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Humatrope (somatropin, rDNA origin, for injection) is a polypeptide hormone of recombinant DNA origin. Humatrope is synthesized in a strain of Escherichia coli that has been modified by the addition of the gene for human GH. The peptide is comprised of 191 amino acid residues and has a molecular weight of about 22,125 daltons. The amino acid sequence of the peptide is identical to that of human GH of pituitary origin.
Humatrope is a sterile, white, lyophilized powder intended for subcutaneous or intramuscular administration after reconstitution to its liquid form. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive.
Each vial of Humatrope contains 5 mg somatropin (15 IU or 225 nanomoles); 25 mg mannitol; 5 mg glycine; and 1.13 mg dibasic sodium phosphate. Each vial is supplied in a combination package with an accompanying 5-mL vial of diluting solution (diluent). The diluent contains Water for Injection with 0.3% metacresol as a preservative and 1.7% glycerin.
Cartridges of Humatrope contain either 6 mg (18 IU), 12 mg (36 IU), or 24 mg (72 IU) of somatropin. Each Humatrope cartridge contains the following:
| Cartridge | |||
| 6 mg (gold) | 12 mg (teal) | 24 mg (purple) | |
| Component | |||
| Somatropin | 6 mg | 12 mg | 24 mg |
| Mannitol | 18 mg | 36 mg | 72 mg |
| Glycine | 6 mg | 12 mg | 24 mg |
| Dibasic sodium phosphate | 1.36 mg | 2.72 mg | 5.43 mg |
Each cartridge is supplied in a combination package with an accompanying syringe containing approximately 3 mL of diluting solution (diluent). The diluent contains Water for Injection; 0.3% metacresol as a preservative; and 1.7%, 0.29%, and 0.29% glycerin in the 6, 12, and 24 mg cartridges, respectively.
The following important adverse reactions are also described elsewhere in the labeling:
Because clinical studies are conducted under varying conditions, adverse reaction rates observed during the clinical studies performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical studies performed with a different somatropin formulation, and may not reflect the adverse reaction rates observed in practice.
Growth Failure Due to Inadequate Secretion of Endogenous Growth Hormone
In an uncontrolled open-label study, 314 treatment-naive children aged >2 years who had GH deficiency were treated with HUMATROPE (0.06 mg/kg 3 times per week) for up to 8 years. Adverse reactions of special interest are reported in Table 2.
Because clinical studies are conducted under varying conditions, adverse reaction rates observed during the clinical studies performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical studies performed with a different somatropin formulation, and may not reflect the adverse reaction rates observed in practice.
Growth Failure Due to Inadequate Secretion of Endogenous Growth Hormone
In an uncontrolled open-label study, 314 treatment-naive children aged >2 years who had GH deficiency were treated with HUMATROPE (0.06 mg/kg 3 times per week) for up to 8 years. Adverse reactions of special interest are reported in Table 2.
Table 2: Adverse Reactions of Special Interest Occurring in Humatrope-Treated Patients with Growth Failure Due to Inadequate Secretion of Endogenous Growth Hormone in an Open-label Study for Up to 8 Years
| Adverse Reaction | HUMATROPEa (n=314) |
| Hypothyroidism | 25% |
| Allergic reaction | 11% |
| Arthralgia | 6% |
| Bone disorder | 4% |
| Edema | 4% |
| Injection site pain/reaction | 4% |
| Neoplasm/tumor | 2% |
| Cardiovascular disorders | 1% |
| Thyroid disorders | 1% |
| Intracranial hypertension | 0%b |
|
a Dose=0.06 mg/kg 3 times per week for up to 8 years. b n=1 |
|
Short Stature Associated with Turner Syndrome
In a randomized, concurrent-controlled (untreated), open-label study until attainment of adult height, the adverse reactions of special interest occurring in 74 patients treated with Humatrope at dose 0.3 mg/kg/week (mean duration 4.1 years) and in 62 untreated patients (mean duration 3.7 years) are reported in Table 3. A similar increase in otitis media was observed in an 18-month placebo-controlled study.
Table 3: Adverse Reactions of Special Interest Occurring in Patients with Turner Syndrome in an Open-label Study Until Attainment of Adult Height
| Untreated (n=62) |
HUMATROPE (n=74) |
|
| Surgical procedure | 27% | 45% |
| Otitis media | 26% | 43% |
| Ear disorders | 5% | 18% |
Idiopathic Short Stature
Adverse reactions occurring in a randomized, placebo-controlled study of HUMATROPE treatment (0.22 mg/kg/week) until attainment of adult height (mean duration of HUMATROPE treatment 3.7 years, mean duration of placebo treatment 3.3 years) are reported in Table 4. Mean fasting serum insulin concentration increased by 10% in the HUMATROPE treatment group at the end of treatment relative to baseline, but remained within the normal reference range.
Table 4: Adverse Reactions Occurring in Patients with Idiopathic Short Stature Treated with HUMATROPE in a Randomized Placebo-controlled Study
| Placebo (n=31) |
HUMATROPE (n=37) |
|
| Scoliosis | 13% | 19% |
| Otitis media | 7% | 16% |
| Hyperlipidemia | 3% | 8% |
| Gynecomastia | 3% | 5% |
| Hip pain | 0 | 3% |
| Arthralgia | 3% | 11% |
| Arthrosis | 7% | 11% |
| Myalgia | 13% | 24% |
| Hypertension | 0 | 3% |
In a dose-response study (239 patients treated for 2 years), among HUMATROPE dose groups [0.24 mg/kg/week (n=78),
0.37 mg/kg/week (n=83), 0.24 mg/kg/week for the first year and 0.37 mg/kg/week thereafter (n=78)], mean fasting blood glucose, mean glycosylated hemoglobin, and the incidence of elevated fasting blood glucose concentrations were similar. One patient developed glucose intolerance and high serum HbA1c.
Short Stature or Growth Failure in SHOX Deficiency
Adverse reactions of special interest from a 2-year randomized, open-label study with HUMATROPE (0.35 mg/kg/wk) compared to no treatment are presented in Table 5. During the 2-year study period, the proportion of patients who had at least one IGF-I concentration greater than 2.0 SD above the age- and gender-appropriate mean was 10 of 27 (37%) for the HUMATROPE-treated group vs. 0 of 24 patients (0%) for the untreated group. The proportion of patients who had at least one IGFBP-3 concentration greater than 2.0 SD above the age and gender appropriate mean was 16 of 27 (59%) for the HUMATROPE treated group vs. 7 of 24 (29%) for the untreated group.
Table 5: Adverse Reactions of Special Interest Occurring in Patients with SHOX Deficiency By Treatment Group in an Open-label Study
| Untreated (n=25) |
HUMATROPE (n=27) |
|
| Arthralgia | 8% | 11% |
| Gynecomastiaa | 0% | 8% |
| Excessive number of cutaneous nevi | 0% | 7% |
| Scoliosis | 0% | 47% |
|
a Percentage calculated for males only: Untreated (0/1), HUMATROPE (1/12) |
||
Small for Gestational Age (SGA) with No Catch-up Growth by Age 2-4 Years
In a 2-year, multicenter, randomized study, 193 pediatric patients were treated with 2 different HUMATROPE treatment regimens: a fixed dose of 0.067 mg/kg/day (FHD group) or an individually adjusted dose regimen (IAD group; starting dose 0.035 mg/kg/day which could be increased as early as Month 3 to 0.067 mg/kg/day based on a validated growth prediction model). Reported adverse reactions included: common childhood infectious diseases, otitis media, headaches, and slipped capital femoral epiphysis (n=1. Six patients (4 in the FHD group and 2 in the IAD group whose dose was increased from 0.035 mg/kg/day to 0.067 mg/kg/day [one at Month 3 and one at Year 1]) had impaired fasting glucose at Year 2. Two of 6 had impaired fasting glucose during the study, and one discontinued HUMATROPE at month 15 as a consequence. At study completion, 20-25% of patients had serum IGF-I SDS values > +2.
The following adverse reactions were reported from an observational study of 340 pediatric patients who received HUMATROPE with an average dosage of 0.041 mg/kg/day (maximum dose: 0.084 mg/kg/day) for an average of 3.0 years: type 2 diabetes mellitus (n=1), carpal tunnel syndrome (n=1) and an exacerbation of preexisting scoliosis (n=1).
