Pronunciation:

(HYU man grothe HOR mone)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Children:

Long-term treatment of growth failure due to lack of adequate endogenous growth hormone secretion (Genotropin®, Humatrope®, Norditropin®, Nutropin®, Nutropin AQ®, Nutropin Depot®, Protropin®, Saizen®)

Long-term treatment of short stature associated with Turner syndrome (Humatrope®, Nutropin®, Nutropin AQ®)

Treatment of Prader-Willi syndrome (Genotropin®)

Treatment of growth failure associated with chronic renal insufficiency (CRI) up until the time of renal transplantation (Nutropin®, Nutropin AQ®)

Long-term treatment of growth failure in children born small for gestational age who fail to manifest catch-up growth by 2 years of age (Genotropin®)

Long-term treatment of idiopathic short stature (nongrowth hormone-deficient short stature) defined by height standard deviation score (SDS) less than or equal to -2.25 and growth rate not likely to attain normal adult height (Humatrope®)

Adults:

AIDS-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®, 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)

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:

Pregnancy Risk Factor:

Lactation:

Contraindications:

Warnings/Precautions:

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. In addition, male patients may be at increased 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.

Adverse Reactions:

Growth hormone deficiency: Antigrowth hormone antibodies, carpal tunnel syndrome (rare), fluid balance disturbances, glucosuria, gynocomastia (rare), headache, hematuria, hyperglycemia (mild), hypoglycemia, hypothyroidism, leukemia, lipoatrophy, muscle pain, increased growth of pre-existing nevi (rare), pain/ local reactions at the injection site, pancreatitis (rare), peripheral edema, exacerbation of psoriasis, rash, seizure, weakness

Idiopathic short stature: Humatrope®: Myalgia (24%), scoliosis (19%), otitis media (16%), arthralgia (11%), arthrosis (11%), hyperlipidemia (8%), gynecomastia (5%), hip pain (3%), hypertension (3%)

Prader-Willi syndrome: Genotropin®: Aggressiveness, arthralgia, edema, hair loss, headache, benign intracranial hypertension, myalgia; fatalities associated with use in this population have been reported

Turner syndrome: Humatrope®: Surgical procedures (45%), otitis media (43%), ear disorders (18%), hypothyroidism (13%), increased nevi (11%), peripheral edema (7%)

Adult growth hormone replacement: ALT/AST increased, arthralgia, back pain, carpal tunnel syndrome, diabetes mellitus, fatigue, flu-like syndrome, gastritis, gastroenteritis, generalized edema, glucose intolerance, gynocomastia (rare), headache, hypertension, hypoesthesia, hypothyroidism, infection (nonviral), insomnia, joint disorder, laryngitis, myalgia, nausea, increased growth of pre-existing nevi, pain, pancreatitis (rare), paresthesia, peripheral edema, pharyngitis, rhinitis, stiffness in extremities, weakness

AIDS wasting or cachexia (limited): Serostim®: Musculoskeletal discomfort (54%), increased tissue turgor (27%), diarrhea (26%), neuropathy (26%), nausea (26%), fatigue (17%), albuminuria (15%), diaphoresis increased (14%), anorexia (12%), anemia (12%), increased AST (12%), insomnia (11%), tachycardia (11%), hyperglycemia (10%), increased ALT (10%)

Postmarketing and/or case reports: Diabetes, diabetic ketoacidosis, glucose intolerance

Short-bowel syndrome: Zorbtive™: Peripheral edema (69% to 81%), edema (facial: 44% to 50%; peripheral 13%), arthralgia (13% to 44%), injection site reaction (19% to 31%), flatulence (25%), abdominal pain (20% to 25%), vomiting (19%), malaise (13%), nausea (13%), diaphoresis increased (13%), rhinitis (7%), dizziness (6%)

Postmarketing and/or case reports: Carpal tunnel syndrome

Small for gestational age: Genotropin®: 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

