnosis and decreased to normal after 1 week of therapy and remained normal (less than 12%) during the 6 months of treatment.
Urea is a little distasteful, but not terribly so, and patients can drink whatever they want, Dr Braden said. “It's a real quality of life issue,” he said.
Dr Braden's study of urea for SIADH was a response to the high cost of tolvaptan and demeclocycline. The cost of tolvaptan for a patient with no Medicare supplement plan D for drugs can be as high as $11,000 per month for a 15–30 mg daily dose, Dr Braden noted. The manufacturers of demeclocycline have increased the price of the drug to $1,000 per month for an average dose of 600 mg twice daily. By comparison, the cost of urea USP 10-15 grams twice daily is between $120 and $240 per month, he said.
- Braden G et al. Urea for SIADH: The first U.S. long-term results. Presented in poster format at Kidney Week 2016 in Chicago, Nov. 15-20.