Somatropin

Pronunciation: (SOE-ma-TROE-pin)
Class: Growth hormone

Trade Names

Accretropin
- Injection, solution 5 mg/mL

Genotropin
- Injection, lyophilized powder for solution 5.8 mg
- Injection, lyophilized powder for solution 13.8 mg

Genotropin Miniquick
- Injection, lyophilized powder for solution 0.2 mg
- Injection, lyophilized powder for solution 0.4 mg
- Injection, lyophilized powder for solution 0.6 mg
- Injection, lyophilized powder for solution 0.8 mg
- Injection, lyophilized powder for solution 1 mg
- Injection, lyophilized powder for solution 1.2 mg
- Injection, lyophilized powder for solution 1.4 mg
- Injection, lyophilized powder for solution 1.6 mg
- Injection, lyophilized powder for solution 1.8 mg
- Injection, lyophilized powder for solution 2 mg

Humatrope
- Injection, lyophilized powder for solution 5 mg
- Injection, lyophilized powder for solution 6 mg
- Injection, lyophilized powder for solution 12 mg
- Injection, lyophilized powder for solution 24 mg

Norditropin
- Injection 5 mg per 1.5 mL
- Injection 10 mg per 1.5 mL
- Injection 15 mg per 1.5 mL

Nutropin
- Injection, lyophilized powder for solution 5 mg
- Injection, lyophilized powder for solution 10 mg

Nutropin AQ
- Injection 10 mg

Omnitrope
- Injection, lyophilized powder for solution 1.5 mg
- Injection, lyophilized powder for solution 5.8 mg
- Injection, solution 5 mg per 1.5 mL

Saizen
- Injection, lyophilized powder for solution 5 mg
- Injection, lyophilized powder for solution 8.8 mg

Serostim
- Injection, lyophilized powder for solution 4 mg
- Injection, lyophilized powder for solution 5 mg
- Injection, lyophilized powder for solution 6 mg

Tev-Tropin
- Injection, lyophilized powder for solution 5 mg

Zorbtive
- Injection, lyophilized powder for solution 8.8 mg

Nutropin AQ Pen Cartridge (Canada)
Saizen click.easy (Canada)
Serostim click.easy (Canada)

Pharmacology

Mimics actions of naturally occurring growth hormone (GH) to stimulate linear and skeletal growth; increases number and size of skeletal muscle cells; increases RBC mass and internal organ size; increases cellular protein synthesis; reduces body fat stores and lipid mobilization, and increases plasma fatty acids.

Pharmacokinetics

Absorption

Somatropin C _max with concentrations of 5.3 mg/mL is approximately 23 ng/mL. C _max with concentrations of 1.3 mg/mL is approximately 17.4 ng/mL. Following a 0.03 mg/kg subcutaneous injection of Genotropin 1.3 mg/mL, about 80% was systemically available compared with that available following IV dosing.

Norditropin

Following a subcutaneous injection of 0.024 mg/kg, the C _max was 13.8 ng/mL 4 to 5 h postdose.

Omnitrope

Following a subcutaneous injection of a single dose of 5 mg, the C _max and T _max are 74 mcg/L and 4 h, respectively.

Distribution

Vd is approximately 1.3 L/kg.

Metabolism

Somatropin undergoes classical protein catabolism in both liver and kidneys.

Elimination

The half-life is approximately 0.4 h (IV) and approximately 3 h (subcutaneous). Mean Cl of subcutaneous administration is about 0.3 L/h/kg.

Norditropin

The mean apparent half-life ranged from 7 to 10 h (subcutaneous).

Omnitrope

Mean terminal half-life is 2.8 h (subcutaneous).

Special Populations

Renal Function Impairment

Patients with chronic renal failure (CRF) and end-stage renal disease have decreased Cl compared with healthy individuals.

Genotropin

No studies have been conducted.

Hepatic Function Impairment
Genotropin

No studies have been conducted.

Children
Genotropin

Pharmacokinetics similar in children and adults.

Gender
Genotropin

Bioavailability similar in men and women.

Race
Genotropin

No studies have been conducted.

Indications and Usage

Long-term treatment of children with growth failure caused by lack of adequate endogenous GH secretion (except Serostim , Zorbtive ).

Accretropin , Genotropin , Humatrope , Norditropin , Nutropin , Nutropin AQ , Omnitrope , Saizen

Replacement of endogenous GH in adults with GH deficiency (GHD) of either childhood- or adult-onset etiology.

Accretropin , Genotropin , Humatrope , Norditropin , Nutropin , Nutropin AQ

Long-term treatment of children with short stature associated with Turner syndrome.