Overdosage/Toxicology:

Drug Interactions:

Decreased effect: Glucocorticoid therapy may inhibit growth-promoting effects

Insulin: Growth hormone may induce insulin resistance in patients with diabetes mellitus; monitor glucose and adjust insulin dose as necessary

Stability:

Somatrem: Protropin®: Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F), avoid freezing; when reconstituted with bacteriostatic water for injection; use within 14 days; when reconstituted with sterile water for injection, use immediately (only one dose per vial) and discard unused portion

Somatropin:

Genotropin®: Store at 2°C to 8°C (36°F to 46°F), do not freeze, protect from light

1.5 mg cartridge: Following reconstitution, store under refrigeration and use within 24 hours; discard unused portion

5.8 mg and 13.8 mg cartridge: Following reconstitution, store under refrigeration and use within 21 days

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), avoid freezing; when reconstituted with 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), avoid freezing; following reconstitution, stable for 14 days under refrigeration. Dilute with solution provided with cartridges ONLY; do not use diluent provided with vials

Norditropin®: Store at 2°C to 8°C (36°F to 46°F), do not freeze; avoid direct light

Cartridge: Must be used within 4 weeks once inserted into pen

Prefilled pen: Must be used within 4 weeks after initial injection

Nutropin®: Before and after reconstitution, store at 2°C to 8°C (36°F to 46°F), avoid freezing

Vial: Reconstitute with bacteriostatic water for injection; use reconstituted vials within 14 days; when reconstituted with sterile water for injection, use immediately and discard unused portion

AQ formulation: Use within 28 days following initial use

Depot formulation: Before suspension, store at 2°C to 8°C (36°F to 46°F), avoid freezing; use suspended solution immediately; dilute only with diluent provided

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.

5 mg vial: Reconstitute with 1-3 mL bacteriostatic water for injection or sterile water for injection; gently swirl; do not shake.

8.8 mg vial: Reconstitute with 2-3 mL bacteriostatic water for injection or sterile water for injection; gently swirl; do not shake.

Serostim®: Prior to reconstitution, store at room temperature 15°C to 30°C (59°F to 86°F); reconstitute with sterile water for injection; store reconstituted solution under refrigeration and use within 24 hours, avoid freezing. Do not use if cloudy

Zorbtive™: Store unopened vials and diluent at room temperature of 15°C to 30°C (59°F to 86°F).

8.8 mg vial: Reconstitute with 1-2 mL bacteriostatic water for injection, use within 14 days; store under refrigeration at 2°C to 8°C (36°F to 46°F); avoid freezing

Mechanism of Action:

Pharmacodynamics/Kinetics:

Duration: Maintains supraphysiologic levels for 18-20 hours

Absorption: I.M., SubQ: Well absorbed

Metabolism: Hepatic and renal (~90%)

Half-life elimination: Preparation and route of administration dependent

Excretion: Urine

Dosage:

Children (individualize dose):

Growth hormone deficiency:

Somatrem: Protropin®: I.M., SubQ: Weekly dosage: 0.3 mg/kg divided into daily doses

Somatropin:

Genotropin®: SubQ: Weekly dosage: 0.16-0.24 mg/kg divided into 6-7 doses

Humatrope®: I.M., SubQ: Weekly dosage: 0.18 mg/kg; maximum replacement dose: 0.3 mg/kg/week; dosing should be divided into equal doses given 3 times/week on alternating days, 6 times/week, or daily

Norditropin®: SubQ: Weekly dosage: 0.024-0.034 mg/kg administered in the evening, divided into doses 6-7 times/week; cartridge and vial formulations are bioequivalent; cartridge formulation does not need to be reconstituted prior to use

Nutropin Depot®: SubQ:

Once-monthly injection: 1.5 mg/kg administered on the same day of each month; patients >15 kg will require more than 1 injection per dose

Twice-monthly injection: 0.75 mg/kg administered twice each month on the same days of each month (eg, days 1 and 15 of each month); patients >30 kg will require more than 1 injection per dose

