GENOTROPIN

1 INDICATIONS AND USAGE 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 ) 1.1 Pediatric Patients 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. 1.2 Adult Patients GENOTROPIN is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria: 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 Childhood Onset (CO) : Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes. Patients who were treated with somatropin for growth hormone deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for growth hormone deficient adults. According to current standards, confirmation of the diagnosis of adult growth hormone deficiency in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.

2 DOSAGE AND ADMINISTRATION 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. GENOTROPIN should be administered subcutaneously ( 2 ) • Pediatric GHD: 0.16 to 0.24 mg/kg/week ( 2.1 ) • Prader-Willi Syndrome: 0.24 mg/kg/week ( 2.1 ) • Small for Gestational Age: Up to 0.48 mg/kg/week ( 2.1 ) • Turner Syndrome: 0.33 mg/kg/week ( 2.1 ) • Idiopathic Short Stature: up to 0.47 mg/kg/week ( 2.1 ) • Adult GHD: Either a non-weight based or a weight based dosing regimen may be followed, with doses adjusted based on treatment response and IGF-I concentrations ( 2.2 ) • Non-weight based dosing: A starting dose of approximately 0.2 mg/day (range, 0.15–0.30 mg/day) may be used without consideration of body weight, and increased gradually every 1–2 months by increments of approximately 0.1–0.2 mg/day. ( 2.2 ) • Weight based dosing: The recommended initial dose is not more than 0.04 mg/kg/week; the dose may be increased as tolerated to not more than 0.08 mg/kg/week at 4–8 week intervals. ( 2.2 ) • GENOTROPIN cartridges are color-coded to correspond to a specific GENOTROPIN PEN delivery device ( 2.3 ) • Injection sites should always be rotated to avoid lipoatrophy ( 2.3 ) 2.1 Dosing of Pediatric Patients General Pediatric Dosing Information The GENOTROPIN dosage and administration schedule should be individualized based on the growth response of each patient. Response to somatropin therapy in pediatric patients tends to decrease with time. However, in pediatric patients, the failure to increase growth rate, particularly during the first year of therapy, indicates the need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age and antibodies to recombinant human GH (rhGH). Treatment with GENOTROPIN for short stature should be discontinued when the epiphyses are fused. Pediatric Growth Hormone Deficiency (GHD) Generally, a dose of 0.16 to 0.24 mg/kg body weight/week is recommended. Prader-Willi Syndrome Generally, a dose of 0.24 mg/kg body weight/week is recommended. Turner Syndrom e Generally, a dose of 0.33 mg/kg body weight/week is recommended. Idiopathic Short Stature Generally, a dose up to 0.47 mg/kg body weight/week is recommended. Small for Gestational Age Recent literature has recommended initial treatment with larger doses of somatropin (e.g., 0.48 mg/kg/week), especially in very short children (i.e., height SDS <–3), and/or older/ pubertal children, and that a reduction in dosage (e.g., gradually towards 0.24 mg/kg/week) should be considered if substantial catch-up growth is observed during the first few years of therapy. On the other hand, in younger SGA children (e.g., approximately <4 years) (who respond the best in general) with less severe short stature (i.e., baseline height SDS values between -2 and -3), consideration should be given to initiating treatment at a lower dose (e.g., 0.24 mg/kg/week), and titrating the dose as needed over time. In all children, clinicians should carefully monitor the growth response, and adjust the somatropin dose as necessary. Generally, a dose of up to 0.48 mg/kg body weight/week is recommended. 2.2 Dosing of Adult Patients Adult Growth Hormone Deficiency (GHD) Either of two approaches to GENOTROPIN dosing may be followed: a non-weight based regimen or a weight based regimen. Non-weight based — based on published consensus guidelines, a starting dose of approximately 0.2 mg/day (range, 0.15–0.30 mg/day) may be used without consideration of body …