Genotropin

Treatment of children with growth failure caused by Prader-Willi syndrome; treatment of growth failure in children born small for gestational age who fail to manifest catch-up growth by 2 yr of age.

Humatrope

Treatment of short stature or growth failure in children with short stature homeobox-containing gene deficiency whose epiphyses are not closed.

Humatrope , Genotropin , Nutropin , Nutropin AQ

Long-term treatment of children with idiopathic short stature.

Norditropin

Treatment of children with short stature associated with Noonan syndrome; treatment of children with short stature born small for gestational age with no catch-up growth by 2 to 4 yr of age.

Nutropin , Nutropin AQ

Treatment of growth failure in children associated with chronic renal insufficiency up to the time of renal transplantation.

Serostim

Treatment of AIDS wasting or cachexia.

Zorbtive

Treatment of short bowel syndrome in patients receiving specialized nutritional support.

Contraindications

Active proliferative or severe nonproliferative diabetic retinopathy; acute critical illness caused by complications following open heart surgery, abdominal surgery, or multiple accidental trauma; acute respiratory failure; closed epiphyses in children when used for growth promotion; Prader-Willi syndrome in children who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment; evidence of tumor activity or active neoplasm; sensitivity to benzyl alcohol ( Nutropin , Omnitrope , Saizen , Serostim , Tev-Tropin , Zorbtive diluent), or glycerin or M-cresol ( Humatrope diluent); hypersensitivity to any component of the product. Intracranial lesion must be inactive and antitumor therapy complete prior to instituting therapy.

Dosage and Administration

AIDS Wasting or Cachexia
Adults Serostim

Subcutaneous (at bedtime) More than 55 kg, 6 mg daily; 45 to 55 kg, 5 mg daily; 35 to 45 kg, 4 mg daily; less than 35 kg, 0.1 mg/kg.

Growth Failure
Children Accretropin

Subcutaneous 0.18 to 0.3 mg/kg/wk (divided into 6 or 7 injections).

Humatrope

IM / Subcutaneous 0.18 mg/kg/wk (divided into equal doses given on 3 alternate days, 6 times/wk, or daily) to a max of 0.3 mg/kg.

Norditropin

Subcutaneous 0.024 to 0.034 mg/kg 6 to 7 times/wk.

Nutropin , Nutropin AQ

Subcutaneous Up to 0.3 mg/kg weekly divided into daily injections; pubertal patients may receive up to 0.7 mg/kg weekly in divided daily doses.

Omnitrope

Subcutaneous 0.16 to 0.24 mg/kg weekly, divided into 6 or 7 daily doses.

Saizen

IM / Subcutaneous 0.06 mg/kg 3 times/wk.

Tev-Tropin

Subcutaneous Up to 0.1 mg/kg 3 times weekly.

Growth Failure Associated With Chronic Renal Insufficiency
Adults Nutropin / Nutropin AQ

Subcutaneous Up to 0.35 mg/kg weekly (divided into daily injections) continued up to time of renal transplantation.

Growth Failure, Prader-Willi Syndrome
Children Genotropin

Subcutaneous 0.24 mg/kg/wk (divided into 6 or 7 injections).

GHD
Adults Genotropin

Subcutaneous Start with up to 0.04 mg/kg/wk given as a daily injection, increasing the dose at 4- to 8-wk intervals according to patient requirements (max, 0.08 mg/kg/wk).

Humatrope

Subcutaneous Start with up to 0.006 mg/kg/day, increasing the dose according to patient requirements (max, 0.0125 mg/kg/day).

Nutropin / Nutropin AQ

Subcutaneous Start with up to 0.006 mg/kg/day, increasing the dose according to patient requirements to a max of 0.025 mg/kg/day in patients younger than 35 yr of age and max of 0.0125 mg/kg daily in patients older than 35 yr of age.

Norditropin

Subcutaneous Start with up to 0.004 mg/kg daily. The dose may be increased to a max of 0.016 mg/kg daily after approximately 6 wk according to patient requirements.

Omnitrope

Subcutaneous Start with no more than 0.04 mg/kg weekly given as a daily injection, increasing the dose at 4- to 8-wk intervals according to individual patient requirements (max, 0.08 mg/kg/wk).

Saizen

Subcutaneous Start with up to 0.005 mg/kg daily. Increase the dose to no more than 0.01 mg/kg daily after 4 wk according to individual patient requirements.

