Somatropin

Introduction Overview

Generic Name

somatropin

Brand Name

Genotropin

Dosage Form

Genotropin Miniquick, Genotropin 12 mg Pen, Genotropin 5 mg Pen Device

Drug Class

Growth hormones

Pharmacokinetics

Absorption:
Somatropin (Genotropin) is administered subcutaneously and exhibits variable but generally efficient absorption from the injection site. After subcutaneous administration, peak plasma concentrations typically occur within 3 to 9 hours depending on the dose and individual patient factors. The rate of absorption may be influenced by injection site, local blood flow, and formulation characteristics. Compared to intravenous administration, subcutaneous absorption results in a bioavailability approximating 80%, leading to sustained plasma profiles suitable for therapeutic effect. Clinical studies have corroborated that Genotropin pen devices and Miniquick maintain consistent absorption profiles, facilitating reliable dosing in pediatric and adult populations.

Distribution:
Following absorption, somatropin distributes primarily throughout the extracellular fluid compartments, with a distribution volume ranging approximately from 0.1 to 0.3 L/kg, suggesting limited extensive tissue binding. Somatropin binds to growth hormone receptors on target cells in skeletal muscle, cartilage, and liver, initiating its physiological effects. It does not significantly bind to plasma proteins except transient receptor interactions. Distribution kinetics are affected by patient-specific factors such as age, body weight, and nutritional status, which are particularly relevant in pediatric growth hormone-deficient populations.

Metabolism:
Metabolism of somatropin involves proteolytic degradation primarily in the liver and kidneys through receptor-mediated endocytosis and lysosomal degradation pathways. Somatropin is metabolized into smaller peptides and amino acids, which are reutilized or excreted. The hepatic mechanism includes binding to growth hormone receptors triggering downstream signaling while concurrently marking the molecule for catabolism. Clearance rates may vary depending on circulating levels of endogenous growth hormone-binding proteins and receptor density, though pharmacokinetic studies show that exogenous Genotropin administration does not significantly alter endogenous somatropin metabolism. Genetic polymorphisms and coexisting diseases may modify metabolic rates and must be considered clinically.

Elimination:
Somatropin exhibits a plasma elimination half-life averaging 2 to 3 hours after subcutaneous administration, with clearance predominantly via renal and hepatic pathways. The catabolized fragments are eliminated in the urine. Renal impairment is not typically a contraindication but may necessitate clinical monitoring of response and potential dose adjustment. The pharmacodynamic effect of somatropin extends beyond plasma clearance due to its receptor-mediated cascade stimulating insulin-like growth factor 1 (IGF-1) production, which has a longer half-life contributing to sustained biological activity. Serial monitoring of IGF-1 levels is often used to assess therapy adequacy and adjust dosing appropriately.

Dosage Forms

Available Dosage Forms:
Genotropin is supplied in multiple dosage forms designed for ease of administration and dose titration, including:
- Genotropin Miniquick: Single-dose growth hormone delivery device containing two-chamber cartridges without preservatives, available in strengths of 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.
- Genotropin 12 mg Pen: Multi-dose cartridges (with preservative m-cresol) designed for use with a pen injector device.
- Genotropin 5 mg Pen Device: Multi-dose cartridges (with preservative) compatible with a pen injector for precise subcutaneous dosing.

Dosages for Adults and Adolescents:
- Pediatric Growth Hormone Deficiency (GHD): Recommended weekly dose is 0.16 to 0.24 mg/kg divided into 6 or 7 subcutaneous injections per week.
- Prader-Willi Syndrome: Dose is 0.24 mg/kg/week.
- Small for Gestational Age (SGA) with no catch-up growth: Up to 0.48 mg/kg/week.
- Turner Syndrome: Dose approximately 0.33 mg/kg/week.
- Idiopathic Short Stature (ISS): Doses up to 0.47 mg/kg/week.
- Adult GHD: Non-weight-based starting dose around 0.2 mg/day (range 0.15–0.30 mg/day), titrated every 1–2 months; alternatively, weight-based dosing not exceeding 0.04 mg/kg/week initially, potentially increasing up to 0.08 mg/kg/week every 4–8 weeks based on response and IGF-1 levels.