Nutropin®, Nutropin® AQ: SubQ: Weekly dosage: 0.3 mg/kg divided into daily doses; pubertal patients: 0.7 mg/kg/week divided daily

Saizen®: I.M., SubQ: 0.06 mg/kg/dose administered 3 times/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

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

Turner syndrome: Humatrope®, Nutropin®, Nutropin® AQ: SubQ: Weekly dosage: 0.375 mg/kg divided into equal doses 3-7 times per week

Prader-Willi syndrome: Genotropin®: SubQ: Weekly dosage: 0.24 mg/kg divided into 6-7 doses

Small for gestational age: Genotropin®: SubQ: Weekly dosage: 0.48 mg/kg divided into 6-7 doses

Idiopathic short stature: Humatrope®: SubQ: Weekly dosage: 0.37 mg/kg divided into equal doses 6-7 times per week

AIDS-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

Adults:

Growth hormone deficiency: 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.

Somatropin:

Norditropin®: SubQ: Initial dose 0.004 mg/kg/day; after 6 weeks of therapy, may increase dose to 0.016 mg/kg/day

Nutropin®, Nutropin® AQ: SubQ: 0.006 mg/kg/day; dose may be increased according to individual requirements, 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 according to individual requirements, up to a maximum of 0.0125 mg/kg/day

Genotropin®: SubQ: Weekly dosage: 0.04 mg/kg divided into 6-7 doses; dose may be increased at 4- to 8-week intervals according to individual requirements, 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, based on individual requirements.

AIDS-wasting or cachexia:

Serostim®: SubQ: Dose should be given once daily at bedtime; patients who continue to lose weight after 2 weeks should be re-evaluated for opportunistic infections or other clinical events; rotate injection sites to avoid lipodystrophy

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:

Monitoring Parameters:

Somatrem (Protropin®): Consider changing to somatropin if antibody binding capacity is >2 mg/L

Prader-Willi syndrome: Monitor for sleep apnea, respiratory infections, snoring (onset of or increased)

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:

Nursing Implications:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Injection, powder for reconstitution [rDNA origin]:

Somatrem: Protropin® [diluent contains benzyl alcohol]: 10 mg [~30 int. units] [DSC]

Somatropin:

Genotropin® [preservative free]: 1.5 mg [4 int. units/mL] [delivers 1.3 mg/mL]

Genotropin® [with preservative]:

5.8 mg [15 int. units/mL] [delivers 5 mg/mL]

13.8 mg [36 int. units/mL] [delivers 12 mg/mL]

Genotropin Miniquick® [preservative free]: 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 [each strength delivers 0.25 mL]

Humatrope®: 5 mg [~15 int. units], 6 mg [18 int. units], 12 mg [36 int. units], 24 mg [72 int. units]

Nutropin® [diluent contains benzyl alcohol]: 5 mg [~15 int. units]; 10 mg [~30 int. units]

Nutropin Depot® [preservative free]: 13.5 mg, 18 mg, 22.5 mg [DSC]

Saizen® [diluent contains benzyl alcohol]: 5 mg [~15 int. units; contains sucrose 34.2 mg]; 8.8 mg [~26.4 int. units; contains sucrose 60.2 mg]

Serostim®: 4 mg [12 int. units; contains sucrose 27.3 mg]; 5 mg [15 int. units; contains sucrose 34.2 mg]; 6 mg [18 int. units; contains sucrose 41 mg]

Zorbtive™: 8.8 mg [~26.4 int. units; contains sucrose 60.19 mg; packaged with diluent containing benzyl alcohol]

Injection, solution [rDNA origin]: Somatropin:

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); 15 mg/1.5 mL (1.5 mL) [prefilled pen]

Nutropin AQ®: 5 mg/mL [~15 int. units/mL] (2 mL) [vial or cartridge]

International Brand Names: