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Special Alerts
Somatropin: Ongoing Safety Review of the Santé Adulte GH Enfant (SAGhE) Study
December 2010
The U.S. Food and Drug Administration (FDA) is informing the public of a French observational (SAGhE) study's results describing a small increased risk of death in adults who were treated with recombinant human growth hormone (somatropin) during childhood for certain types of short stature (eg, idiopathic growth hormone deficiency, idiopathic or gestational short stature). The study population included people who received somatropin between 1985 and 1996 and whose vital status and cause of death were determined through September 2009. There were 93 observed deaths in the somatropin group versus 70 expected deaths in the general French population. The data suggests an increase in mortality due to bone tumors and cardiovascular events (eg, subarachnoid or intracerebral hemorrhage) in the somatropin group. The risk of death was reported to be increased when higher than recommended doses of somatropin were used.
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has initiated a safety review but confirms that there is no immediate concern. Prescribers are reminded to strictly follow the indications for use and approved doses. The FDA is currently reviewing available information on the potential risk as well. The FDA and European Medicines Agency are recommending that patients continue this medication unless their healthcare providers discontinue the treatment.
Further information may be found at:
U.S.: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm237969.htm
Europe: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2010/12/news_detail_001167.jsp&murl=menus/news_and_events/news_and_events.jsp&mid=WC0b01ac058004d5c1&jsenabled=true
Pronunciation
(soe ma TROE pin)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Children:
Treatment of growth failure due to inadequate endogenous growth hormone secretion (Genotropin®, Humatrope®, Norditropin®, Nutropin®, Nutropin AQ®, Omnitrope®, Saizen®, Tev-Tropin®)
Treatment of short stature associated with Turner syndrome (Genotropin®, Humatrope®, Norditropin®, Nutropin®, Nutropin AQ®)
Treatment of Prader-Willi syndrome (Genotropin®, Omnitrope®)
Treatment of growth failure associated with chronic renal insufficiency (CRI) 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 2-4 years of age (Humatrope®, Norditropin®)
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®, Nutropin®, Nutropin AQ®, Omnitrope®)
Treatment of short stature or growth failure associated with short stature homeobox gene (SHOX) deficiency (Humatrope®)
Treatment of short stature associated with Noonan syndrome (Norditropin®)
Adults:
HIV patients with wasting or cachexia with concomitant antiviral therapy (Serostim®)
Replacement of endogenous growth hormone in patients with adult growth hormone deficiency who meet both of the following criteria (Genotropin®, Humatrope®, Norditropin®, Nutropin®, Nutropin AQ®, Omnitrope®, Saizen®):
Biochemical diagnosis of adult growth hormone deficiency by means of a subnormal response to a standard growth hormone stimulation test (peak growth hormone ≤5 mcg/L). Confirmatory testing may not be required in patients with congenital/genetic growth hormone deficiency or multiple pituitary hormone deficiencies due to organic diseases.
and
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, confirmed as an adult before replacement therapy is initiated
Treatment of short-bowel syndrome (Zorbtive®)
Use: Unlabeled/Investigational
Investigational: Pediatric HIV patients with wasting/cachexia (Serostim®); HIV-associated adipose redistribution syndrome (HARS) (Serostim®)
Pregnancy Risk Factor
B/C (depending upon manufacturer)
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. Reproduction studies have not been conducted with all agents. During normal pregnancy, maternal production of endogenous growth hormone decreases as placental growth hormone production increases. Data with somatropin use during pregnancy is limited.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to growth hormone or any component of the formulation; growth promotion in pediatric patients with closed epiphyses; progression or recurrence of any underlying intracranial lesion or actively growing intracranial tumor; acute critical illness due to complications following open heart or abdominal surgery; multiple accidental trauma or acute respiratory failure; evidence of active malignancy; active proliferative or severe nonproliferative diabetic retinopathy; use in patients with Prader-Willi syndrome without growth hormone deficiency (except Genotropin®) or in patients with Prader-Willi syndrome with growth hormone deficiency who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment
Warnings/Precautions
Concerns related to adverse effects:
• Fluid retention: May occur frequently in adults during use; manifestations of fluid retention (eg, edema, arthralgia, myalgia, nerve compression syndromes/paresthesias) are generally transient and dose dependent.
