Somatropin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Subcutaneous:

Norditropin FlexPro: 5 mg/1.5 mL (1.5 mL); 10 mg/1.5 mL (1.5 mL); 15 mg/1.5 mL (1.5 mL); 30 mg/3 mL (3 mL) [contains phenol]

Nutropin AQ NuSpin 5: 5 mg/2 mL (2 mL) [contains phenol]

Nutropin AQ NuSpin 10: 10 mg/2 mL (2 mL) [contains phenol]

Nutropin AQ NuSpin 20: 20 mg/2 mL (2 mL) [contains phenol]

Nutropin AQ Pen: 20 mg/2 mL (2 mL [DSC]) [contains phenol]

Omnitrope: 5 mg/1.5 mL (1.5 mL) [contains benzyl alcohol]

Omnitrope: 10 mg/1.5 mL (1.5 mL) [contains phenol]

Solution Reconstituted, Injection:

Humatrope: 5 mg (1 ea)

Humatrope: 6 mg (1 ea); 12 mg (1 ea); 24 mg (1 ea) [contains glycerin, metacresol]

Saizen: 5 mg (1 ea); 8.8 mg (1 ea)

Saizen Click.Easy: 8.8 mg (1 ea [DSC])

Saizenprep: 8.8 mg (1 ea) [contains metacresol]

Solution Reconstituted, Subcutaneous:

Genotropin: 5 mg (1 ea); 12 mg (1 ea) [contains metacresol]

Omnitrope: 5.8 mg (1 ea)

Serostim: 4 mg (1 ea) [contains benzyl alcohol]

Serostim: 5 mg (1 ea); 6 mg (1 ea)

Zomacton: 5 mg (1 ea) [contains benzyl alcohol]

Zomacton: 10 mg (1 ea) [contains metacresol]

Zorbtive: 8.8 mg (1 ea) [contains benzyl alcohol]

Solution Reconstituted, Subcutaneous [preservative free]:

Genotropin MiniQuick: 0.2 mg (1 ea); 0.4 mg (1 ea); 0.6 mg (1 ea); 0.8 mg (1 ea); 1 mg (1 ea); 1.2 mg (1 ea); 1.4 mg (1 ea); 1.6 mg (1 ea); 1.8 mg (1 ea); 2 mg (1 ea)

Pharmacology

Mechanism of Action

Somatropin is a purified polypeptide hormones of recombinant DNA origin; somatropin contains the identical sequence of amino acids found in human growth hormone; human growth hormone assists growth of linear bone, skeletal muscle, and organs by stimulating chondrocyte proliferation and differentiation, lipolysis, protein synthesis, and hepatic glucose output; stimulates erythropoietin which increases red blood cell mass; exerts both insulin-like and diabetogenic effects; enhances the transmucosal transport of water, electrolytes, and nutrients across the gut

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: Nutropin AQ: 50 mL/kg; Norditropin: 43.9 ± 14.9 L; Zorbtive: 12 ± 1 L

Metabolism

Hepatic and renal

Excretion

Urine (0.1%, as unchanged drug)

Half-Life Elimination

Genotropin: SubQ: 3 hours

Humatrope: SubQ: 3.8 hours

Norditropin: SubQ: ~7 to 10 hours

Nutropin, Nutropin AQ: SubQ: 2.1 ± 0.43 hours

Omnitrope: SubQ: 2.5 to 2.8 hours

Saizen: SubQ: ~2 hours

Serostim: SubQ: 4.28 ± 2.15 hours

Zomacton: SubQ: ~2.7 hours

Zorbtive: SubQ: 4 ± 2 hours

Use in Specific Populations

Special Populations: Renal Function Impairment

Patients with chronic renal failure and ESRD have decreased clearance.

Special Populations: Hepatic Function Impairment

Reduction in clearance has been noted in patients with severe hepatic impairment.

Use: Labeled Indications

Growth failure (pediatric patients):

Treatment of growth failure due to inadequate endogenous growth hormone secretion (Genotropin, Humatrope, Norditropin, Nutropin, Nutropin AQ, Omnitrope, Saizen, Tev-Tropin, Zomacton).

Treatment of short stature associated with Turner syndrome (Genotropin, Humatrope, Norditropin, Nutropin, Nutropin AQ, Omnitrope, Zomacton).

Treatment of Prader-Willi syndrome (Genotropin, Norditropin, Omnitrope).

Treatment of growth failure associated with chronic kidney disease up until the time of renal transplantation (Nutropin, Nutropin AQ).

Treatment of growth failure in children born small for gestational age who fail to manifest catch-up growth by 2 years of age (Genotropin, Omnitrope) or by 2 to 4 years of age (Humatrope, Norditropin, Zomacton)

Treatment of idiopathic short stature (nongrowth hormone-deficient short stature), defined by height standard deviation score (SDS) ≤-2.25 and growth rate not likely to attain adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom other causes associated with short stature have been excluded (Genotropin, Humatrope, Norditropin, Nutropin, Nutropin AQ, Omnitrope, Zomacton).

