Humatrope (Somatropin)

HUMATROPE is a recombinant human growth hormone indicated for:

• Pediatric Patients:
  growth failure due to inadequate secretion of endogenous growth hormone (GH); short stature associated with Turner syndrome; Idiopathic Short Stature (ISS), height standard deviation score (SDS) <-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range; short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency; short stature born small for gestational age (SGA) with no catch-up growth by 2 years to 4 years of age. (
  1.1 Pediatric Patients

  HUMATROPE is indicated for the treatment of pediatric patients with:

  • growth failure due to inadequate secretion of endogenous growth hormone (GH),
  • short stature associated with Turner syndrome,
  • Idiopathic Short Stature (ISS), height standard deviation score (SDS) <-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range,
  • short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency,
  • short stature born small for gestational age (SGA) with no catch-up growth by 2 years to 4 years of age.
  )
• Adult Patients:
  replacement of endogenous GH in adults with GH deficiency. (
  1.2 Adult Patients

  HUMATROPE is indicated for the replacement of endogenous GH in adults with GH deficiency.
  )

• Administer by subcutaneous injection to the back of upper arm, abdomen, buttock, or thigh with regular rotation of injection sites. (
  2.1 Administration and Use Instructions

  • Therapy with HUMATROPE should be supervised by a physician who is experienced in the diagnosis and management of patients with the conditions for which HUMATROPE is indicated
    [see Indications and Usage ]
    .
  • Fundoscopic examination should be performed routinely before initiating treatment with HUMATROPE to exclude preexisting papilledema, and periodically thereafter
    [see Warnings and Precautions ]
    .
  • Leave HUMATROPE at room temperature for 10 minutes prior to administration.
  • Administer HUMATROPE by subcutaneous injection to the back of the upper arm, abdomen, buttock, or thigh with regular rotation of injection sites to avoid lipoatrophy.
  )
• Pediatric Dosage
  - divide the calculated weekly dosage into equal doses given either 6, or 7 days per week.
  • GHD:
    0.18 mg/kg/week to 0.3 mg/kg/week. (
    2.2 Pediatric Dosage

    • Individualize dosage for each patient based on the growth response.
    • Divide the calculated weekly HUMATROPE dosage into equal doses given either 6 or 7 days per week.
    • The recommended weekly dose in milligrams (mg) per kilogram (kg) of body weight for pediatric patients is:
      • Pediatric GH Deficiency:
        0.18 mg/kg/week to 0.3 mg/kg/week (0.026 to 0.043 mg/kg/day)
      • Turner Syndrome:
        Up to 0.375 mg/kg/week (up to.054 mg/kg/day)
      • Idiopathic Short Stature:
        Up to 0.37 mg/kg/week (up to 0.053 mg/kg/day)
      • SHOX Deficiency:
        0.35 mg/kg/week (0.05 mg/kg/day)
      • Small for Gestational Age (SGA):
        Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day)
        • In very short pediatric patients, height SDS less than -3, and older pubertal pediatric patients consider initiating treatment with a larger dose of HUMATROPE (up to 0.067 mg/kg/day). Consider a gradual reduction in dosage if substantial catch-up growth is observed during the first few years of therapy. In pediatric patients less than 4 years of age with less severe short stature, baseline height SDS values between -2 and -3, consider initiating treatment at 0.033 mg/kg/day and titrate the dose as needed.
    • Assess compliance and evaluate other causes of poor growth such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human GH if patients experience failure to increase height velocity, particularly during the first year of treatment.
    • Discontinue HUMATROPE for stimulation of linear growth once epiphyseal fusion has occurred
      [see Contraindications ]
      .
    )
  • Turner Syndrome:
    Up to 0.375 mg/kg/week. (
    2.2 Pediatric Dosage