• Hypersensitivity: Reactions are possible; monitor closely.
• Intracranial hypertension (IH): IH with headache, nausea, papilledema, visual changes, and/or vomiting has been reported with somatropin; 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 failure and Prader-Willi syndrome may be at increased risk for IH.
• Neoplasm: Use in contraindicated with active malignancy. Monitor patients with pre-existing tumors or growth failure secondary to an intracranial lesion for recurrence or progression of underlying disease; discontinue therapy with evidence of recurrence. 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. Monitor patients for any malignant transformation of skin lesions.
• Pancreatitis: Has been rarely reported; incidence in children (especially girls) with Turner syndrome may be greater than adults.
• Slipped capital epiphyses: Patients with growth hormone deficiency may develop slipped capital 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. The safety of continuing somatropin in patients who develop these illnesses during therapy has not been established; use with caution.
• Childhood-onset adult growth hormone deficiency (GHD): Children with epiphyseal closure who are treated with somatropin replacement therapy should be reassessed before continuation of therapy at reduced dose recommended for GH deficient adults.
• Diabetes mellitus (DM): Use with caution in patients with diabetes or with risk factors for impaired glucose tolerance; may decrease insulin sensitivity. Risk factors for diabetes in this population include obesity, Turner syndrome, or a family history of DM. Adjustment of antidiabetic medications may be necessary.
• Hypoadrenalism: Patients with hypoadrenalism may require increased dosages of glucocorticoids (especially cortisone acetate and prednisone) due to somatropin-mediated inhibition of 11 beta-hydroxysteroid dehydrogenase type 1; undiagnosed central hypoadrenalism may be unmasked. Excessive glucocorticoid therapy may inhibit the growth promoting effects of somatropin in children; monitor and adjust glucocorticoids carefully.
• Hypopituitarism: Closely monitor other hormonal replacement treatments in patients with hypopituitarism.
• Hypothyroidism: Untreated/undiagnosed hypothyroidism may decrease response to therapy; monitor thyroid function test periodically and initiate/adjust thyroid replacement therapy as needed.
• Noonan syndrome: Safety and efficacy have not been established for the treatment of Noonan syndrome in children with significant cardiac disease.
• Obesity: Increased incidence of adverse events may occur when using a weight-based dosing regimen.
• Prader-Willi syndrome: Fatalities have 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, sleep apnea, respiratory impairment, or unidentified respiratory infection; male patients with one or more of these factors 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. In addition, evaluation of and/or monitoring for sleep apnea and respiratory infections are recommended.
• 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, cardiovascular disorders (including stroke, aortic aneurysm, hypertension), and thyroid disease, monitor carefully
Special populations:
• Elderly: May be more sensitive to the actions of somatropin; consider lower starting doses.
• HIV patients: Patients with HIV infection should be maintained on antiretroviral therapy to prevent the potential increase in viral replication.
Dosage form specific issues:
• Benzyl alcohol: Products may contain benzyl alcohol which has been associated with "gasping syndrome" in neonates; when administering to newborns, reconstitute with sterile water or saline for injection.
• M-cresol: Some products may contain m-cresol as a preservative.
Other warnings/precautions:
• Administration: Not for I.V. injection. Subcutaneous administration sites must be rotated to prevent tissue atrophy.
Adverse Reactions
Growth hormone deficiency: Adverse reactions reported with growth hormone deficiency vary greatly by age. Generally, percentages are less in pediatric patients than adults, and many of the reactions reported in adults are dose related. Percentages reported also vary by product. Below is a listing by age group; events reported more commonly overall are noted with an asterisk (*).
Children: Antibodies development, arthralgia, benign intracranial hypertension, edema, eosinophilia, glycosuria, Hb A1c increased, headache, hematoma, hematuria, hyperglycemia (mild), hypertriglyceridemia, hypoglycemia, hypothyroidism, injection site reaction, intracranial tumor, leg pain, lipoatrophy, leukemia, meningioma, muscle pain, papilledema, pseudotumor cerebri, psoriasis exacerbation, rash, scoliosis progression, seizure, slipped capital femoral epiphysis, weakness
Adults: Acne, ALT increased, AST increased, arthralgia*, back pain, bronchitis, carpal tunnel syndrome, chest pain, cough, depression, diabetes mellitus (type 2), diaphoresis, dizziness, edema*, fatigue, flu-like syndrome*, gastritis, glucose intolerance, glucosuria, headache*, hyperglycemia (mild), hypertension, hypoesthesia, hypothyroidism, infection, insomnia, insulin resistance, joint disorder, leg edema, muscle pain, myalgia*, nausea, pain in extremities, paresthesia*, peripheral edema*, pharyngitis, retinopathy, rhinitis, skeletal pain*, stiffness in extremities, surgical procedure, upper respiratory tract infection, weakness
Additional/postmarketing reactions observed with growth hormone deficiency: Gynecomastia, increased growth of pre-existing nevi, pancreatitis
HARS: Serostim®: Limited to >10%: Edema (peripheral) (19% to 45%), arthralgia (28% to 37%), pain (extremity) (5% to 19%), hypoesthesia (9% to 15%), headache (4% to 14%), blood glucose increased (4% to 14%), paresthesia (11% to 13%), myalgia (3% to 13%)
Idiopathic short stature: Percentages reported using Humatrope® versus placebo: Myalgia (24%), scoliosis (19%), otitis media (16%), arthralgia (11%), arthrosis (11%), hyperlipidemia (8%), gynecomastia (5%), hip pain (3%), hypertension (3%). Additional adverse reactions listed as reported using other products from ISS NCGS Cohort (frequencies <1%): Aggressiveness, benign intracranial hypertension, diabetes, edema, hair loss, headache, injection site reaction
Prader-Willi syndrome: Genotropin® (frequency not defined): Aggressiveness, arthralgia, edema, hair loss, headache, benign intracranial hypertension, myalgia; fatalities associated with use in this population have been reported
Turner syndrome: Percentages reported using Humatrope® compared to untreated patients. Additional adverse reactions reported from other products, frequency not specified: Surgical procedures (45%), otitis media (43%), ear disorders (18%), joint pain, respiratory illness, urinary tract infection
HIV patients with wasting or cachexia: Serostim® (limited to ≥5%): Musculoskeletal disorders (arthralgia, arthrosis, myalgia: 78%), peripheral edema (26%), headache (13%), nausea (9%), paresthesia (8%), edema (6%), gynecomastia (6%), hypoesthesia (5%)
Short-bowel syndrome: Zorbtive® (limited to >10%): Peripheral edema (69% to 81%), facial edema (44% to 50%), arthralgia (31% to 44%), nausea (13% to 31%), injection site pain (up to 31%), flatulence (25%), injection site reaction (19% to 25%), abdominal pain (13% to 25%), vomiting (19%), pain (6% to 19%), chest pain (up to 19%), dehydration (up to 19%), infection (up to 19%), rhinitis (up to 19%), hearing symptoms (13%), dizziness (6% to 13%), rash (6% to 13%), diaphoresis (up to 13%), generalized edema (up to 13%), malaise (up to 13%), moniliasis (up to 13%), myalgia (up to 13%)
SHOX deficiency: Humatrope®: Arthralgia (11%), gynecomastia (8%), excessive cutaneous nevi (7%), scoliosis (4%)
Small for gestational age: Genotropin®, Humatrope® (frequency not defined): Mild, transient hyperglycemia; benign intracranial hypertension (rare); central precocious puberty; jaw prominence (rare); aggravation of pre-existing scoliosis (rare); injection site reactions; progression of pigmented nevi; carpal tunnel syndrome (rare) diabetes mellitus (rare); otitis media; headache; slipped capital femoral epiphysis
Drug Interactions
Antidiabetic Agents: Somatropin may diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy modification
Cortisone: Somatropin may diminish the therapeutic effect of Cortisone. Growth hormone may reduce the conversion of cortisone to the active cortisol metabolite. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
PredniSONE: Somatropin may diminish the therapeutic effect of PredniSONE. Growth hormone may reduce the conversion of prednisone to the active prednisolone metabolite. Risk D: Consider therapy modification
Storage
Genotropin®: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Following reconstitution of 5.8 mg and 13.8 mg cartridge, store under refrigeration and use within 21 days.