Specific Patient Populations:
- Pediatric patients require dosing based on weight and growth response, with careful monitoring to avoid premature epiphyseal closure or adverse metabolic effects.
- Adults with GHD undergo individualized dosing with gradual up-titration informed by IGF-1 concentrations and clinical response.
- Patients with Prader-Willi Syndrome have restricted dosing and require monitoring for respiratory complications.
- Genotropin is contraindicated in patients with closed epiphyses as dosing would not promote skeletal growth.
- The drug includes preservative-free formulations (Miniquick) suitable for patients with sensitivity to preservatives such as m-cresol.

Administration Devices:
- Genotropin Pen Device offers dosing accuracy, ease of use, and portability with a 2-year usable lifespan post initial use.
- Genotropin Miniquick is designed for single-dose administration requiring no refrigeration post-reconstitution for 28 days.
- Pen needles sizes compatible include 29G, 30G, and 31G for patient comfort.

Clinical guidelines emphasize rotation of injection sites and strict adherence to injection protocols to optimize efficacy and minimize injection-site reactions.

Mechanism Of Action

Genotropin (somatropin) functions as a recombinant human growth hormone analog that closely mimics the molecular structure and activity of endogenous human growth hormone secreted by the anterior pituitary. Its primary mechanism involves binding to specific growth hormone receptors (GHR) on the surface of target cells, mainly in the liver, cartilage, bone, and muscle tissues, activating intracellular signaling pathways.

Upon receptor binding, somatropin triggers dimerization of the GHR, activating the associated Janus kinase 2 (JAK2) tyrosine kinase. This activation leads to phosphorylation and recruitment of signal transducers and activators of transcription (STATs), particularly STAT5, which translocate to the nucleus and modulate the transcription of genes involved in growth-related processes including insulin-like growth factor 1 (IGF-1) synthesis. IGF-1 circulates systemically and mediates many of the somatropin effects, such as stimulation of chondrocyte proliferation in the growth plates of bones, promoting linear bone growth.

Additionally, Genotropin enhances protein synthesis by increasing amino acid uptake and RNA translation in muscle cells, facilitating muscle mass accrual and repair. It also promotes lipolysis by increasing hormone-sensitive lipase activity, reducing adipose tissue. Glucose metabolism modulation occurs via somatropin’s insulin-antagonistic effects, increasing gluconeogenesis and reducing insulin sensitivity in peripheral tissues.

Clinical implications of Genotropin’s mechanism include restoration of normal growth patterns in pediatric patients with growth hormone deficiency and augmentation of anabolic processes in adults with GH deficiency, improving body composition, bone density, and metabolic functions. Comparative studies demonstrate that Genotropin’s receptor affinity and pharmacodynamic profile are consistent with endogenous GH and similar recombinant products like Norditropin and Omnitrope, ensuring therapeutic equivalency. Research continues to explore optimized delivery methods and dosing regimens to mimic the physiological pulsatile secretion of natural GH, thereby maximizing efficacy and minimizing adverse effects.

Pharmacological Actions

Mimics endogenous human growth hormone by activating growth hormone receptors on target tissues.
Stimulates hepatic production and systemic release of insulin-like growth factor 1 (IGF-1), mediating growth and anabolic effects.
Promotes linear bone growth by stimulating proliferation and differentiation of chondrocytes in the epiphyseal growth plates.
Enhances protein synthesis in muscle tissues, leading to increased muscle mass and strength.
Stimulates lipolysis, leading to mobilization and reduction of adipose tissue stores.
Exerts insulin-antagonistic effects, modulating glucose metabolism and influencing insulin sensitivity.
Improves bone mineral density and promotes skeletal maturation in GH-deficient patients.
Supports metabolic homeostasis by influencing carbohydrate, lipid, and protein metabolism.
Enhances tissue repair and regeneration by promoting cellular proliferation and differentiation.
Normalizes growth velocity and height outcomes in pediatric patients with growth hormone deficiency.
Ameliorates symptoms associated with adult growth hormone deficiency, including decreased energy and muscle wasting.
Stimulates renal function and sodium retention, contributing to plasma volume regulation.
Improves overall body composition by increasing lean body mass and reducing fat mass.
Modulates immune function indirectly via systemic effects on metabolism and cellular growth.