Alternative dosing regimen Genotropin , Humatrope , Norditropin , Nutropin , Nutropin AQ , Omnitrope , Saizen

Subcutaneous Alternatively, start with approximately 0.15 to 0.3 mg/day. Increase the dose gradually every 1 to 2 mo by increments of 0.1 to 0.2 mg/day, according to individual patient requirements. The dose may be decreased based on adverse reactions or serum insulin-like growth factor 1 (IGF-1) levels above the age- and gender-specific normal range. Consider a lower starting dose for older patients, who are more prone to adverse reactions.

Idiopathic Short Stature
Children Genotropin

Subcutaneous Up to 0.47 mg/kg weekly divided into 6 or 7 injections.

Humatrope

Subcutaneous 0.37 mg/kg divided into equal doses given 6 to 7 times/wk.

Nutropin , Nutropin AQ

Subcutaneous Start with up to 0.3 mg/kg weekly divided into daily doses.

Short Bowel Syndrome
Adults Zorbtive

Subcutaneous 0.1 mg/kg daily (max, 8 mg/day), rotating the injection sites. Administration for more than 4 wk has not been adequately studied. Treat moderate fluid retention and arthralgia symptomatically, or reduce the dose by 50%. Discontinue treatment for up to 5 days for severe toxicities. Upon resolution of symptoms, resume treatment at 50% of the original dose. Permanently discontinue treatment if severe toxicity persists or does not disappear in 5 days.

Short for Gestational Age
Children Genotropin

Subcutaneous 0.48 mg/kg weekly (divided into 6 or 7 injections).

Norditropin

Subcutaneous Up to 0.067 mg/kg daily.

Short Stature Associated With Noonan Syndrome
Children Norditropin

Subcutaneous 0.066 mg/kg daily.

Short Stature Associated With Turner Syndrome
Children Accretropin

Subcutaneous 0.36 mg/kg weekly divided into 6 or 7 injections.

Genotropin

Subcutaneous 0.33 mg/kg weekly divided into 6 or 7 injections.

Humatrope

Subcutaneous Up to 0.375 mg/kg/wk (divided into equal doses given either daily or on 3 alternate days).

Norditropin

Up to 0.067 mg/kg daily.

Nutropin / Nutropin AQ

Subcutaneous Up to 0.375 mg/kg/wk (divided into equal doses 3 to 7 times/wk).

Short Stature Homeobox
Children Humatrope

Subcutaneous 0.35 mg/kg weekly in equal divided daily doses.

Storage/Stability

Accretropin

Store refrigerated at 36° to 46°F. Avoid freezing and shaking. Once opened, discard after 14 days.

Genotropin

Store lyophilized powder refrigerated at 36° to 46°F. Do not freeze. Protect from light. After reconstitution, store refrigerated at 36° to 46°F for up to 24 h for the 1.5 mg cartridge or up to 28 days for the 5.8 and 13.8 mg cartridge. Store Genotropin Miniquick delivery device prior to dispensing refrigerated or at or below 77°F for up to 3 mo. After reconstitution, the Genotropin Miniquick delivery device may be stored refrigerated for up to 24 h before use. Use once, then discard.

Humatrope

Store cartridges and vials refrigerated at 36° to 46°F. Avoid freezing.

Cartridges

After reconstitution, cartridges are stable for up to 28 days when stored refrigerated at 36° to 46°F. Avoid freezing. Store without the needle attached.

Vials

After reconstitution with Humatrope diluent or bacteriostatic water for injection, vials are stable for up to 14 days when stored refrigerated at 36° to 46°F. Avoid freezing. After reconstitution with sterile water, use only 1 dose per Humatrope vial and discard unused portion. If not used immediately, store refrigerated at 36° to 46°F and use within 24 h.

Norditropin

Unused cartridges and prefilled pens should be stored refrigerated at 36° to 46°F. Do not freeze. Avoid direct light. After the Norditropin cartridge has been inserted into the delivery system ( NordiPen 5 ), it must be stored refrigerated in the pen at 36° to 46°F and used within 4 wk, or stored for up to 3 wk at not more than 77°F. Discard unused portion. After the Norditropin cartridge has been inserted into the delivery system ( NordiPen 15 ), it must be stored refrigerated in the pen at 36° to 46°F and used within 4 wk. Discard unused portion after 4 wk. After the initial injection, the Norditropin NordiFlex (5 mg per 1.5 mL or 10 mg per 1.5 mL) prefilled pen must be stored either in the refrigerator at 36° to 46°F and used within 4 wk, or stored for up to 3 wk at no more than 77°F. Discard unused portion. After the initial injection, the Norditropin NordiFlex 15 mg per 1.5 mL prefilled pen must be stored refrigerated at 36° to 46°F and used within 4 wk. Discard unused portion after 4 wk.

