Saizen (Somatropin) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

Somatropin inhibits 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) in adipose/hepatic tissue and may significantly impact the metabolism of cortisol and cortisone. As a consequence, in patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked requiring glucocorticoid replacement therapy. In addition, patients treated with glucocorticoid replacement therapy for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses; this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of the 11βHSD-1 enzyme.

Excessive glucocorticoid therapy may attenuate the growth promoting effects of somatropin in children. Therefore, glucocorticoid replacement therapy should be carefully adjusted in children with concomitant GH and glucocorticoid deficiency to avoid both hypoadrenalism and an inhibitory effect on growth.

There was no evidence in the controlled studies of an interaction between Saizen^® and any of the drugs commonly used in the treatment of routine pediatric problems/illnesses.

Limited published data indicate that somatropin treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in man. These data suggest that somatropin administration may alter the clearance of compounds known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine). Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CP450 liver enzymes. However, formal drug interaction studies have not been conducted.

In adult women on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal (see DOSAGE AND ADMINISTRATION).

In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral agent may require adjustment when somatropin therapy is initiated (see PRECAUTIONS, General).

OVERDOSAGE SECTION

Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Moreover, overdose with somatropin is likely to cause fluid retention.

Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess human growth hormone.

CONTRAINDICATIONS SECTION

Saizen^® is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients.

Saizen^® reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol (see Warnings).

Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses.

Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy.

In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor.

Somatropin should not be used to treat patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (see WARNINGS).

Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Saizen^® is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.