These Highlights Do Not Include All The Information Needed To Use Genotropin Safely And Effectively. See Full Prescribing Information For Genotropin

Adult Onset (AO): Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or

INSTRUCTIONS FOR USE

GENOTROPIN 12 (JEEN-o-tro-pin 12)

GENOTROPIN PEN 12 is a medical device used to mix and inject doses of reconstituted GENOTROPIN (somatropin) for injection. Use this device only for administration of GENOTROPIN.

GENOTROPIN PEN 12 is a reusable multi-dose device holding a 2-chamber cartridge of GENOTROPIN, used to mix and inject GENOTROPIN during a 2 year use period.

For your injection you will need:

• •
  1 GENOTROPIN PEN 12 device
• •
  1 GENOTROPIN 12 mg single-patient-use 2-chamber cartridge
• •
  1 new 29 gauge (29 G), 30 gauge (30 G), or 31 gauge (31 G) Becton Dickinson pen needle
• •
  Alcohol swab (not included)
• •
  1 sharps disposal container. See "Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 12" in Step 14.

Parts of the GENOTROPIN PEN 12 (See Figure A )

Storage instructions for your GENOTROPIN PEN 12

• •
  Between uses, store your pen (with the cartridge) in the refrigerator between 36°F to 46°F (2°C to 8°C) in its protective case. Always remove the needle before storing.
• •
  Do not freeze. Protect from light.
• •
  Throw away the cartridge within 28 days after mixing, even if the cartridge is not empty.
• •
  When travelling, keep your pen in its protective case and carry it in an insulated bag to protect it from heat or freezing. Put your pen back in the refrigerator as soon as possible.

Using your GENOTROPIN PEN 12

Step 1.

Wash your hands well with soap and water before using the GENOTROPIN PEN 12.

Step 14. Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 12

Put the used needles and cartridges in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the needles and cartridges in the household trash.

If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:

• •
  Made of a heavy-duty plastic,
• •
  Can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out,
• •
  Upright and stable during use,
• •
  Leak-resistant, and
• •
  Properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and cartridges. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

• •
  Do not reuse needles.
• •
  Do not throw away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this.
• •
  Do not recycle your used sharps disposal container.

Important: Always keep the sharps disposal container out of the reach of children.

Dispose of the entire GENOTROPIN PEN 12 as electronic waste per state and local regulations.

Caring for your Pen

To clean your pen, wipe the outside surface with a damp cloth. Do not put the pen in water as this may damage your pen. Do not use alcohol or any other cleaning agents to clean the pen, as they may damage the plastic body. To clean the needle guard, wipe it with a damp cloth or alcohol pad.

Display Information

If you have any questions about your dose or your treatment with GENOTROPIN, call your healthcare provider right away.

Use this device only for the person for whom it was prescribed.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Caution: Federal law restricts this device to sale by or on the order of a physician.

Manufactured by:

Pharmacia & Upjohn Company LLC

A subsidiary of Pfizer Inc.

New York, NY 10001

U.S. License No. 1216

LAB-0224-10.0

Revised August 2024

Short-Term

Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Furthermore, overdose with somatropin is likely to cause fluid retention.

Long-Term

Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth hormone [see Dosage and Administration (2)].

In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm has been reported. Intracranial tumors, in particular meningiomas, were the most common of these second neoplasms. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence [see Contraindications (4)].

Monitor all patients with a history of GHD secondary to an intracranial neoplasm routinely while on somatropin therapy for progression or recurrence of the tumor.

Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, practitioners should thoroughly consider the risks and benefits of starting somatropin in these patients. If treatment with somatropin is initiated, these patients should be carefully monitored for development of neoplasms.

Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes, of preexisting nevi.

Risk Summary

Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal studies (rats and rabbits), there was no evidence of embryo‑fetal or neonatal harm following somatropin administration during organogenesis at doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area (see Data).

The estimated background risk of 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.

Data

Animal Data

Animal reproduction studies with somatropin during the period of organogenesis at doses of 0.3, 1, and 3.3 mg/kg/day administered subcutaneously (SC) in pregnant rats and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly in pregnant rabbits were not teratogenic (highest doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area).

In perinatal and postnatal studies in rats, somatropin doses of 0.3, 1, and 3.3 mg/kg/day produced growth‑promoting effects in the dams but not in the fetuses. Young rats at the highest dose showed increased weight gain during suckling but the effect was not apparent by 10 weeks of age. No adverse effects were observed on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offspring due to somatropin.

Risk Summary

There is no information regarding the presence of somatropin in human milk. Limited published data indicate that exogenous somatropin does not increase normal breastmilk concentrations of growth hormone. No adverse effects related to somatropin in the breastfeed infant have been reported. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GENOTROPIN and any potential adverse effects on the breastfed infant from GENOTROPIN or from the underlying maternal condition.

Somatropin is a human growth hormone produced by recombinant DNA technology in Escherichia coli. The protein is comprised of 191 amino acid residues and has a molecular weight of 22,124 daltons. The amino acid sequence is identical to that of human growth hormone of pituitary origin.

GENOTROPIN (somatropin) for injection is a sterile, white, lyophilized powder in a single-patient-use or single-dose, two-chamber cartridge intended for subcutaneous injection after reconstitution. The front chamber contains somatropin and the rear chamber contains diluent.

GENOTROPIN 5 mg is a single-patient-use, two-chamber cartridge. GENOTROPIN 5 mg is designed for use with a reusable device (GENOTROPIN PEN 5) for product reconstitution and drug delivery. After reconstitution, each mL contains 5 mg of somatropin, dibasic sodium phosphate (0.27 mg), glycine (2 mg), mannitol (41 mg), metacresol (3 mg) (as a preservative), monobasic sodium phosphate (0.28 mg) and water for injection. The reconstituted concentration is 5 mg/mL with a deliverable volume of 1 mL.

GENOTROPIN 12 mg is a single‑patient‑use, two-chamber cartridge. GENOTROPIN 12 mg is designed for use with a reusable device (GENOTROPIN PEN 12) for product reconstitution and drug delivery. After reconstitution, each mL contains 12 mg of somatropin, dibasic sodium phosphate (0.4 mg), glycine (2 mg), mannitol (40 mg), metacresol (3 mg) (as a preservative), monobasic sodium phosphate (0.41 mg) and water for injection. The reconstituted concentration is 12 mg/mL with a deliverable volume of 1 mL.

GENOTROPIN MINIQUICK is a single-dose Growth Hormone Delivery Device containing a two-chamber cartridge supplied in the following strengths: 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, or 2 mg. After reconstitution, each 0.25 mL contains 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, or 2 mg of somatropin, dibasic sodium phosphate (0.03 mg), glycine (0.21 mg), mannitol (12.5 mg), monobasic sodium phosphate (0.05 mg) and water for injection. Each cartridge provides a deliverable volume of 0.25 mL.

The reconstituted recombinant somatropin solution has an osmolality of approximately 300 mOsm/kg, and a pH of approximately 6.7.

When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site [see Dosage and Administration (2.3)].

GENOTROPIN (somatropin) for injection is a white, lyophilized powder in a single-patient-use or single-dose, two-chamber cartridge intended for subcutaneous injection after reconstitution. The front chamber contains somatropin and the rear chamber contains the diluent.

GENOTROPIN lyophilized powder is available in the following packages:

5 mg single‑patient‑use two-chamber cartridge (with preservative)

• •
  After reconstitution the final concentration is 5 mg/mL
• •
  For use with the GENOTROPIN PEN 5 Growth Hormone Delivery Device.
• •
  Package of 1    NDC 0013-2626-81

12 mg single‑patient‑use two-chamber cartridge (with preservative)

• •
  After reconstitution the final concentration is 12 mg/mL
• •
  For use with the GENOTROPIN PEN 12 Growth Hormone Delivery Device.
• •
  Package of 1    NDC 0013-2646-81

GENOTROPIN MINIQUICK, a single-dose Growth Hormone Delivery Device containing a two-chamber cartridge of GENOTROPIN (without preservative)

• •
  After reconstitution, each GENOTROPIN MINIQUICK delivers 0.25 mL, regardless of strength.

GENOTROPIN MINIQUICK is available in the following strengths, each in a package of 7:

Cases of pancreatitis have been reported rarely in children and adults receiving somatropin treatment, with some evidence supporting a greater risk in children compared with adults. Published literature indicates that girls who have Turner syndrome may be at greater risk than other somatropin-treated children. Pancreatitis should be considered in any somatropin–treated patient, especially a child, who develops persistent severe abdominal pain.

In patients on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal [see Dosage and Administration (2.2)].

