Usual Adult Dose for Adult Human Growth Hormone Deficiency

Weight Based Regimen:
Initial dose: Not more than 0.004 mg/kg subcutaneously once a day (or a total of 0.04 mg/kg per week in divided doses).
Maximum dose: 0.016 mg/kg once a day (0.08 mg/kg per week in divided doses)

Non-Weight Based Regimen:
Approximately 0.2 mg subcutaneously once a day (range: 0.15 to 0.3 mg once a day)

Comments:

• The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
• May increase dose (weight or non-weight based) at 4 to 8 week intervals, by increments of approximately 0.1 to 0.2 mg per day (not more than 0.004 mg/kg per day), based on clinical response and serum IGF-I concentrations.
• The dose should be decreased as necessary on the basis of adverse events and/or serum IGF-I concentrations above the age- and gender-specific normal range.
• Maintenance dosages vary considerably from person to person, and between male and female patients.
• Obese individuals are more likely to manifest adverse effects when treated with a weight-based regimen. -To reach the defined treatment goal, estrogen-replete women may need higher doses than men.

Uses: Replacement of endogenous growth hormone (GH) in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:

• Adult Onset (AO): Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
• Childhood Onset (CO): Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes. Reevaluate patients treated for childhood GHD whose epiphyses are closed before continuing therapy at the reduced dose level recommended for adults.
• Confirmation of the diagnosis of adult GHD in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.

Usual Adult Dose for Cachexia

0.1 mg/kg subcutaneously once a day at bedtime

Under 35 kg/ 75 lbs: 0.1 mg/kg subcutaneously once a day at bedtime
35 to 45 kg/ 75 to 99 lbs: 4 mg subcutaneously once a day at bedtime
45 to 55 kg/ 99 to 121 lbs: 5 mg subcutaneously once a day at bedtime
Over 55 kg/ 121 lbs: 6 mg subcutaneously once a day at bedtime

Maximum dose: 6 mg once a day

Comments:

• Most of the effect on work output and lean body mass were seen after 12 weeks of treatment.
• There are no data on safety or efficacy with use beyond 48 weeks.
• There are no data on safety or efficacy of intermittent treatment.

Use: Treatment of HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance.

Usual Adult Dose for Short Bowel Syndrome

Approximately 0.1 mg/kg subcutaneously once a day

Maximum dose: 8 mg once a day

Duration of therapy: 4 weeks

Comments:

• Administration for more than 4 weeks has not been adequately studied.
• Use in conjunction with optimal management of Short Bowel Syndrome (SBS).
• Optimal management of SBS may include dietary adjustments, enteral feedings, parenteral nutrition, fluid, and micronutrient supplements, as needed.
• Specialized nutritional support may consist of a high carbohydrate, low-fat diet, adjusted for patient requirements and preferences.
• Nutritional supplements may be added at the discretion of the treating physician.
• Changes to concomitant medications should be avoided.
• Patients and physicians should monitor for adverse events.

Use: Treatment of Short Bowel Syndrome in patients receiving specialized nutritional support.

Usual Pediatric Dose for Pediatric Growth Hormone Deficiency

Pediatric Growth Hormone Deficiency (GHD):
0.024 to 0.034 mg/kg subcutaneously once a day, 6 to 7 times a week

Prader-Willi syndrome (PWS):
Up to 0.24 mg/kg per week; divided over 6 or 7 days of subcutaneous injections

Comments:

• The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
• GHD: Generally, a dose of 0.16 to 0.3 mg/kg body weight per week is recommended.
• GHD: In pubertal patients, a weekly dosage of up to 0.7 mg/kg divided into daily doses may be used.
• PWS: Generally, a dose of 0.16 to 0.24 mg/kg body weight per week is recommended.
• Individualize dosage and administration schedule based on the growth response.
• Serum insulin-like growth factor I (IGF-I) levels may be useful during dose titration.
• Response to therapy in pediatric patients tends to decrease with time, however, failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone.
• Treatment for short stature should be discontinued when the epiphyses are fused.

Uses:

• Treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH).
• Treatment of pediatric patients who have growth failure due to Prader-Willi syndrome (PWS). The diagnosis of PWS should be confirmed by appropriate genetic testing

Usual Pediatric Dose for Turner Syndrome

Up to 0.067 mg/kg subcutaneously once a day

Comments:

• Generally, a dose of 0.375 mg/kg body weight per week is recommended.
• The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
• Individualize dosage and administration schedule based on the growth response.
• Serum insulin-like growth factor I (IGF-I) levels may be useful during dose titration.
• Response to therapy in pediatric patients tends to decrease with time, however, failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone.
• Treatment for short stature should be discontinued when the epiphyses are fused.

Use: Treatment of short stature associated with Turner Syndrome (TS).

Usual Pediatric Dose for Idiopathic Short Stature

Up to 0.053 mg/kg subcutaneously once a day

Comments:

• Generally, a dose of up to 0.47 mg/kg body weight per week is recommended.
• The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
• Individualize dosage and administration schedule based on the growth response.
• Serum insulin-like growth factor I (IGF-I) levels may be useful during dose titration.
• Response to therapy in pediatric patients tends to decrease with time, however, failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone.
• Treatment for short stature should be discontinued when the epiphyses are fused.

Use: Treatment of idiopathic short stature (ISS), also called non-GHD short stature, defined by height SDS lower than -2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means.

Usual Pediatric Dose for Growth Retardation - Chronic Renal Failure

Up to 0.35 mg/kg of body weight per week, divided into daily subcutaneous injections

Duration of therapy: Therapy may be continued up to the time of renal transplantation.

Comments:

• Therapy should be used in conjunction with optimal management of chronic kidney disease.
• Individualize dosage and administration schedule based on the growth response.
• Response to therapy in pediatric patients tends to decrease with time, however, failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone.
• Treatment for short stature should be discontinued when the epiphyses are fused.
• To optimize therapy for dialysis patients, the following injection schedules are recommended:
• Hemodialysis patients: administer at night just prior to going to sleep, or at least 3 to 4 hours after hemodialysis to prevent hematoma formation due to heparin.
• Chronic Cycling Peritoneal Dialysis (CCPD): administer in the morning after dialysis is completed.
• Chronic Ambulatory Peritoneal Dialysis (CAPD): administer in the evening at the time of the overnight exchange.

Use: Treatment of growth failure secondary to chronic kidney disease (CKD) up to the time of renal transplantation.

Usual Pediatric Dose for Noonan's Syndrome

Up to 0.066 mg/kg subcutaneously once a day

Comments:

• Not all Noonan syndrome patients have short stature; some will achieve a normal adult height without treatment.
• Establish that the patient does have short stature before starting treatment.
• Individualize dosage and administration schedule based on the growth response.
• Serum insulin-like growth factor I (IGF-I) levels may be useful during dose titration.
• Response to therapy in pediatric patients tends to decrease with time, however, failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone.
• Treatment for short stature should be discontinued when the epiphyses are fused.

Use: Treatment of pediatric patients with short stature associated with Noonan Syndrome

Usual Pediatric Dose for Short Stature for Age

Small for Gestational Age (SGA):
Up to 0.067 mg/kg subcutaneously daily

Short stature homeobox-containing gene (SHOX) deficiency:
0.05 mg/kg subcutaneously once a day (0.35 mg/kg per week in divided doses)

Comments:

• The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
• SGA: Generally, a dose of up to 0.48 mg/kg body weight per week is recommended.
• SGA: Recent literature recommends initial treatment with larger doses (e.g., 0.067 mg/kg once a day), especially in very short children (HSDS of lower than -3), and/or older/pubertal children.
• SGA: In younger children (approximately less than 4 years, who respond the best in general) with less severe short stature (baseline HSDS values between -2 and -3), consider initiating treatment at a lower dose (0.033 mg/kg/day), and titrating the dose as needed over time.
• Individualize dosage and administration schedule based on the growth response.
• Serum insulin-like growth factor I (IGF-I) levels may be useful during dose titration.
• Response to therapy in pediatric patients tends to decrease with time, however, failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age, and antibodies to recombinant human growth hormone.
• Treatment for short stature should be discontinued when the epiphyses are fused.

Uses:

• Treatment of pediatric patients with short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years.
• Treatment of short stature or growth failure in children with short stature homeobox-containing gene (SHOX) deficiency.

Usual Pediatric Dose for Cachexia

0.04-0.07 mg/kg subcutaneously once a day

Comments:

• Safety and effectiveness in pediatric patients with HIV have not been established.
• Somatropin clearance appears similar in adults and children, but no pharmacokinetic studies have been conducted in children with HIV.
• Two small studies (total of 16 patients) of up to 26 weeks duration showed therapy was well tolerated with safety observations consistent with the adult studies.

Use: Treatment of HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance

Renal Dose Adjustments

The dosage in children with chronic renal disease must be adjusted according to the individual response to therapy.

Liver Dose Adjustments

Data not available

Dose Adjustments

Pediatric Growth Hormone Deficiency:
Small for Gestational Age (SGA)

• Consider a dose reduction (e.g., gradually towards 0.033 mg/kg once a day) if substantial catch-up growth is observed during the first few years of therapy.

Adult Growth Hormone Deficiency:

• Decrease the dose as needed for adverse events and/or serum IGF-1 levels above age and gender specific normal range.
• Maintenance doses vary considerably from person to person.
• Consider a lower starting dose and smaller dose increments for older patients, who are more prone to adverse effects than younger individuals.
• Obese individuals are more likely to manifest adverse effects when treated with a weight-based regimen.
• To reach the defined treatment goal, estrogen-replete women may need higher doses than men.
• Oral estrogen use may increase the dose requirements in women.

HIV Wasting or Cachexia:

• Treatment with 0.1 mg/kg every other day was associated with fewer side effects and similar improvement in work output as compared to daily dosing.
• Consider a starting dose of 0.1 mg/kg every other day in patients at increased risk for adverse effects.
• Consider a dose reduction (of daily dosing amount, or of dosing frequency) for drug related side effects.

Short Bowel Syndrome:

• Treat moderate fluid retention and arthralgias symptomatically, or reduce dose by 50%.
• Discontinue for up to 5 days for severe toxicities; when symptoms resolve, resume at 50% of original dose.
• Permanently discontinue if severe toxicity recurs or does not disappear within 5 days.

Dialysis

Children with chronic renal disease:

• Hemodialysis: administer at night just prior to going to sleep, or at least 3 to 4 hours after hemodialysis to prevent hematoma formation due to heparin.
• Chronic Cycling Peritoneal Dialysis (CCPD): administer in the morning after dialysis is completed.
• Chronic Ambulatory Peritoneal Dialysis (CAPD): administer in the evening at the time of the overnight exchange.

Other Comments

Administration advice:

• Alternate injection sites.

General:

• Therapy should be supervised by specialists experienced in the diagnosis and management of growth hormone (GH) deficiency.