Genotropin (somatropin) injection, for subcutaneous use
Summary about Genotropin
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.
Genotropin is a man-made copy of natural growth hormone. It has been used to treat more than 83,000 children around the world for more than 30 years.
Genotropin is approved by the Food and Drug Administration (FDA) for the treatment of several growth disorders in children and adults, including:
- Growth hormone deficiency (GHD) in children
- Small for gestational age (SGA) in children
- Idiopathic short stature (ISS)† in children
- Prader-Willi syndrome (PWS)‡ in children
- Turner syndrome (TS) in girls and
- Growth hormone deficiency (GHD) in adults
Genotropin is administered by injection under the skin with one of two device options including:
- GENOTROPIN Pen, a multi-dose pen with digital display, and
- GENOTROPIN MiniQuick, a portable option for families on the go.
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.
Genotropin 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
- Diabetic retinopathy.
Genotropin (somatropin) |
|
Active Ingredient |
Somatropin |
Administration Route |
Subcutaneous |
Alcohol Warning |
No data about the interaction |
Available Strength |
GENOTROPIN lyophilized powder:
GENOTROPIN MINIQUICK Growth Hormone Delivery Device containing a two-chamber cartridge of GENOTROPIN (without preservative)
|
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 Following a 0.03 mg/kg subcutaneous (SC) injection in the thigh of 1.3 mg/mL GENOTROPIN to adult GHD patients, approximately 80% of the dose was systemically available as compared with that available following intravenous dosing. Results were comparable in both male and female patients. Similar bioavailability has been observed in healthy adult male subjects. In healthy adult males, following an SC injection in the thigh of 0.03 mg/kg, the extent of absorption (AUC) of a concentration of 5.3 mg/mL GENOTROPIN was 35% greater than that for 1.3 mg/mL GENOTROPIN. The mean (± standard deviation) peak (Cmax) serum levels were 23.0 (± 9.4) ng/mL and 17.4 (± 9.2) ng/mL, respectively. In a similar study involving pediatric GHD patients, 5.3 mg/mL GENOTROPIN yielded a mean AUC that was 17% greater than that for 1.3 mg/mL GENOTROPIN. The mean Cmax levels were 21.0 ng/mL and 16.3 ng/mL, respectively. Adult GHD patients received two single SC doses of 0.03 mg/kg of GENOTROPIN at a concentration of 1.3 mg/mL, with a one- to four-week washout period between injections. Mean Cmax levels were 12.4 ng/mL (first injection) and 12.2 ng/mL (second injection), achieved at approximately six hours after dosing. There are no data on the bioequivalence between the 12 mg/mL formulation and either the 1.3 mg/mL or the 5.3 mg/mL formulations. Distribution The mean volume of distribution of GENOTROPIN following administration to GHD adults was estimated to be 1.3 (± 0.8) L/kg. Metabolism The metabolic fate of GENOTROPIN involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products are returned to the systemic circulation. The mean terminal half-life of intravenous GENOTROPIN in normal adults is 0.4 hours, whereas subcutaneously administered GENOTROPIN has a half-life of 3.0 hours in GHD adults. The observed difference is due to slow absorption from the subcutaneous injection site. Excretion The mean clearance of subcutaneously administered GENOTROPIN in 16 GHD adult patients was 0.3 (± 0.11) L/hrs/kg. Special Populations Pediatric: The pharmacokinetics of GENOTROPIN are similar in GHD pediatric and adult patients. Gender: No gender studies have been performed in pediatric patients; however, in GHD adults, the absolute bioavailability of GENOTROPIN was similar in males and females. Race: No studies have been conducted with GENOTROPIN to assess pharmacokinetic differences among races. Renal or hepatic insufficiency: No studies have been conducted with GENOTROPIN in these patient populations. |
Cost |
Approximate Retail Price
from http://www.goodrx.com/Genotropin lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
lyophilisate for solution for injection:
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 GHD: 0.16 to 0.24 mg/kg/week
Prader-Willi Syndrome: 0.24 mg/kg/week Small for Gestational Age: Up to 0.48 mg/kg/week Turner Syndrome: 0.33 mg/kg/week Idiopathic Short Stature: up to 0.47 mg/kg/week 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 Non-weight based dosing: A starting dose of approximately 0.2mg/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 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. |
Drug Class |
H01AC – Somatropin and somatropin agonists |
Drug Unit |
mg/ml |
Food Warning |
No known interactions |
Included In
|
Genotropin 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 Genotropin available. |
Is Proprietary |
Yes |
Label Details |
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020280s088lbl.pdf |
Legal Status |
Legal.
Is not subject to the Controlled Substances Act. |
Manufacturer |
Pfizer Inc. |
Maximum Intake |
0.0125 mg/kg/day |
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/2016/020280s088lbl.pdf |
Prescription Status |
Prescription drug |
Proprietary Name |
Genotropin |
Related Drugs |
Tesamorelin, Mecasermin rinfabate, Sermorelin, Mecasermin, Somatrem |
RxCUI |
202828 |
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.genotropin.com/
https://www.drugs.com/pro/genotropin.html
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ffebf88b-d257-4542-9808-74d9b7167765
https://www.drugbank.ca/drugs/DB00052