Genotropin® Miniquick®: Store in refrigerator prior to dispensing, but may be stored ≤25°C (77°F) for up to 3 months after dispensing. Once reconstituted, solution must be refrigerated and used within 24 hours. Discard unused portion.
Humatrope®:
Vial: Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F); do not freeze. When reconstituted with provided diluent or bacteriostatic water for injection, use within 14 days. When reconstituted with sterile water for injection, use within 24 hours and discard unused portion.
Cartridge: 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.
Norditropin®: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Avoid direct light.
Cartridge: When refrigerated, must be used within 4 weeks once inserted into pen. Orange cartridges (5 mg/1.5 mL) may also be stored up to 3 weeks at ≤25°C (77°F).
Prefilled pen: When refrigerated, must be used within 4 weeks after initial injection. Orange and blue prefilled pens may also be stored up to 3 weeks at ≤25°C (77°F).
Nutropin®: Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F); do not freeze.
Nutropin® vial: Use reconstituted vials within 14 days. When reconstituted with sterile water for injection, use immediately and discard unused portion.
Nutropin® AQ formulations: Use within 28 days following initial use.
Omnitrope®:
Powder for injection: Prior to reconstitution, store under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Reconstitute with provided diluent. Swirl gently; do not shake. Following reconstitution with the provided diluents, the 5.8 mg vial may be stored under refrigeration for up to 3 weeks. Store vial in carton to protect from light.
Solution: Prior to use, store under refrigeration at 2°C to 8°C (36°F to 46°F). Once the cartridge is loaded into the pen delivery system, store under refrigeration for up to 21 days after first use.
Saizen®: Prior to reconstitution, store at room temperature 15°C to 30°C (59°F to 86°F). Following reconstitution with bacteriostatic water for injection, reconstituted solution should be refrigerated and used within 14 days. When reconstituted with sterile water for injection, use immediately and discard unused portion. The Saizen® easy click cartridge, when reconstituted with the provided bacteriostatic water, should be stored under refrigeration and used within 21 days.
Serostim®: Prior to reconstitution, store at room temperature 15°C to 30°C (59°F to 86°F). When reconstituted with sterile water for injection, use immediately and discard unused portion.
Tev-Tropin®: Prior to reconstitution, store at 2°C to 8°C (36°F to 46°F). Following reconstitution with bacteriostatic NS, solution should be refrigerated and used within 14 days. Some cloudiness may occur; do not use if cloudiness persists after warming to room temperature.
Zorbtive®: Store unopened vials and diluent at room temperature of 15°C to 30°C (59°F to 86°F). Store reconstituted vial under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 14 days; do not freeze.
Reconstitution
Genotropin®: Reconstitute with diluent provided.
Genotropin 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: 5 mg: Reconstitute with 1.5-5 mL diluent provided. Swirl gently; do not shake.
Nutropin®: Vial:
5 mg: Reconstitute with 1-5 mL bacteriostatic water for injection. Swirl gently, do not shake.
10 mg: Reconstitute with 1-10 mL bacteriostatic water for injection. Swirl gently, do not shake.
Omnitrope® powder: Reconstitute with provided diluent. Swirl gently; do not shake.
Saizen®: Vial:
5 mg: Reconstitute with 1-3 mL bacteriostatic water for injection or sterile water for injection. Gently swirl; do not shake.
8.8 mg: Reconstitute with 2-3 mL bacteriostatic water for injection or sterile water for injection. Gently swirl; do not shake.
Serostim®: Vial: Reconstitute with 0.5-1 mL sterile water for injection.
Tev-Tropin®: Reconstitute with 1-5 mL of diluent provided. Gently swirl; do not shake. May use preservative-free NS for use in newborns.
Zorbtive®: 8.8 mg vial: Reconstitute with 1-2 mL bacteriostatic water for injection. Swirl gently.
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
Pharmacodynamics/Kinetics
Duration: Maintains supraphysiologic levels for 18-20 hours
Absorption: I.M., SubQ: Well absorbed
Distribution: ~1 L/kg
Metabolism: Hepatic and renal (~90%)
Bioavailability: SubQ: ~70% to 90%; Note: Variable; product-dependent
Half-life elimination: Preparation and route of administration dependent; SubQ: ~2-4 hours
Excretion: Urine (small amount)
Dosage
Children (individualize dose):
Chronic renal insufficiency (CRI): Nutropin®, Nutropin® AQ: SubQ: Weekly dosage: 0.35 mg/kg 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 deficiency:
Genotropin®, Omnitrope®: SubQ: Weekly dosage: 0.16-0.24 mg/kg divided into equal doses 6-7 days per week
Humatrope®: SubQ: Weekly dosage: 0.18-0.3 mg/kg divided into equal doses 6-7 days per week
Norditropin®: SubQ: 0.024-0.034 mg/kg/day, 6-7 days per week
Nutropin®, Nutropin® AQ: SubQ: Weekly dosage: 0.3 mg/kg divided into equal daily doses; pubertal patients: ≤0.7 mg/kg divided into equal daily doses
Tev-Tropin®: SubQ: Up to 0.1 mg/kg administered 3 days per week
Saizen®: I.M., SubQ: Weekly dosage: 0.18 mg/kg 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
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
HIV patients with wasting or cachexia (unlabeled use): Serostim®: SubQ: Limited data; doses of 0.04 mg/kg/day were reported in five children, 6-17 years of age; doses of 0.07 mg/kg/day were reported in six children, 8-14 years of age
Idiopathic short stature:
Genotropin®, Omnitrope®: SubQ: Weekly dosage: 0.47 mg/kg divided into equal doses 6-7 days per week
Humatrope®: SubQ: Weekly dosage: 0.37 mg/kg divided into equal doses 6-7 days per week
Nutropin®, Nutropin AQ®: SubQ: Weekly dosage: Up to 0.3 mg/kg divided into equal daily doses
Noonan syndrome: Norditropin®: SubQ: Up to 0.066 mg/kg/day
Prader-Willi syndrome: Genotropin®, Omnitrope®: SubQ: Weekly dosage: 0.24 mg/kg divided into equal doses 6-7 days per week
SHOX deficiency: Humatrope®: SubQ: Weekly dosage: 0.35 mg/kg divided into equal doses 6-7 days per week
Small for gestational age:
Genotropin®, Omnitrope®: SubQ: Weekly dosage: 0.48 mg/kg divided into equal doses 6-7 days per week
Humatrope®: SubQ: Weekly dosage: 0.47 mg/kg divided into equal doses 6-7 days per week
Norditropin®: SubQ: Up to 0.067 mg/kg/day
Alternate dosing (small for gestational age): In older/early pubertal children or children with very short stature, consider initiating therapy at higher doses (0.067 mg/kg/day) and then consider reducing the dose (0.033 mg/kg/day) if substantial catch-up growth observed. In younger children (<4 years) with less severe short stature, consider initiating therapy with lower doses (0.033 mg/kg/day) and then titrating the dose upwards as needed.
Turner syndrome:
Genotropin®: SubQ: Weekly dosage: 0.33 mg/kg divided into equal doses 6-7 days per week
Humatrope®: SubQ: Weekly dosage: 0.375 mg/kg divided into equal doses 6-7 days per week
Norditropin®: SubQ: Up to 0.067 mg/kg/day
Nutropin®, Nutropin® AQ: SubQ: Weekly dosage: ≤0.375 mg/kg divided into equal doses 3-7 days per week
Adults:
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-I levels.
Weight-based dosing:
Norditropin®: SubQ: Initial dose ≤0.004 mg/kg/day; after 6 weeks of therapy, may increase dose up to 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: ≤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 6-7 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 not more than 0.01 mg/kg/day after 4 weeks
Nonweight-based dosing:
SubQ: Initial: 0.2 mg/day (range: 0.15-0.3 mg/day); may increase every 1-2 months by 0.1-0.2 mg/day based on response and/or serum IGF-I levels
Dosage adjustment with estrogen supplementation (growth hormone deficiency): Larger doses of somatropin may be needed for women taking oral estrogen replacement products; dosing not affected by topical products
HARS (unlabeled 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 12-24 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.
HIV patients with wasting or cachexia: Serostim®: SubQ: 0.1 mg/kg once daily at bedtime (maximum: 6 mg/day). Alternately, patients at risk for side effects may be started at 0.1 mg/kg every other day. Patients who continue to lose weight after 12 weeks should be re-evaluated for opportunistic infections or other clinical events; rotate injection sites to avoid lipodystrophy Adjust dose if needed to manage side effects.
Daily dose based on body weight:
<35 kg: 0.1 mg/kg
35-45 kg: 4 mg
45-55 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 by 50%
Severe toxicity: Discontinue therapy for up to 5 days; when symptoms resolve, restart at 50% of dose. If severe toxicity recurs or does not disappear within 5 days after discontinuation, permanently discontinue treatment.
Elderly: Patients ≥65 years of age may be more sensitive to the action of growth hormone and more prone to adverse effects; in general, dosing should be cautious, beginning at low end of dosing range
Dosage adjustment in renal impairment Reports indicate patients with chronic renal failure tend to have decreased clearance; specific dosing suggestions not available
Dosage adjustment in hepatic impairment: Clearance may be reduced in patients with severe hepatic dysfunction; specific dosing suggestions not available
Administration: I.M.
Not all products are approved for I.M. administration. Rotate administration sites to avoid tissue atrophy.
Administration: Other
Do not shake; administer SubQ or I.M. (not all products are approved for I.M. administration). Rotate administration sites to avoid tissue atrophy. When administering to newborns, do not reconstitute with a diluent that contains benzyl alcohol; sterile water for injection may be used as an alternative. Norditropin® cartridge must be administered using the corresponding color-coded NordiPen® injection pen. Solution in the Omnitrope® cartridges must be administered using the Omnitrope® pen; when installing a new cartridge, prime pen prior to first use. When administering Tev-Tropin®, SubQ injections of solutions >1 mL not recommended.
Monitoring Parameters
Growth curve, Tanner staging (children), periodic thyroid function tests, bone age (annually), periodical urine testing for glucose, somatomedin C (IGF-I) levels; funduscopic examinations at initiation of therapy and periodically during treatment; serum phosphorus, alkaline phosphatase and parathyroid hormone. If growth deceleration is observed in children treated for growth hormone deficiency, and not due to other causes, evaluate for presence of antibody formation. Periodic blood glucose monitoring; strict blood glucose monitoring in patients with diabetes. Progression or recurrence of pre-existing tumors or malignant transformation of skin lesions. Note: Practice guidelines recommend monitoring for efficacy and adverse effects every 1-2 months during dose titration and semiannually, thereafter (TES, 2006).
CRI: Progression of renal osteodystrophy
Prader-Willi syndrome: Monitor for sleep apnea, respiratory infections, snoring (onset of or increased)
Turner syndrome: Ear disorders including otitis media; cardiovascular disorders
Noonan syndrome: Prior to use, verify short stature syndrome.