Treatment of short stature or growth failure associated with short stature homeobox gene (SHOX) deficiency (Humatrope, Zomacton).

Treatment of short stature associated with Noonan syndrome (Norditropin)

Growth hormone deficiency (adults): Replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following criteria (Genotropin, Humatrope, Norditropin, Nutropin, Nutropin AQ, Omnitrope, Saizen, Zomacton):

Adult-onset: Patients who have adult growth hormone deficiency whether alone or with multiple hormone deficiencies (hypopituitarism) as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma

or

Childhood-onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes, confirmed as an adult before replacement therapy is initiated

HIV-associated wasting, cachexia: Treatment of HIV patients with wasting or cachexia (Serostim).

Short bowel syndrome: Treatment of short-bowel syndrome in patients receiving specialized nutritional support (Zorbtive).

Use: Off Label

HIV-associated adipose redistribution syndrome (HARS) (Serostim)b

Data from a randomized, double-blind, placebo-controlled, multicenter study support the use of somatropin (Serostim) in the treatment of HIV-associated adipose redistribution syndrome (HARS). Somatropin produced greater relative loss of visceral adipose tissue and trunk fat

Contraindications

Hypersensitivity to somatropin or any component of the formulation; growth promotion in pediatric patients with closed epiphyses; acute critical illness due to increased complications/mortality following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure; active malignancy; active proliferative or severe nonproliferative diabetic retinopathy.

Additional product-specific contraindications:

Pediatric patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (Genotropin, Humatrope, Norditropin, Nutropin, Nutropin AQ, Omnitrope, Saizen, Zomacton).

Patients with Prader-Willi syndrome who have a history of upper airway obstruction or sleep apnea (Genotropin, Humatrope, Norditropin, Nutropin, Nutropin AQ, Omnitrope, Zomacton).

Canadian labeling: Additional contraindications (not in US labeling): Note: Product-specific contraindications may vary; refer to manufacturer's labeling.

Active intracranial tumor; critically ill patients; pregnancy and lactation; renal transplant; diabetes mellitus.

Dosage and Administration

Dosing: Adult

Note: Nutropin (lyophilized powder) has been discontinued in the US for more than 1 year.

Growth hormone deficiency: Adjust dose based on individual requirements: To minimize adverse events in older or overweight patients, reduced dosages may be necessary. During therapy, dosage should be decreased if required by the occurrence of side effects or excessive IGF-1 levels.

Weight-based dosing: Note: Obese patients are more likely to experience adverse effects when treated with a weight-based regimen; use is not recommended.

Norditropin: SubQ: Initial dose: 0.004 mg/kg/day; dose may be increased up to a maximum of 0.016 mg/kg/day.

Nutropin, Nutropin AQ: SubQ: ≤0.006 mg/kg/day; dose may be increased up to a maximum of 0.025 mg/kg/day in patients ≤35 years of age, or up to a maximum of 0.0125 mg/kg/day in patients >35 years of age.

Humatrope: SubQ: Initial: 0.006 mg/kg/day; dose may be increased up to a maximum of 0.0125 mg/kg/day.

Genotropin, Omnitrope: SubQ: Weekly dosage: ≤0.04 mg/kg divided into equal doses 6 to 7 days per week; dose may be increased at 4- to 8-week intervals to a maximum of 0.08 mg/kg/week.

Saizen: SubQ: ≤0.005 mg/kg/day; dose may be increased to ≤0.01 mg/kg/day after 4 weeks.

Zomacton: SubQ: 0.006 mg/kg/day; dose may be increased up to a maximum of 0.0125 mg/kg/day

Non-weight-based dosing:

Initial:

≤60 years of age: SubQ: 0.2 to 0.4 mg/day (higher doses may be needed if transitioning from pediatric treatment) (AACE [Cook 2009]; ES [Fleseriu 2016]; manufacturer's labeling).

>60 years of age: SubQ: 0.1 to 0.2 mg/day (AACE [Cook 2009]; ES [Fleseriu 2016]).

Patients with diabetes or glucose intolerance: SubQ: 0.1 to 0.2 mg/day (AACE [Cook 2009]).

Dosage adjustment: May increase every 1 to 2 months by 0.1 to 0.2 mg/day based on response and/or serum IGF-1 levels (AACE [Cook 2009]; ES [Fleseriu 2016]; manufacturer's labeling).

Dosage adjustment with estrogen supplementation: Higher doses of somatropin may be needed for women and patients taking oral estrogen replacement products; dosing not affected by topical products.

