Contraindication Added to Growth Hormone Product
Children whose short stature is due to a certain congenital disorder and who are severely obese or have severe breathing problems must not receive Pfizer Inc.'s growth hormone product, according to a company letter circulated Friday by the Food and Drug Administration (FDA).
The "Dear Health Care Professional" letter, dated May 30, stated that the company had received seven reports describing the deaths of children with Prader-Willi syndrome who received growth hormone therapy.
According to Prader-Willi Syndrome Association (USA), two of the seven reports were from the United States, and the other five from elsewhere in the world.
Pfizer's Genotropin, a recombinant human growth hormone known by the generic name somatropin, is the only such product with FDA-approved labeling for the long-term treatment of children whose short stature is due to Prader-Willi syndrome. This indication was added three years ago on the basis of two clinical studies involving no more than two dozen children total.
Prader-Willi syndrome occurs in one of every 12,00015,000 persons, according to the patient advocacy association, and is characterized by diminished skeletal-muscle tone in infants, excessive or rapid weight gain between ages 1 and 6 years, food foraging, obsession with food, learning problems, distinctive facial features, and hypogonadism. Short stature not otherwise explained by a person's genetics is considered a minor criterion for the diagnosis of Prader-Willi syndrome, the association said.
The Pfizer letter noted that the patients who died had at least one of the following risk factors: severe obesity, history of respiratory impairment or sleep apnea, or unidentified respiratory-tract infection.
Genotropin's labeling (PDF) was revised in April to warn clinicians about the need to evaluate patients with Prader-Willi syndrome for the presence of an upper-airway obstruction before starting growth hormone therapy and to interupt the treatment if signs of an obstruction occur. Also, patients should be evaluated for sleep apnea and monitored for signs of respiratory-tract infection.
Three other somatropin products are marketed in the United States for indications unrelated to Prader-Willi syndrome: Humatrope, by Eli Lilly and Co.; Nutropin, by Genentech Inc.; and Saizen, by Serono Inc. Escherichia coli is used in the synthesis of Genotropin, Humatrope, and Nutropin, and mouse cells are used in the manufacture of Saizen.
Neither FDA nor Prader-Willi Syndrome Association (USA) identified the source or sources of the growth hormone product linked to the deaths.