Safety and effectiveness of GENOTROPIN in pediatric patients have been established in growth failure due to Prader-Willi syndrome (PWS), growth failure in children born small for gestational age (SGA) with no catch-up growth by age 2 years, growth failure associated with Turner syndrome, idiopathic short stature (ISS) and growth failure due to inadequate secretion of endogenous growth hormone.

Growth Failure Due to Prader-Willi Syndrome (PWS)

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with growth failure due to Prader-Willi syndrome based on data from two randomized, open-label, controlled clinical trials with GENOTROPIN in 43 pediatric patients. There have been reports of sudden death after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin [see Contraindications (4), Warnings and Precautions (5.2), Clinical Studies (14.2)].

Short Stature in Pediatric Patients Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with short stature born SGA with no catch-up growth based on data from 4 randomized, open-label, controlled clinical trials with GENOTROPIN in 209 pediatric patients [see Clinical Studies (14.3)].

Short Stature associated with Turner Syndrome

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with short stature associated with Turner syndrome based on data from two randomized, open-label, clinical trials with GENOTROPIN in 38 pediatric patients [see Clinical Studies (14.4)].

Idiopathic Short Stature (ISS)

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with ISS based on data from one randomized, open-label, clinical trial with GENOTROPIN in 102 pediatric patients [see Clinical Studies (14.5)].

The safety and effectiveness of GENOTROPIN in patients aged 65 and over have not been evaluated in clinical studies. Elderly patients may be more sensitive to the action of GENOTROPIN, and therefore may be more prone to develop adverse reactions. A lower starting dose and smaller dose increments should be considered for older patients [see Dosage and Administration (2.2)].

GENOTROPIN is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria:

Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment [see Drug Interactions (7.1)].

Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with growth hormone deficiency, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of GENOTROPIN or other somatropins.

In the case of growth hormone, antibodies with binding capacities lower than 2 mg/mL have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/mL, interference with the growth response was observed.

In 419 pediatric patients evaluated in clinical studies with GENOTROPIN lyophilized powder, 244 had been treated previously with GENOTROPIN or other growth hormone preparations and 175 had received no previous growth hormone therapy. Antibodies to growth hormone (anti-hGH antibodies) were present in six previously treated patients at baseline. Three of the six became negative for anti-hGH antibodies during 6 to 12 months of treatment with GENOTROPIN. Of the remaining 413 patients, eight (1.9%) developed detectable anti-hGH antibodies during treatment with GENOTROPIN; none had an antibody binding capacity >2 mg/L. There was no evidence that the growth response to GENOTROPIN was affected in these antibody-positive patients.

• •
  Acute Critical Illness (4)
• •
  Children with Prader-Willi syndrome who are severely obese or have severe respiratory impairment – reports of sudden death (4)
• •
  Active Malignancy (4)
• •
  Hypersensitivity to somatropin or excipients (4)
• •
  Active Proliferative or Severe Non-Proliferative Diabetic Retinopathy (4)
• •
  Children with closed epiphyses (4)

Fluid retention during somatropin replacement therapy in adults may occur. Clinical manifestations of fluid retention (e.g., edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent.

The following important adverse reactions are also described elsewhere in the labeling:

• •
  Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1)]
• •
  Fatalities in children with Prader-Willi syndrome [see Warnings and Precautions (5.2)]
• •
  Neoplasms [see Warnings and Precautions (5.3)]
• •
  Glucose intolerance and diabetes mellitus [see Warnings and Precautions (5.4)]
• •
  Intracranial hypertension [see Warnings and Precautions (5.5)]
• •
  Severe hypersensitivity [see Warnings and Precautions (5.6)]
• •
  Fluid retention [see Warnings and Precautions (5.7)]
• •
  Hypoadrenalism [see Warnings and Precautions (5.8)]
• •
  Hypothyroidism [see Warnings and Precautions (5.9)]
• •
  Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5.10)]
• •
  Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5.11)]
• •
  Otitis media and cardiovascular disorders in patients with Turner syndrome [see Warnings and Precautions (5.12)]
• •
  Lipoatrophy [see Warnings and Precautions (5.13)]
• •
  Pancreatitis [see Warnings and Precautions (5.15)]

Inhibition of 11ß-Hydroxysteroid Dehydrogenase Type 1: May require the initiation of glucocorticoid replacement therapy. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance doses (7.1, 7.2).

• •
  Glucocorticoid Replacement: Should be carefully adjusted (7.2)
• •
  Cytochrome P450-Metabolized Drugs: Monitor carefully if used with somatropin (7.3)
• •
  Oral Estrogen: Larger doses of somatropin may be required in women (7.4)
• •
  Insulin and/or Oral/Injectable Hypoglycemic Agents: May require adjustment (7.5)

Two randomized, open-label, clinical trials were conducted that evaluated the efficacy and safety of GENOTROPIN in Turner syndrome patients with short stature. Turner syndrome patients were treated with GENOTROPIN alone or GENOTROPIN plus adjunctive hormonal therapy (ethinylestradiol or oxandrolone). A total of 38 patients were treated with GENOTROPIN alone in the two studies. In Study 055, 22 patients were treated for 12 months, and in Study 092, 16 patients were treated for 12 months. Patients received GENOTROPIN at a dose between 0.13 to 0.33 mg/kg/week.

SDS for height velocity and height are expressed using either the Tanner (Study 055) or Sempé (Study 092) standards for age-matched normal children as well as the Ranke standard (both studies) for age-matched, untreated Turner syndrome patients. As seen in Table 6, height velocity SDS and height SDS values were smaller at baseline and after treatment with GENOTROPIN when the normative standards were utilized as opposed to the Turner syndrome standard.

Both studies demonstrated statistically significant increases from baseline in all of the linear growth variables (i.e., mean height velocity, height velocity SDS, and height SDS) after treatment with GENOTROPIN (see Table 6). The linear growth response was greater in Study 055 wherein patients were treated with a larger dose of GENOTROPIN.

INSTRUCTIONS FOR USE

GENOTROPIN 5 (JEEN-o-tro-pin 5)

GENOTROPIN PEN 5 is a medical device used to mix and inject doses of reconstituted GENOTROPIN (somatropin) for injection. Use this device only for administration of GENOTROPIN.

GENOTROPIN PEN 5 is a reusable multi-dose device holding a 2-chamber cartridge of GENOTROPIN, used to mix and inject GENOTROPIN during a 2 year use period.

For your injection you will need:

• •
  1 GENOTROPIN PEN 5 device
• •
  1 GENOTROPIN 5 mg single-patient-use 2-chamber cartridge
• •
  1 new 29 gauge (29 G), 30 gauge (30 G), or 31 gauge (31 G) Becton Dickinson pen needle
• •
  Alcohol swab (not included)
• •
  1 sharps disposal container. See "Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 5" in Step 14.

Parts of the GENOTROPIN PEN 5 (See Figure A )

Storage instructions for your GENOTROPIN PEN 5

• •
  Between uses, store your pen (with the cartridge) in the refrigerator 36°F to 46°F (2°C to 8°C) in its protective case. Always remove the needle before storing.
• •
  Do not freeze. Protect from light.
• •
  Throw away the cartridge within 28 days after mixing, even if the cartridge is not empty.
• •
  When travelling, keep your pen in its protective case and carry it in an insulated bag to protect it from heat or freezing. Put your pen back in the refrigerator as soon as possible.

Using your GENOTROPIN PEN 5

Step 1.

Wash your hands well with soap and water before using the GENOTROPIN PEN 5.

Step 14. Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 5

Put the used needles and cartridges in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the needles and cartridges in the household trash.

If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:

• •
  Made of a heavy-duty plastic,
• •
  Can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out,
• •
  Upright and stable during use,
• •
  Leak-resistant, and
• •
  Properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and cartridges. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

• •
  Do not reuse needles.
• •
  Do not throw away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this.
• •
  Do not recycle your used sharps disposal container.

Important: Always keep the sharps disposal container out of the reach of children.

Dispose of the entire GENOTROPIN PEN 5 as electronic waste per state and local regulations.

Customizing your Pen

Caring for your Pen

To clean your pen, wipe the outside surface with a damp cloth. Do not put the pen in water or this may damage your pen. Do not use alcohol or any other cleaning agents to clean the pen, as they may damage the plastic body. To clean the needle guard, wipe it with a damp cloth or alcohol pad.

Display Information:

If you have any questions about your dose or your treatment with GENOTROPIN, call your healthcare provider right away.

Use this device only for the person for whom it was prescribed.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Caution: Federal law restricts this device to sale by or on the order of a physician.

Manufactured by:

Pharmacia & Upjohn Company LLC

A subsidiary of Pfizer Inc.

New York, NY 10001

U.S. License No. 1216

LAB-0225-10.0

Revised August 2024

Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and IGF-I may increase during somatropin therapy.

GENOTROPIN is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone.

GENOTROPIN is indicated for the 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 [see Contraindications (4) ].

GENOTROPIN is indicated for the treatment of growth failure in pediatric patients born small for gestational age (SGA) who fail to manifest catch-up growth by age 2 years.

GENOTROPIN is indicated for the treatment of growth failure associated with Turner syndrome.

GENOTROPIN is indicated for the treatment of idiopathic short stature (ISS), also called non-growth hormone-deficient short stature, defined by height standard deviation score (SDS) ≤-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.

GENOTROPIN is a recombinant human growth hormone indicated for:

• •
  Pediatric: Treatment of children with growth failure due to growth hormone deficiency (GHD), Prader-Willi syndrome, Small for Gestational Age, Turner syndrome, and Idiopathic Short Stature (1.1)
• •
  Adult: Treatment of adults with either adult onset or childhood onset GHD (1.2)

In vitro, preclinical, and clinical tests have demonstrated that GENOTROPIN lyophilized powder is therapeutically equivalent to human growth hormone of pituitary origin and achieves similar pharmacokinetic profiles in normal adults. In pediatric patients who have growth hormone deficiency (GHD), have Prader-Willi syndrome (PWS), were born small for gestational age (SGA), have Turner syndrome (TS), or have Idiopathic short stature (ISS), treatment with GENOTROPIN stimulates linear growth. In patients with GHD or PWS, treatment with GENOTROPIN also normalizes concentrations of IGF-I (Insulin-like Growth Factor-I/Somatomedin C). In adults with GHD, treatment with GENOTROPIN results in reduced fat mass, increased lean body mass, metabolic alterations that include beneficial changes in lipid metabolism, and normalization of IGF-I concentrations.

In addition, the following actions have been demonstrated for GENOTROPIN and/or somatropin.

The 5 mg and 12 mg GENOTROPIN single-patient-use cartridges:

• •
  Store GENOTROPIN lyophilized powder under refrigeration at 36°F to 46°F (2°C to 8°C) until the expiration date. Store in the package to protect from light. Do not freeze.
• •
  After reconstitution, store the pen (with the cartridge) in the pen box with the pen cap on to protect from light. Store under refrigeration at 36°F to 46°F (2°C to 8°C) between each use, for up to 28 days. Do not shake. Discard the cartridge and any unused medication after 28 days. Use a GENOTROPIN PEN 5, a medical device, to reconstitute the 5 mg two-chamber cartridge, and use a GENOTROPIN PEN 12 to reconstitute the 12 mg two-chamber cartridge.

The 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1.0 mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg and 2 mg single-dose Growth Hormone Delivery Devices containing a two-chamber cartridge (GENOTROPIN MINIQUICK):

• •
  Store GENOTROPIN MINIQUICK under refrigeration at 36°F to 46°F (2°C to 8°C) until the expiration date. If needed, may be stored for up to 3 months at room temperature at or below 77°F (25°C) prior to reconstitution. Do not freeze.
• •
  After reconstitution, store GENOTROPIN MINIQUICK in the package with the pen cap on to protect from light. If needed, may be stored under refrigeration at 36°F to 46°F (2°C to 8°C) for up to 24 hours before use. Do not shake. The GENOTROPIN MINIQUICK should be used only once and then discarded.

• •
  Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk (5.1)
• •
  Prader-Willi Syndrome in Children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment
  
  Discontinue treatment if these signs occur (5.2)
• •
  Neoplasm: Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin in particular meningiomas in patients treated with radiation to the head for their first neoplasm (5.3)
• •
  Impaired Glucose Tolerance and Diabetes Mellitus: May be unmasked
  
  Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment (5.4)
• •
  Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction (5.5)
• •
  Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention (5.6)
• •
  Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome – especially in adults): May occur frequently. Reduce dose as necessary (5.7)
• •
  Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism (5.8)
• •
  Hypothyroidism: May first become evident or worsen. Monitor thyroid function periodically (5.9)
• •
  Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the onset of a limp or hip/knee pain (5.10)
• •
  Progression of Preexisting Scoliosis: Monitor any child with scoliosis for progression of the curve (5.11)
• •
  Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain (5.15)

Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin [see Contraindications (4)]. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (42% vs. 19%) among somatropin-treated patients (doses 5.3–8 mg/day) compared to those receiving placebo. The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with somatropin in patients having acute critical illnesses should be weighed against the potential risk.

The weekly dose should be divided into 6 or 7 subcutaneous injections. GENOTROPIN must not be injected intravenously.

Therapy with GENOTROPIN should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with growth failure associated with growth hormone deficiency (GHD), Prader-Willi syndrome (PWS), Turner syndrome (TS), those who were born small for gestational age (SGA) or Idiopathic Short Stature (ISS), and adult patients with either childhood onset or adult onset GHD.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs [see Contraindications (4)].

GENOTROPIN is a white, lyophilized powder available as:

• •
  For injection: 5 mg or 12 mg in a single-patient-use two-chamber cartridge
• •
  For injection: 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, or 2 mg in a single‑dose Growth Hormone Delivery Device containing a two-chamber cartridge (GENOTROPIN MINIQUICK)

The following adverse reactions have been identified during post-approval use of somatropin or GENOTROPIN. Because these adverse events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins [see Warnings and Precautions (5.6)].

Leukemia has been reported in a small number of GHD children treated with somatropin, somatrem (methionylated rhGH) and GH of pituitary origin. It is uncertain whether these cases of leukemia are related to GH therapy, the pathology of GHD itself, or other associated treatments such as radiation therapy. On the basis of current evidence, experts have not been able to conclude that GH therapy per se was responsible for these cases of leukemia. The risk for children with GHD, if any, remains to be established [see Contraindications (4) and Warnings and Precautions (5.3)].

The following serious adverse reactions have been observed with use of somatropin (including events observed in patients who received brands of somatropin other than GENOTROPIN): acute critical illness [see Warnings and Precautions (5.1)], sudden death [see Warnings and Precautions (5.2)], intracranial tumors [see Warnings and Precautions (5.3)], central hypothyroidism [see Warnings and Precautions (5.9)], cardiovascular disorders, and pancreatitis [see Warnings and Precautions (5.15)].

Slipped capital femoral epiphysis and osteonecrosis/avascular necrosis (including Legg-Calvé-Perthes disease) have been reported in children treated with growth hormone [see Warnings and Precautions (5.10)]. Cases have been reported with GENOTROPIN.

The following additional adverse reactions have been observed during the appropriate use of somatropin: headaches (children and adults), gynecomastia (children), and significant diabetic retinopathy.

New-onset type 2 diabetes mellitus has been reported.

The long-term efficacy and safety of GENOTROPIN in patients with idiopathic short stature (ISS) were evaluated in one randomized, open-label, clinical trial that enrolled 177 children. Patients were enrolled on the basis of short stature, stimulated GH secretion >10 ng/mL, and prepubertal status (criteria for idiopathic short stature were retrospectively applied and included 126 patients). All patients were observed for height progression for 12 months and were subsequently randomized to GENOTROPIN or observation only and followed to final height. Two GENOTROPIN doses were evaluated in this trial: 0.23 mg/kg/week (0.033 mg/kg/day) and 0.47 mg/kg/week (0.067 mg/kg/day). Baseline patient characteristics for the ISS patients who remained prepubertal at randomization (n= 105) were: mean (± SD): chronological age 11.4 (1.3) years, height SDS -2.4 (0.4), height velocity SDS -1.1 (0.8), and height velocity 4.4 (0.9) cm/yr, IGF-1 SDS -0.8 (1.4). Patients were treated for a median duration of 5.7 years. Results for final height SDS are displayed by treatment arm in Table 7. GENOTROPIN therapy improved final height in ISS children relative to untreated controls. The observed mean gain in final height was 9.8 cm for females and 5.0 cm for males for both doses combined compared to untreated control subjects. A height gain of 1 SDS was observed in 10% of untreated subjects, 50% of subjects receiving 0.23 mg/kg/week and 69% of subjects receiving 0.47 mg/kg/week.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a small number of patients treated with somatropins. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose. Fundoscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by fundoscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome and Prader-Willi syndrome may be at increased risk for the development of IH.

Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation, and may not reflect the adverse reaction rates observed in practice.

The safety and efficacy of GENOTROPIN in the treatment of pediatric patients with Prader-Willi syndrome (PWS) were evaluated in two randomized, open-label, controlled clinical trials. Patients received either GENOTROPIN or no treatment for the first year of the studies, while all patients received GENOTROPIN during the second year. GENOTROPIN was administered as a daily SC injection, and the dose was calculated for each patient every 3 months. In Study 1, the treatment group received GENOTROPIN at a dose of 0.24 mg/kg/week during the entire study. During the second year, the control group received GENOTROPIN at a dose of 0.48 mg/kg/week. In Study 2, the treatment group received GENOTROPIN at a dose of 0.36 mg/kg/week during the entire study. During the second year, the control group received GENOTROPIN at a dose of 0.36 mg/kg/week.

Patients who received GENOTROPIN showed significant increases in linear growth during the first year of study, compared with patients who received no treatment (see Table 3). Linear growth continued to increase in the second year, when both groups received treatment with GENOTROPIN.

Changes in body composition were also observed in the patients receiving GENOTROPIN (see Table 4). These changes included a decrease in the amount of fat mass, and increases in the amount of lean body mass and the ratio of lean-to-fat tissue, while changes in body weight were similar to those seen in patients who received no treatment. Treatment with GENOTROPIN did not accelerate bone age, compared with patients who received no treatment.

Patients being treated with GENOTROPIN (and/or their parents) should be informed about the potential benefits and risks associated with GENOTROPIN treatment. This information is intended to better educate patients (and caregivers); it is not a disclosure of all possible adverse or intended effects.

Patients and caregivers who will administer GENOTROPIN should receive appropriate training and instruction on the proper use of GENOTROPIN from the physician or other suitably qualified health care professional. A puncture-resistant container for the disposal of used syringes and needles should be strongly recommended. Patients and/or parents should be thoroughly instructed in the importance of proper disposal, and cautioned against any reuse of needles and syringes. This information is intended to aid in the safe and effective administration of the medication.

GENOTROPIN is supplied in a two-chamber cartridge, with the lyophilized powder in the front chamber and a diluent in the rear chamber. A reconstitution device is used to mix the diluent and powder.

The GENOTROPIN 5 mg and 12 mg cartridges are color-coded to help ensure proper use with the GENOTROPIN PEN delivery device. The 5 mg cartridge has a green tip to match the green pen window on the Pen 5, while the 12 mg cartridge has a purple tip to match the purple pen window on the Pen 12.

Follow the directions for reconstitution provided with each device. Do not shake; shaking may cause denaturation of the active ingredient.

Please see accompanying directions for use of the reconstitution and/or delivery device.

The GENOTROPIN 5 and 12 mg cartridges are color-coded to help ensure proper use with the GENOTROPIN PEN delivery device. The 5 mg cartridge has a green tip to match the green pen window on the Pen 5, while the 12 mg cartridge has a purple tip to match the purple pen window on the Pen 12.

Parenteral drug products should always be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. GENOTROPIN MUST NOT BE INJECTED if the solution is cloudy or contains particulate matter. Use it only if it is clear and colorless.

GENOTROPIN may be given in the thigh, buttocks, or abdomen; the site of SC injections should be rotated daily to help prevent lipoatrophy.

There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin. If during treatment with somatropin, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively [see Contraindications (4)].

Limited published data indicate that somatropin treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance in man. These data suggest that somatropin administration may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine). Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CYP450 liver enzymes. However, formal drug interaction studies have not been conducted.

NDC 0013-2653-02

Pfizer

Genotropin^®

(somatropin) for injection

1 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2658-02

Pfizer

Genotropin^®

(somatropin) for injection

2 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

Pfizer

Genotropin^®

5 mg

(somatropin) for injection

NDC 0013-2626-81

For subcutaneous injection

Rx only

1 Two-Chamber Cartridge

PAA185820

OPEN HERE

GENOTROPIN lyophilized powder was compared with placebo in six randomized clinical trials involving a total of 172 adult GHD patients. These trials included a 6-month double-blind treatment period, during which 85 patients received GENOTROPIN and 87 patients received placebo, followed by an open-label treatment period in which participating patients received GENOTROPIN for up to a total of 24 months. GENOTROPIN was administered as a daily SC injection at a dose of 0.04 mg/kg/week for the first month of treatment and 0.08 mg/kg/week for subsequent months.

Beneficial changes in body composition were observed at the end of the 6-month treatment period for the patients receiving GENOTROPIN as compared with the placebo patients. Lean body mass, total body water, and lean/fat ratio increased while total body fat mass and waist circumference decreased. These effects on body composition were maintained when treatment was continued beyond 6 months. Bone mineral density declined after 6 months of treatment but returned to baseline values after 12 months of treatment.

Pfizer

Genotropin^®

12 mg

(somatropin) for injection

NDC 0013-2646-81

For subcutaneous injection

Rx only

1 Two-Chamber Cartridge

PAA185893

OPEN HERE

NDC 0013-2649-02

Pfizer

Genotropin^®

(somatropin) for injection

0.2 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2650-02

Pfizer

Genotropin^®

(somatropin) for injection

0.4 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2651-02

Pfizer

Genotropin^®

(somatropin) for injection

0.6 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2652-02

Pfizer

Genotropin^®

(somatropin) for injection

0.8 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2654-02

Pfizer

Genotropin^®

(somatropin) for injection

1.2 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2655-02

Pfizer

Genotropin^®

(somatropin) for injection

1.4 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2656-02

Pfizer

Genotropin^®

(somatropin) for injection

1.6 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2657-02

Pfizer

Genotropin^®

(somatropin) for injection

1.8 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

The microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. GH and somatropin inhibit 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. As a consequence, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required in patients treated with somatropin. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment; this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1 [see Warnings and Precautions (5.8)].

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1 mg

NDC 0013-2653-01

PAA142733

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

2 mg

NDC 0013-2658-01

PAA142738

LOT

EXP

Genotropin^®

(somatropin) for injection

Two-chamber cartridge

For s.c. injection. 5 mg/mL

Refrigerate. Protect from light.

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

5 mg

NDC 0013-2626-81

LOT/EXP

PAA185891

Genotropin^®

(somatropin) for injection

Two-chamber cartridge

For s.c. injection. 12 mg/mL

Refrigerate. Protect from light.

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

12 mg

NDC 0013-2646-81

LOT/EXP

PAA185895

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.2 mg

NDC 0013-2649-01

PAA142719

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.4 mg

NDC 0013-2650-01

PAA142720

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.6 mg

NDC 0013-2651-01

PAA142731

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.8 mg

NDC 0013-2652-01

PAA142732

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.2 mg

NDC 0013-2654-01

PAA142734

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.4 mg

NDC 0013-2655-01

PAA142735

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.6 mg

NDC 0013-2656-01

PAA142736

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.8 mg

NDC 0013-2657-01

PAA142737

LOT

EXP

Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. New-onset Type 2 diabetes mellitus has been reported. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs (i.e., insulin or oral/injectable agents) may require adjustment when somatropin therapy is instituted in these patients.

In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral/injectable agent may require adjustment when somatropin therapy is initiated [see Warnings and Precautions (5.4)].

Carcinogenicity studies have not been conducted with GENOTROPIN. No potential mutagenicity of GENOTROPIN was revealed in a battery of tests including induction of gene mutations in bacteria (the Ames test), gene mutations in mammalian cells grown in vitro (mouse L5178Y cells), and chromosomal damage in intact animals (bone marrow cells in rats).

In a fertility study in male and female rats receiving SC doses during gametogenesis (2 weeks prior to mating for females and 9 weeks prior to mating for males) and continuing up to 7 days of pregnancy, 3.3 mg/kg/day (approximately 24 times human dose by body surface area) produced anestrus or extended estrus cycles in females and fewer and less motile sperm in males. Lower copulation and pregnancy rates were also observed at 3.3 mg/kg/day. At 1 mg/kg/day (approximately 7 times human dose by body surface area), rats showed slightly extended estrus cycles, whereas at 0.3 mg/kg/day no effects were noted (approximately 2 times human dose by body surface).

Slipped capital femoral epiphyses may occur more frequently in patients with endocrine disorders (including GHD and Turner syndrome) or in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin, including GENOTROPIN. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during GENOTROPIN therapy should be evaluated for slipped capital femoral epiphysis and osteonecrosis and managed accordingly.

Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated Turner syndrome patients. Scoliosis is also commonly seen in untreated patients with Prader-Willi syndrome. Physicians should be alert to these abnormalities, which may manifest during somatropin therapy.

Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.

Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth‑promoting effects of somatropin in children. Therefore, glucocorticoid replacement dosing should be carefully adjusted in children receiving concomitant somatropin and glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth.

Adult Onset (AO): Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or

INSTRUCTIONS FOR USE

GENOTROPIN 12 (JEEN-o-tro-pin 12)

GENOTROPIN PEN 12 is a medical device used to mix and inject doses of reconstituted GENOTROPIN (somatropin) for injection. Use this device only for administration of GENOTROPIN.

GENOTROPIN PEN 12 is a reusable multi-dose device holding a 2-chamber cartridge of GENOTROPIN, used to mix and inject GENOTROPIN during a 2 year use period.

For your injection you will need:

• •
  1 GENOTROPIN PEN 12 device
• •
  1 GENOTROPIN 12 mg single-patient-use 2-chamber cartridge
• •
  1 new 29 gauge (29 G), 30 gauge (30 G), or 31 gauge (31 G) Becton Dickinson pen needle
• •
  Alcohol swab (not included)
• •
  1 sharps disposal container. See "Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 12" in Step 14.

Parts of the GENOTROPIN PEN 12 (See Figure A )

Storage instructions for your GENOTROPIN PEN 12

• •
  Between uses, store your pen (with the cartridge) in the refrigerator between 36°F to 46°F (2°C to 8°C) in its protective case. Always remove the needle before storing.
• •
  Do not freeze. Protect from light.
• •
  Throw away the cartridge within 28 days after mixing, even if the cartridge is not empty.
• •
  When travelling, keep your pen in its protective case and carry it in an insulated bag to protect it from heat or freezing. Put your pen back in the refrigerator as soon as possible.

Using your GENOTROPIN PEN 12

Step 1.

Wash your hands well with soap and water before using the GENOTROPIN PEN 12.

Step 14. Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 12

Put the used needles and cartridges in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the needles and cartridges in the household trash.

If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:

• •
  Made of a heavy-duty plastic,
• •
  Can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out,
• •
  Upright and stable during use,
• •
  Leak-resistant, and
• •
  Properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and cartridges. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

• •
  Do not reuse needles.
• •
  Do not throw away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this.
• •
  Do not recycle your used sharps disposal container.

Important: Always keep the sharps disposal container out of the reach of children.

Dispose of the entire GENOTROPIN PEN 12 as electronic waste per state and local regulations.

Caring for your Pen

To clean your pen, wipe the outside surface with a damp cloth. Do not put the pen in water as this may damage your pen. Do not use alcohol or any other cleaning agents to clean the pen, as they may damage the plastic body. To clean the needle guard, wipe it with a damp cloth or alcohol pad.

Display Information

If you have any questions about your dose or your treatment with GENOTROPIN, call your healthcare provider right away.

Use this device only for the person for whom it was prescribed.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Caution: Federal law restricts this device to sale by or on the order of a physician.

Manufactured by:

Pharmacia & Upjohn Company LLC

A subsidiary of Pfizer Inc.

New York, NY 10001

U.S. License No. 1216

LAB-0224-10.0

Revised August 2024

Short-Term

Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Furthermore, overdose with somatropin is likely to cause fluid retention.

Long-Term

Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth hormone [see Dosage and Administration (2)].

In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm has been reported. Intracranial tumors, in particular meningiomas, were the most common of these second neoplasms. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence [see Contraindications (4)].

Monitor all patients with a history of GHD secondary to an intracranial neoplasm routinely while on somatropin therapy for progression or recurrence of the tumor.

Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, practitioners should thoroughly consider the risks and benefits of starting somatropin in these patients. If treatment with somatropin is initiated, these patients should be carefully monitored for development of neoplasms.

Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes, of preexisting nevi.

Risk Summary

Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal studies (rats and rabbits), there was no evidence of embryo‑fetal or neonatal harm following somatropin administration during organogenesis at doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area (see Data).

The estimated background risk of 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.

Data

Animal Data

Animal reproduction studies with somatropin during the period of organogenesis at doses of 0.3, 1, and 3.3 mg/kg/day administered subcutaneously (SC) in pregnant rats and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly in pregnant rabbits were not teratogenic (highest doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area).

In perinatal and postnatal studies in rats, somatropin doses of 0.3, 1, and 3.3 mg/kg/day produced growth‑promoting effects in the dams but not in the fetuses. Young rats at the highest dose showed increased weight gain during suckling but the effect was not apparent by 10 weeks of age. No adverse effects were observed on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offspring due to somatropin.

Risk Summary

There is no information regarding the presence of somatropin in human milk. Limited published data indicate that exogenous somatropin does not increase normal breastmilk concentrations of growth hormone. No adverse effects related to somatropin in the breastfeed infant have been reported. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GENOTROPIN and any potential adverse effects on the breastfed infant from GENOTROPIN or from the underlying maternal condition.

Somatropin is a human growth hormone produced by recombinant DNA technology in Escherichia coli. The protein is comprised of 191 amino acid residues and has a molecular weight of 22,124 daltons. The amino acid sequence is identical to that of human growth hormone of pituitary origin.

GENOTROPIN (somatropin) for injection is a sterile, white, lyophilized powder in a single-patient-use or single-dose, two-chamber cartridge intended for subcutaneous injection after reconstitution. The front chamber contains somatropin and the rear chamber contains diluent.

GENOTROPIN 5 mg is a single-patient-use, two-chamber cartridge. GENOTROPIN 5 mg is designed for use with a reusable device (GENOTROPIN PEN 5) for product reconstitution and drug delivery. After reconstitution, each mL contains 5 mg of somatropin, dibasic sodium phosphate (0.27 mg), glycine (2 mg), mannitol (41 mg), metacresol (3 mg) (as a preservative), monobasic sodium phosphate (0.28 mg) and water for injection. The reconstituted concentration is 5 mg/mL with a deliverable volume of 1 mL.

GENOTROPIN 12 mg is a single‑patient‑use, two-chamber cartridge. GENOTROPIN 12 mg is designed for use with a reusable device (GENOTROPIN PEN 12) for product reconstitution and drug delivery. After reconstitution, each mL contains 12 mg of somatropin, dibasic sodium phosphate (0.4 mg), glycine (2 mg), mannitol (40 mg), metacresol (3 mg) (as a preservative), monobasic sodium phosphate (0.41 mg) and water for injection. The reconstituted concentration is 12 mg/mL with a deliverable volume of 1 mL.

GENOTROPIN MINIQUICK is a single-dose Growth Hormone Delivery Device containing a two-chamber cartridge supplied in the following strengths: 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, or 2 mg. After reconstitution, each 0.25 mL contains 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, or 2 mg of somatropin, dibasic sodium phosphate (0.03 mg), glycine (0.21 mg), mannitol (12.5 mg), monobasic sodium phosphate (0.05 mg) and water for injection. Each cartridge provides a deliverable volume of 0.25 mL.

The reconstituted recombinant somatropin solution has an osmolality of approximately 300 mOsm/kg, and a pH of approximately 6.7.

When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site [see Dosage and Administration (2.3)].

GENOTROPIN (somatropin) for injection is a white, lyophilized powder in a single-patient-use or single-dose, two-chamber cartridge intended for subcutaneous injection after reconstitution. The front chamber contains somatropin and the rear chamber contains the diluent.

GENOTROPIN lyophilized powder is available in the following packages:

5 mg single‑patient‑use two-chamber cartridge (with preservative)

• •
  After reconstitution the final concentration is 5 mg/mL
• •
  For use with the GENOTROPIN PEN 5 Growth Hormone Delivery Device.
• •
  Package of 1    NDC 0013-2626-81

12 mg single‑patient‑use two-chamber cartridge (with preservative)

• •
  After reconstitution the final concentration is 12 mg/mL
• •
  For use with the GENOTROPIN PEN 12 Growth Hormone Delivery Device.
• •
  Package of 1    NDC 0013-2646-81

GENOTROPIN MINIQUICK, a single-dose Growth Hormone Delivery Device containing a two-chamber cartridge of GENOTROPIN (without preservative)

• •
  After reconstitution, each GENOTROPIN MINIQUICK delivers 0.25 mL, regardless of strength.

GENOTROPIN MINIQUICK is available in the following strengths, each in a package of 7:

Cases of pancreatitis have been reported rarely in children and adults receiving somatropin treatment, with some evidence supporting a greater risk in children compared with adults. Published literature indicates that girls who have Turner syndrome may be at greater risk than other somatropin-treated children. Pancreatitis should be considered in any somatropin–treated patient, especially a child, who develops persistent severe abdominal pain.

In patients on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal [see Dosage and Administration (2.2)].

Safety and effectiveness of GENOTROPIN in pediatric patients have been established in growth failure due to Prader-Willi syndrome (PWS), growth failure in children born small for gestational age (SGA) with no catch-up growth by age 2 years, growth failure associated with Turner syndrome, idiopathic short stature (ISS) and growth failure due to inadequate secretion of endogenous growth hormone.