HIV-associated adipose redistribution syndrome (off-label use): Serostim: SubQ: Induction: 4 mg once daily at bedtime for 12 weeks; Maintenance: 2 mg or 4 mg every other day at bedtime for 12 to 24 weeks. Note: Every-other-day dosing during induction has also been studied. Although a greater response was seen with daily dosing, it was associated with an increased incidence of adverse events (Grunfeld 2007; Kotler 2004).

HIV-associated wasting, cachexia:

Serostim: SubQ: Initial: 0.1 mg/kg once daily at bedtime (maximum: 6 mg/day); patients at risk for side effects (eg, glucose intolerance) may be started at 0.1 mg/kg every other day. Adjust dose (ie, reduce the total daily dose or the number of doses per week) if needed to manage side effects.

Daily dose based on body weight:

<35 kg: 0.1 mg/kg.

35 to 45 kg: 4 mg.

45 to 55 kg: 5 mg.

>55 kg: 6 mg.

Short-bowel syndrome: Zorbtive: SubQ: 0.1 mg/kg once daily for 4 weeks (maximum: 8 mg/day).

Fluid retention (moderate) or arthralgias: Treat symptomatically or reduce dose to 0.05 mg/kg once daily (maximum: 4 mg/day).

Severe toxicity: Discontinue therapy for up to 5 days; when symptoms resolve, restart at 0.05 mg/kg once daily (maximum: 4 mg/day). Permanently discontinue treatment if severe toxicity recurs or does not disappear within 5 days after discontinuation.

Dosing: Geriatric

Consider a lower starting dose and smaller dose increments.

Growth hormone deficiency: Initial: SubQ: 0.1 to 0.2 mg/day. Longer timer time intervals between dose titration and smaller dose changes may be needed in older patients (AACE [Cook 2009]; ES [Fleseriu 2016]).

Dosing: Pediatric

Note: Nutropin (lyophilized powder) has been discontinued in the US for more than 1 year.

AIDS-related wasting or cachexia: Serostim: Children ≥6 years and Adolescents: Limited data available: SubQ: 0.04-0.07 mg/kg/day for 4 weeks; dosing based on two small trials of pediatric patients (n=11; age: 6-17 years)

Chronic renal insufficiency: Children and Adolescents: Nutropin, Nutropin AQ: SubQ: 0.35 mg/kg weekly divided into daily injections; continue until the time of renal transplantation

Dosage recommendations in patients treated for CRI who require dialysis:

Hemodialysis: Administer dose at night prior to bedtime or at least 3-4 hours after hemodialysis to prevent hematoma formation from heparin

CCPD: Administer dose in the morning following dialysis

CAPD: Administer dose in the evening at the time of overnight exchange

Growth hormone inadequacy: Children and Adolescents: Note: Therapy should be discontinued when patient has reached satisfactory adult height, when epiphyses have fused, or when the patient ceases to respond. Growth of 5 cm/year or more is expected; if growth rate does not exceed 2.5 cm in a 6-month period, double the dose for the next 6 months; if there is still no satisfactory response, discontinue therapy.

Genotropin, Omnitrope: SubQ: 0.16-0.24 mg/kg weekly divided into daily doses (6-7 doses)

Humatrope: SubQ: 0.18-0.3 mg/kg weekly divided into equal doses 6-7 days/week

Norditropin: SubQ: 0.024-0.034 mg/kg/dose 6-7 times per week

Nutropin, Nutropin AQ: SubQ: 0.3 mg/kg weekly divided into daily doses; in pubertal patients, dosage may be increased to 0.7 mg/kg weekly divided into daily doses

Saizen: IM, SubQ: 0.18 mg/kg weekly divided into equal daily doses or as 0.06 mg/kg/dose administered 3 days per week or as 0.03 mg/kg/dose administered 6 days per week

Tev-Tropin: SubQ: 0.3 mg/kg divided 3 times per week

Idiopathic short stature: Children and Adolescents:

Genotropin, Omnitrope: SubQ: 0.47 mg/kg weekly divided into equal doses 6-7 days/week

Humatrope: SubQ: 0.37 mg/kg weekly divided into daily doses (6-7 doses)

Nutropin, Nutropin AQ: SubQ: Up to 0.3 mg/kg weekly divided into daily doses

Noonan syndrome: Children and Adolescents: Norditropin: SubQ: Up to 0.066 mg/kg/day

Prader-Willi syndrome: Children and Adolescents: Genotropin, Omnitrope: SubQ: 0.24 mg/kg weekly divided daily into 6-7 doses per week

SGA at birth who fail to catch-up by 2-4 years of age: Children:

Genotropin, Omnitrope: 0.48 mg/kg weekly divided daily into 6-7 doses per week

Humatrope: SubQ: 0.47 mg/kg weekly divided into equal doses 6-7 days/week

Norditropin: SubQ: Up to 0.469 mg/kg weekly divided into equal doses 7 days/week

Alternate dosing (small for gestational age): In older/early pubertal children or children with very short stature, consider initiating therapy at higher doses (0.469 mg/kg weekly divided into equal doses 7 days/week); then consider reducing the dose (0.231 mg/kg weekly) if substantial catch-up growth observed. In younger children (<4 years) with less severe short stature, consider initiating therapy with lower doses (0.231 mg/kg weekly) and then titrating the dose upwards as needed.

