Managed Care - March 2008 - (Page 57) TOMORROW’S MEDICINE Recently-Approved Sapropterin Reduces Phenylalanine Levels When diet is not enough, a well known metabolic disorder can now be managed better through medication Thomas Morrow, MD P henylketonuria (PKU) is a disease that most of the readers of this column have probably heard about as a result of having their own children screened for the condition at birth. It is an inherited disease that follows simple Mendelian genetic inheritance patterns (remember the classroom discussions involving the Punnett square?) with 1 in 4 children who are born to carriers inheriting the disease. Prevalence varies from 1 in 12,000 to 1 in 25,000 births in the United States, with those of northern European and native American descent having a higher probability of having PKU than those of African, Hispanic, or Asian ancestry. There are an estimated 50,000 patients diagnosed with PKU in the developed world. The cause of the disorder is a damaging mutation of the phenylalanine hydroxylase (PAH) gene that sits on chromosome 12. This gene codes for PAH, an enzyme that converts phenylalanine (Phe), an essential amino acid, to tyrosine (see “Role of Phenylalanine” on page 58). But a Phe-controlled diet results in an increased carbohydrate intake that can lead to weight gain. Noncompliance is a huge problem because of the limits on the types and amounts of foods, as well as the palatability of the foods that are available. New treatment In December 2007, the FDA approved a new drug, sapropterin dihydrochloride (trade name Kuvan), just three years after the submission of the IND (investigational new drug) application. Kuvan is indicated to reduce blood levels of phenylalanine in patients with hyperphenylalaninemia because of BH4-responsive phenylketonuria. Kuvan is to be used in conjunction with a low-Phe diet. Kuvan works with the enzyme PAH to reduce Phe levels. Thus, if there is a total absence of PAH, or if the enzyme is damaged to a great extent, treatment with Kuvan will not lower Phe levels. The recommended starting dose is 10 mg/kg/day taken once daily. Kuvan is available in 100 mg tablets. These are dissolved in either water or apple juice and taken at approximately the same time each day. Phe serum levels should be measured before therapy is initiated, after one week of treatment, and periodically during the first month of treatment. If a dramatic response is noted, decreasing the dose to 5 mg/kg/day is recommended. If a response is not noted, increasing the dose to 20 mg/kg/day is recommended. Serum levels would be measured over the next month. A >30 percent decrease in Phe level from baseline is considered a positive response. It is important to maintain a Phe-controlled diet Thomas Morrow, MD, is the immediate past president of the National Association of Managed Care Physicians. He has 23 years of managed care experience at the payer or health plan level. Diet Until recently, the only treatment for those affected by PKU was a low phenylalanine diet, meaning a diet low in all major sources of protein, as well as foods containing flour and corn and some fruits and vegetables. For infants, this means a special formula with little or no breast milk. For older children and teenagers, food preparation involves careful measuring, calculating, and monitoring of day-to-day intake of phenylalanine. It also calls for routine monitoring of blood levels of phenylalanine to maintain levels within strict limits. Diet therapy was originally thought to be needed only during early childhood development. It is now recommended that adults also follow a strict Phe diet. MARCH 2008 / MANAGED CARE 57
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