Humatrope (somatropin) injection, for subcutaneous use
Summary about Humatrope
Growth hormone (GH) or somatotropin is a peptide produced by the somatotroph cells in the anterior pituitary gland. It binds to a transmembrane receptor and leads to the production of insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3), and the acid-labile subunit (ALS). This 3-peptide compound is brought to target cells, binds to IGF-I receptor, and stimulates metabolic functions. In infancy, childhood and adolescence GH is essential for normal linear growth.
Humatrope (somatropin) injections for subcutaneous use is a man-made form of human growth hormone. It was first approved in 1987 to treat children who are growing slowly because they do not make enough growth hormone on their own.
Figure 1: Humatrope pens (Source: https://www.humatrope.com)
Humatrope is used to treat children who are short or growing slowly because of they:
- Do not make enough growth hormone on their own
- Have Turner Syndrome
- Have idiopathic short stature, which means they are shorter than 98.8% of other children of the same age and sex, are growing at a rate not likely to allow them to reach normal adult height, and for whom no other cause of short stature can be found
- Have SHOX deficiency
- Were born smaller than normal for the number of weeks of pregnancy and do not catch up in height by 2 to 4 years of age
Humatrope is also used to treat adults who have growth hormone deficiency that began either in:
- Adulthood (as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma); or
- Childhood. Patients treated for growth hormone deficiency in childhood whose bones have stopped growing should be reevaluated to determine if they should continue growth hormone
The goal of GH therapy in pediatric patients is to sustain normal linear growth and achieve a normal adult height. In addition to promoting linear growth, GH has favourable effects on muscle accretion and bone mineral density. GH stimulates osteoblast and osteoclast differentiation and promotes the accretion of bone mass. GH stimulates the proliferation of adipose precursor cells, restricts their differentiation into mature adipocytes, and limits deposition of fat in the abdominal visceral area. Consequently, children with growth hormone deficiency (GHD) demonstrate reduced linear growth, reduced lean body mass, increased body fat with disproportionate deposition of visceral and truncal fat, subnormal bone mineral density and lipid abnormalities. Untreated patients with adult onset GHD demonstrate all the pediatric consequences with the exception of a linear growth effect. Untreated adults with GHD have also decreased muscle strength, impaired cardiac function, and decreased quality of life.
Humatrope is contrainidicated in following cases:
- Acute critical illness
- Children with Prader-Willi Syndrome who are severely obese or have severe respiratory impairment – reports of sudden death
- Active malignancy
- Hypersensitivity to somatropin or its excipients
- Active proliferative or severe non-proliferative diabetic retinopathy
- Children with closed epiphyses
- Known hypersensitivity to somatropin or excipients.
Humatrope (somatropin) |
|
Active Ingredient |
Somatropin |
Administration Route |
Subcutaneous |
Alcohol Warning |
No data about interaction |
Available Strength |
Humatrope is a sterile, white lyophilized powder available in the following vial and cartridge sizes:
Humatrope cartridges should be used only with the appropriate corresponding pen device. |
Breastfeeding Warning |
Caution is recommended. Excretion into human milk is unknown.
Following subcutaneous administration of radiolabelled medication in animal studies, radioactivity was transferred to milk reaching four times the concentration found in maternal plasma. However, absorption of the intact protein in the gastrointestinal tract of the infant is considered extremely unlikely. |
Clinical Pharmacology |
Pharmacodynamics
Tissue Growth: Skeletal Growth: Cell Growth: Organ Growth: Protein Metabolism: Carbohydrate Metabolism: Lipid Metabolism: Mineral Metabolism: Connective Tissue Metabolism: Pharmacokinetics Absorption Humatrope has been studied following intramuscular, subcutaneous, and intravenous administration in adult volunteers. The absolute bioavailability of somatropin is 75% and 63% after subcutaneous and intramuscular administration, respectively. Distribution The volume of distribution of somatropin after intravenous injection is about 0.07 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. In healthy volunteers, mean somatropin clearance is 0.14 L/hr/kg. The mean half-life of intravenous somatropin is 0.36 hours, whereas subcutaneously and intramuscularly administered somatropin have mean half-lives of 3.8 and 4.9 hours, respectively. The longer half-life observed after subcutaneous or intramuscular administration is due to slow absorption from the injection site. Excretion 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. Specific Populations: 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. Gender: 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. Race: No data are available. Renal, hepatic insufficiency: No studies have been performed with Humatrope.
|
Cost |
Approximate Retail Price from http://www.goodrx.com/Humatrope lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
|
Dosage Form |
Injection for subcutaneous use |
Dose Schedule |
Pediatric GH deficiency: 0.18 to 0.30 mg/kg/week
Turner syndrome: Up to 0.375 mg/kg/week Idiopathic short stature: Up to 0.37 mg/kg/week SHOX deficiency: 0.35 mg/kg/week Small for gestational age: Up to 0.47 mg/kg/week Adult GH deficiency: 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. 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. Weight-based dosing. The recommended initial daily dose is not more than 0.006 mg/kg (6 μg/kg); the dose may be increased to a maximum of 0.0125 mg/kg (12.5 μg/kg) daily. |
Drug Class |
H01AC – Somatropin and somatropin agonists |
Drug Unit |
mg/vial |
Food Warning |
No known interactions |
Included In
|
Humatrope sometimes is covered by health insurance if considered medically necessary, but some patients have had coverage denied. The Magic Foundation offers help making the case for coverage or appealing a denial, and outlines patients’ experiences getting approval. |
Interacting Drug |
Inhibitors 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 dosesGlucocorticoid Replacement Therapy: Should be carefully adjustedCytochrome P450-Metabolized Drugs: Monitor carefully if used with somatropinOral Estrogen: Larger doses of somatropin may be required in womenInsulin and/or Oral/Injectable Hypoglycemic Agents: May require adjustment |
Is Available Generically |
No. There is currently no therapeutically equivalent version of Humatrope available. |
Is Proprietary |
Yes |
Label Details |
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019640s084lbl.pdf |
Legal Status |
Legal.
Is not subject to the Controlled Substances Act. |
Manufacturer |
Eli Lilly and Company |
Maximum Intake |
0.0125 mg/kg (12.5 μg/kg) daily |
Mechanism of Action |
Somatropin binds to the human growth hormone receptor (GHR). Upon binding, soatropin causes dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both JAK2 and GHR. These events recruit and/or activate a variety of signaling molecules, including MAP kinases, insulin receptor substrates, phosphatidylinositol 3′ phosphate kinase, diacylglycerol, protein kinase C, intracellular calcium, and Stat transcription factors. These signaling molecules contribute to the GH-induced changes in enzymatic activity, transport function, and gene expression that ultimately culminate in changes in growth and metabolism. |
Non Proprietary Name |
Somatropin |
Overdosage |
Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Furthermore, 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 growth hormone |
Pregnancy Category |
AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. |
Pregnancy Warning |
Use is not recommended unless clearly needed.
Animal studies did not show any teratogenicity or adverse effects on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offspring; a slight increase in fetal death and increased body weight of pups, and reduced pregnancy rate, increased litter size, irregular estrus cycles, and decreased sperm motility in the parents were seen. There are no controlled data in human pregnancy. |
Prescribing Info |
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019640s084lbl.pdf |
Prescription Status |
Prescription drug |
Proprietary Name |
Humatrope |
Related Drugs |
Tesamorelin, Mecasermin rinfabate, Sermorelin, Mecasermin, Somatrem |
RxCUI |
197123 |
Warning |
Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk. Prader-Willi Syndrome in Children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment for GHD. Discontinue treatment if these signs occur. 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. 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. Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction. Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention. Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome – especially in adults): May occur frequently. Reduce dose as necessary. Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism. Hypothyroidism: May first become evident or worsen. Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the onset of a limp or hip/knee pain. Progression of Preexisting Scoliosis: May develop. Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain. |
Links:
https://www.humatrope.com/
https://www.drugs.com/pro/humatrope.html
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a774e1ae-3997-49ee-8b0e-99a2b315d409
https://www.drugbank.ca/drugs/DB00052