Dietary Considerations
Prader-Willi syndrome: All patients should have effective weight control (use is contraindicated in severely-obese patients).
Short-bowel syndrome: Intravenous parenteral nutrition requirements may need reassessment as gastrointestinal absorption improves.
Patient Education
This drug can only be administered by injection. If self-administered, you will be instructed by prescriber on proper storage, reconstitution, injection technique, and syringe/needle disposal. Report immediately pain, redness, burning, drainage, or swelling at injection site. If you have diabetes, monitor glucose levels closely. Report immediately swelling of extremities, headache, nausea or vomiting, any rash, sudden change in vision, increased urination, thirst, or weight loss.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause aggression (in pediatric patients with Prader-Willi syndrome)
Mental Health: Effects on Psychiatric Treatment
Contraindicated in pediatric patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment; fatalities have been reported.
Nursing: Physical Assessment/Monitoring
Perform funduscopic examinations at initiation of therapy and periodically during treatment. Instruct patients with diabetes to monitor glucose levels closely (may induce insulin intolerance). Instruct patient in proper use if self-administered (storage, reconstitution, injection techniques, and syringe/needle disposal). Pediatrics: Monitor growth curve; annually determine bone age.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [rDNA origin]:
Genotropin Miniquick®: 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1 mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg, 2 mg [delivers 0.25 mL]
Genotropin®: 5.8 mg [delivers 5 mg/mL]
Genotropin®: 13.8 mg [delivers 12 mg/mL]
Humatrope®: 5 mg, 6 mg, 12 mg, 24 mg
Nutropin®: 5 mg, 10 mg [contains benzyl alcohol (in diluent)]
Omnitrope®: 5.8 mg [contains benzyl alcohol (in diluent)]
Saizen®: 5 mg [contains benzyl alcohol (in diluent), sucrose 34.2 mg]
Saizen®: 8.8 mg [contains benzyl alcohol (in diluent), sucrose 60.2 mg]
Saizen®: 8.8 mg [contains sucrose 60.2 mg]
Serostim®: 4 mg [contains benzyl alcohol (in diluent), sucrose 27.3 mg]
Serostim®: 5 mg [contains sucrose 34.2 mg]
Serostim®: 6 mg [contains sucrose 41 mg]
Tev-Tropin®: 5 mg [contains benzyl alcohol (in diluent)]
Zorbtive®: 8.8 mg [contains benzyl alcohol (in diluent), sucrose 60.19 mg]
Injection, solution [rDNA origin]:
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) [prefilled pen]
Norditropin®: 5 mg/1.5 mL (1.5 mL); 15 mg/1.5 mL (1.5 mL) [cartridge]
Norditropin® NordiFlex®: 5 mg/1.5 mL (1.5 mL); 10 mg/1.5 mL (1.5 mL); 30 mg/3 mL (3 mL) [prefilled pen]
Nutropin AQ Pen®: 10 mg/2 mL (2 mL); 20 mg/2 mL (2 mL) [cartridge]
Nutropin AQ®: 10 mg/2 mL (2 mL) [vial]
Nutropin AQ® NuSpin™: 5 mg/2 mL (2 mL); 10 mg/2 mL (2 mL); 20 mg/2 mL (2 mL) [prefilled pen]
Omnitrope®: 5 mg/1.5 mL (1.5 mL) [contains benzyl alcohol; cartridge]
Omnitrope®: 10 mg/1.5 mL (1.5 mL) [cartridge]
Pricing: U.S. (www.drugstore.com)
Solution (Norditropin)
5 mg/1.5 mL (1.5): $351.06
15 mg/1.5 mL (1.5): $1055.30
Solution (Norditropin NordiFlex Pen)
5 mg/1.5 mL (1.5): $376.00
10 mg/1.5 mL (1.5): $775.98
15 mg/1.5 mL (1.5): $1099.94
Solution (reconstituted) (Genotropin)
5 mg (1): $381.99
12 mg (1): $954.97
Solution (reconstituted) (Genotropin MiniQuick)
0.2 mg (7): $116.99
0.4 mg (7): $237.99
0.6 mg (7): $341.99
0.8 mg (7): $455.99
1 mg (7): $566.98
1.2 mg (7): $649.83
1.4 mg (7): $796.97
1.6 mg (7): $906.98
2 mg (7): $1085.94
Solution (reconstituted) (Omnitrope)
5.8 mg (1): $287.00
Solution (reconstituted) (Saizen)
5 mg (1): $369.23
8.8 mg (1): $599.97
Solution (reconstituted) (Saizen Click.Easy)
8.8 mg (1): $568.97
Solution (reconstituted) (Tev-Tropin)
5 mg (1): $239.56
References
American Association of Clinical Endocrinologists (AACE) Growth Hormone Task Force, “AACE Medical Guidelines for Clinical Practice for Growth Hormone Use in Adults and Children -- 2003 Update,” Endocr Pract, 2003, 9(1):64-76.
Blum WF, Crowe BJ, Quigley CA, et al, “Growth Hormone is Effective in Treatment of Short Stature Associated With SHOX Deficiency: Two-year Results of a Randomized, Controlled, Multi-Center Trial,” J Clin Endocrinol Metab, 2007, 92(1):219-28.
Clayton PE, Cianfarani S, Czernichow P, et al, “Consensus Statement: Management of the Child Born Small for Gestational Age Through to Adulthood: A Consensus Statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society,” J Clin Endrocrinol Metab, 2007, 92(3):804-10.
Cohen P, Rogol AD, Deal CL, et al, “Consensus Statement on the Diagnosis and Treatment of Children With Idiopathic Short Stature: A Summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop,” J Clin Endocrinol Metab, 2008, 93(11):4210-7.
Cook DM, Ludlam WH, and Cook MB. “Route of Estrogen Administration Helps to Determine Growth Hormone (GH) Replacement Dose in GH-Deficient Adults,” J Clin Endocrinol Metab, 1999, 84(11):3956-60.
“Evaluation and Treatment of Adult Growth-Hormone Deficiency: An Endocrine Society Clinical Practice Guideline,” The Endocrine Society (TES). Available at http://www.endo-society.org/guidelines/final/upload/042506_CG_HormoneBook.pdf
Fuglsang J, Lauszus F, Orskov H, et al, “Placental Growth Hormone During Pregnancy in a Growth Hormone Deficient Woman With Type 1 Diabetes Compared to a Matching Diabetic Control Group,” Growth Horm IGF Res, 2004, 14(1):66-70.
GH Research Society, “Consensus Guidelines for the Diagnosis and Treatment of Growth Hormone (GH) Deficiency in Childhood and Adolescence: Summary Statement of the GH Research Society,” J Clin Endocrinol Metab, 2000, 85(11):3990-3.
Grunfeld C, Thompson M, Brown SJ, et al, “Recombinant Human Growth Hormone to Treat HIV-Associated Adipose Redistribution Syndrome: 12-Week Induction and 24-Week Maintenance Therapy. Study 24380 Investigators Group,” J Acquir Immune Defic Syndr, 2007, 45(3):286-97.
Howrie DL, “Growth Hormone for the Treatment of Growth Failure in Children,” Clin Pharm, 1987, 6(4):283-91.
Kotler DP, Muurahainen N, Grunfeld C, et al, “Effects of Growth Hormone on Abnormal Visceral Adipose Tissue Accumulation and Dyslipidemia in HIV-Infected Patients. Serostim in Adipose Redistribution Syndrome Study Group,” J Acquir Immune Defic Synd, 2004, 35(3):239-52.
Molitch ME, Clemmons DR, Malozowski S, et al, “Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline,” J Clin Endocrinol Metab, 2006, 91(5):1621-34.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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