3 DOSAGE FORMS AND STRENGTHS 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) For injection: 5 mg or 12 mg lyophilized powder in a single‐patient‐use two‐chamber cartridge ( 3 ) 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 lyophilized powder in a single-dose Growth Hormone Delivery Device containing a two-chamber cartridge (GENOTROPIN MINIQUICK) ( 3 )

4 CONTRAINDICATIONS • 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 ) GENOTROPIN is contraindicated in patients with: • Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated 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 [see Warnings and Precautions (5.1) ]. • Prader-Willi Syndrome in Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see Warnings and Precautions (5.2) ]. • Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. • Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropins [see Warnings and Precautions (5.6) ] . • Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. • Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses.

6 ADVERSE REACTIONS 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) ] Other common somatropin-related adverse reactions include injection site reactions/rashes and lipoatrophy ( 6.1 ) and headaches ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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. Clinical Trials in children with GHD In clinical studies with GENOTROPIN in pediatric GHD patients, the following events were reported infrequently: injection site reactions, including pain or burning associated with the injection, fibrosis, nodules, rash, inflammation, pigmentation, or bleeding; lipoatrophy; headache; hematuria; hypothyroidism; and mild hyperglycemia. Clinical Trials in PWS In two clinical studies with GENOTROPIN in pediatric patients with Prader-Willi syndrome, the following drug-related events were reported: edema, aggressiveness, arthralgia, benign intracranial hypertension, hair loss, headache, and myalgia. Clinical Trials in children with SGA In clinical studies of 273 pediatric patients born small for gestational age treated with GENOTROPIN, the following clinically significant events were reported: mild transient hyperglycemia, one patient with benign intracranial hypertension, two patients with central precocious puberty, two patients with jaw prominence, and several patients with aggravation of preexisting scoliosis, injection site reactions, and self-limited progression of pigmented nevi. Anti-hGH antibodies were not detected in any of the patients treated with GENOTROPIN. Clinical Trials in children with Turner Syndrome In two clinical studies with GENOTROPIN in pediatric patients with Turner syndrome, the most frequently reported adverse events were respiratory illnesses (influenza, tonsillitis, otitis, sinusitis), joint pain, and urinary tract infection. The only treatment-related adverse event that occurred in more than 1 patient was joint pain. Clinical Trials in children with Idiopathic Short Stature In two open-label clinical studies with GENOTROPIN in pediatric patients with ISS, the most commonly encountered adverse events include upper respiratory tract infections, influenza, tonsillitis, nasopharyngitis, gastroenteritis, headaches, increased appetite, pyrexia, fracture, altered mood, and arthralgia. In one of the two studies, during GENOTROPIN treatment, the mean IGF-1 standard deviation (SD) scores were maintained in the normal range. IGF-1 SD scores above +2 SD were observed as follows: 1 subject (3%), 10 subjects …

7 DRUG INTERACTIONS 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 ) 7.1 11 β-Hydroxysteroid Dehydrogenase Type 1 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 )] . 7.2 Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment 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. 7.3 Cytochrome P450-Metabolized Drugs 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. 7.4 Oral Estrogen 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) ]. 7.5 Insulin and/or Oral/Injectable Hypoglycemic Agents 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) ].

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 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. 8.2 Lactation 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. 8.4 Pediatric Use 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 eff …

12.1 Mechanism of Action 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.

11 DESCRIPTION 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.

10 OVERDOSAGE 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) ].

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied 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: Strength NDC Number 0.2 mg NDC 0013-2649-02 0.4 mg NDC 0013-2650-02 0.6 mg NDC 0013-2651-02 0.8 mg NDC 0013-2652-02 1 mg NDC 0013-2653-02 1.2 mg NDC 0013-2654-02 1.4 mg NDC 0013-2655-02 1.6 mg NDC 0013-2656-02 1.8 mg NDC 0013-2657-02 2 mg NDC 0013-2658-02 16.2 Storage and Handling 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 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.