    • Individualize dosage for each patient based on the growth response.
    • Divide the calculated weekly HUMATROPE dosage into equal doses given either 6 or 7 days per week.
    • The recommended weekly dose in milligrams (mg) per kilogram (kg) of body weight for pediatric patients is:
      • Pediatric GH Deficiency:
        0.18 mg/kg/week to 0.3 mg/kg/week (0.026 to 0.043 mg/kg/day)
      • Turner Syndrome:
        Up to 0.375 mg/kg/week (up to.054 mg/kg/day)
      • Idiopathic Short Stature:
        Up to 0.37 mg/kg/week (up to 0.053 mg/kg/day)
      • SHOX Deficiency:
        0.35 mg/kg/week (0.05 mg/kg/day)
      • Small for Gestational Age (SGA):
        Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day)
        • In very short pediatric patients, height SDS less than -3, and older pubertal pediatric patients consider initiating treatment with a larger dose of HUMATROPE (up to 0.067 mg/kg/day). Consider a gradual reduction in dosage if substantial catch-up growth is observed during the first few years of therapy. In pediatric patients less than 4 years of age with less severe short stature, baseline height SDS values between -2 and -3, consider initiating treatment at 0.033 mg/kg/day and titrate the dose as needed.
    • Assess compliance and evaluate other causes of poor growth such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human GH if patients experience failure to increase height velocity, particularly during the first year of treatment.
    • Discontinue HUMATROPE for stimulation of linear growth once epiphyseal fusion has occurred
      [see Contraindications ]
      .
    )
  • ISS:
    Up to 0.37 mg/kg/week. (
    2.2 Pediatric Dosage

    • Individualize dosage for each patient based on the growth response.
    • Divide the calculated weekly HUMATROPE dosage into equal doses given either 6 or 7 days per week.
    • The recommended weekly dose in milligrams (mg) per kilogram (kg) of body weight for pediatric patients is:
      • Pediatric GH Deficiency:
        0.18 mg/kg/week to 0.3 mg/kg/week (0.026 to 0.043 mg/kg/day)
      • Turner Syndrome:
        Up to 0.375 mg/kg/week (up to.054 mg/kg/day)
      • Idiopathic Short Stature:
        Up to 0.37 mg/kg/week (up to 0.053 mg/kg/day)
      • SHOX Deficiency:
        0.35 mg/kg/week (0.05 mg/kg/day)
      • Small for Gestational Age (SGA):
        Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day)
        • In very short pediatric patients, height SDS less than -3, and older pubertal pediatric patients consider initiating treatment with a larger dose of HUMATROPE (up to 0.067 mg/kg/day). Consider a gradual reduction in dosage if substantial catch-up growth is observed during the first few years of therapy. In pediatric patients less than 4 years of age with less severe short stature, baseline height SDS values between -2 and -3, consider initiating treatment at 0.033 mg/kg/day and titrate the dose as needed.
    • Assess compliance and evaluate other causes of poor growth such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human GH if patients experience failure to increase height velocity, particularly during the first year of treatment.
    • Discontinue HUMATROPE for stimulation of linear growth once epiphyseal fusion has occurred
      [see Contraindications ]
      .
    )
  • SHOX Deficiency:
    0.35 mg/kg/week. (
    2.2 Pediatric Dosage