Nutropin

Store refrigerated at 36° to 46°F. Avoid freezing. After reconstitution with bacteriostatic water for injection (benzyl alcohol preserved), store refrigerated at 36° to 46°F for up to 14 days. Avoid freezing. Nutropin AQ vial, cartridge, and NuSpin injection device contents are stable for 28 days after initial use when stored refrigerated at 36° to 46°F. Do not freeze.

Omnitrope

Store refrigerated at 36° to 46°F. Do not freeze. Protect from light.

Cartridges

After first use, store at 36° to 46°F for a max of 21 days.

Vials

After reconstitution, store at 36° to 46°F for up to 24 h (1.5 mg) or 3 weeks (5.8 mg).

Saizen

Store at 59° to 86°F. After reconstitution of the 5 mg or 8.8 mg vials with bacteriostatic water for injection, store refrigerated at 36° to 46°F for up to 14 days. Avoid freezing. After reconstitution of the 8.8 click.easy cartridge with bacteriostatic water for injection, store refrigerated at 36° to 46°F for up to 21 days. Avoid freezing.

Serostim

Store at 59° to 86°F. After reconstitution with sterile water for injection, use immediately and discard any unused portion. After reconstitution with bacteriostatic water for injection, the solution may be stored refrigerated at 36° to 46°F for up to 14 days. Avoid freezing.

Tev-Tropin

Store refrigerated at 36° to 46°F. After reconstitution, store refrigerated at 36° to 46°F for up to 14 days. Do not freeze.

Zorbtive

Store at 59° to 86°F. After reconstitution with bacteriostatic water for injection, store the reconstituted solution refrigerated at 36° to 46°F for up to 14 days. Avoid freezing.

Drug Interactions

Corticosteroids

Somatropin may interfere with the metabolic conversion of cortisol and cortisone to their active metabolites. Glucocorticoids may inhibit growth-promoting effects of somatropin.

CYP-450 substrates (eg, anticonvulsants, cyclosporine)

Somatropin may alter the Cl of drugs metabolized by CYP liver enzymes.

Insulin, oral hypoglycemic agents

Because somatropin decreases insulin sensitivity, diabetic patients receiving drug therapy may require adjustments in the insulin or oral hypoglycemic dosage when somatropin is started or stopped.

Oral estrogens

Larger doses of somatropin may be required in women receiving oral estrogens.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (8%); tachycardia, vasodilatation (1% to less than 10%); dependent edema (1% to less than 5%).

CNS

Headache (18%); paresthesia (17%); dizziness, hypoesthesia (7%); asthenia, fatigue, hypesthesia (6%); insomnia, phantom pain (1% to less than 10%); anorexia, anxiety, hypertonia, somnolence, peripheral neuropathy (1% to less than 5%); intracranial hypertension; intracranial tumors, particularly meningiomas; malaise.

Dermatologic

Acne (6%); alopecia, bullous eruption, skin disorder (1% to less than 10%); maculopapular rash, rash, verruca (1% to less than 5%); growth of existing nevi (rare); pruritus.

EENT

Otitis media (86%); ear disorders (18%); pharyngitis (14%); visual field defect (1% to less than 10%); conjunctivitis (1% to less than 5%); diabetic retinopathy, ear or hearing symptoms.

GI

Nausea (9%); gastroenteritis (8%); melena, mouth disorder, rectal hemorrhage, steatorrhea (1% to less than 10%); abdominal pain, constipation, dyspepsia, vomiting (1% to less than 5%); acute pancreatitis, dry mouth, flatulence, hemorrhoids, pancreatitis in children, tenesmus (postmarketing).

Genitourinary

Gynecomastia (8%); gastritis (6%); abnormal urine, breast enlargement, dysuria, UTI, vaginal fungal infection (1% to less than 10%); male breast neoplasm, renal calculus (1% to less than 5%); female breast pain; gynecomastia in children (postmarketing).

Hematologic-Lymphatic

Eosinophilia (12%); decreased prothrombin, purpura (1% to less than 10%); lymphadenopathy (1% to less than 5%); leukemia (postmarketing).

Lab Tests

Elevated glycosolated Hgb (14%); increased AST (13%); increased fasting serum insulin levels (10%); increased levels of alkaline phosphatase, inorganic phosphate, and parathyroid hormone.

Local

Injection-site inflammation, injection-site pain (1% to less than 10%); lipoatrophy, rash.

Metabolic-Nutritional

Hypothyroidism (16%); hyperlipidemia (8%); abnormal glucose tolerance (6%); hypertriglyceridemia (5%); hypomagnesemia (1% to less than 10%); hyperglycemia, periorbital edema (1% to less than 5%); dehydration, fluid retention.

Musculoskeletal

Arthralgia (36%); myalgia (30%); arthralgia and joint disorders (27%); scoliosis (19%); pain in the extremities (15%); arthrosis, back pain, skeletal pain (11%); stiffness in the extremities (8%); leg pain (5%); hip pain (3%); arthropathy, bursitis, cramps (1% to less than 10%); carpal tunnel syndrome, musculoskeletal pain, rigors (1% to less than 5%); progression of preexisting scoliosis in children.

Respiratory

Upper respiratory tract infection (16%); rhinitis (14%); bronchitis (9%); bronchospasm, dyspnea (7%); increased cough, respiratory disorder (6%); respiratory tract infection (1% to less than 10%); pneumonia, sinusitis (1% to less than 5%).

Miscellaneous

Surgical procedures (45%); peripheral edema (42%); edema (41%); flu-like symptoms (23%); peripheral swelling (18%); leg edema (15%); pain (14%); infection (13%); increased nevi (11%); hematoma (9%); increased sweating (8%); generalized edema (6%); fungal infection, periorbital edema (1% to less than 10%); accident, chest pain, face edema, fever, flu-like symptoms, herpes simplex, moniliasis, night sweats, viral infection (1% to less than 5%); bacterial infection; fluid retention, including peripheral swelling; sepsis; slipped capital femoral epiphysis in children; sudden death in children with Prader-Willi syndrome.

Precautions

Monitor Be alert for signs of acromegaly. Monitor glucose levels periodically. Routinely monitor patients with preexisting tumors or GHD secondary to an intracranial lesion for progression or recurrence of the underlying disease process. Monitor patients with a history of scoliosis for progression of the condition. Monitor standard hormonal replacement therapy closely when administering somatropin to patients with hypopituitarism. Carefully monitor patients for any malignant transformation of skin lesions. Monitor patients with Turner syndrome for CV disorders (eg, stroke). Monitor thyroid function tests and signs of respiratory infection.

Pregnancy

Genotropin , Omnitrope , Saizen , Serostim , Zorbtive

Category B .

Accretropin , Humatrope , Norditropin , Nutropin , Nutropin AQ , Tev-Tropin

Category C .

Lactation

Undetermined.

Children

Some diluents may contain benzyl alcohol, which can cause gasping syndrome in premature infants.

Serostim

Safety and effectiveness in children with HIV or short bowel syndrome have not been established.

Elderly

Elderly patients may be more sensitive to the action of somatropin; therefore, start with a lower dose and smaller dose increments.

Acute critical illness

Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery, or multiple accidental trauma, and patients with acute respiratory failure have been reported. Administration is contraindicated.

Atrophy

Tissue atrophy may occur if somatropin is administered subcutaneously at the same site over a long period of time.

CV disorders

Patients with Turner syndrome are at increased risk for CV disorders (eg, hypertension, stroke).

Fatalities

Death has been reported in children with Prader-Willi syndrome after starting somatropin.

Fluid retention

May occur frequently in adult patients receiving somatropin.

GHD confirmation

Reevaluate patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood before continuing therapy at the reduced dose recommended for GHD adults.

Hypothyroidism

May develop during therapy; monitor thyroid function.

Insulin resistance

May be induced with therapy; monitor for glucose intolerance.

Intracranial hypertension

Intracranial hypertension, with headache, nausea, papilledema, visual changes, or vomiting, has been reported in few patients.

Intracranial lesion

Frequently examine patients with history of lesion.

Laboratory values

Serum levels of alkaline phosphatase, IGF-1, inorganic phosphorus, and parathyroid hormone may increase.

Otitis media

Patients with Turner syndrome are at increased risk of ear and hearing disorders.

Progression of scoliosis

Progression of preexisting scoliosis can occur in children who experience rapid growth.

Slipped capital epiphysis

May be seen in children with advanced renal osteodystrophy; may be affected by GH. Be alert to development of limp or complaints of hip or knee pain.

Undiagnosed hypothyroidism

Undiagnosed or untreated hypothyroidism may prevent an optimal response to somatropin, particularly the growth response in children.

Overdosage

Symptoms

Acromegaly, fluid retention, hypoglycemia followed by hyperglycemia (chronic overdosage).

Patient Information

• Instruct patients with diabetes to monitor blood sugar closely and to report variations to health care provider.
• Tell children and parents to report limp or complaints of hip or knee pain to health care provider as soon as possible.
• Instruct patient to report these symptoms to health care provider: headache; localized muscle pain; mild, transient edema; weakness.

Copyright © 2009 Wolters Kluwer Health.