Growth Failure Due to Prader-Willi Syndrome (PWS)

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with growth failure due to Prader-Willi syndrome based on data from two randomized, open-label, controlled clinical trials with GENOTROPIN in 43 pediatric patients. There have been reports of sudden death after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin [see Contraindications (4), Warnings and Precautions (5.2), Clinical Studies (14.2)].

Short Stature in Pediatric Patients Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with short stature born SGA with no catch-up growth based on data from 4 randomized, open-label, controlled clinical trials with GENOTROPIN in 209 pediatric patients [see Clinical Studies (14.3)].

Short Stature associated with Turner Syndrome

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with short stature associated with Turner syndrome based on data from two randomized, open-label, clinical trials with GENOTROPIN in 38 pediatric patients [see Clinical Studies (14.4)].

Idiopathic Short Stature (ISS)

Safety and effectiveness of GENOTROPIN have been established in pediatric patients with ISS based on data from one randomized, open-label, clinical trial with GENOTROPIN in 102 pediatric patients [see Clinical Studies (14.5)].

The safety and effectiveness of GENOTROPIN in patients aged 65 and over have not been evaluated in clinical studies. Elderly patients may be more sensitive to the action of GENOTROPIN, and therefore may be more prone to develop adverse reactions. A lower starting dose and smaller dose increments should be considered for older patients [see Dosage and Administration (2.2)].

GENOTROPIN is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria:

Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment [see Drug Interactions (7.1)].

Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with growth hormone deficiency, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of GENOTROPIN or other somatropins.

In the case of growth hormone, antibodies with binding capacities lower than 2 mg/mL have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/mL, interference with the growth response was observed.

In 419 pediatric patients evaluated in clinical studies with GENOTROPIN lyophilized powder, 244 had been treated previously with GENOTROPIN or other growth hormone preparations and 175 had received no previous growth hormone therapy. Antibodies to growth hormone (anti-hGH antibodies) were present in six previously treated patients at baseline. Three of the six became negative for anti-hGH antibodies during 6 to 12 months of treatment with GENOTROPIN. Of the remaining 413 patients, eight (1.9%) developed detectable anti-hGH antibodies during treatment with GENOTROPIN; none had an antibody binding capacity >2 mg/L. There was no evidence that the growth response to GENOTROPIN was affected in these antibody-positive patients.

• •
  Acute Critical Illness (4)
• •
  Children with Prader-Willi syndrome who are severely obese or have severe respiratory impairment – reports of sudden death (4)
• •
  Active Malignancy (4)
• •
  Hypersensitivity to somatropin or excipients (4)
• •
  Active Proliferative or Severe Non-Proliferative Diabetic Retinopathy (4)
• •
  Children with closed epiphyses (4)

Fluid retention during somatropin replacement therapy in adults may occur. Clinical manifestations of fluid retention (e.g., edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent.

The following important adverse reactions are also described elsewhere in the labeling:

• •
  Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1)]
• •
  Fatalities in children with Prader-Willi syndrome [see Warnings and Precautions (5.2)]
• •
  Neoplasms [see Warnings and Precautions (5.3)]
• •
  Glucose intolerance and diabetes mellitus [see Warnings and Precautions (5.4)]
• •
  Intracranial hypertension [see Warnings and Precautions (5.5)]
• •
  Severe hypersensitivity [see Warnings and Precautions (5.6)]
• •
  Fluid retention [see Warnings and Precautions (5.7)]
• •
  Hypoadrenalism [see Warnings and Precautions (5.8)]
• •
  Hypothyroidism [see Warnings and Precautions (5.9)]
• •
  Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5.10)]
• •
  Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5.11)]
• •
  Otitis media and cardiovascular disorders in patients with Turner syndrome [see Warnings and Precautions (5.12)]
• •
  Lipoatrophy [see Warnings and Precautions (5.13)]
• •
  Pancreatitis [see Warnings and Precautions (5.15)]

Inhibition of 11ß-Hydroxysteroid Dehydrogenase Type 1: May require the initiation of glucocorticoid replacement therapy. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance doses (7.1, 7.2).

• •
  Glucocorticoid Replacement: Should be carefully adjusted (7.2)
• •
  Cytochrome P450-Metabolized Drugs: Monitor carefully if used with somatropin (7.3)
• •
  Oral Estrogen: Larger doses of somatropin may be required in women (7.4)
• •
  Insulin and/or Oral/Injectable Hypoglycemic Agents: May require adjustment (7.5)

Two randomized, open-label, clinical trials were conducted that evaluated the efficacy and safety of GENOTROPIN in Turner syndrome patients with short stature. Turner syndrome patients were treated with GENOTROPIN alone or GENOTROPIN plus adjunctive hormonal therapy (ethinylestradiol or oxandrolone). A total of 38 patients were treated with GENOTROPIN alone in the two studies. In Study 055, 22 patients were treated for 12 months, and in Study 092, 16 patients were treated for 12 months. Patients received GENOTROPIN at a dose between 0.13 to 0.33 mg/kg/week.

SDS for height velocity and height are expressed using either the Tanner (Study 055) or Sempé (Study 092) standards for age-matched normal children as well as the Ranke standard (both studies) for age-matched, untreated Turner syndrome patients. As seen in Table 6, height velocity SDS and height SDS values were smaller at baseline and after treatment with GENOTROPIN when the normative standards were utilized as opposed to the Turner syndrome standard.

Both studies demonstrated statistically significant increases from baseline in all of the linear growth variables (i.e., mean height velocity, height velocity SDS, and height SDS) after treatment with GENOTROPIN (see Table 6). The linear growth response was greater in Study 055 wherein patients were treated with a larger dose of GENOTROPIN.

INSTRUCTIONS FOR USE

GENOTROPIN 5 (JEEN-o-tro-pin 5)

GENOTROPIN PEN 5 is a medical device used to mix and inject doses of reconstituted GENOTROPIN (somatropin) for injection. Use this device only for administration of GENOTROPIN.

GENOTROPIN PEN 5 is a reusable multi-dose device holding a 2-chamber cartridge of GENOTROPIN, used to mix and inject GENOTROPIN during a 2 year use period.

For your injection you will need:

• •
  1 GENOTROPIN PEN 5 device
• •
  1 GENOTROPIN 5 mg single-patient-use 2-chamber cartridge
• •
  1 new 29 gauge (29 G), 30 gauge (30 G), or 31 gauge (31 G) Becton Dickinson pen needle
• •
  Alcohol swab (not included)
• •
  1 sharps disposal container. See "Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 5" in Step 14.

Parts of the GENOTROPIN PEN 5 (See Figure A )

Storage instructions for your GENOTROPIN PEN 5

• •
  Between uses, store your pen (with the cartridge) in the refrigerator 36°F to 46°F (2°C to 8°C) in its protective case. Always remove the needle before storing.
• •
  Do not freeze. Protect from light.
• •
  Throw away the cartridge within 28 days after mixing, even if the cartridge is not empty.
• •
  When travelling, keep your pen in its protective case and carry it in an insulated bag to protect it from heat or freezing. Put your pen back in the refrigerator as soon as possible.

Using your GENOTROPIN PEN 5

Step 1.

Wash your hands well with soap and water before using the GENOTROPIN PEN 5.

Step 14. Throwing away (disposing of) used needles, cartridges and your GENOTROPIN PEN 5

Put the used needles and cartridges in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the needles and cartridges in the household trash.

If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:

• •
  Made of a heavy-duty plastic,
• •
  Can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out,
• •
  Upright and stable during use,
• •
  Leak-resistant, and
• •
  Properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and cartridges. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

• •
  Do not reuse needles.
• •
  Do not throw away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this.
• •
  Do not recycle your used sharps disposal container.

Important: Always keep the sharps disposal container out of the reach of children.

Dispose of the entire GENOTROPIN PEN 5 as electronic waste per state and local regulations.

Customizing your Pen

Caring for your Pen

To clean your pen, wipe the outside surface with a damp cloth. Do not put the pen in water or this may damage your pen. Do not use alcohol or any other cleaning agents to clean the pen, as they may damage the plastic body. To clean the needle guard, wipe it with a damp cloth or alcohol pad.

Display Information:

If you have any questions about your dose or your treatment with GENOTROPIN, call your healthcare provider right away.

Use this device only for the person for whom it was prescribed.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Caution: Federal law restricts this device to sale by or on the order of a physician.

Manufactured by:

Pharmacia & Upjohn Company LLC

A subsidiary of Pfizer Inc.

New York, NY 10001

U.S. License No. 1216

LAB-0225-10.0

Revised August 2024

Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and IGF-I may increase during somatropin therapy.

GENOTROPIN is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone.

GENOTROPIN is indicated for the 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 [see Contraindications (4) ].