    • Individualize dosage for each patient based on the growth response.
    • Divide the calculated weekly HUMATROPE dosage into equal doses given either 6 or 7 days per week.
    • The recommended weekly dose in milligrams (mg) per kilogram (kg) of body weight for pediatric patients is:
      • Pediatric GH Deficiency:
        0.18 mg/kg/week to 0.3 mg/kg/week (0.026 to 0.043 mg/kg/day)
      • Turner Syndrome:
        Up to 0.375 mg/kg/week (up to.054 mg/kg/day)
      • Idiopathic Short Stature:
        Up to 0.37 mg/kg/week (up to 0.053 mg/kg/day)
      • SHOX Deficiency:
        0.35 mg/kg/week (0.05 mg/kg/day)
      • Small for Gestational Age (SGA):
        Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day)
        • In very short pediatric patients, height SDS less than -3, and older pubertal pediatric patients consider initiating treatment with a larger dose of HUMATROPE (up to 0.067 mg/kg/day). Consider a gradual reduction in dosage if substantial catch-up growth is observed during the first few years of therapy. In pediatric patients less than 4 years of age with less severe short stature, baseline height SDS values between -2 and -3, consider initiating treatment at 0.033 mg/kg/day and titrate the dose as needed.
    • Assess compliance and evaluate other causes of poor growth such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human GH if patients experience failure to increase height velocity, particularly during the first year of treatment.
    • Discontinue HUMATROPE for stimulation of linear growth once epiphyseal fusion has occurred
      [see Contraindications ]
      .
    )
  • SGA:
    Up to 0.47 mg/kg/week. (
    2.2 Pediatric Dosage

    • Individualize dosage for each patient based on the growth response.
    • Divide the calculated weekly HUMATROPE dosage into equal doses given either 6 or 7 days per week.
    • The recommended weekly dose in milligrams (mg) per kilogram (kg) of body weight for pediatric patients is:
      • Pediatric GH Deficiency:
        0.18 mg/kg/week to 0.3 mg/kg/week (0.026 to 0.043 mg/kg/day)
      • Turner Syndrome:
        Up to 0.375 mg/kg/week (up to.054 mg/kg/day)
      • Idiopathic Short Stature:
        Up to 0.37 mg/kg/week (up to 0.053 mg/kg/day)
      • SHOX Deficiency:
        0.35 mg/kg/week (0.05 mg/kg/day)
      • Small for Gestational Age (SGA):
        Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day)
        • In very short pediatric patients, height SDS less than -3, and older pubertal pediatric patients consider initiating treatment with a larger dose of HUMATROPE (up to 0.067 mg/kg/day). Consider a gradual reduction in dosage if substantial catch-up growth is observed during the first few years of therapy. In pediatric patients less than 4 years of age with less severe short stature, baseline height SDS values between -2 and -3, consider initiating treatment at 0.033 mg/kg/day and titrate the dose as needed.
    • Assess compliance and evaluate other causes of poor growth such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human GH if patients experience failure to increase height velocity, particularly during the first year of treatment.
    • Discontinue HUMATROPE for stimulation of linear growth once epiphyseal fusion has occurred
      [see Contraindications ]
      .
    )
• Adult Dosage
  - Either of the following two dosing regimens may be used:
  • Non-weight based dosing: Initiate with a dose of approximately 0.2 mg/day (range: 0.15 mg/day-0.3 mg/day) and increase the dose every 1-2 months by increments of approximately 0.1 mg/day-0.2 mg/day, according to individual patient requirements (
    2.3 Adult Dosage

    • Patients who were treated with somatropin for GH deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin for GH deficient adults.
    • Consider using a lower starting dose and smaller dose increment increases for geriatric patients as they may be at increased risk for adverse reactions with HUMATROPE than younger individuals
      [see Use in Specific Populations ]
      .
    • Women may require higher doses and patients receiving oral estrogen may require higher doses
      [see Drug Interactions ]
      .
    • Administer the prescribed dose daily.
    • Either of two HUMATROPE dosing regimens may be used:
      • Non-weight based:
        • Initiate HUMATROPE with a dose of approximately 0.2 mg/day (range, 0.15 mg/day to 0.3 mg/day) and increase the dose every 1-2 months by increments of approximately 0.1 mg/day to 0.2 mg/day, according to individual patient requirements based on the clinical response and serum insulin-like growth factor 1 (IGF-1) concentrations.
        • Use the patient's clinical response, adverse reactions, and determination of age- and gender-adjusted serum IGF-1 concentrations as guidance in dose titration.
        • Maintenance dosages will vary considerably from person to person, and between male and female patients.
      • Weight-based:
        • Initiate HUMATROPE at 0.006 mg/kg daily and increase the dose according to individual patient requirements to a maximum of 0.0125 mg/kg daily.
        • Use the patient's clinical response, adverse reactions, and determination of age- and gender-adjusted serum IGF-1 concentrations as guidance in dose titration.
        • Maintenance dosages will vary considerably from person to person, and between male and female patients
        • Not recommended for obese patients as they are more likely to experience adverse reactions with this regimen.
    )
  • Weight-based dosing (Not recommended for obese patients): Initiate at 0.006 mg/kg daily and increase the dose according to individual patient requirements to a maximum of 0.0125 mg/kg daily (
    2.3 Adult Dosage

