AIDS-related wasting or cachexia: Serostim: Limited data available:
Children 6 to 8 years: SubQ: 0.04 mg/kg/day for 4 weeks.
Children ≥8 years and Adolescents: SubQ: 0.04 to 0.07 mg/kg/day for 4 weeks.
Growth failure secondary to chronic kidney disease (CKD): Children and Adolescents: Nutropin AQ: SubQ: 0.35 mg/kg weekly divided into daily injections; continue until the time of renal transplantation.
Growth hormone deficiency (GHD): Note: Therapy should be continued until growth velocity decreases to <2 to 2.5 cm/year; the decision to discontinue prior to this must be individualized (PES [Grimberg 2016]).
Children and Adolescents:
Guideline recommendations: SubQ: Initial dose: 0.16 to 0.24 mg/kg weekly divided into equal doses 6 to 7 days/week. Dose should be individualized based on patient response; treat with the lowest effective dose (GRS [Collett-Solberg 2019]; PES [Grimberg 2016]).
Product-specific dosing:
Genotropin, Omnitrope: SubQ: 0.16 to 0.24 mg/kg weekly divided into equal doses 6 to 7 days/week.
Humatrope: SubQ: 0.18 to 0.3 mg/kg weekly divided into equal doses 6 to 7 days/week.
Norditropin: SubQ: 0.17 to 0.24 mg/kg weekly divided into equal doses 6 to 7 days/week.
Nutropin AQ: SubQ: 0.3 mg/kg weekly divided into daily doses; although the manufacturer suggests that 0.7 mg/kg weekly may be used in pubertal patients, the Pediatric Endocrine Society recommends against the use of higher doses in puberty due to increased adverse effects, long-term risk of higher dose, and increased health care costs (PES [Grimberg 2016]).
Saizen: SubQ: 0.18 mg/kg weekly divided into equal doses 3, 6, or 7 days/week. Note: Pediatric Endocrine Society recommends dosing 6 to 7 days/week due to improved weight gain and height standard deviation score (HtSDS) compared to 3-times-weekly dosing (PES [Grimberg 2016]).
Zomacton: SubQ: 0.18 to 0.3 mg/kg weekly divided into equal doses 3, 6, or 7 days/week. Note: Pediatric Endocrine Society recommends dosing 6 to 7 days/week due to improved weight gain and HtSDS compared to 3-times-weekly dosing (PES [Grimberg 2016]).
Idiopathic short stature (ISS): Note: Guidelines recommend against the routine use of somatropin in every child with HtSDS ≤−2.25; decision to use should be made on a case-by-case basis (PES [Grimberg 2016]).
Children and Adolescents:
Guideline recommendations: SubQ: Initial dose: 0.24 mg/kg weekly divided into equal doses 6 to 7 days/week. Individualize dose based on patient response; some patients may require up to 0.47 mg/kg weekly in divided doses (PES [Grimberg 2016]).
Product-specific dosing:
Genotropin, Norditropin, Omnitrope: SubQ: Up to 0.47 mg/kg weekly divided into equal doses 6 to 7 days/week.
Humatrope: SubQ: Up to 0.37 mg/kg weekly divided into equal doses 6 to 7 days/week.
Nutropin AQ: SubQ: Up to 0.3 mg/kg weekly divided into daily doses.
Zomacton: SubQ: Up to 0.37 mg/kg weekly divided into equal doses 3, 6, or 7 days/week. Note: Pediatric Endocrine Society recommends dosing 6 to 7 days/week due to improved weight gain and HtSDS compared to 3-times-weekly dosing (PES [Grimberg 2016]).
Noonan syndrome: Children and Adolescents: Norditropin: SubQ: Up to 0.46 mg/kg weekly divided in equal doses 6 to 7 days/week.
Prader-Willi syndrome: Children and Adolescents: Genotropin, Norditropin, Omnitrope: SubQ: 0.24 mg/kg weekly divided daily into 6 to 7 doses/week.
Small for gestational age (SGA) at birth who fail to catch-up by 2 to 4 years of age: Children:
Guideline recommendations: SubQ: 35 to 70 mcg/kg/day once daily; initiate doses at the higher end of the dosing range in patients with significant growth retardation (Clayton 2007).