GENOTROPIN is indicated for the treatment of growth failure in pediatric patients born small for gestational age (SGA) who fail to manifest catch-up growth by age 2 years.

GENOTROPIN is indicated for the treatment of growth failure associated with Turner syndrome.

GENOTROPIN is indicated for the treatment of idiopathic short stature (ISS), also called non-growth hormone-deficient short stature, defined by height standard deviation score (SDS) ≤-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.

GENOTROPIN is a recombinant human growth hormone indicated for:

• •
  Pediatric: Treatment of children with growth failure due to growth hormone deficiency (GHD), Prader-Willi syndrome, Small for Gestational Age, Turner syndrome, and Idiopathic Short Stature (1.1)
• •
  Adult: Treatment of adults with either adult onset or childhood onset GHD (1.2)

In vitro, preclinical, and clinical tests have demonstrated that GENOTROPIN lyophilized powder is therapeutically equivalent to human growth hormone of pituitary origin and achieves similar pharmacokinetic profiles in normal adults. In pediatric patients who have growth hormone deficiency (GHD), have Prader-Willi syndrome (PWS), were born small for gestational age (SGA), have Turner syndrome (TS), or have Idiopathic short stature (ISS), treatment with GENOTROPIN stimulates linear growth. In patients with GHD or PWS, treatment with GENOTROPIN also normalizes concentrations of IGF-I (Insulin-like Growth Factor-I/Somatomedin C). In adults with GHD, treatment with GENOTROPIN results in reduced fat mass, increased lean body mass, metabolic alterations that include beneficial changes in lipid metabolism, and normalization of IGF-I concentrations.

In addition, the following actions have been demonstrated for GENOTROPIN and/or somatropin.

The 5 mg and 12 mg GENOTROPIN single-patient-use cartridges:

• •
  Store GENOTROPIN lyophilized powder under refrigeration at 36°F to 46°F (2°C to 8°C) until the expiration date. Store in the package to protect from light. Do not freeze.
• •
  After reconstitution, store the pen (with the cartridge) in the pen box with the pen cap on to protect from light. Store under refrigeration at 36°F to 46°F (2°C to 8°C) between each use, for up to 28 days. Do not shake. Discard the cartridge and any unused medication after 28 days. Use a GENOTROPIN PEN 5, a medical device, to reconstitute the 5 mg two-chamber cartridge, and use a GENOTROPIN PEN 12 to reconstitute the 12 mg two-chamber cartridge.

The 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1.0 mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg and 2 mg single-dose Growth Hormone Delivery Devices containing a two-chamber cartridge (GENOTROPIN MINIQUICK):

• •
  Store GENOTROPIN MINIQUICK under refrigeration at 36°F to 46°F (2°C to 8°C) until the expiration date. If needed, may be stored for up to 3 months at room temperature at or below 77°F (25°C) prior to reconstitution. Do not freeze.
• •
  After reconstitution, store GENOTROPIN MINIQUICK in the package with the pen cap on to protect from light. If needed, may be stored under refrigeration at 36°F to 46°F (2°C to 8°C) for up to 24 hours before use. Do not shake. The GENOTROPIN MINIQUICK should be used only once and then discarded.

• •
  Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk (5.1)
• •
  Prader-Willi Syndrome in Children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment
  
  Discontinue treatment if these signs occur (5.2)
• •
  Neoplasm: Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin in particular meningiomas in patients treated with radiation to the head for their first neoplasm (5.3)
• •
  Impaired Glucose Tolerance and Diabetes Mellitus: May be unmasked
  
  Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment (5.4)
• •
  Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction (5.5)
• •
  Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention (5.6)
• •
  Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome – especially in adults): May occur frequently. Reduce dose as necessary (5.7)
• •
  Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism (5.8)
• •
  Hypothyroidism: May first become evident or worsen. Monitor thyroid function periodically (5.9)
• •
  Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the onset of a limp or hip/knee pain (5.10)
• •
  Progression of Preexisting Scoliosis: Monitor any child with scoliosis for progression of the curve (5.11)
• •
  Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain (5.15)

Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin [see Contraindications (4)]. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (42% vs. 19%) among somatropin-treated patients (doses 5.3–8 mg/day) compared to those receiving placebo. The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with somatropin in patients having acute critical illnesses should be weighed against the potential risk.

The weekly dose should be divided into 6 or 7 subcutaneous injections. GENOTROPIN must not be injected intravenously.

Therapy with GENOTROPIN should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with growth failure associated with growth hormone deficiency (GHD), Prader-Willi syndrome (PWS), Turner syndrome (TS), those who were born small for gestational age (SGA) or Idiopathic Short Stature (ISS), and adult patients with either childhood onset or adult onset GHD.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs [see Contraindications (4)].

GENOTROPIN is a white, lyophilized powder available as:

• •
  For injection: 5 mg or 12 mg in a single-patient-use two-chamber cartridge
• •
  For injection: 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, or 2 mg in a single‑dose Growth Hormone Delivery Device containing a two-chamber cartridge (GENOTROPIN MINIQUICK)

The following adverse reactions have been identified during post-approval use of somatropin or GENOTROPIN. Because these adverse events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins [see Warnings and Precautions (5.6)].

Leukemia has been reported in a small number of GHD children treated with somatropin, somatrem (methionylated rhGH) and GH of pituitary origin. It is uncertain whether these cases of leukemia are related to GH therapy, the pathology of GHD itself, or other associated treatments such as radiation therapy. On the basis of current evidence, experts have not been able to conclude that GH therapy per se was responsible for these cases of leukemia. The risk for children with GHD, if any, remains to be established [see Contraindications (4) and Warnings and Precautions (5.3)].

The following serious adverse reactions have been observed with use of somatropin (including events observed in patients who received brands of somatropin other than GENOTROPIN): acute critical illness [see Warnings and Precautions (5.1)], sudden death [see Warnings and Precautions (5.2)], intracranial tumors [see Warnings and Precautions (5.3)], central hypothyroidism [see Warnings and Precautions (5.9)], cardiovascular disorders, and pancreatitis [see Warnings and Precautions (5.15)].

Slipped capital femoral epiphysis and osteonecrosis/avascular necrosis (including Legg-Calvé-Perthes disease) have been reported in children treated with growth hormone [see Warnings and Precautions (5.10)]. Cases have been reported with GENOTROPIN.

The following additional adverse reactions have been observed during the appropriate use of somatropin: headaches (children and adults), gynecomastia (children), and significant diabetic retinopathy.

New-onset type 2 diabetes mellitus has been reported.

The long-term efficacy and safety of GENOTROPIN in patients with idiopathic short stature (ISS) were evaluated in one randomized, open-label, clinical trial that enrolled 177 children. Patients were enrolled on the basis of short stature, stimulated GH secretion >10 ng/mL, and prepubertal status (criteria for idiopathic short stature were retrospectively applied and included 126 patients). All patients were observed for height progression for 12 months and were subsequently randomized to GENOTROPIN or observation only and followed to final height. Two GENOTROPIN doses were evaluated in this trial: 0.23 mg/kg/week (0.033 mg/kg/day) and 0.47 mg/kg/week (0.067 mg/kg/day). Baseline patient characteristics for the ISS patients who remained prepubertal at randomization (n= 105) were: mean (± SD): chronological age 11.4 (1.3) years, height SDS -2.4 (0.4), height velocity SDS -1.1 (0.8), and height velocity 4.4 (0.9) cm/yr, IGF-1 SDS -0.8 (1.4). Patients were treated for a median duration of 5.7 years. Results for final height SDS are displayed by treatment arm in Table 7. GENOTROPIN therapy improved final height in ISS children relative to untreated controls. The observed mean gain in final height was 9.8 cm for females and 5.0 cm for males for both doses combined compared to untreated control subjects. A height gain of 1 SDS was observed in 10% of untreated subjects, 50% of subjects receiving 0.23 mg/kg/week and 69% of subjects receiving 0.47 mg/kg/week.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a small number of patients treated with somatropins. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose. Fundoscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by fundoscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome and Prader-Willi syndrome may be at increased risk for the development of IH.

Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation, and may not reflect the adverse reaction rates observed in practice.

The safety and efficacy of GENOTROPIN in the treatment of pediatric patients with Prader-Willi syndrome (PWS) were evaluated in two randomized, open-label, controlled clinical trials. Patients received either GENOTROPIN or no treatment for the first year of the studies, while all patients received GENOTROPIN during the second year. GENOTROPIN was administered as a daily SC injection, and the dose was calculated for each patient every 3 months. In Study 1, the treatment group received GENOTROPIN at a dose of 0.24 mg/kg/week during the entire study. During the second year, the control group received GENOTROPIN at a dose of 0.48 mg/kg/week. In Study 2, the treatment group received GENOTROPIN at a dose of 0.36 mg/kg/week during the entire study. During the second year, the control group received GENOTROPIN at a dose of 0.36 mg/kg/week.