    • Patients who were treated with somatropin for GH deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin for GH deficient adults.
    • Consider using a lower starting dose and smaller dose increment increases for geriatric patients as they may be at increased risk for adverse reactions with HUMATROPE than younger individuals
      [see Use in Specific Populations ]
      .
    • Women may require higher doses and patients receiving oral estrogen may require higher doses
      [see Drug Interactions ]
      .
    • Administer the prescribed dose daily.
    • Either of two HUMATROPE dosing regimens may be used:
      • Non-weight based:
        • Initiate HUMATROPE with a dose of approximately 0.2 mg/day (range, 0.15 mg/day to 0.3 mg/day) and increase the dose every 1-2 months by increments of approximately 0.1 mg/day to 0.2 mg/day, according to individual patient requirements based on the clinical response and serum insulin-like growth factor 1 (IGF-1) concentrations.
        • Use the patient's clinical response, adverse reactions, and determination of age- and gender-adjusted serum IGF-1 concentrations as guidance in dose titration.
        • Maintenance dosages will vary considerably from person to person, and between male and female patients.
      • Weight-based:
        • Initiate HUMATROPE at 0.006 mg/kg daily and increase the dose according to individual patient requirements to a maximum of 0.0125 mg/kg daily.
        • Use the patient's clinical response, adverse reactions, and determination of age- and gender-adjusted serum IGF-1 concentrations as guidance in dose titration.
        • Maintenance dosages will vary considerably from person to person, and between male and female patients
        • Not recommended for obese patients as they are more likely to experience adverse reactions with this regimen.
    )
• See Full Prescribing Information for reconstitution instructions. (
  2.4 Reconstitution of Cartridges

  • Each single-patient-use HUMATROPE cartridge is designed for use only with the appropriate corresponding HumatroPen^®supplied separately.
    • Reconstitute each cartridge of HUMATROPE using only the diluent syringe that accompanies the cartridge. Do not shake. The reconstituted solution should be clear.
    • Inspect visually for particulate matter and discoloration. If the resulting solution is cloudy or contains particulate matter do not use.
    • The somatropin concentrations for the reconstituted HUMATROPE cartridges are as follows in Table 1:

      Table 1: Somatropin Concentration of HUMATROPE Cartridges.

      Cartridge	Somatropin Concentration
      6 mg	2.08 mg/mL
      12 mg	4.17 mg/mL
      24 mg	8.33 mg/mL

  • Reconstituted cartridges of HUMATROPE are stable for up to 28 days when refrigerated at 36° to 46°F (2° to 8°C). Do not leave at room temperature more than 30 minutes per day. Avoid freezing the reconstituted cartridge. Protect HUMATROPE from light during storage.
  • For patients with known hypersensitivity to the diluent supplied with the HUMATROPE cartridge
    [see Warnings and Precautions ]
    , do not use HUMATROPE cartridge.
  )

Each single-patient-use HUMATROPE cartridge is designed for use only with the appropriate corresponding HumatroPen^® supplied separately.

HUMATROPE is a white lyophilized powder available as follows:

• For injection: 6 mg in a single-patient-use cartridge (gold)
• For injection: 12 mg in a single-patient-use cartridge (teal)
• For injection: 24 mg in a single-patient-use cartridge (purple)

Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have not been conducted with HUMATROPE.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.