Product-specific dosing:
Genotropin, Omnitrope: Up to 0.48 mg/kg weekly divided daily into 6 to 7 doses/week.
Humatrope, Norditropin: SubQ: Up to 0.47 mg/kg weekly divided into equal doses 6 to 7 days/week.
Zomacton: SubQ: Up to 0.47 mg/kg weekly divided into equal doses 3, 6, or 7 days/week. Note: Expert guidelines for other indications recommend against 3-times-weekly dosing (PES [Grimberg 2016]).
Short stature homeobox gene (SHOX) deficiency: Children and Adolescents: Humatrope, Zomacton: SubQ: 0.35 mg/kg weekly divided into equal doses 6 to 7 days/week.
Turner syndrome: Children and Adolescents:
Guideline recommendations: Children ≥4 years and Adolescents: SubQ: 0.35 to 0.375 mg/kg weekly divided into equal doses 7 days/week. Higher doses may be considered in patients with poor height prognosis. Maximum dose should be based on specific product labeling (Gravholt 2017).
Product-specific dosing:
Genotropin; Omnitrope: SubQ: 0.33 mg/kg weekly divided into equal doses 6 to 7 days/week.
Humatrope: SubQ: 0.375 mg/kg weekly divided into equal doses 6 to 7 days/week.
Norditropin: SubQ: Up to 0.47 mg/kg weekly divided into equal doses 6 to 7 days/week.
Nutropin AQ: SubQ: Up to 0.375 mg/kg weekly divided into equal doses 6 to 7 days/week.
Zomacton: SubQ: Up to 0.375 mg/kg weekly divided into equal doses 3, 6, or 7 days/week. Note: Expert guidelines for other indications recommend against 3-times-weekly dosing (PED [Grimberg 2016]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; patients with chronic renal failure and end-stage renal disease tend to have decreased clearance.
There are no dosage adjustments provided in the manufacturer's labeling; clearance may be reduced in patients with severe hepatic impairment.
(For additional information see "Recombinant human growth hormone (somatropin): Drug information")
Growth hormone deficiency: In patients who were treated with somatropin for growth hormone deficiency (GHD) during childhood and whose epiphyses are closed, reevaluate the need for continued therapy during adulthood. Due to a high degree of interindividual variability with absorption and sensitivity, starting with low non–weight-based doses and slowly titrating is generally preferred to traditional weight-based dosing regimens (AACE/ACE [Yuen 2019]).
Non–weight-based dosing:
Initial:
Patients ≤60 years of age without diabetes mellitus, glucose intolerance, or obesity: SUBQ: 0.2 to 0.4 mg/day; in patients transitioning from pediatric treatment, higher doses (eg, 50% of the dose used in childhood) may be needed (AACE/ACE [Yuen 2019]; ES [Fleseriu 2016]; manufacturer's labeling).
Patients >60 years of age, or with diabetes mellitus, glucose intolerance, or obesity: SUBQ: 0.1 to 0.2 mg/day (AACE/ACE [Yuen 2019]; ES [Fleseriu 2016]).
Dosage adjustment: May increase by 0.1 to 0.2 mg/day every 1 to 2 months based on response and/or serum IGF-1 levels (AACE/ACE [Yuen 2019]; ES [Fleseriu 2016]; manufacturer's labeling).
Duration of therapy: Consider discontinuing therapy if no benefits are achieved after 12 to 18 months; may continue indefinitely in patients who benefit from therapy (AACE/ACE [Yuen 2019]).
Weight-based dosing: Note: Initiating somatropin with weight-based dosing is generally not recommended due to greater risk of dose-dependent adverse effects (eg, edema), particularly in patients with obesity (AACE/ACE [Yuen 2019]; ES [Fleseriu 2016]; manufacturer’s labeling).
Norditropin: SUBQ: Initial: 0.004 mg/kg/day; dose may be increased up to a maximum of 0.016 mg/kg/day.
Nutropin AQ: SUBQ: Initial: ≤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/week divided into equal doses administered 6 or 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 up 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.