SHOX deficiency: Children and Adolescents: Humatrope: SubQ: 0.35 mg/kg weekly divided into equal doses 6-7 days per week

Turner syndrome: Children and Adolescents:

Genotropin; Omnitrope: SubQ: 0.33 mg/kg weekly divided into 6-7 doses/week

Humatrope: SubQ: 0.375 mg/kg weekly divided into equal doses 6-7 days/week

Nutropin, Nutropin AQ: SubQ: Up to 0.375 mg/kg weekly divided into equal doses 3-7 times/week

Reconstitution

Genotropin:

Cartridge: Reconstitute with diluent provided.

MiniQuick: Reconstitute with diluent provided. Consult the instructions provided with the reconstitution device.

Humatrope:

Cartridge: Consult HumatroPen User Guide for complete instructions for reconstitution. Dilute with solution provided with cartridges ONLY; do not use diluent provided with vials.

Vial: Reconstitute with 1.5 to 5 mL diluent provided. Swirl gently; do not shake. If sensitivity to the diluent occurs, reconstitute with SWFI.

Nutropin: Reconstitute each vial with 1 to 10 mL bacteriostatic water for injection (benzyl alcohol preserved). Swirl gently, do not shake. If sensitivity to the diluent occurs or for use in newborns, reconstitute with sterile water for injection.

Nutropin AQ: Allow device to come to room temperature and gently swirl; if solution is cloudy, do not use.

Omnitrope vial: Reconstitute with provided diluent. Swirl gently; do not shake.

Saizen:

Cartridge: Consult instructions provided with reconstitution device.

Vial: Reconstitute 5 mg vial with 1 to 3 mL and 8.8 mg vial with 2 to 3 mL bacteriostatic water for injection (benzyl alcohol preserved). If sensitivity to the diluent occurs, reconstitute with sterile water for injection. Gently swirl; do not shake.

Saizen [Canadian product]: Preparation instructions vary depending on formulation; refer to the Canadian product monograph for detailed information.

Serostim:

4 mg vial: Reconstitute with 0.5 to 1 mL bacteriostatic water for injection (benzyl alcohol preserved). For patients sensitive to benzyl alcohol, reconstitute with SWFI.

5 or 6 mg vial: Reconstitute with 0.5 to 1 mL SWFI.

Tev-Tropin: Note: Only use the provided diluent for the 5 mg and 10 mg vial; diluents differ, do not interchange. Some cloudiness may occur; do not use if cloudiness persists after warming to room temperature.

5 mg vial: Reconstitute with 1 to 5 mL of provided diluent. Swirl gently; do not shake. If sensitivity to the diluent occurs or for use in newborns, reconstitute with SWFI.

10 mg vial: Reconstitute with 1 mL of provided diluent. Use the 25-gauge mixing needle provided. Swirl gently; do not shake.

Zomacton: Note: Only use the provided diluent for the 5 mg and 10 mg vial; diluents differ, do not interchange. Some cloudiness may occur; do not use if cloudiness persists after warming to room temperature.

5 mg vial: Reconstitute with 1 to 5 mL of provided diluent. Swirl gently; do not shake. If sensitivity to the diluent occurs or for use in newborns, pregnancy or breastfeeding, reconstitute with normal saline.

10 mg vial: Reconstitute with 1 mL of provided diluent. Use the 25-gauge mixing needle provided. Swirl gently; do not shake.

Zorbtive: Reconstitute with 1 to 2 mL of diluent based on patient weight. Swirl gently; do not shake. The provided diluent is bacteriostatic water for injection preserved with benzyl alcohol; SWFI may be used in patients unable to receive benzyl alcohol. If powder is reconstituted with provided diluent and stored prior to use, allow refrigerated solution to come to room temperature prior to administration.

Administration

SubQ: Do not shake. Administer SubQ; do not inject IV. Rotate administration sites (back of upper arm, abdomen, buttock, or thigh) to avoid tissue atrophy.

Storage

Genotropin:

Cartridge: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Following reconstitution, may store under refrigeration for up to 28 days.

Miniquick: Store at 2°C to 8°C (36°F to 46°F) prior to dispensing; may be stored ≤25°C (77°F) for up to 3 months after dispensing. Store in original carton to protect from light; do not freeze. Once reconstituted, solution must be refrigerated and used within 24 hours. Discard unused portion.