Therapeutic Or Clinical Uses

Treatment of pediatric growth failure due to inadequate secretion of endogenous growth hormone.
Management of growth failure in children with Prader-Willi syndrome confirmed by genetic testing.
Therapy for Turner syndrome-associated short stature in pediatric patients.
Promotion of growth in children born small for gestational age who fail to exhibit catch-up growth.
Treatment of idiopathic short stature in pediatric patients whose epiphyses are not closed and who lack other causes of short stature.
Replacement therapy for adults with growth hormone deficiency of childhood onset.
Replacement therapy for adults with growth hormone deficiency of adult onset, due to pituitary or hypothalamic disease, surgery, radiation, or trauma.
Improvement of body composition, bone density, and exercise capacity in adult GH-deficient patients.
Treatment of HIV-associated wasting syndrome (off-label usage in some contexts).
Supportive therapy to improve metabolic parameters in adults with GH deficiency.
Adjunct therapy in certain syndromes characterized by short stature and growth retardation.
Potential benefit in wound healing and tissue repair in specific clinical scenarios.
Investigational uses in aging-related frailty and muscle wasting disorders (clinical trials ongoing).

Side Or Adverse Effects

Injection site reactions including pain, itching, redness, or skin changes.
Peripheral edema manifesting as swelling, particularly in extremities.
Rapid weight gain related to fluid retention.
Muscle and joint pain, including arthralgia and myalgia.
Numbness or tingling sensations (paresthesia) in hands or feet.
Gastrointestinal discomfort such as stomach pain, bloating, or gas.
Headaches and back pain reported during early treatment phases.
Upper respiratory symptoms including cold, flu-like symptoms, stuffy nose, sneezing, sore throat, and ear pain.
Serious breathing problems especially in Prader-Willi syndrome patients with obesity or respiratory impairment.
Carpal tunnel syndrome due to nerve compression from fluid retention or tissue growth.
Potential increase in intracranial pressure leading to headaches, visual disturbances, and nausea.
Hyperglycemia and exacerbation of diabetes mellitus in susceptible individuals.
Pancreatitis presenting as severe upper abdominal pain radiating to the back, nausea, and vomiting.
Allergic reactions including urticaria, rash, and in rare cases anaphylaxis.
Possible development or worsening of scoliosis in pediatric patients due to rapid growth.
Rarely, injection site lipohypertrophy or lipoatrophy with repeated injections.

Precautions

Use cautiously in patients with a history of malignancy; rule out active tumors before initiation.
Monitor patients with pre-existing diabetes or glucose intolerance due to possible hyperglycemic effects.
Careful evaluation needed in patients with respiratory disorders, especially Prader-Willi syndrome with sleep apnea or obesity.
Avoid use in patients with closed epiphyses as it will not stimulate growth and may cause adverse skeletal effects.
Perform regular assessments for signs of increased intracranial pressure, including headache and vision changes.
Rotate injection sites to minimize local skin reactions and tissue changes.
Assess thyroid function periodically as somatropin can alter thyroid hormone metabolism.
Continuous monitoring of IGF-1 levels to tailor dosing and avoid over-treatment.
Be alert to development of signs of pancreatitis or severe abdominal symptoms during therapy.
Avoid abrupt discontinuation; tapering may be required to prevent withdrawal symptoms.
Use caution in patients with scoliosis; rapid growth may exacerbate curvature.
Pregnancy should be considered carefully; benefits versus risks must be evaluated by the physician.
Genotropin contains m-cresol preservative in certain formulations; contraindicated in patients with known hypersensitivity.
Children with brain tumors or radiation history should be closely monitored for tumor recurrence.
Avoid use in serious acute critical illness such as patients with recent major surgery, trauma, or respiratory failure.

Warnings

Do not use Genotropin in patients with active malignancy due to potential tumor growth stimulation.
Contraindicated in patients with acute critical illness secondary to complications of surgery, trauma, or respiratory failure.
Use contraindicated in patients with closed epiphyses as there will be no skeletal benefit.
Not recommended in patients with diabetic retinopathy as it may exacerbate retinal changes.
Severe respiratory complications including sudden death reported in severely obese children with Prader-Willi syndrome under Genotropin treatment; avoid in this group.
Hypersensitivity reactions including anaphylaxis may occur; monitor patients closely especially during initial dosing.
Somatropin may increase intracranial pressure; discontinue therapy if symptoms like headache and vision changes arise.
Potential for glucose intolerance and diabetes mellitus exacerbation; monitor glucose levels regularly.
Long-term overdosing may lead to acromegaly-like symptoms and excessive skeletal growth.
Avoid intravenous administration; only subcutaneous injection is approved and safe.
Use caution when administering in patients with scoliosis due to risk of progression during treatment.
Monitor lipid profile and cardiovascular status as GH therapy may alter metabolism.
May cause fluid retention leading to edema and contribute to cardiovascular stress.
Patients should be instructed to report any joint pain, carpal tunnel symptoms, or neurological symptoms immediately.
Avoid use during pregnancy unless clearly needed and prescribed by a specialist.

Contraindication

Hypersensitivity to somatropin or any excipients including preservatives such as m-cresol.
Active malignancy or evidence of tumor recurrence or progression.
Closed epiphyses in pediatric patients; no growth potential remains.
Severe respiratory impairment or sleep apnea in children with Prader-Willi syndrome, especially if obese.
Diabetic retinopathy with active proliferative or severe non-proliferative changes.
Acute critical illness from complications following major surgery, trauma, or respiratory failure.
Serious illness due to lung failure or complicated by recent surgery, injury, or medical trauma.
Known hypersensitivity reactions to any recombinant human growth hormone products.
Use in premature infants or very young infants due to risk of severe adverse reactions.
Patients with uncontrolled diabetes mellitus until glycemic control is achieved.
Use is not recommended in patients with untreated hypothyroidism or adrenal insufficiency.
Patients undergoing cancer therapy until malignancy is inactive and treatment is complete.
Patients with pituitary tumors or intracranial tumors unless stable and under medical surveillance.
Use contraindicated in patients with active proliferative diabetic eye disease.
Known allergy to benzyl alcohol in formulations containing this preservative.

Drug Interactions

Concomitant use with corticosteroids (e.g., prednisone, dexamethasone) may inhibit somatropin effects on growth.
Insulin and oral hypoglycemic agents may require dose adjustments as somatropin can alter glucose metabolism and induce insulin resistance.
Hormone replacement therapies, including estrogen-containing birth control pills, may alter somatropin metabolism via hepatic enzyme induction.
Drugs influencing cytochrome P450 enzymes could indirectly affect somatropin metabolism and clearance.
Somatropin may decrease the bioavailability and efficacy of antidiabetic medications necessitating close monitoring.
Concomitant use of somatropin with thyroid hormone replacement requires monitoring of thyroid function tests.
Interactions with protease inhibitors or other agents affecting protein metabolism have not been extensively studied but should be monitored cautiously.
Potential interactions with other growth factors or anabolic steroids may increase side effect risk.
Somatropin may interfere with laboratory tests, including thyroid function tests and cortisol levels.
Drugs causing fluid retention may potentiate adverse effects such as edema when combined with somatropin.
Close monitoring required when using somatropin alongside medications that affect blood sugar levels.
No significant interactions reported with commonly used analgesics and antibiotics.
Herbal products like St. John’s Wort may alter metabolism of somatropin indirectly by hepatic enzyme induction.
Drug interactions may vary based on individual patient metabolism and comorbidities.
Healthcare providers should review all medications to identify and manage any potential drug-drug interactions.

Preparations Of The Drug

Genotropin Miniquick: Single-dose growth hormone delivery device with two-chamber cartridges, preservative-free.
Genotropin 12 mg Pen Device: Multi-dose cartridges with m-cresol preservative, compatible with pen injectors.
Genotropin 5 mg Pen Device: Multi-dose cartridges with preservative for subcutaneous administration using pen devices.
Cartridges designed for precise dosing, inserted into Genotropin pen injector devices.
Pen needles available in 29, 30, and 31 gauge sizes for patient comfort.
Storage requirements include refrigeration between 2°C to 8°C; Miniquick can be stored up to 3 months at room temperature before reconstitution.
After reconstitution, storage under refrigeration is required for up to 28 days with the pen cap on, and medication must not be shaken.
Discard unused medication after 28 days post-reconstitution to maintain efficacy and safety.
Packaging designed to protect from light and contamination with single-patient-use recommendations.
Available in multiple dose strengths to facilitate individualized dosing from 0.2 mg to 2 mg per dose in Miniquick, and 5 mg and 12 mg multi-dose cartridges.
Preservative m-cresol is present in pen devices but absent in Miniquick preparation for patients sensitive to preservatives.
Manufactured and distributed by Pfizer Inc., Division of Pharmacia & Upjohn Co.
Biosimilar products on the market include brands such as Norditropin, Humatrope, Omnitrope, Saizen, and Zomacton, with various formulations and strengths.
Preparation devices include instructions for use to ensure accurate dosing and aseptic technique.
Each pen device has a use period of 2 years from the first administration to maintain device integrity.