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 adverse 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 adverse 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; decreased clearance in patients with chronic renal failure and end-stage renal disease.
There are no dosage adjustments provided in the manufacturer's labeling; reduced clearance in patients with severe hepatic impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cartridge, Injection:
Humatrope: 6 mg (1 ea); 12 mg (1 ea); 24 mg (1 ea) [contains glycerin, metacresol]
Cartridge, Subcutaneous:
Genotropin: 5 mg (1 ea); 12 mg (1 ea) [contains metacresol]
Prefilled Syringe, 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)
Solution Cartridge, Subcutaneous:
Omnitrope: 5 mg/1.5 mL (1.5 mL) [contains benzyl alcohol]
Omnitrope: 10 mg/1.5 mL (1.5 mL) [contains phenol]
Solution Pen-injector, 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]
Solution Reconstituted, Injection:
Humatrope: 5 mg (1 ea [DSC])
Saizen: 5 mg (1 ea); 8.8 mg (1 ea)
Saizenprep: 8.8 mg (1 ea) [contains metacresol]
Solution Reconstituted, Subcutaneous:
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]
Zomacton (for Zoma-Jet 10): 10 mg (1 ea [DSC]) [contains metacresol]
Zorbtive: 8.8 mg (1 ea) [contains benzyl alcohol]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Pen-injector, Subcutaneous:
Genotropin GoQuick: 5 mg (1 ea); 5.3 mg (1 ea); 12 mg (1 ea) [contains metacresol]
Prefilled Syringe, Subcutaneous:
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)
Solution Cartridge, Subcutaneous:
Omnitrope: 5 mg/1.5 mL (1.5 mL) [contains benzyl alcohol]
Omnitrope: 10 mg/1.5 mL (1.5 mL); 15 mg/1.5 mL (1.5 mL) [contains phenol]
Saizen: 6 mg/1.03 mL (1.03 mL); 12 mg/1.5 mL (1.5 mL); 20 mg/2.5 mL (2.5 mL) [contains phenol]
Solution Pen-injector, Subcutaneous:
Norditropin NordiFlex Pen: 5 mg/1.5 mL (1.5 mL); 10 mg/1.5 mL (1.5 mL); 15 mg/1.5 mL (1.5 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]
Solution Reconstituted, Injection:
Humatrope: 6 mg (1 ea); 12 mg (1 ea) [contains metacresol]
Humatrope: 24 mg (1 ea) [contains glycerin, metacresol]
Saizen: 5 mg (1 ea); 10 units ([DSC])
Solution Reconstituted, Subcutaneous:
Humatrope: 5 mg ([DSC]) [contains metacresol]
Saizen: 8.8 mg ([DSC]) [contains benzyl alcohol]
Serostim: 5 mg (1 ea)
Serostim: 8.8 mg ([DSC]) [contains benzyl alcohol]
Parenteral: SubQ: Administer by SubQ injection only; not for IV injection; do not shake. Administer into the back of the upper arm, thigh, buttock, or abdomen; rotate administration sites to avoid tissue atrophy.
Product-specific information:
Omnitrope: Solution in the Omnitrope cartridges must be administered using the Omnitrope pen; see product labeling for details on correct installation of cartridge; prime pen prior to first use.
Zomacton: When administering Zomacton, use a standard sterile disposable needle or ZOMA-Jet Needle-Free injection device for SubQ injection; see product labeling for proper use of the injection device.
Timing of administration for treatment of growth failure due to chronic kidney disease:
Hemodialysis (HD): Administer at night just prior to sleeping and at least 3 to 4 hours after dialysis.
Peritoneal dialysis (PD):
Chronic cycling peritoneal dialysis: Administer in the morning after dialysis.
Continuous ambulatory peritoneal dialysis (CAPD): Administer in the evening at the time of the overnight exchange.
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.
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 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.
Treatment of growth failure due to inadequate endogenous growth hormone secretion (Genotropin, Humatrope, Norditropin, Nutropin AQ, Omnitrope, Saizen, Zomacton: FDA approved in pediatric patients [age not specified]).
Treatment of short stature associated with Turner syndrome (Genotropin, Humatrope, Norditropin, Nutropin AQ, Omnitrope, Zomacton: FDA approved in pediatric patients [age not specified]).
Treatment of Prader-Willi syndrome (Genotropin, Norditropin, Omnitrope: FDA approved in pediatric patients [age not specified]).
Treatment of growth failure associated with chronic kidney disease (CKD) up until the time of renal transplantation (Nutropin AQ: FDA approved in pediatric patients [age not specified]).
Treatment of growth failure in children born small for gestational age (SGA) who fail to manifest catch-up growth by 2 to 4 years of age (Genotropin, Humatrope, Norditropin, Omnitrope, Zomacton: FDA approved in pediatric patients [age not specified]).
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 normal adult height (Genotropin, Humatrope, Norditropin, Nutropin AQ, Omnitrope, Zomacton: FDA approved in pediatric patients [age not specified]).
Treatment of short stature or growth failure associated with short stature homeobox gene (SHOX) deficiency (Humatrope, Zomacton: FDA approved in pediatric patients [age not specified]).
Treatment of short stature associated with Noonan syndrome (Norditropin: FDA approved in pediatric patients [age not specified]).
HIV patients with wasting or cachexia with concomitant antiviral therapy (Serostim: FDA approved in adults).
Replacement of endogenous growth hormone in patients with growth hormone deficiency (adult onset or childhood onset) (Genotrope, Humatrope, Norditropin, Nutropin AQ, Omnitrope, Saizen, Zomacton: FDA approved in adults).
Treatment of short-bowel syndrome in patients receiving specialized nutritional support (Zorbtive: FDA approved in adults).
Humatrope may be confused with homatropine
Somatrem may be confused with somatropin
Somatropin may be confused with homatropine, sumatriptan
Beers Criteria: Growth hormone is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older except as hormone replacement in patients with growth hormone deficiency due to an established etiology that is based on a rigorous diagnosis by evidence-based criteria due to its minimal impact on body composition and its association with causing edema, arthralgia, carpal tunnel syndrome, gynecomastia, and impaired fasting glucose (Beers Criteria [AGS 2019]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
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 have severe obesity or severe respiratory impairment (Genotropin, Humatrope, Norditropin, 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 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 (Serostim only).
Patients with Prader-Willi syndrome who have uncontrolled diabetes, active psychosis (Genotropin only).
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.
• Glucose tolerance: Somatropin may decrease insulin sensitivity. Previously undiagnosed impaired glucose tolerance or diabetes mellitus may be detected; new-onset type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus may occur. Diabetic ketoacidosis and hyperosmolar hyperglycemic state 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. 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. 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. 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 with Turner syndrome may be greater than adults.
• 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:
• Adrenal insufficiency: 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) adrenal insufficiency with somatropin therapy; patients with previously diagnosed adrenal insufficiency may require increased glucocorticoid doses. Excessive glucocorticoid therapy may inhibit the growth-promoting effects of somatropin in children.
• Chronic kidney disease: 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 chronic kidney disease patients; be alert to the development of a limp or complaints of hip or knee pain.
• Hypothyroidism: Patients who have or are at risk for pituitary hormone deficiency(ies) may be at risk for central (secondary) hypothyroidism; patients with Turner syndrome have an increased risk of developing autoimmune thyroid disease and primary hypothyroidism. Untreated/undiagnosed hypothyroidism may decrease response to somatropin therapy, particularly the growth response in children.
• 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. 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. 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.
• 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).
Special populations:
• Older adults: Older adult patients may be more sensitive to the actions of somatropin; consider lower starting doses and smaller dose increments.
• Pediatric: Failure to increase growth rate, particularly during the first year of therapy, indicates need for close assessment of adherence and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age, and antibodies to recombinant human growth hormone.
• Renal transplant recipients: No studies have been completed evaluating Nutropin AQ in patients with renal transplant; use of Nutropin AQ 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).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Corticosteroids (Systemic). Risk C: Monitor therapy
Cortisone: May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Cortisone. Risk C: Monitor therapy
Estrogen Derivatives: May diminish the therapeutic effect of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider therapy modification
Macimorelin: Products that Affect Growth Hormone may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
PredniSONE: May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of PredniSONE. Risk C: Monitor therapy
Thyroid Products: Somatropin may diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Adequate somatropin use prior to conception may improve fertility in females with hypopituitarism (Vila 2019).
During normal pregnancy, maternal production of endogenous growth hormone decreases as placental growth hormone production increases. Data with somatropin use during pregnancy in females 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]).
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 (PES [Grimberg 2016]).
Idiopathic short stature: Height, weight, pubertal development, and adverse events every 3 to 6 months (Cohen 2008).
Small for gestational age at birth who fail to catch up: Prior to treatment, measure fasting glucose, insulin, and lipid levels; IGF-I and IGFBP-3 levels; and blood pressure. Fasting serum glucose and insulin levels annually; more frequent and intense monitoring may be needed in patients at risk for type 2 diabetes; fasting serum lipids and blood pressure periodically (Lee 2003).
Turner syndrome: Height every 4 to 6 months in the first year and then every 6 months; IGF-I annually (Gravholdt 2017).
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 A1c, 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 (adults): 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.
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
Distribution: Vd: Nutropin AQ: 50 mL/kg; Norditropin: 43.9 ± 14.9 L; Zorbtive: 12 ± 1 L.
Metabolism: Hepatic and renal.
Bioavailability: SubQ: Nutropin AQ; Saizen; Serostim; Zorbtive: 70% to 90%.
Half-life elimination:
Genotropin: SubQ: 3 hours.
Humatrope: SubQ: 3.8 hours.
Norditropin: SubQ: ~7 to 10 hours.
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.
Excretion: Urine.
Altered kidney function: Patients with chronic renal failure and ESRD have decreased clearance.
Hepatic function impairment: Reduction in clearance has been noted in patients with severe hepatic impairment.
Cartridge (Genotropin Subcutaneous)
5 mg (per each): $835.63
12 mg (per each): $2,005.55
Cartridge (Humatrope Injection)
6 mg (per each): $1,063.51
12 mg (per each): $2,127.02
24 mg (per each): $4,254.05
Prefilled Syringe (Genotropin MiniQuick Subcutaneous)
0.2 mg (per each): $36.43
0.4 mg (per each): $72.87
0.6 mg (per each): $109.30
0.8 mg (per each): $145.73
1 mg (per each): $182.17
1.2 mg (per each): $218.60
1.4 mg (per each): $255.03
1.6 mg (per each): $291.45
1.8 mg (per each): $327.90
2 mg (per each): $364.32
Solution (reconstituted) (Omnitrope Subcutaneous)
5.8 mg (per each): $378.05
Solution (reconstituted) (Saizen Injection)
5 mg (per each): $862.24
8.8 mg (per each): $1,379.57
Solution (reconstituted) (Saizenprep Injection)
8.8 mg (per each): $1,379.57
Solution (reconstituted) (Serostim Subcutaneous)
4 mg (per each): $534.77
5 mg (per each): $668.46
6 mg (per each): $802.15
Solution (reconstituted) (Zomacton Subcutaneous)
5 mg (per each): $348.00
10 mg (per each): $696.00
Solution (reconstituted) (Zorbtive Subcutaneous)
8.8 mg (per each): $1,693.18
Solution Cartridge (Omnitrope Subcutaneous)
5 mg/1.5 mL (per mL): $441.08
10 mg/1.5 mL (per mL): $882.15
Solution Pen-injector (Norditropin FlexPro Subcutaneous)
5 mg/1.5 mL (per mL): $586.16
10 mg/1.5 mL (per mL): $1,172.32
15 mg/1.5 mL (per mL): $1,758.48
30 mg/3 mL (per mL): $1,758.48
Solution Pen-injector (Nutropin AQ NuSpin 10 Subcutaneous)
10 mg/2 mL (per mL): $754.41
Solution Pen-injector (Nutropin AQ NuSpin 20 Subcutaneous)
20 mg/2 mL (per mL): $1,508.81
Solution Pen-injector (Nutropin AQ NuSpin 5 Subcutaneous)
5 mg/2 mL (per mL): $377.20
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