Genotropin
Genotropin
Generic Name
Genotropin
Mechanism
Genotropin binds to the growth‑hormone receptor (GHR) on target cells, triggering the JAK2‑STAT signaling cascade. This leads to:
• Activation of transcription factors (STAT5) → increased hepatic IGF‑1 production.
• Peripheral actions: IGF‑1 mediates anabolic effects on bone, muscle, and cartilage; it also stimulates glucose uptake and lipolysis.
• Direct cellular effects: Somatostatin‑like activity on osteoblasts and adipocytes, promoting growth and tissue remodeling.
The net effect is increased longitudinal bone growth and improved body composition.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Subcutaneous | Bioavailability ~70–80 % after 1‑2 h; peak at 3–5 h. |
| Distribution | Volume of distribution ≈ 0.6 L/kg | Primarily extracellular fluid. |
| Metabolism | Proteolytic cleavage to amino acids | No major hepatic metabolism. |
| Elimination | Renal and proteolytic degradation | Half‑life ≈ 4–8 h; steady‑state achieved after 2–3 weeks. |
| Drug–Drug Interactions | Minimal | Concomitant GH‑stimulating agents may alter IGF‑1 dynamics. |
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Indications
- Children
* Growth hormone deficiency (GHD) (isolated or syndromic).
* Turner's syndrome (short stature, low IGF‑1).
* Prader‑Willi syndrome (short stature, poor growth).
* Chronic renal insufficiency with growth failure.
* Sotos syndrome, Noonan syndrome (if growth failure).
• Adults
* Adult GH deficiency (secondary to pituitary disease, surgery, irradiation).
* Acromegaly‑related deficiencies (post‑resection, when GH is still needed).
* Short‑stature due to GH deficiency or other causes.
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Contraindications
Contraindications
• Known hypersensitivity to somatropin or excipients.
• Active malignancy or history of cancers associated with GH therapy (e.g., glioma, sarcoma).
Warnings
• Intracranial hypertension: monitor signs (headache, visual changes).
• Diabetes mellitus: GH is insulin‑antagonistic; screen and monitor glucose.
• Uncontrolled hypothyroidism: may blunt GH response; treat thyroid first.
• Cushingoid features: avoid in hypercortisolemic states.
Precautions
• Pregnancy/Breastfeeding: category C; use only if benefits outweigh risks.
• Pediatric obesity: risk of exacerbating insulin resistance.
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Dosing
| Population | Starting Dose | Titration | Max Dose | Route | Injection Tips |
| Children (≤12 yrs) | 0.025 mg/kg/day (split BID) | Increase 0.005 mg/kg every 4–6 weeks | 0.3 mg/kg/day | Subcutaneous | Use 27‑g needle, inject into abdomen, thigh, or buttock. Rotate sites. |
| Adolescents (≥13 yrs) | 0.035–0.05 mg/kg/day | Titrate based on IGF‑1 SDS & growth velocity | 0.07 mg/kg/day | SC | Same as above. |
| Adults | 0.1 mg/day | Increase 0.1 mg every 4–6 weeks | 0.4–0.8 mg/day | SC | Inject in thigh, abdomen, or buttock; rotate sites. |
• Timing: Administer at night (preferably 7–10 h before bedtime) to mimic endogenous GH rhythm.
• Reconstitution: Dilute vial with 1 mL sterile water; shake gently.
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Adverse Effects
| Adverse Effect | Frequency | Notes |
| Injection‑site reactions (pain, erythema, induration) | Common | Use smaller needles; rotate sites. |
| Fluid retention / peripheral edema | Common | Monitor weight, ankle swelling. |
| Headache / visual changes | Common | Evaluate for intracranial hypertension. |
| Hyperglycemia / impaired glucose tolerance | Common | Baseline glucose, periodic HbA1c. |
| Joint / muscle pain | Common | Often transient. |
| Hypothyroidism | Rare | Check TSH/FT4 at baseline and 3–6 mo. |
| Tumorigenesis (malignancy risk) | Rare | Long‑term data suggests low incremental risk when used appropriately. |
| Hypersensitivity | Very rare | Discontinue; evaluate. |
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Monitoring
| Parameter | Frequency | Target/Goal |
| IGF‑1 level (SDS) | Every 3–6 mo | 0 to +2 SDS (adjusted by age, sex). |
| Height velocity (cm/year) | Every 6 mo | ≥10 cm/year in children; >5 cm/year in adolescents. |
| Glucose/HbA1c | Every 3–6 mo | <110 mg/dL fasting; HbA1c <5.7% (or 95th percentile in children. |
| MRI/CT for suspected tumors | As clinically indicated | Baseline for high‑risk patients. |
| Visual acuity/acuity | Every 3–6 mo | Screen for papilledema. |
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Clinical Pearls
- Night‑time dosing: GH secretion peaks before sleep; giving Genotropin at bedtime improves IGF‑1 response.
- Site rotation: Reduces local lipodystrophy; use the “circular” rotation technique (abdomen, thigh, buttock).
- Needle size: 27‑g, 3‑mm is optimal for most adults; 30‑g may reduce pain but increases injection volume.
- IGF‑1 monitoring: IGF‑1 SDS is a more reliable marker than height velocity alone; adjust dose after 3–6 months.
- Diabetes risk: Screen pre‑treatment and at 6 months; consider metformin if glucose rises >125 mg/dL.
- Adult patients with GH deficiency: Even modest dose increases (0.1 mg/day increments) can significantly improve body composition and quality of life.
- Pediatric obesity: GH can worsen insulin resistance; consider BMI monitoring and lifestyle counseling.
- Turner syndrome: Initiate at 0.05 mg/kg/day; consider adding aromatase inhibitors if early puberty begins.
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• Genotropin remains the cornerstone of recombinant growth hormone therapy, offering proven benefits for growth, body composition, and metabolic health when used with careful dose titration and vigilant monitoring.