Adult-Onset GH Deficiency
In the first 6 months of controlled blinded studies during which patients received either HUMATROPE or placebo, patients who received HUMATROPE experienced an increase in edema (17% vs. 4%) and peripheral edema (12% vs. 0%). Edema, muscle pain, joint pain, and joint disorder were reported early in therapy and tended to be transient or responsive to dosage titration.
Two of 113 patients developed carpal tunnel syndrome after beginning maintenance therapy without a low dose (0.00625 mg/kg/day) lead-in phase. Symptoms abated in these patients after dosage reduction.
Adverse reactions with ≥5% overall occurrence rate during 12 or 18 months of replacement therapy with
HUMATROPE are shown in Table 6 (adult-onset patients) and in Table 7 (childhood-onset patients).
Table 6: Adverse Reactions with ≥5% Overall Occurrence in Adult-Onset Growth Hormone-Deficient Patients Treated with HUMATROPE for 18 Months as Compared with 6-Month Placebo and 12-Month HUMATROPE Exposure
| Adverse Reaction | 18 Months Exposure [Placebo (6 Months)/Humatrope (12 Months)] (n=44) |
18 Months Humatrope Exposure (n=52) |
| Edema | 11% | 21% |
| Arthralgia | 14% | 17% |
| Paresthesia | 14% | 17% |
| Myalgia | 9% | 14% |
| Pain | 14% | 14% |
| Peripheral edema | 18% | 12% |
| Headache | 7% | 8% |
| Hypertension | 5% | 8% |
| Joint disorder | 2% | 6% |
| Rhinitis | 11% | 13% |
| Back pain | 9% | 10% |
| Acne | 0% | 6% |
| Surgical procedure | 2% | 6% |
| Flu syndrome | 7% | 4% |
Childhood-Onset GH Deficiency
Two double-blind, placebo-controlled studies were conducted in 67 adult patients who had received previous somatropin treatment during childhood. Patients were randomized to receive either placebo injections or HUMATROPE (0.00625 mg/kg/day for the first 4 weeks, then 0.0125 mg/kg/day thereafter) for the first 6 months, followed by open-label use of HUMATROPE for the next 12 months for all patients. During the placebo-controlled phase (first 6 months) of the study, elevations of serum glutamic oxaloacetic transferase were reported more for HUMATROPE-treated (13% vs. 0%) than placebo-treated patients.
Table 7: Adverse Reactions with ≥5% Overall Occurrence in Childhood-Onset Growth Hormone-Deficient Patients Treated with HUMATROPE for 18 Months as Compared with 6-Month Placebo and 12-Month HUMATROPE Exposure
| Adverse Reaction | 18 Months Exposure [Placebo (6 Months)/Humatrope (12 Months)] (n=30) |
18 Months Humatrope Exposure (n=32) |
| AST a increased | 7% | 13% |
| Headache | 7% | 9% |
| Asthenia | 3% | 6% |
| Edema | 10% | 6% |
| Myalgia | 7% | 6% |
| Pain | 10% | 6% |
| ALT a increased | 7% | 6% |
| Flu syndrome | 10% | 16% |
| Cough increased | 0% | 6% |
| Hypesthesia | 0% | 6% |
| Rhinitis | 7% | 6% |
| Respiratory disorder | 7% | 3% |
| Gastritis | 7% | 0% |
| Pharyngitis | 7% | 3% |
|
a Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase |
||
The following adverse reactions have been identified during post-approval use of somatropin or HUMATROPE. 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.
Severe Hypersensitivity Reactions — Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins
Neurologic — Headaches (common in pediatric patients and occasional in adults)
Skin — Increase in size or number of cutaneous nevi
Endocrine — Gynecomastia
Gastrointestinal — Pancreatitis
Metabolic — New-onset type 2 diabetes mellitus
Musculoskeletal and connective tissue disorders – Osteonecrosis in pediatric patients
Neoplasia — Leukemia has been reported in a small number of GH deficient pediatric patients treated with somatropin
Table 8 includes a list of drugs with clinically important drug interactions when administered concomitantly with HUMATROPE and instructions for preventing or managing them.
Table 8: Clinically Important Drug Interactions with HUMATROPE
| Replacement Glucocorticoid Treatment | |
| Clinical Impact: | 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. HUMATROPE inhibits 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Initiation of HUMATROPE may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. |
| Intervention: | Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of HUMATROPE [see Warnings and Precautions (5.8)]. |
| Examples: | Cortisone acetate and prednisone may be effected more than others since conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1. |
| Non-Replacement Glucocorticoid Treatment in Pediatric Patients | |
| Clinical Impact: | Non-replacement glucocorticoid treatment, including supraphysiologic glucocorticoid treatment, may attenuate the growth promoting effects of HUMATROPE in pediatric patients. |
| Intervention: | Carefully adjust glucocorticoid dosing in pediatric patients receiving glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth. |
| Cytochrome P450-Metabolized Drugs | |
| Clinical Impact: | Limited published data indicate that somatropin treatment increases cytochrome P450 (CP450)-mediated antipyrine clearance. HUMATROPE may alter the clearance of compounds known to be metabolized by CP450 liver enzymes. |
| Intervention: | Careful monitoring is advisable when HUMATROPE is administered in combination with drugs metabolized by CP450 liver enzymes. |
| Oral Estrogen | |
| Clinical Impact: | Oral estrogens may reduce the serum IGF-1 response to HUMATROPE. |
| Intervention: | Patients receiving oral estrogen may require greater HUMATROPE dosages [see Dosage and Administration (2.3)]. |
| Insulin and/or Other Hypoglycemic Agents | |
| Clinical Impact: | Treatment with HUMATROPE may decrease insulin sensitivity, particularly at higher doses. |
| Intervention: | Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other hypoglycemic agents [see Warnings and Precautions (5.4)]. |
HUMATROPE contains somatropin, which is not a controlled substance.
Inappropriate use of somatropin may result in significant negative health consequences.
Somatropin is not associated with drug related withdrawal adverse reactions.
Included as part of the PRECAUTIONS section.
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 doses of somatropin [see Contraindications (4)]. Two placebo-controlled clinical studies in non-GH 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 5.3-8.0 mg/day) compared to those receiving placebo. The safety of continuing HUMATROPE treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. HUMATROPE is not indicated for the treatment of non-GH deficient adults.
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. 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)]. HUMATROPE is not indicated for the treatment of pediatric patients who have growth failure due to Prader-Willi syndrome.
There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy [see Contraindications (4)]. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with HUMATROPE. Discontinue HUMATROPE if there is evidence of recurrent activity.
An increased risk of a second neoplasm in pediatric cancer survivors who were treated with radiation to the brain/head and who developed subsequent GH deficiency and were treated with somatropin 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. Monitor all patients receiving HUMATROPE who have a history of GH deficiency secondary to an intracranial neoplasm for progression or recurrence of the tumor.
Because pediatric patients with certain rare genetic causes of short stature have an increased risk of developing malignancies, thoroughly consider the risks and benefits of starting HUMATROPE in these patients. If HUMATROPE is initiated, carefully monitor patients for development of neoplasms.
Monitor all patients receiving HUMATROPE carefully for increased growth, or potential malignant changes, of preexisting nevi. Advise patients/caregivers to report marked changes in behavior, onset of headaches, vision disturbances and/or changes in skin pigmentation or changes in the appearance of pre-existing nevi.
Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New onset type 2 diabetes mellitus has been reported in patients taking somatropin. Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked. Monitor glucose levels periodically in all patients receiving HUMATROPE, 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. The doses of antidiabetic agents may require adjustment when HUMATROPE is initiated.
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 HUMATROPE to exclude preexisting papilledema, and periodically thereafter. If papilledema is observed by fundoscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with HUMATROPE can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome may be at increased risk for the development of IH.
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. Do not use HUMATROPE in patients with known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Do not use HUMATROPE cartridges in patients with known hypersensitivity to metacresol or glycerin [see Dosage and Administration (2.4), Contraindications [(4)].
Fluid retention during somatropin replacement therapy may frequently 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.
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 HUMATROPE treatment. Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism [see Drug Interactions (7)].
Undiagnosed/untreated hypothyroidism may prevent an optimal response to HUMATROPE, in particular, the growth response in pediatric patients. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with GH deficiency, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests performed, and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.
Slipped capital femoral epiphysis may occur more frequently 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. Evaluate pediatric patients receiving HUMATROPE with the onset of a limp or complaints of hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly.
Somatropin increases the growth rate, and progression of existing scoliosis can occur in patients who experience rapid growth. Somatropin has not been shown to increase the occurrence of scoliosis. Monitor patients with a history of scoliosis for progression of scoliosis.
Cases of pancreatitis have been reported in pediatric patients and adults receiving somatropins. The risk may be greater risk in pediatric patients compared with adults. Published literature indicates that girls who have Turner syndrome may be at greater risk than other pediatric patients receiving somatropins. Pancreatitis should be considered in patients who develop abdominal pain.
When somatropins are administered subcutaneously at the same site over a long period of time, tissue atrophy may result. Rotate injection sites when administering HUMATROPE to reduce this risk [see Dosage and Administration (2.1)].
Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone and IGF-I may increase after HUMATROPE therapy.
Carcinogenicity, mutagenicity and impairment of fertility studies have not been conducted with HUMATROPE.
Acute overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with somatropin is likely to cause fluid retention. Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess endogenous growth hormone.
HUMATROPE is contraindicated in patients with:
Somatropin binds to dimeric GH receptors located within the cell membranes of target tissue cells. This interaction results in intracellular signal transduction and subsequent induction of transcription and translation of GH-dependent proteins including IGF-1, IGF BP-3 and acid-labile subunit. Somatropin has direct tissue and metabolic effects or mediated indirectly by IGF-1, including stimulation of chondrocyte differentiation, and proliferation, stimulation of hepatic glucose output, protein synthesis and lipolysis.
Somatropin stimulates skeletal growth in pediatric patients with GHD as a result of effects on the growth plates (epiphyses) of long bones. The stimulation of skeletal growth increases linear growth rate (height velocity) in most somatropin-treated pediatric patients. Linear growth is facilitated in part by increased cellular protein synthesis.
Subcutaneous administration of a single dose of Humatrope (0.033 mg/kg body weight) in healthy volunteers (10 males, 10 females) resulted in an increased median IGF-1 level from 202 ng/mL (men) and 107 ng/mL (women) predose to maximal level of 362 ng/mL (men) and 234 ng/mL (women) after a median of 21 hours (men) and 14 hours (women).
HUMATROPE has been studied following intramuscular, subcutaneous, and intravenous administration in healthy adult subjects. A single subcutaneous dose administration of HUMATROPE 0.1 mg/kg (0.27 IU/kg) in healthy subjects (n=8) resulted in a mean (SD) Cmax of 63.3 (18.2) ng/mL at median Tmax of 4.0 (range 3 to 8) hours. The absolute bioavailability of somatropin is 75% after subcutaneous administration.
The mean (SD) volume of distribution of somatropin after single dose subcutaneous injection of 0.1 mg/kg (0.27 IU/kg) in healthy subjects is about 0.96 (0.3) L/kg.
Metabolism — Extensive metabolism studies have not been conducted. The metabolic fate of somatropin involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products of somatropin is returned to the systemic circulation.
Excretion — In healthy subjects, mean somatropin clearance is 0.18 (0.03) L/hr/kg following subcutaneous administration. The mean half-life of subcutaneous somatropin is 3.8 (1.4) hours. The long half-life observed after subcutaneous administration is due to slow absorption from the injection site. Urinary excretion of intact HUMATROPE has not been measured. Small amounts of somatropin have been detected in the urine of pediatric patients following replacement therapy.
Geriatric patients — The pharmacokinetics of HUMATROPE have not been studied in patients greater than 65 years of age.
Pediatric patients — The pharmacokinetics of HUMATROPE in pediatric patients are similar to those of adults.
Male and Female Patients — No gender-specific pharmacokinetic studies have been performed with HUMATROPE. The available literature indicates that the pharmacokinetics of somatropin are similar in men and women. Patients with Renal or hepatic impairment — No studies have been performed with HUMATROPE.
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 HUMATROPE or other somatropins.
In a clinical study with HUMATROPE during the first 6 months of HUMATROPE therapy in 314 naive patients, 1.6% developed specific antibodies to HUMATROPE (binding capacity ≥0.02 mg/L). None had antibody concentrations which exceeded 2 mg/L. Throughout 8 years of this same study, two patients (0.6%) had binding capacity >2 mg/L. Neither patient demonstrated a decrease in growth velocity at or near the time of increased antibody production. It has been reported that growth attenuation from pituitary-derived GH may occur when antibody concentrations are >1.5 mg/L.
Advise the patient to read the FDA-approved patient labeling (Instructions for Use).
