Pharmaceutical Approval Update: Somatropin (Recombinant DNA origin) Injection (Norditropin)

Posted by James

Manufacturer: Novo Nordisk, Princeton, NJ Indications:

Pediatric Patients: Norditropin is indicated for the long-term treatment of children with growth failure due to inadequate secretion of endogenous growth hormone (GH). GH is also known as somatotropin.

Adult Patients: Norditropin injection cartridges (soma-tropin) can replace endogenous GH in adults with GH deficiency who meet either of these criteria:

Adult onset: Patients with GH deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma.

Childhood onset: Patients who were deficient in GH during childhood as a result of congenital, genetic, acquired, or idiopathic causes. The confirmation of the diagnosis of adult GH deficiency in both groups usually requires an appropriate GH stimulation test. However, confirmatory GH stimulation testing may not be necessary in patients with congenital or genetic GH deficiency or multiple pituitary hormone deficiencies resulting from organic disease. canadian discount drugs

Drug Class: Somatropin is a polypeptide hormone of recombinant DNA (rDNA) origin that stimulates growth in humans. The hormone is synthesized by a special strain of Escherichia coli bacteria that has been modified by the addition of a plasmid that carries the gene for human GH. Somatropin of rDNA origin contains the identical sequence of 191 amino acids constituting the naturally occurring pituitary human GH. The molecular weight is about 22,000 daltons.

Uniqueness of Drug: If a child’s short stature is caused by a deficiency of human GH, the child might benefit from GH therapy. Children who have GH deficiency may be able to achieve their full growth potential with daily injections of GH.

In adults who require replacement of endogenous GH, soma-tropin may also be beneficial. GH therapy may help adults with GH deficiency regulate body fat distribution, muscle mass, and bone mineral density.

Warnings: Somatropin cartridges must be used with their corresponding color-coded NordiPen (injection pen) delivery device. The cartridge must not be inserted into a pen with a different color code. The mortality rate may be increased in patients with acute critical illness resulting from complications following open-heart surgery, abdominal surgery, or multiple accidental trauma or in those with acute respiratory failure.

The safety of continuing somatropin in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of continuing treatment in patients experiencing acute critical illnesses should be weighed against the potential risk.
buy antibiotics without prescription

Fatalities have occurred after somatropin therapy was initiated in pediatric patients with Prader-Willi syndrome who had one or more of these risk factors: severe obesity, a history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females.

Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before treatment with somatropin begins. During treatment, if patients show signs of upper airway obstruction or new-onset sleep apnea, therapy should be interrupted.

For patients with Prader-Willi syndrome, an effective weight-control program is essential. These patients should be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively. Unless patients with Prader-Willi syndrome also have GH deficiency, somatropin is not indicated for the long-term treatment of pediatric patients with growth failure caused by genetically confirmed Prader-Willi syndrome.

Precautions: The product should be injected under the regular guidance of a physician experienced in the diagnosis and management of pediatric patients with GH deficiency or of adults with either childhood-onset or adult-onset GH deficiency.

Somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during treatment. Glucose levels should be monitored periodically in all patients, especially in those with risk factors for diabetes mellitus, such as obesity (including obese patients with Prader-Willi syndrome), Turner syndrome, or a family history of diabetes mellitus.

Patients with pre-existing type-1 or type-2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of insulin or oral anti-hyperglycemic agents may need to be adjusted when soma-tropin therapy is instituted in these patients. kamagra uk

Patients with pre-existing tumors or GH deficiency secondary to an intracranial lesion should be examined routinely for progression or recurrence of the underlying disease process. In children, the literature has not shown a relationship between somatropin replacement therapy and CNS tumor recurrence or new extracranial tumors. However, in childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients receiving somatropin after their first neoplasm. Intracranial tumors, especially meningiomas in patients receiving radiation to the head for their first neoplasm, were the most common of these second neoplasms. In adults, it is unknown whether there is any relationship between somatropin therapy and CNS tumor recurrence.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, or vomiting has been reported in a small number of patients. Symptoms usually occurred within the first eight weeks after the initiation of somatropin therapy. In all cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or after a reduction of the somatropin dose.

Funduscopic examination should be performed routinely before treatment with somatropin begins to exclude preexisting papilledema and, periodically, during the course of somatropin therapy. If papilledema is observed by funduscopy during treatment, somatropin should be stopped. If soma-tropin-induced IH is diagnosed, somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome, chronic renal insufficiency, and Prader-Willi syndrome may be at increased risk for IH.

In patients with hypopituitarism (multiple hormone deficiencies), standard hormonal replacement should be monitored closely when somatropin is administered. Undiagnosed or untreated hypothyroidism may prevent an optimal response to somatropin, especially the growth response in children.

Patients with Turner syndrome have an inherently increased risk for autoimmune thyroid disease and primary hypothyroidism. In patients with GH deficiency, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients should have periodic thyroid function tests, and thyroid hormone replacement therapy should be initiated or adjusted when indicated.

Patients should be monitored carefully for any malignant transformation of skin lesions. When subcutaneous (SQ) soma-tropin is administered at the same site over a long period of time, tissue atrophy may result. This can be avoided if the physician uses alternative injection sites. kamagra soft tablets

As with any protein product, local or systemic allergic reactions may occur. Parents and patients should be informed that such reactions are possible and that they should seek prompt medical attention if a reaction occurs.

Pediatric Patients. A slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders (including pediatric GH deficiency and Turner syndrome) or in patients undergoing rapid growth. Children with an onset of a limp or a complaint of hip or knee pain during somatropin therapy should be evaluated.

Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases the growth rate, patients with a history of scoliosis who are receiving so-matropin should be monitored for the progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities, including sco-liosis, are commonly seen in untreated patients with Turner syndrome. Scoliosis is also common in untreated patients with Prader-Willi syndrome. Physicians should be alert to these abnormalities, which may become manifested during soma-tropin therapy.

Adults. Patients with epiphyseal closure who were treated with somatropin in childhood should be re-evaluated according to the criteria in the indications before continuing soma-tropin therapy at the reduced dose level recommended for GH-deficient adults. Fluid retention may occur during soma-tropin replacement in adults. Clinical manifestations of fluid retention are usually transient and dose-dependent. Experience with prolonged treatment in adults is limited.

Dosage and Administration:

Pediatric Patients. The dosage and schedule of administration of somatropin must be tailored for each patient. For the treatment of GH insufficiency in children, a dose of 0.024 to 0.034 mg/kg per day of body weight, six to seven times a week, by SQ injection is recommended. The thigh is the preferred site of injection, but the injection site should be rotated.

Somatropin treatment of growth failure resulting from GH deficiency should be discontinued when the epiphyses are fused. Patients who do not respond adequately during soma-tropin therapy should be evaluated to determine the cause of unresponsiveness. kamagra oral jelly 100mg

Adults. The recommended dosage at the start of therapy is not more than 0.004 mg/kg given as a daily SQ injection. The dosage may be increased to no more than 0.016 mg/kg per day after approximately six weeks according to individual patient requirements.

Clinical response, side effects, and determination of age-adjusted and sex-adjusted serum insulin growth factor-I (IGF-I) levels may be used to guide dose titration. Alternatively, according to the more recent literature, a starting dose of approximately 0.2 mg/day (from 0.15 to 0.30 mg/day) may be used without regard to body weight. This dose can be increased gradually every one to two months by increments of approximately 0.1 to 0.2 mg/day, according to individual requirements based on clinical responses and serum IGF-I concentrations. During therapy, the somatropin dose should be decreased if required by the occurrence of adverse events or serum IGF-I levels above the age and sex-specific normal range.

Maintenance dosages vary considerably. A lower starting dose and smaller dose increments should be considered for older patients, who are more prone to the adverse effects of somatropin than younger patients. Obese patients are also more likely to experience adverse effects when treated with a weight-based regimen. To reach defined treatment goals, estrogen-replete women may need higher doses than men. Oral estrogen administration may increase the dose requirements in women.

All Patients. The injection cartridges are administered via the NordiPen injection pen. Each cartridge size has a color-coded corresponding pen that is graduated to deliver the appropriate dose based on the concentration of somatropin in the cartridge. Somatropin must not be injected if the solution is cloudy or if it contains particulate matter. The solution should be used only if it is clear and colorless.

Commentary: The newest FDA indication for somatropin is for short stature in children with Noonan syndrome. When the pituitary gland does not produce or release enough GH, a deficiency results. In children, GH is a primary regulator of growth. In adults, GH helps regulate metabolism and helps keep bones and muscles healthy. buy levitra uk

Noonan syndrome is a rare autosomal dominant genetic syndrome commonly characterized by short stature, congenital heart defects, and unique facial features. Patients can have widely set or down-slanting eyes and a webbed neck. Congenital heart disease occurs in half of affected patients. Up to 80% of children with Noonan syndrome have significant short stature. Few treatment options are available to help their physical development, and the approval of the drug marks an exciting advance for children with this rare condition. Soma-tropin injection has received an orphan drug designation.