Humatrope:

Cartridge: Protect from light during storage. Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F); do not freeze. Following reconstitution with provided diluent, stable for 28 days under refrigeration. Do not leave at room temperature for >30 minutes per day.

Vial: Protect from light during storage. Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F); do not freeze. When reconstituted with provided diluent, use within 14 days. When reconstituted with sterile water for injection, use immediately and discard unused portion.

Norditropin: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Avoid direct light. Pens in use may be stored in refrigerator and used within 4 weeks after initial injection or may be stored up to 3 weeks at ≤25°C (77°F). Discard unused portion.

Nutropin: Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F); do not freeze. Use vials reconstituted with bacteriostatic water for injection (benzyl alcohol preserved) within 14 days; when reconstituted with sterile water for injection, use immediately and discard unused portion.

Nutropin AQ: Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F); do not freeze. Use within 28 days following initial use. Protect from light.

Omnitrope:

Cartridge: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Once the cartridge is loaded into the pen delivery system, store under refrigeration for up to 28 days after first use.

Vial: Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Following reconstitution, store under refrigeration for up to 3 weeks. Store vial in carton to protect from light.

Saizen:

Cartridge: Store at 15°C to 30°C (59°F to 86°F). Following reconstitution with the provided diluent, store under refrigeration for up to 21 days. Avoid freezing.

Vial: Store at 15°C to 30°C (59°F to 86°F). Following reconstitution with bacteriostatic water for injection (benzyl alcohol preserved), store under refrigeration for up to 14 days. Following reconstitution with sterile water for injection, use immediately and discard unused portion. Avoid freezing.

Saizen [Canadian product]: Storage conditions vary depending on formulation; refer to the Canadian product monograph for detailed information.

Serostim: Prior to reconstitution, store at 15°C to 30°C (59°F to 86°F). Following reconstitution with sterile water for injection, use immediately and discard unused portion. Following reconstitution with bacteriostatic water for injection (benzyl alcohol preserved), store under refrigeration for up to 14 days; avoid freezing.

Tev-Tropin: Prior to reconstitution, store at 2°C to 8°C (36°F to 46°F). Following reconstitution with the provided diluent, store under refrigeration and use within 14 days (5 mg vial) or 28 days (10 mg vial); do not freeze.

Zomacton: Prior to reconstitution, store at 2°C to 8°C (36°F to 46°F). Following reconstitution with the provided diluent, store under refrigeration and use within 14 days (5 mg vial) or 28 days (10 mg vial); do not freeze. If the 5 mg vial is reconstituted with NS (instead of provided diluent), use immediately after reconstitution (for only one dose), then discard unused portion.

Zorbtive: Store intact vials and diluent at 15°C to 30°C (59°F to 86°F). Following reconstitution with the provided diluent (bacteriostatic water for injection containing benzyl alcohol), may store under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 14 days; do not freeze. If reconstituted with sterile water for injection, solution should be used immediately.

Drug Interactions

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Corticosteroids (Systemic): May diminish the therapeutic effect of Somatropin. Monitor therapy

Cortisone: May diminish the therapeutic effect of Somatropin. Somatropin may diminish the therapeutic effect of Cortisone. Growth hormone may reduce the conversion of cortisone to the active cortisol metabolite. Monitor therapy

Estrogen Derivatives: May diminish the therapeutic effect of Somatropin. Shown to be a concern with oral hormone replacement therapy in postmenopausal women. Management: Monitor for reduced growth hormone efficacy. A larger somatropin dose may be required to reach treatment goal. This interaction does not appear to apply to non-orally administered estrogens (e.g., transdermal, vaginal ring). Exceptions: Ethinyl Estradiol; Mestranol. Consider therapy modification

Macimorelin: Growth Hormone Products may diminish the diagnostic effect of Macimorelin. Avoid combination

PredniSONE: May enhance the therapeutic effect of Somatropin. Somatropin may diminish the therapeutic effect of PredniSONE. Growth hormone may reduce the conversion of prednisone to the active prednisolone metabolite. Monitor therapy

Thyroid Products: Somatropin may diminish the therapeutic effect of Thyroid Products. Exceptions: Liothyronine. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (≤69%), facial edema (≤50%), edema (adults: ≤41%; children: ≤3%), lower extremity edema (adults: ≤15%)

Central nervous system: Pain (≤19%), hypoesthesia (≤15%), headache (adults: ≤18%; children: ≤7%), paresthesia (≤13%)

Endocrine & metabolic: Hypothyroidism (children: ≤16%; adults: ≤5%), elevated glycosylated hemoglobin (children: ≤14%), eosinophilia (children: ≤12%)

Gastrointestinal: Nausea (≤13%), flatulence (≤25%), abdominal pain (≤25%), vomiting (≤19%)

