Zomacton (somatropin) injection, for subcutaneous use

Zomacton (somatropin)

Active Ingredient

Administration Route

Alcohol Warning

Available Strength

• 5 mg vial with a 5 mL vial of bacteriostatic 0.9% sodium chloride [preserved with benzyl alcohol]
• 10 mg vial with a syringe of 1 mL of bacteriostatic water [preserved with metacresol] with a 25G reconstitution needle
• 10 mg vial with a syringe of 1 mL of bacteriostatic water [preserved with metacresol] with a vial adapter

Breastfeeding Warning

Following subcutaneous administration of radiolabelled medication in animal studies, radioactivity was transferred to milk reaching four  times the concentration found in maternal plasma. However, absorption of the intact protein in the gastrointestinal tract of the infant is considered extremely unlikely.

Clinical Pharmacology

Tissue Growth:
The primary and most intensively studied action of somatropin is the stimulation of linear growth. This effect is demonstrated in children with GHD.

Skeletal Growth:
The measurable increase in bone length after administration of somatropin results from its effect on the cartilaginous growth areas of long bones. Studies in vitro have shown that the incorporation of sulfate into proteoglycans is not due to a direct effect of somatropin, but rather is mediated by the somatomedins or insulin-like growth factors (IGFs). The somatomedins, among them IGF-I, are polypeptide hormones which are synthesized in the liver, kidney, and various other tissues. IGF-I levels are low in the serum of hypopituitary dwarfs and hypophysectomized humans or animals, and increase after treatment with somatropin.

Cell Growth:
It has been shown that the total number of skeletal muscle cells is markedly decreased in children with short stature lacking endogenous GH compared with normal children, and that treatment with somatropin results in an increase in both the number and size of muscle cells.

Organ Growth:
Somatropin influences the size of internal organs, and it also increases red cell mass.

Protein Metabolism:
Linear growth is facilitated in part by increased cellular protein synthesis. This synthesis and growth are reflected by nitrogen retention which can be quantitated by observing the decline in urinary nitrogen excretion and blood urea nitrogen following the initiation of somatropin therapy.

Carbohydrate Metabolism:
Hypopituitary children sometimes experience fasting hypoglycemia that may be improved by treatment with somatropin. In healthy subjects, large doses of somatropin may impair glucose tolerance. Although the precise mechanism of the diabetogenic effect of somatropin is not known, it is attributed to blocking the action of insulin rather than blocking insulin secretion. Insulin levels in serum actually increase as somatropin levels increase. Administration of human growth hormone to normal adults and patients with growth hormone deficiency results in increases in mean serum fasting and postprandial insulin levels, although mean values remain in the normal range. In addition, mean fasting and postprandial glucose and hemoglobin A1c levels remain in the normal range.

Lipid Metabolism:
Somatropin stimulates intracellular lipolysis, and administration of somatropin leads to an increase in plasma free fatty acids and triglycerides. Untreated GHD is associated with increased body fat stores, including increased abdominal visceral and subcutaneous adipose tissue. Treatment of growth hormone deficient patients with somatropin results in a general reduction of fat stores, and decreased serum levels of low density lipoprotein (LDL) cholesterol.

Mineral Metabolism:
Administration of somatropin results in an increase in total body potassium and phosphorus and to a lesser extent sodium. This retention is thought to be the result of cell growth. Serum levels of phosphate increase in children with GHD after somatropin therapy due to metabolic activity associated with bone growth. Serum calcium levels are not altered. Although calcium excretion in the urine is increased, there is a simultaneous increase in calcium absorption from the intestine. Negative calcium balance, however, may occasionally occur during somatropin treatment.

Connective Tissue Metabolism:
Somatropin stimulates the synthesis of chondroitin sulfate and collagen, and increases the urinary excretion of hydroxyproline.

Pharmacokinetics

Absorption

Somatropin has been studied following subcutaneous, and intravenous administration in adult healthy subjects. A single subcutaneous dose of 4 mg ZOMACTON in healthy subjects (n=54) with suppressed endogenous growth hormone resulted in a mean (SD) Cmax of 38.1 (19.3) ng/mL after approximately 4.5 hours. The absolute bioavailability of somatropin is approximately 70% after subcutaneous administration.

Distribution

The mean (SD) apparent volume of distribution of somatropin after single dose subcutaneous administration of 4 mg ZOMACTON in healthy subjects is 53.3 (24.6) L.

Metabolism

Extensive metabolism studies have not been conducted. The metabolic fate of somatropin involves classical protein catabolism in both the liver and kidneys.

Excretion

In healthy subjects, mean somatropin clearance is 0.133 L/min following intravenous administration. The mean elimination half-life of intravenous somatropin is 0.42 hours, whereas subcutaneously administered somatropin has a mean half-life of 2.3 hours. The longer half-life observed after subcutaneous administration is due to slow absorption from the injection site. Urinary excretion of intact somatropin has not been measured.

Specific Populations

Geriatric patients: The pharmacokinetics of somatropin have not been studied in patients greater than 65 years of age.

Pediatric patients: The pharmacokinetics of somatropin in pediatric patients are similar to those of adults.

Male and Female Patients. No gender-specific pharmacokinetic studies have been performed with somatropin. The available literature indicates that the pharmacokinetics of somatropin are similar in men and women.

Patients with Renal or Hepatic Impairment: No studies have been performed with somatropin.

Cost

from  http://www.goodrx.com/Zomacton

Injectible powder for injection:

• 5 mg (1 powder for injection): $311.26

lyophilisate for solution for injection:

• 10 mg (1 powder for injection): $614.02

Dosage Form

Dose Schedule

• Pediatric dosage:

– Divide the calculated weekly dosage into equal doses given either 3, 6, or 7 days per week

– The recommended weekly dose is 0.18 mg/kg/week to 0.3 mg/kg/week

• Adult dosage:

Either of the following two dosing regimens may be used:

– Non-weight based dosing: Initiate with a dose of approximately 0.2 mg/day (range, 0.15 mg/day-0.3 mg/day) and increase the dose every 1­2 months by increments of approximately 0.1 mg/day-0.2 mg/day, according to individual patient requirements.

– Weight-based dosing (Not recommended for obese patients): Initiate at 0.006 mg/kg daily and increase the dose according to individual patient requirements to a maximum of 0.0125 mg/kg daily

Drug Class

Drug Unit

Food Warning

Included In
Health Insurance Plan

Interacting Drug

Is Available Generically

Is Proprietary

Label Details

Legal Status

Is not subject to the Controlled Substances Act.

Manufacturer

Maximum Intake

Mechanism of Action

Non Proprietary Name

Overdosage

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

Pregnancy Category

AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Pregnancy Warning

Animal studies did not show any teratogenicity or adverse effects on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offspring; a slight increase in fetal death and increased body weight of pups, and reduced pregnancy rate, increased litter size, irregular estrus cycles, and decreased sperm motility in the parents were seen. There are no controlled data in human pregnancy.

Prescribing Info

Prescription Status

Proprietary Name

Related Drugs

RxCUI

Warning

Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk.

Prader-Willi Syndrome in Children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment for GHD. Discontinue treatment if these signs occur.

Neoplasm: Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin – in particular meningiomas in patients treated with radiation to the head for their first neoplasm.

Impaired Glucose Tolerance and Diabetes Mellitus: May be unmasked. Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment.

Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction.

Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention.

Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome – especially in adults): May occur frequently. Reduce dose as necessary.

Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism.

Hypothyroidism: May first become evident or worsen.

Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the

onset of a limp or hip/knee pain.

Progression of Preexisting Scoliosis: May develop.

Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain.