Brand names: Genotropin, Humatrope, Norditropin, Nutropin AQ, Omnitrope, ... show all 9 brands Saizen, Serostim, Zomacton, Zorbtive
Drug class: Pituitary

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Somatropin is a recombinant human growth hormone (hGH).^{1 2 3 5 6 7 8 9 10}

Uses for Somatropin

Short Stature or Growth Failure in Pediatric Patients

Treatment of growth failure in children due to inadequate secretion of endogenous growth hormone (designated an orphan drug by FDA).^{1 2 3 5 6 7 8 11} The Pediatric Endocrine Society recommends growth hormone treatment to normalize adult height and avoid extreme shortness in children and adolescents with growth hormone deficiency (GHD) because the benefits, impact on physical and psychosocial disability, outweigh potential harms.¹⁰⁰

Treatment of short stature associated with Turner syndrome (designated an orphan drug by FDA).^{1 2 3 5 6 8 11}

Treatment of idiopathic short stature (ISS) when height standard deviation score (SDS) is less than -2.25 and associated with growth rates unlikely to permit attainment of adult height in the normal range; other causes of short stature should be excluded and epiphyseal must be open.^{1 2 3 5 6 8} The Pediatric Endocrine Society suggests a shared decision-making approach instead of routine use of somatropin for children with ISS.¹⁰⁰

Treatment of short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency (designated an orphan drug by FDA).^{1 6 11}

Treatment of short stature born small for gestational age (SGA) with no catch-up growth by 2 to 4 years of age (designated an orphan drug by FDA).^{1 2 5 6 8 11}

Treatment of short stature associated with Noonan syndrome (designated an orphan drug by FDA).^{2 11}

Treatment of growth failure due to genetically confirmed Prader-Willi syndrome (designated an orphan drug by FDA).^{2 5 8 11}

Treatment of growth failure associated with chronic kidney disease (CKD), in conjunction with optimal CKD management, up to the time of renal transplantation (designated an orphan drug by FDA).^{3 11 40}

Growth Hormone Deficiency in Adults

Replacement of endogenous growth hormone in adults with GHD including those with childhood-onset GHD following epiphyseal closure (designated an orphan drug by FDA).^{1 2 3 5 6 7 8 11}

American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) and Endocrine Society (ES) have issued guidelines for management of GHD in adults.^{101 102 103}

HIV-associated Wasting or Cachexia

Treatment of HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance; concomitant antiretroviral therapy is necessary (designated an orphan drug by FDA).^{9 11 42 43}

Short Bowel Syndrome in Adults

Treatment of short bowel syndrome (SBS) in adult patients receiving specialized nutritional support (designated an orphan drug by FDA).^{10 11 44}

When combined with glutamine and an optimal oral diet, growth hormone treatment may improve macronutrient and fluid absorption in patients with SBS.^{10 44 45}

Other Uses

American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) strongly recommend against administering human growth hormone for athletic performance enhancement^{† [off-label]}, or to treat aging (or aging related conditions)^{† [off-label]} in patients without a recognized medical condition.¹⁰¹

Related/similar drugs

Genotropin, Norditropin, Saizen, Omnitrope, Ngenla, Nutropin, Zomacton

Somatropin Dosage and Administration

General

Pretreatment Screening

• Perform fundoscopic examination to exclude preexisting papilledema.^{1 2 3 5 6 7 8 9 10}

• Obtain a baseline serum insulin-like growth factor-1 (IGF-1) concentration.^{1 2 3 5 6 7 8 100 101 102 103}

• Obtain hip X-rays prior to initiating somatropin therapy in pediatric patients with short stature due to chronic kidney disease.³

• Evaluate for signs of upper airway obstruction and sleep apnea in patients with Prader-Willi syndrome.^{1 2 3 5 6 7 8}

Patient Monitoring

• Perform periodic fundoscopic examination.^{1 2 3 5 6 7 8 9} .¹⁰

• Monitor for signs and symptoms of intracranial hypertension (e.g., visual changes, headache, nausea and/or vomiting).^{1 2 3 5 6 7 8 9 10 100}

• Monitor glucose levels periodically in all patients, especially in those with risk factors for type 2 diabetes mellitus (e.g., obesity, family history, Turner syndrome).^{1 2 3 5 6 7 8 10}

• Monitor patients with preexisting diabetes mellitus or impaired glucose tolerance, and adjust antihyperglycemic drugs doses as needed.^{1 2 3 5 6 7 8 9 10}

• Perform standard cancer screening and monitoring for malignancy development.^{101 102} Monitor patients with preexisting tumors for progression or recurrence.¹

• Monitor patients for reduced cortisol levels.^{1 2 3 5 6 7 8 100 101}

• Perform periodic thyroid function tests.^{1 2 3 5 6 7 8 100 101 102 103}

• Monitor for cardiovascular disorders and otitis media in patients with Turner syndrome.^{3 5 8}

• Monitor serum inorganic phosphorous, alkaline phosphatase, and parathyroid hormone as appropriate.^{1 2 3 5 6 7 8}

• In pediatric patients, assess compliance and evaluate other causes of poor growth such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone if patients experience failure to increase height velocity, particularly during the first year of treatment.^{1 2 3 5 6 7 8}

• In adults with growth hormone deficiency (GHD), monitor serum IGF-1 concentrations periodically every 1–2 months during dosage titration, then every 6 to 12 months once maintenance dosage is achieved.^{1 2 3 5 6 7 8 101 102 103}

Other General Considerations

• Somatropin treatment should be supervised by a physician experienced in the diagnosis and management of the specific indication for which the drug is being used.^{1 2 3 5 6 7 8 9}

• Somatropin products are not considered biosimilar to one another and are not interchangeable.⁴⁷

Administration

Administer by sub-Q injection.^{1 5 6 7 8 9 10}

Available in single-dose or multi-dose vial kits containing lyophilized powder and diluent vials, two-chamber cartridges containing lyophilized powder and diluent, and cartridge kits containing lyophilized powder and diluent in prefilled syringes; all require reconstitution prior to administration, and some require product specific delivery devices.^{1 5 6 7 8 9 10}

Also available as a solution for sub-Q administration in ready-to-use prefilled pens, injection devices, or cartridges.^{2 3 5}

Available as a solution in single-patient use prefilled pen devices or in cartridges for use with product specific pen devices.^{2 3 5}

Caution patients and/or their caregivers against sharing or reuse of syringes, needles, and/or devices; carefully instruct on the proper, safe disposal of needles, syringes, and unused drug, and supply the patient and/or caregiver with a puncture-resistant container for the proper, safe disposal of such equipment after use.^{1 2 3 5 6 7 8 9 10}

Sub-Q Injection

Administer by sub-Q injection into back of the upper arm, abdomen, buttock, or thigh.^{1 2 3 5 6 7 8 9}

Rotate injection sites.^{1 2 3 5 6 7 8 9 10}

Zorbtive: Administer sub-Q at a 90° angle into top side of thigh, areas around belly button, back of upper arms, or buttocks or hips.¹⁰ Do not inject into areas where skin is tender, bruised, red, or hard.¹⁰

Reconstitution

Vials, lyophilized powder

Follow manufacturer reconstitution instructions for diluent selection, diluent volume, and technique.^{1 5 6 7 9 10}

Aim diluent stream gently against vial wall, and swirl gently, never shake, until the powder is completely dissolved and the solution is clear.^{1 5 6 7 9 10}

Cartridges, lyophilized powder

Follow manufacturer reconstitution instructions for preparation-specific technique.^{1 7 8}

Employ gentle movements to mix and completely dissolve powder into diluent, never shake the cartridge.^{1 7 8}

Dosage

Pediatric Patients

Pediatric Growth Hormone Deficiency

Sub-Q

Somatropin dosage is weight-based and expressed in weekly dosages that should be divided and administered in equal doses.¹⁰⁰

Divide the weekly dosage and administer daily 3 to 7 times a week.^{1 2 3 5 6 7 8}

Usual recommended dosage 0.16–0.24 mg/kg per week.^{1 2 3 5 6 7 8 100} Dosages up to 0.3 mg/kg per week or up to 0.7 mg/kg per week in pubertal patients recommended in FDA-approved labeling for some preparations.^{1 3 6 7 100}

The Pediatric Endocrine Society recommends using lowest effective dosage based on growth response.¹⁰⁰

Once epiphyseal fusion has occurred, discontinue somatropin for stimulation of linear growth.^{1 2 3 5 6 7 8}

Turner Syndrome

Sub-Q

Dosages up to 0.375 mg/kg per week commonly recommended; lower (0.33 mg/kg per week) or higher (0.47 mg/kg per week) weekly dosages also found in the FDA approved labeling of some preparations.^{1 2 3 5 6 8}

Divide and administer dosage into daily sub-Q injections 3–7 times a week.^{1 2 3 5 6 8}

Once epiphyseal fusion has occurred, discontinue somatropin for stimulation of linear growth.^{1 2 3 5 6 8}

Idiopathic Short Stature

Sub-Q

Pediatric Endocrine Society recommends initial dosage of 0.24 mg/kg per week divided and administered daily.¹⁰⁰ Some patients may require up to 0.47 mg/kg per week, however, there are no data to support dosages >0.47 mg/kg per week.¹⁰⁰

Weekly dosages up to 0.3 mg/kg, 0.37 mg/kg, or 0.47 mg/kg recommended in FDA approved labeling; most manufacturers recommended dividing weekly dosage into 6 or 7 daily sub-Q injections; manufacturer of Zomacton states to divide weekly dosage into equal doses given either 3, 6, or 7 days per week.^{1 2 3 5 6 8 100}

Once epiphyseal fusion has occurred, discontinue somatropin for stimulation of linear growth.^{1 2 3 5 6 8}

SHOX-D

Sub-Q

0.35 mg/kg per week.^{1 6}

Divide and administer in equal doses given over 3, 6, or 7 daily subcutaneous doses per week.^{1 6}

Once epiphyseal fusion has occurred, discontinue somatropin for stimulation of linear growth.^{1 6}

Small for Gestational Age

Sub-Q

Up to 0.47 or 0.48 mg/kg per week.^{1 2 5 6 8}

Divide and administer in equal doses given 3, 6, or 7 days a week.^{1 2 5 6 8}

Consider a gradual reduction in dosage if substantial catch-up growth is observed during the first few years of therapy.^{1 2 6 8}

Once epiphyseal fusion has occurred, discontinue somatropin for stimulation of linear growth.^{1 2 3 5 6 7 8}

Noonan Syndrome

Sub-Q

Up to 0.46 mg/kg per week.²

Divide and administer in equal doses given 6 or 7 days a week.²

Once epiphyseal fusion has occurred, discontinue somatropin for stimulation of linear growth.²

Prader-Willi Syndrome

Sub-Q

0.24 mg/kg per week.^{2 5 8}

Divide and administer in equal doses given 6 or 7 days a week.^{2 5 8}

Once epiphyseal fusion has occurred, discontinue somatropin for stimulation of linear growth.^{2 5 8}

Growth Failure Secondary to Chronic Kidney Disease

Sub-Q

Up to 0.35 mg/kg per week.³

Divide and administer in equal daily doses.³

Continue up until the time of renal transplantation.³

To optimize therapy for patients who require dialysis, the following guidelines for injection schedule are recommended:

Hemodialysis Patients: Administer injection at night just prior to going to sleep or at least 3–4 hours after hemodialysis to prevent hematoma formation due to heparin.³

Chronic Cycling Peritoneal Dialysis (CCPD) Patients: Administer injection in the morning after dialysis completion.³

Chronic Ambulatory Peritoneal Dialysis (CAPD) Patients: Administer injection in the evening at the time of the overnight exchange.³

Adults

Growth Hormone Deficiency

Dosing may be non-weight-based or weight-based.^{1 2 3 5 6 7}

Individualize dosage based on age, gender, BMI, and other factors to improve effectiveness and reduce adverse effects of therapy,¹⁰¹

Nonweight-based-dosing

Sub-Q

American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) and Endocrine Society guidelines recommend individualized, non-weight-based dosing, starting with a dose that is appropriate for age and comorbid condition (e.g., obesity, diabetes mellitus), and then titrating according to clinical response, adverse effects, and age- and gender-adjusted serum IGF-1 levels.^{101 102 103}

Recommended initial dosage in patients <30 years of age: 0.4–0.5 mg/day^{1 2 3 5 6 7 8 101 102 103}

Recommended initial dosage in patients 30 to 60 years of age: 0.2 to 0.3 mg/day^{1 2 3 5 6 7 8 101 102 103}

Recommended initial dosage in patients >60 years of age, or concurrent diabetes mellitus, previous gestational diabetes, or obesity: 0.1–0.2 mg/day.^{1 2 3 5 6 7 8 101 102 103}

Higher doses may be required in younger patients and in females taking oral estrogen replacement.^{101 102 103}

Titrate by 0.1–0.2 mg/day increments every 1–2 months until clinical response achieved.^{1 2 3 5 6 7 8 101 102 103}

Titrate by smaller increments and/or longer time intervals in geriatric patients.^{1 2 3 5 6 7 8 101 102 103}

Weight-based dosing

Sub-Q

Initial recommended dosage: 0.004-0.006 mg/kg per day.^{1 2 3 5 6 7 8}

Weight-based dosing not recommended in obese patients due to risk of adverse reactions.^{101 102 103}

Titrate at 4–8 week intervals according to individual patient requirements until maximum dosage range of 0.01–0.016 mg/kg per day; in patients receiving Nutropin AQ, manufacturer states that maximum dosage is 0.025 mg/kg per day in patients ≤35 years of age and 0.0125 mg/kg per day in patients >35 years of age.^{1 2 3 5 6 7 8}

Transitioning from Pediatric to Adult Treatment

Sub-Q

In patients transitioning from pediatric to adult treatment, after epiphyseal closure and re-evaluation of need for treatment continuation, the AACE/ACE guideline recommends somatropin resumption at 50% of the dosage used in childhood.¹⁰¹

HIV-associated Wasting or Cachexia

Sub-Q

Recommended initial dosage of Serostim is 0.1 mg/kg once daily (up to a total dose of 6 mg) at bedtime as described in Table 1.⁹

In patients at increased risk of adverse events (e.g., glucose intolerance), consider initial dosage of 0.1 mg/kg every other day.⁹

In patients experiencing growth hormone-induced adverse effects, consider reducing total daily dose or number of doses administered per week.⁹

No efficacy and safety data in patients treated with somatropin continuously for more than 48 weeks.⁹ Also no data on patients receiving intermittent treatment with somatropin.⁹

Short Bowel Syndrome

Sub-Q

Recommended dosage of somatropin (Zorbtive) is 0.1 mg/kg once daily to a maximum daily dose of 8 mg for 4 weeks.¹⁰

Dosage adjustment for fluid retention and arthralgia/carpal tunnel syndrome (moderate toxicity): Reduce dosage to 0.05 mg/kg once daily (maximum total dose of 4 mg) or treat symptomatically with analgesics.¹⁰

Dosage adjustment for fluid retention and arthralgia/carpal tunnel syndrome (severe toxicity): Discontinue for up to 5 days; upon symptom resolution, resume therapy at a dosage of 0.05 mg/kg once daily (maximum total dose of 4 mg).¹⁰ Permanently discontinue therapy if severe toxicity recurs or does not resolve within 5 days.¹

Special Populations

Hepatic Impairment

No dosage recommendations at this time.^{1 2 3 5 6 7 8 9 10}

Renal Impairment

No dosage recommendations at this time.^{1 2 3 5 6 7 8 9 10}

Geriatric Patients

Lower initial doses and smaller dose adjustment increments are recommended by manufacturer and some guidelines.^{1 2 3 5 6 7 8 9 10 101 102}

Cautions for Somatropin

Contraindications

• Acute critical illness after open heart surgery, abdominal surgery, or multiple accidental trauma, or acute respiratory failure.^{1 2 3 5 6 7 8 9 10}

• Hypersensitivity to somatropin or any of the excipients.^{1 2 3 5 6 7 8 9 10}

• Active malignancy.^{1 2 3 5 6 7 8 9 10 101 102}

• Active proliferative or severe non-proliferative diabetic retinopathy.^{1 2 3 5 6 7 8 9 10 101}

• Pediatric patients with closed epiphyses.^{1 2 3 5 6 7 8}

• Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea or have severe respiratory impairment, due to the risk of sudden death.^{1 2 3 5 6 7 8}

Warnings/Precautions

Increased Mortality in Patients with Acute Critical Illness

Increased mortality reported in patients continuing pharmacologic somatropin doses while experiencing acute critical illness following open heart surgery, abdominal surgery, or multiple accidental trauma, or acute respiratory failure.^{1 2 3 5 6 7 8 9 10}

Safety of continuing growth hormone replacement dosages in growth hormone deficient patients experiencing concurrent acute critical illness not established.^{1 2 3 5 6 7 8}

Weigh risks against benefits of somatropin continuation in non-growth hormone deficient adults experiencing concurrent acute critical illnesses.^{3 5 7 8}

Some manufacturers recommend discontinuance of therapy in patients with acute critical illness.¹⁰

Sudden Death in Pediatric Patients with Prader-Willi Syndrome

Sudden death reported in pediatric patients with Prader-Willi syndrome who had at least one of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection.¹

Males may be at greater risk.^{1 2 3 5 6 7 8}

Before initiation, evaluate patients with Prader-Willi syndrome for signs of upper airway obstruction and sleep apnea.^{1 2 3 5 6 7 8}

If signs of upper airway obstruction (including onset of, or increased, snoring) and/or new onset sleep apnea occur, interrupt treatment.^{1 2 3 5 6 7 8}

Monitor all patients with Prader-Willi syndrome for signs of respiratory infection; diagnose as early as possible and treat aggressively.^{1 2 3 5 6 7 8}

Ensure effective weight control in patients with Prader-Willi syndrome treated with somatropin.^{1 2 3 5 6 7 8}

Increased Risk of Neoplasms – Active Malignancy

Increased risk of malignancy progression in patients with active malignancy.^{1 2 6 10 101 102}

Complete malignancy treatment; the preexisting malignancy should be inactive before initiating somatropin.^{1 2 6 10 101 102}

Discontinue if malignancy recurs.^{1 2 6 10}

Increased Risk of Neoplasms – Risk of Second Neoplasm in Pediatric Patients

Increased risk of a second neoplasm observed in pediatric cancer survivors with acquired GHD who were treated with somatropin following radiation to the brain/head for their first neoplasm.^{1 2 3 5 6 7 8 10 100}

Intracranial tumors, in particular meningiomas, were most common second neoplasms.^{1 2 3 5 6 7 8 10 100}

In adults, relationship between somatropin treatment and CNS tumor recurrence is unknown.^{1 2 3 5 6 7 8 10}

Monitor for tumor progression or recurrence in patients with history of intracranial neoplasm.^{1 2 3 5 6 7 8 9 10}

Increased Risk of Neoplasms – New Malignancy during Treatment

Consider risks and benefits of initiating growth hormone in children with certain rare genetic causes of short stature with an increased risk of malignancies.^{1 2 3 5 6 7 8 100}

Consider risks and benefits of starting somatropin (Serostim) because malignancies are more common in HIV positive patients.⁹

Monitor carefully for increased growth or potential malignant changes of preexisting nevi.^{1 2 3 5 6 7 8 9 10}

Advise patients/caregivers to report marked changes in behavior, onset of headaches, vision disturbances, and/or changes in skin pigmentation.^{1 2 6}

Some experts recommend standard cancer screening and long-term monitoring in adults receiving growth hormone therapy.¹⁰¹

Glucose Intolerance and Diabetes Mellitus

May decrease insulin sensitivity, particularly at higher doses, and/or unmask previously undiagnosed pre-diabetes, impaired glucose tolerance, or overt type 2 diabetes mellitus (DM).^{1 2 3 5 6 7 8 10 103}

New onset type 2 DM, new onset impaired glucose intolerance, and exacerbation of preexisting DM reported.^{1 2 3 5 6 7 8 10}

Diabetic ketoacidosis and diabetic coma reported.^{9 10}

Monitor glucose levels periodically in all patients, especially in those with risk factors for type 2 DM (e.g., obesity, family history, Turner syndrome).^{1 2 3 5 6 7 8 10}

Monitor patients with preexisting type 1 DM, type 2 DM, pre-diabetes, or impaired glucose tolerance; adjust antihyperglycemic drugs and/or doses.^{1 2 3 5 6 7 8 9 10 100 102}

Guidelines suggest using lower initial doses in adult patients with concurrent DM, obesity, older age, and previous gestational DM.¹⁰¹

Intracranial Hypertension

Intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting reported.^{1 2 3 5 6 7 8 9 10}

Symptoms usually occur within 8 weeks after initiation or dosage increases; signs and symptoms resolve rapidly after cessation or dosage reduction.^{1 2 3 5 6 7 8 9 10 100}

Perform fundoscopic examination before initiating treatment; reassess periodically.^{1 2 3 5 6 7 8 9 10}

If symptoms of intracranial hypertension (e.g., visual changes, headache, nausea and/or vomiting) occur, perform fundoscopic examination.^{1 2 3 5 6 7 8 9 10 100} Stop treatment if papilledema observed.^{1 2 3 5 6 7 8 9 10 100}

May restart treatment at a lower dose after signs and symptoms have resolved.^{1 2 3 5 6 7 8 9}

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic reactions and angioedema, reported.^{1 2 3 5 6 7 8 9 10}

If allergic reaction occurs, discontinue somatropin, initiate appropriate treatment, and seek medical attention.^{1 2 3 5 6 7 8 9 10}

Do not use in patients with known hypersensitivity to somatropin or any excipients, including those with hypersensitivity to diluent excipients (e.g., metacresol, glycerin).^{1 2 3 5 6 7 8 9 10}

Fluid Retention/Carpal Tunnel Syndrome/Arthralgia

Fluid retention may occur frequently.^{1 2 3 5 6 7 8 9 10} Increased tissue turgor (swelling, particularly in the hands and feet) and musculoskeletal discomfort/arthralgia (pain, swelling and/or stiffness) may occur.^{9 10}

Clinical manifestations (e.g., edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) are transient, dose-dependent,^{101 102} and may occur more frequently with weight-based regimens in obese or older patients.^{1 2 3 5 6 7 8 9 43 44 45 103}

Spontaneous resolution, resolution following treatment with analgesics, or after reducing frequency of dosing observed.^{9 10}

If symptoms of carpal tunnel syndrome do not resolve by decreasing dosage, some manufacturers recommend treatment discontinuance.^{9 10}

Hypoadrenalism

Patients with or at risk of pituitary hormone deficiency may be at increased risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism during somatropin therapy.^{1 2 3 5 6 7 8 10 101 102 103}

Patients treated with glucocorticoid replacement may require an increase in their maintenance or stress doses.^{1 2 3 5 6 7 8 10 101 103}

Monitor for reduced serum cortisol levels and/or need for glucocorticoid dosage increases.^{1 2 3 5 6 7 8 10 100 101 103}

Hypothyroidism

Undiagnosed or untreated hypothyroidism may prevent optimal response to somatropin.^{1 2 3 5 6 7 8}

Increased risk of autoimmune thyroid disease and primary hypothyroidism in patients with Turner syndrome.^{1 2 3 5 6 7 8}

Perform periodic thyroid function tests; initiate or adjust thyroid hormone replacement therapy when indicated.^{1 2 3 5 6 7 8 100 101 102 103}

Manufacturer of Zorbtive states to evaluate thyroid function before initiation and following 4 weeks of treatment in patients with suspected and/or diagnosed hypopituitarism; correct thyroid function when indicated.¹⁰

Slipped Capital Femoral Epiphysis in Pediatric Patients

Slipped capital femoral epiphysis may occur more frequently in pediatric patients undergoing rapid growth or in those with endocrine disorders (e.g., GHD, Turner syndrome).^{1 2 3 5 6 7 8}

Evaluate pediatric patients at the onset of a limp or complaints of persistent hip or knee pain.^{1 2 3 5 6 7 8}

Progression of Preexisting Scoliosis in Pediatric Patients

Somatropin does not increase the occurrence of scoliosis.^{1 2 3 5 6 7 8}

Progression of existing scoliosis can occur in patients who experience rapid growth;^{1 2 3 5 6 7 8} monitor for scoliosis progression in patients with GHD receiving somatropin.^{1 2 3 5 6 7 8 100}

Pancreatitis

Pancreatitis reported.^{1 2 3 5 6 7 8 9 10}

Risk may be greater in pediatric patients than adults; girls with Turner syndrome may be at greater risk than other somatropin-treated patients.^{1 2 3 5 6 7 8 9 10}

Consider pancreatitis in patients who develop persistent severe abdominal pain.^{1 2 3 5 6 7 8 9 10}

Lipoatrophy

Rotate injection sites to reduce risk of lipoatrophy.^{1 2 3 5 6 7 8 9 10}

Cardiovascular Disorders in Patients with Turner Syndrome

Monitor patients with Turner syndrome for cardiovascular disorders (e.g., hypertension, aortic aneurysm or dissection, stroke).^{3 5 8}

Otitis Media in Patients with Turner Syndrome

Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome.^{3 5 8}

Osteodystrophy in Pediatric Patients with Chronic Kidney Disease

Monitor for evidence of progression of renal osteodystrophy in patients with CKD.³

Obtain hip X-rays prior to initiating somatropin.³

Monitor patients for limping or complaint of hip or knee pain.³

Benzyl Alcohol

Benzyl alcohol may be a component of somatropin products or the diluent used for reconstitution.^{5 6 7 9 10}

Consult somatropin preparation-specific labeling to find a benzyl alcohol-free product or alternative diluents to decrease benzyl alcohol exposure in high-risk patients.^{6 7}

Confirmation of Childhood-Onset Adult Growth Hormone Deficiency

Appropriate growth hormone provocative testing is required to confirm the diagnosis of adult GHD except for adults with multiple other pituitary hormone deficiencies due to organic disease or patients with congenital/genetic GHD.^{5 7}

Laboratory Tests

Monitor patients for increased serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and insulin-like growth factor-1 (IGF-1).^{1 2 3 5 6 7 8}

Concomitant Antiretroviral Therapy in HIV-associated Wasting or Cachexia

No significant somatropin-associated increase in viral burden observed in patients on concomitant antiretroviral therapy.^{9 42 43}

Maintain antiretroviral therapy in patients with HIV for the duration of Serostim treatment.⁹

Immunogenicity

Potential for development of immunogenicity to somatropin.^{1 2 3 5 6 7 8 9}

Antibodies with binding capacities <2 mg/L have not been associated with growth attenuation.^{2 3 5 7 8}

Interference with growth response was observed when binding capacity was >2 mg/L in a small number of treated patients.^{2 3 5 7 8}

Specific Populations

Pregnancy

Limited available human data.^{1 2 3 5 6 7 8 9 10}

Due to insufficient evidence regarding safety or efficacy, routine use of somatropin for conception or continued use during pregnancy in women with GHD is not recommended according to American Association of Clinical Endocrinologists/American College of Endocrinology and Endocrine Society guidelines.^{101 103}

Consult preparation-specific labeling to find a benzyl alcohol-free product or alternative diluents to avoid fetal benzyl alcohol exposure during pregnancy.^{6 7}

Lactation

No data on presence of somatropin in human milk.^{1 2 6 10}

Limited data indicate exogenous somatropin does not increase normal breastmilk concentrations of growth hormone, and no adverse effects on the breastfed infant have been reported with somatropin.^{1 2 6 10}

Consider benefits of breast-feeding and importance of somatropin to the woman along with potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.^{1 2 6 10}

Consult preparation-specific labeling to find a benzyl alcohol-free product or alternative diluents to avoid benzyl alcohol exposure to the breastfed infant.^{6 7}

Pediatric Use

Safety and efficacy established in pediatric patients with growth failure due to GHD, Turner syndrome, idiopathic short stature, SHOX-D , born small for gestational age with no catch-up growth by 2 to 4 years of age, Prader-Willi syndrome, CKD, and Noonan syndrome.^{1 2 3 5 6 7 8}

Risks of growth hormone therapy specific to pediatric patients include risk of sudden death in patients with Prader-Willi syndrome, risk of second neoplasm in cancer survivors treated with radiation to the brain and/or head, intracranial hypertension, slipped capital femoral epiphysis, progression of preexisting scoliosis, and pancreatitis.^{1 2 3 5 6 7 8 9 10 101 102}

Safety and efficacy of somatropin in pediatric patients with HIV not established.⁹

Benzyl alcohol may be a component of somatropin products or the diluent used for reconstitution.^{5 6 7 9 10}

Consult preparation-specific labeling to find a benzyl alcohol-free product or alternative diluents to decrease benzyl alcohol exposure in high-risk patients.^{6 7}

Geriatric Use

Limited data in patients ≥65 years of age.^{1 2 3 5 6 7 8 9 10} Elderly patients may be more sensitive, more prone to adverse reactions, and may require lower initial somatropin doses with smaller dosage adjustment increments.^{1 2 3 5 6 7 8 9 10 101 102}

Hepatic Impairment

Clearance decreased; clinical significance unknown.^{3 7 10}

Renal Impairment

Clearance decreased; clinical significance unknown.^{3 7 9 10}

Common Adverse Effects

Common adverse reactions: upper respiratory infection, fever, pharyngitis, headache, injection site reactions (such as pain, numbness, redness, and swelling), rashes, lipoatrophy, otitis media, edema, arthralgia, flatulence, abdominal pain, carpal tunnel syndrome, paresthesia, myalgia, peripheral edema, flu syndrome, impaired glucose tolerance.^{1 2 3 5 6 7 8 9 10}

Drug Interactions

Not known to be metabolized by CYP isoenzymes or other drug metabolizing enzymes.^{1 2 3 5 6 7 8 9 10}

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

Concern for growth hormone-induced changes in CYP isoenzyme activity.^{1 2 3 5 6 7 8 9 10 30}

Monitor carefully if used concomitantly with drugs metabolized by CYP isoenzymes.^{1 2 3 5 6 7 8 9 10} No data are available on drug interactions with HIV protease inhibitors or non-nucleoside reverse transcriptase inhibitors and somatropin.⁹

Specific Drugs

Somatropin Pharmacokinetics

Absorption

Bioavailability

Bioavailability following sub-Q injection ranges between 70-90%.^{1 3 6 7 8 9 10}

Elimination

Metabolism

Protein catabolism in both the liver and kidneys; extensive metabolism studies not conducted.^{1 2 3 5 6 7 8 9 10}

Half-life

Half-life following sub-Q injection of different preparations in various populations (e.g., adult GHD, HIV-associated wasting) or healthy volunteers ranges from 2 to 10 hours (median 3 hours).^{1 2 5 6 7 9 10}

Special Populations

Renal Impairment: Reduced clearance observed; accumulation in children with CKD or ESRD not reported.^{3 7 9 10}

Hepatic Impairment: Reduced clearance observed with severe impairment; clinical significance unknown.^{3 7 10}

Similar pharmacokinetics observed in elderly versus adults, children versus adults, male versus females, and healthy adults and children versus those with GHD.^{1 2 3 5 6 7 8 9 10}

Stability

Storage

Parenteral

Do not store under conditions of extreme heat or cold; do not freeze.^{1 2 3 5 6 7 8 9 10} Store in original carton to protect from light and physical damage.^{1 2 3 5 6 7 8 9 10} Do not shake.^{1 2 3 5 6 7 8 9 10}

Powder for injection in single-dose vials, multidose vials, cartridge kits, or two-chamber cartridges

Humatrope, Omnitrope, Zomacton, Genotropin: 2–8°C.^{1 5 6 7 8}

Serostim, Saizen, and Zorbtive: 15–30°C.^{9 10}

Genotropin Miniquick: 2–25°C for up to 3 months after dispensing.⁸

Consult specific labeling for storage and stability following reconstitution.^{1 5 6 7 8 9 10}

Solution for injection in cartridges or single-patient use prefilled pen

Norditropin, Nutropin AQ, Omnitrope: 2–8°C.^{2 3 5}

Consult specific labeling for storage and stability after first use.^{2 3 5}

Actions

• Somatropin (recombinant) is identical to that of human growth hormone of pituitary origin.^{1 2 3 5 6 7 8 9 10}

• Binds to human growth hormone receptor in the cell membrane of target cells.^{1 2 3 5 6 7 8} Effects including normalization of IGF-1 concentrations, stimulation of chondrocyte differentiation and proliferation, stimulation of hepatic glucose output, protein synthesis, and lipolysis.^{1 2 3 5 6 7 8}

• In children, growth hormone stimulation of skeletal growth increases linear growth rate (height velocity).^{1 2 3 5 6 7 8}

• Reduced fat mass, increased lean body mass, metabolic alterations that include beneficial changes in lipid metabolism, reduction in body fat stores, and normalization of IGF-1 concentrations reported in somatropin-treated growth hormone-deficient adults.^{3 5 7 8}

• Improved nitrogen balance and increased protein-sparing lipid oxidation; decreased trunk fat, decreased total body fat, and increased lean body mass occur in somatropin-treated adults with HIV-associated wasting or cachexia.⁹

• Growth hormone and IGF-1 receptors are found in intestinal mucosa.¹⁰ Transmucosal transport of water, electrolytes, and nutrients is enhanced by growth hormone administration.¹⁰

Advice to Patients

• Advise patients and caregivers to review the instructions for use that accompanies the somatropin preparation, including device specific instructions.^{1 2 3 5 6 7 8 9 10} Consult the manufacturer or specialty pharmacy customer support services for assistance or additional training, if needed.^{1 2 3 5 6 7 8 9 10}

• Advise patients and caregivers of proper needle disposal, caution against any reuse of needles, sharing of devices and/or needles, and disposal of used cartridges and needles in an appropriate container.^{1 2 3 5 6 7 8 9 10}

• Advise childhood cancer survivors and caregivers of the increased risk of secondary neoplasms and to immediately report marked changes in behavior, onset of headaches, vision disturbances, and/or changes in skin pigmentation or changes in the appearance of preexisting nevi.^{1 2 6}

• Advise patients and caregivers that impaired glucose intolerance, type 2 diabetes mellitus, or exacerbation of preexisting diabetes mellitus can occur and to monitor blood glucose.^{1 2 6}

• Advise patients and caregivers that somatropin can cause intracranial hypertension and to immediately report any visual changes, headache, and nausea and/or vomiting to their healthcare provider.^{1 2 6 10}

• Advise patients and caregivers that fluid retention may occur and to contact their healthcare provider if symptoms (e.g., edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) occur.^{1 2 6 10}

• Advise patients and caregivers that hypoadrenalism may develop in those at risk and to report hyperpigmentation, extreme fatigue, dizziness, weakness, or weight loss to their healthcare provider.^{1 2 6 10}

• Advise patients and caregivers that periodic thyroid function tests may be required in those at risk.^{1 2 6 10}

• Advise patients and caregivers that pancreatitis may develop and to report any new onset abdominal pain to their healthcare provider.^{1 2 6 10}

• Advise patients and caregivers that hypersensitivity reactions (anaphylaxis and angioedema) are possible, and to seek prompt medical attention if an allergic reaction occurs.^{1 2 6}

• Advise caregivers to report the development of a limp or complaints of hip or knee pain in somatropin-treated children with chronic kidney disease.³

• Advise patients and caregivers to rotate injection sites to decrease the risk of lipoatrophy; do not inject into skin that is tender, bruised, red, or hard.^{1 2 3 5 6 7 8 9 10}

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.^{2 10}

• Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.⁶

• Inform patients of other important precautionary information.^{1 2 3 5 6 7 8 9 10}

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Human growth hormone is not subject to control under the Federal Controlled Substances Act of 1970; however, distribution and possession for use other than recognized indications is criminalized.⁴⁶

Medical Disclaimer