Immunologic: Antibody development (children: ≤24%; binding capacity ≥0.02 mg/mL: 2%; binding capacity >2 mg/mL: <1%)

Infection: Infection (adults: ≤13%)

Local: Pain at injection site (≤31%), injection site reaction (≤19%)

Neuromuscular & skeletal: Arthralgia (≤44%), arthropathy (adults: ≤27%; children: 11%), myalgia (≤30%), scoliosis (children: ≤19%; exacerbation or new), limb pain (4% to 19%), swelling of extremities (18%), ostealgia (adults: ≤11%)

Otic: Otitis media (children: ≤16%)

Respiratory: Upper respiratory tract infection (≤16%)

1% to 10%:

Cardiovascular: Chest pain (adults: ≤5%), hypertension (≤8%)

Central nervous system: Fatigue (6% to 9%), nipple pain (≤6%), depression (adults: ≤5%), insomnia (adults: ≤5%), carpal tunnel syndrome (1% to <5%), sleep apnea (adults)

Dermatologic: Diaphoresis (≤8%), melanocytic nevus (≤2%)

Endocrine & metabolic: Impaired glucose tolerance/prediabetes (10%), hyperglycemia (1% to 9%), hyperlipidemia (children: ≤8%), gynecomastia (≤6%), dependent edema (adults: ≤5%), diabetes mellitus (≤5%; includes exacerbation and new-onset), hypertriglyceridemia (≤5%), fluid retention (3% to 5%)

Genitourinary: Breast hypertrophy (≤6%), breast neoplasm (≤6%), breast swelling (≤6%), breast tenderness (≤6%), mastalgia (≤6%), urinary tract infection (children: ≤3%)

Hematologic & oncologic: Hematoma (children: ≤9%)

Infection: Influenza (children: ≤3%)

Neuromuscular & skeletal: Stiffness (adults: ≤8%; includes extremities and musculoskeletal), joint stiffness (4% to 8%), joint swelling (5% to 6%), lower extremity pain (children: ≤5%), arthralgia of hip (children: ≤3%), tonsillitis (children: ≤3%), abnormal bone growth (children: ≤2%; including disproportional growth of lower jaw)

Ophthalmic: Periorbital edema (1% to <5%)

Otic: Otitis (children: ≤3%)

Respiratory: Bronchitis (9%), flu-like symptoms (≤8%), sinusitis (children: ≤3%), dyspnea (adults)

Frequency not defined:

Central nervous system: Aggressive behavior (children), seizure (children)

Dermatologic: Alopecia (children), exacerbation of psoriasis (children), rash at injection site (children)

Endocrine & metabolic: Fluid volume disorder (children), glycosuria (adults), hypoglycemia (children)

Gastrointestinal: Gastroenteritis (children)

Genitourinary: Hematuria (children)

Hematologic & oncologic: Meningioma (children)

Local: Bleeding at injection site (children), burning sensation at injection site (children), erythema at injection site (children), fibrosis at injection site (children), inflammation at injection site (children), injection site nodule (children), injection site numbness (children), local skin hyperpigmentation (children; injection site), swelling at injection site (children)

Neuromuscular & skeletal: Asthenia (adults), lipoatrophy (children), musculoskeletal disease (discomfort)

Respiratory: Pharyngitis (children)

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, arthritis, avascular necrosis of femoral head (Legg-Calve-Perthes disease), benign neoplasm (children; new or recurring), bone fracture, brain neoplasm, cardiac disease, CNS neoplasm (children), decreased T4, diabetic coma, diabetic ketoacidosis, diabetic retinopathy, hypersensitivity reaction, illness (acute critical), increased serum alkaline phosphatase, intracranial hypertension (includes benign intracranial hypertension in children), leukemia, malignant neoplasm (includes new or recurring), nerve compression, pancreatitis, papilledema, precocious puberty, slipped capital femoral epiphysis, visual disturbance

Warnings/Precautions

Concerns related to adverse effects:

• Fluid retention: Fluid retention may occur in adults; manifestations of fluid retention (eg, edema, arthralgia, myalgia, nerve compression syndromes [including carpal tunnel syndrome]/paresthesias) are generally transient and dose dependent. Discontinue therapy if symptoms of carpal tunnel syndrome do not resolve by decreasing the dose or frequency of somatropin.
• Glucose tolerance: Somatropin may decrease insulin sensitivity. Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be detected; new-onset type 2 diabetes mellitus, and exacerbation of preexisting diabetes mellitus may occur. Diabetic ketoacidosis and diabetic coma have been reported in some patients. Discontinuing somatropin may improve glucose tolerance in some patients. Adjustment of antidiabetic medications may be necessary.
• Hypersensitivity: Serious systemic hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported.
• Intracranial hypertension: Intracranial hypertension with headache, nausea, papilledema, visual changes, and/or vomiting has been reported; symptoms usually occur within the first 8 weeks of therapy and signs and symptoms of intracranial hypertension may rapidly resolve after discontinuation or reduction of dose. Funduscopic examination prior to initiation of therapy and periodically thereafter is recommended. Treatment should be discontinued in patients who develop papilledema; resuming treatment at a lower dose may be considered once IH-associated signs and symptoms have resolved. Patients with Turner syndrome, chronic renal impairment and Prader-Willi syndrome may be at increased risk for intracranial hypertension.
• Lipoatrophy: Lipoatrophy has been reported at injection sites when used at the same site for a prolonged period. Ensure proper injection technique and rotate injection sites.
• Neoplasm: Increased risk of malignancy progression in patients with active malignancy; any preexisting malignancy should be inactive and treatment complete prior to initiating therapy; discontinue therapy with evidence of recurrence or progression. Monitor patients with preexisting tumors or growth hormone deficiency secondary to an intracranial lesion for recurrence or progression of underlying disease. An increased risk of second neoplasm has been reported in childhood cancer survivors treated with somatropin; the most common second neoplasms were meningiomas in patients treated with radiation to the head for their first neoplasm. Patients with HIV and pediatric patients with short stature (genetic cause) have increased baseline risk of developing malignancies; consider risk/benefits prior to initiation of therapy and monitor these patients carefully. Monitor all patients for any malignant transformation of skin lesions. Rule out pituitary tumor (or other brain tumors) prior to initiation of treatment because growth hormone deficiency may be an early sign of the presence of these tumors.
• Pancreatitis: Has been rarely reported; incidence in children (especially girls) with Turner syndrome may be greater than adults. Consider pancreatitis diagnosis if abdominal pain occurs.
• Slipped capital femoral epiphyses: Patients with endocrine disorders (including growth hormone deficiency and Turner syndrome) or in patients undergoing rapid growth may develop slipped capital femoral epiphyses more frequently; evaluate any child with new onset of a limp or with complaints of hip or knee pain.

Disease-related concerns:

• Acute critical illness: Initiation of somatropin is contraindicated with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure; mortality may be increased. Discontinuation of therapy may be necessary in patients with an acute critical illness.
• Childhood-onset adult growth hormone deficiency: Patients who were treated with somatropin for growth hormone deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin for growth hormone deficiency in adults.
• Chronic kidney disease: Periodically monitor children with growth failure secondary to chronic kidney disease (CKD) for evidence of progression of renal osteodystrophy. Slipped capital femoral epiphysis or avascular necrosis of the femoral head may be seen in children with advanced renal osteodystrophy. Obtain x-rays of the hip prior to initiating somatropin in CKD patients; be alert to the development of a limp or complaints of hip or knee pain.
• Hypoadrenalism: Patients who have or are at risk for pituitary hormone deficiency(ies) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism with somatropin therapy; patients with previously diagnosed hypoadrenalism may require increased dosages of glucocorticoids due to the effects of somatropin. Excessive glucocorticoid therapy may inhibit the growth-promoting effects of somatropin in children; monitor for reduced serum cortisol levels and/or need to adjust glucocorticoids carefully.
• Hypothyroidism: Patients who have or are at risk for pituitary hormone deficiency(ies) may be at risk for reduced thyroid function (central hypothyroidism) and patients with Turner syndrome have an increased risk of developing autoimmune thyroid disease and primary hypothyroidism. Untreated/undiagnosed hypothyroidism may decrease response to therapy, particularly the growth response in children. Monitor thyroid function periodically and initiate/adjust thyroid replacement therapy as needed.
• Noonan syndrome: Safety has not been established for the treatment of Noonan syndrome in children with significant cardiac disease.
• Prader-Willi syndrome: Sudden death has been reported in pediatric patients with Prader-Willi syndrome following the use of growth hormone. The reported fatalities occurred in patients with one or more risk factors, including severe obesity, history of upper airway obstruction or sleep apnea, respiratory impairment, or unidentified respiratory infection; male patients may be at greater risk. Monitor for sleep apnea, upper airway obstruction, and respiratory infections prior to initiation of therapy and periodically thereafter. Treatment interruption is recommended in patients who show signs of upper airway obstruction, including the onset of, or increased, snoring and/or new-onset sleep apnea. All patients with Prader-Willi syndrome should have effective weight control. Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, use is not indicated for the long-term treatment of pediatric patients who have growth failure due to Prader-Willi syndrome.
• Scoliosis: Progression of scoliosis may occur in children experiencing rapid growth; monitor for worsening of scoliosis.
• Turner syndrome: Patients with Turner syndrome are at increased risk for otitis media and other ear/hearing disorders, autoimmune thyroid disease, primary hypothyroidism, and cardiovascular disorders (eg, hypertension, aortic aneurysm/dissection, stroke). Monitor patients with Turner syndrome for these conditions.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Elderly patients may be more sensitive to the actions of somatropin; consider lower starting doses and smaller dose increments.
• HIV patients: Patients with HIV infection should be maintained on antiretroviral therapy to prevent the potential increase in viral replication.
• Pediatric: Failure to increase growth rate, particularly during the first year of therapy, indicates need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age, and antibodies to recombinant human GH.
• Renal transplant recipients: No studies have been completed evaluating Nutropin or Nutropin AQ in patients with renal transplant. Use is not indicated in patients with functioning renal allografts.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Diluent may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
• M-cresol: Some products may contain m-cresol as a preservative.
• Multiple-dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).

Monitoring Parameters

Treatment of growth hormone deficiency (children): Growth response; funduscopic exam prior to treatment; progression of scoliosis in patients with a history of scoliosis; clinical evidence of slipped capital femoral epiphysis, such as a limp or hip or knee pain; thyroid function; glucose in patients with risk factors for glucose intolerance; progression or recurrence of tumor in patients treated for growth deficiency secondary to a tumor or tumor development in at risk patients; progression of preexisting nevi. In addition, guidelines recommend a physical exam at every visit; monitoring serum IGF-1; adrenal and thyroid function in patients with growth hormone deficiency due to multiple pituitary hormone deficiencies; funduscopic exam if symptoms of intracranial hypertension occur (Grimberg [PES 2016])

Chronic kidney disease: Progression of renal osteodystrophy.

Idiopathic short stature: Height, weight, pubertal development and adverse events every 3 to 6 months (Cohen 2008).

Prader-Willi syndrome: Signs of upper airway obstruction (including onset of or increased snoring), sleep apnea, respiratory infections; effective weight control.

Turner syndrome: Ear disorders including otitis media; cardiovascular disorders (eg, stroke, aortic aneurysm/dissection, hypertension).

Noonan syndrome: Prior to use, verify short stature syndrome.

Treatment of growth hormone deficiency (adults): Monitor clinical response, serum IGF-1, and side effects every 1 to 2 months during dose titration. Once at maintenance dose, monitor serum IGF-1, fasting glucose, hemoglobin A_1c, BMI, waist circumference/waist to hip ratio, thyroid function (free T₄), adrenal function, lipid profile, blood pressure, clinical response and side effects every 6 months. Bone mineral density should be evaluated prior to therapy and DXA scan repeated every 1.5 to 3 years if initial bone scan is abnormal (AACE [Cook 2009]; ES [Fleseriu 2016]; ES [Molitch 2011]).

Short bowel syndrome: Diet should be optimized prior to therapy and nutritional status monitored during treatment; colonoscopy prior to therapy (in patients with residual colon) especially if risk factors for colon cancer are present (Steiger 2006). In addition, monitor for progression of preexisting nevi; glucose in patients with risk factors for glucose intolerance; thyroid function prior to and 4 weeks after treatment initiation in patients with suspected or diagnosed hypopituitarism; funduscopic examination at initiation of therapy

Pregnancy

Pregnancy Considerations

During normal pregnancy, maternal production of endogenous growth hormone decreases as placental growth hormone production increases. Data with somatropin use during pregnancy in women with hypopituitarism is limited; however, adequate replacement prior to conception may improve fertility (Vila 2019). The Endocrine Society guidelines for hormonal replacement in hypopituitarism suggest discontinuation of somatropin during pregnancy (ES [Fleseriu 2016]).

Patient Education

What is this drug used for?

• It is used to help with growth and to treat growth hormone deficiency.
• It is used to treat short bowel syndrome.
• It is used to help patients with HIV gain weight.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Loss of strength and energy
• Muscle pain
• Joint pain
• Stiff muscles
• Trouble sleeping
• Abdominal pain
• Vomiting
• Injection site irritation
• Hair loss
• Common cold symptoms
• Diarrhea
• Passing gas
• Back pain
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss.
• Low thyroid level like constipation; difficulty handling heat or cold; memory problems; mood changes; or burning, numbness, or tingling feeling.
• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes.
• Shortness of breath
• Excessive weight gain
• Mood changes
• Depression
• Behavioral changes
• Skin discoloration
• Chest pain
• Fast heartbeat
• Sweating a lot
• Numbness or tingling of hands or feet
• Swelling of arms or legs
• Bone pain
• Mole changes
• Nausea
• Vomiting
• Injection site redness or edema
• Injection site skin breakdown
• Infection (children)
• Abnormal breathing (children)
• Hip or knee pain (children)
• Abnormal gait (children)
• Increased intracranial pressure like vision changes, severe headache, nausea, or vomiting.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.