Patients who received GENOTROPIN showed significant increases in linear growth during the first year of study, compared with patients who received no treatment (see Table 3). Linear growth continued to increase in the second year, when both groups received treatment with GENOTROPIN.

Changes in body composition were also observed in the patients receiving GENOTROPIN (see Table 4). These changes included a decrease in the amount of fat mass, and increases in the amount of lean body mass and the ratio of lean-to-fat tissue, while changes in body weight were similar to those seen in patients who received no treatment. Treatment with GENOTROPIN did not accelerate bone age, compared with patients who received no treatment.

Patients being treated with GENOTROPIN (and/or their parents) should be informed about the potential benefits and risks associated with GENOTROPIN treatment. This information is intended to better educate patients (and caregivers); it is not a disclosure of all possible adverse or intended effects.

Patients and caregivers who will administer GENOTROPIN should receive appropriate training and instruction on the proper use of GENOTROPIN from the physician or other suitably qualified health care professional. A puncture-resistant container for the disposal of used syringes and needles should be strongly recommended. Patients and/or parents should be thoroughly instructed in the importance of proper disposal, and cautioned against any reuse of needles and syringes. This information is intended to aid in the safe and effective administration of the medication.

GENOTROPIN is supplied in a two-chamber cartridge, with the lyophilized powder in the front chamber and a diluent in the rear chamber. A reconstitution device is used to mix the diluent and powder.

The GENOTROPIN 5 mg and 12 mg cartridges are color-coded to help ensure proper use with the GENOTROPIN PEN delivery device. The 5 mg cartridge has a green tip to match the green pen window on the Pen 5, while the 12 mg cartridge has a purple tip to match the purple pen window on the Pen 12.

Follow the directions for reconstitution provided with each device. Do not shake; shaking may cause denaturation of the active ingredient.

Please see accompanying directions for use of the reconstitution and/or delivery device.

The GENOTROPIN 5 and 12 mg cartridges are color-coded to help ensure proper use with the GENOTROPIN PEN delivery device. The 5 mg cartridge has a green tip to match the green pen window on the Pen 5, while the 12 mg cartridge has a purple tip to match the purple pen window on the Pen 12.

Parenteral drug products should always be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. GENOTROPIN MUST NOT BE INJECTED if the solution is cloudy or contains particulate matter. Use it only if it is clear and colorless.

GENOTROPIN may be given in the thigh, buttocks, or abdomen; the site of SC injections should be rotated daily to help prevent lipoatrophy.

There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin. If during treatment with somatropin, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively [see Contraindications (4)].

Limited published data indicate that somatropin treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance in man. These data suggest that somatropin administration may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine). Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CYP450 liver enzymes. However, formal drug interaction studies have not been conducted.

NDC 0013-2653-02

Pfizer

Genotropin^®

(somatropin) for injection

1 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2658-02

Pfizer

Genotropin^®

(somatropin) for injection

2 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

Pfizer

Genotropin^®

5 mg

(somatropin) for injection

NDC 0013-2626-81

For subcutaneous injection

Rx only

1 Two-Chamber Cartridge

PAA185820

OPEN HERE

GENOTROPIN lyophilized powder was compared with placebo in six randomized clinical trials involving a total of 172 adult GHD patients. These trials included a 6-month double-blind treatment period, during which 85 patients received GENOTROPIN and 87 patients received placebo, followed by an open-label treatment period in which participating patients received GENOTROPIN for up to a total of 24 months. GENOTROPIN was administered as a daily SC injection at a dose of 0.04 mg/kg/week for the first month of treatment and 0.08 mg/kg/week for subsequent months.

Beneficial changes in body composition were observed at the end of the 6-month treatment period for the patients receiving GENOTROPIN as compared with the placebo patients. Lean body mass, total body water, and lean/fat ratio increased while total body fat mass and waist circumference decreased. These effects on body composition were maintained when treatment was continued beyond 6 months. Bone mineral density declined after 6 months of treatment but returned to baseline values after 12 months of treatment.

Pfizer

Genotropin^®

12 mg

(somatropin) for injection

NDC 0013-2646-81

For subcutaneous injection

Rx only

1 Two-Chamber Cartridge

PAA185893

OPEN HERE

NDC 0013-2649-02

Pfizer

Genotropin^®

(somatropin) for injection

0.2 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2650-02

Pfizer

Genotropin^®

(somatropin) for injection

0.4 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2651-02

Pfizer

Genotropin^®

(somatropin) for injection

0.6 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2652-02

Pfizer

Genotropin^®

(somatropin) for injection

0.8 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2654-02

Pfizer

Genotropin^®

(somatropin) for injection

1.2 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2655-02

Pfizer

Genotropin^®

(somatropin) for injection

1.4 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2656-02

Pfizer

Genotropin^®

(somatropin) for injection

1.6 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

NDC 0013-2657-02

Pfizer

Genotropin^®

(somatropin) for injection

1.8 mg Genotropin MiniQuick^®

For single subcutaneous injection only

Growth Hormone Delivery Device

Rx only

7 Pack

The microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. GH and somatropin inhibit 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. As a consequence, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required in patients treated with somatropin. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment; this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1 [see Warnings and Precautions (5.8)].

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1 mg

NDC 0013-2653-01

PAA142733

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

2 mg

NDC 0013-2658-01

PAA142738

LOT

EXP

Genotropin^®

(somatropin) for injection

Two-chamber cartridge

For s.c. injection. 5 mg/mL

Refrigerate. Protect from light.

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

5 mg

NDC 0013-2626-81

LOT/EXP

PAA185891

Genotropin^®

(somatropin) for injection

Two-chamber cartridge

For s.c. injection. 12 mg/mL

Refrigerate. Protect from light.

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

12 mg

NDC 0013-2646-81

LOT/EXP

PAA185895

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.2 mg

NDC 0013-2649-01

PAA142719

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.4 mg

NDC 0013-2650-01

PAA142720

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.6 mg

NDC 0013-2651-01

PAA142731

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

0.8 mg

NDC 0013-2652-01

PAA142732

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.2 mg

NDC 0013-2654-01

PAA142734

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.4 mg

NDC 0013-2655-01

PAA142735

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.6 mg

NDC 0013-2656-01

PAA142736

LOT

EXP

Genotropin^®

(somatropin) for injection

Genotropin MiniQuick^®

Growth Hormone Delivery Device

Pharmacia & Upjohn Co

Div of Pfizer Inc, NY, NY 10017

1.8 mg

NDC 0013-2657-01

PAA142737

LOT

EXP

Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. New-onset Type 2 diabetes mellitus has been reported. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs (i.e., insulin or oral/injectable agents) may require adjustment when somatropin therapy is instituted in these patients.

In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral/injectable agent may require adjustment when somatropin therapy is initiated [see Warnings and Precautions (5.4)].

Carcinogenicity studies have not been conducted with GENOTROPIN. No potential mutagenicity of GENOTROPIN was revealed in a battery of tests including induction of gene mutations in bacteria (the Ames test), gene mutations in mammalian cells grown in vitro (mouse L5178Y cells), and chromosomal damage in intact animals (bone marrow cells in rats).

In a fertility study in male and female rats receiving SC doses during gametogenesis (2 weeks prior to mating for females and 9 weeks prior to mating for males) and continuing up to 7 days of pregnancy, 3.3 mg/kg/day (approximately 24 times human dose by body surface area) produced anestrus or extended estrus cycles in females and fewer and less motile sperm in males. Lower copulation and pregnancy rates were also observed at 3.3 mg/kg/day. At 1 mg/kg/day (approximately 7 times human dose by body surface area), rats showed slightly extended estrus cycles, whereas at 0.3 mg/kg/day no effects were noted (approximately 2 times human dose by body surface).

Slipped capital femoral epiphyses may occur more frequently in patients with endocrine disorders (including GHD and Turner syndrome) or in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin, including GENOTROPIN. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during GENOTROPIN therapy should be evaluated for slipped capital femoral epiphysis and osteonecrosis and managed accordingly.

Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated Turner syndrome patients. Scoliosis is also commonly seen in untreated patients with Prader-Willi syndrome. Physicians should be alert to these abnormalities, which may manifest during somatropin therapy.

Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.

Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth‑promoting effects of somatropin in children. Therefore, glucocorticoid replacement dosing should be carefully adjusted in children receiving concomitant somatropin and glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth.