somatropin
Somatropin
Generic Name
Somatropin
Mechanism
- GH receptor activation: Binds the type‑I GH receptor (GHR) on target cells, inducing dimerization and phosphorylation of JAK2 kinase.
- STAT signaling: Activated JAK2 phosphorylates STAT5, which dimerizes and translocates to the nucleus to drive transcription of target genes.
- IGF‑1 synthesis: Induces hepatic and peripheral production of insulin‑like growth factor‑1 (IGF‑1), mediating many of GH’s anabolic effects.
- Metabolic modulation: Promotes lipolysis, insulin sensitivity, and amino‑acid uptake, while suppressing glucagon release.
Pharmacokinetics
- Absorption: Subcutaneous injection yields peak serum concentrations (~2–3 ng/mL) within 1–2 hours; bioavailability ≈ 70 % with once‑daily dosing.
- Distribution: Primarily extracellular fluid; volume of distribution ≈ 1 L; minimal protein binding (~10 %).
- Metabolism & Elimination: Cleared mainly by the kidneys (~12 % excretion unchanged) and by proteolytic degradation in plasma; elimination half‑life 1–2 hours (post‑dose), but pharmacodynamic effects persist longer due to IGF‑1 feedback.
- Factors affecting PK: Age, sex, renal function, and body composition influence clearance; no dose adjustment needed for mild‑moderate renal impairment.
Indications
- Children
- Growth hormone deficiency (GHD)
- Idiopathic short stature (ISS)
- Turner syndrome with short stature
- Prader‑Willi syndrome (short‑stature phenotype)
- Chronic kidney disease‑associated short stature
- Adults
- Adult GHD (diagnosed by two provocative tests)
- Turner syndrome (adult height deficit)
- Laron syndrome (IGF‑1 signaling defect)
- HIV‑associated lipodystrophy (to improve body composition)
- Other
- Short‑lived growth hormone‑deficient patients awaiting transplant
- Pediatric patients with chronic illnesses causing catch‑up growth deficiency
Contraindications
- Contraindicated in:
- Laron syndrome (defective GH receptor)
- Uncontrolled diabetes mellitus
- Active malignancy or history of cancer with GH‑dependent growth
- Hypersensitivity to somatropin, recombinant proteins, or excipients
- Warnings
- Monitor for glucose intolerance; adjust antidiabetic meds as needed.
- Potential fluid‑retention → monitor for edema or congestive heart failure.
- Risk of intracranial hypertension (especially in adolescent females); assess symptoms.
- Excess IGF‑1 may increase cancer risk; consider baseline and periodic age‑adjusted IGF‑1 levels.
Dosing
| Population | Typical dose | Frequency | Notes |
| Children | 0.025 mg/kg/day (max ~0.05 mg/kg) | SC once daily | Adjust for height velocity; taper at puberty onset. |
| Adults | 0.1 mg/kg/week (split 0.02–0.05 mg/kg/day) | SC once daily or 4–5 days/week | Begin at 0.1–0.15 mg/kg/week based on IGF‑1 response. |
| Pregnancy / Lactation | Not recommended | — | Limited data; risk of unknown fetal effects. |
• Preparation: Reconstitute lyophilized vial with sterile diluent to required concentration.
• Route: Subcutaneous injection, rotating sites (abdomen, thigh, upper arm).
• Storage: Refrigerated 2–8 °C; do not freeze; use within 28 days after reconstitution.
Adverse Effects
- Common (≤10 % incidence)
- Injection‑site reactions (pain, pruritus, erythema)
- Headache
- Peripheral edema
- Abdominal pain
- Tendinopathy
- Serious (≤1 % incidence)
- Glucose intolerance / type‑2 diabetes
- Severe edema → pulmonary hypertension or heart failure
- Intracranial hypertension (especially in adolescent girls)
- Acute renal failure (rare)
- Tumor growth in pre‑existing malignancy
Monitoring
| Parameter | Frequency | Target / Action | ||
| IGF‑1 level | Every 3–6 months (pre‑treatment baseline, 1‑month, then every 3–6 months) | Age‑adjusted norm; adjust dose if >2 SD above or <1 SD below. | ||
| Height velocity | Every 3 months (children) | ≥0.5 cm/wk | Increase dose if 95 th percentile | Adjust dose or monitor for edema |
| Fasting glucose / HbA1c | Every 3 months | <5.6 % (or ≤6.5 % if diabetic) | Adjust antidiabetic therapy | |
| Blood pressure | Every visit | <120/80 mmHg | Evaluate fluid‑retention | |
| Liver enzymes | Every 6–12 months | ≤2× ULN | Consider dose adjustment if elevated | |
| Ophthalmologic exam | At baseline and annually (adolescents) | Fundoscopic changes | Refer to ophthalmology if signs of papilledema |
Clinical Pearls
- IGF‑1 as Dose Guide: Use age‑adjusted IGF‑1 percentiles rather than raw values; a rapid rise (>2 SD) often signals dose overshoot.
- Adolescent Females & Headache: A sudden onset of pulsatile headache in a teenage female on somatropin warrants urgent neuro‑imaging to rule out intracranial hypertension.
- Subclinical Diabetes: Even pre‑diabetic hyperglycemia may exacerbate with GH; screen and consider early adjustment of diabetes regimen.
- Body Fat Redistribution: In HIV patients, somatropin improves lean mass and decreases visceral adiposity; monitor waist‑hip ratio for surrogate efficacy.
- Combination with anabolic steroids: GH can potentiate anabolic steroid side‑effects (e.g., hypertension); avoid concurrent use without close monitoring.
- Dose Tapering at Puberty: A gradual taper over 6–12 months reduces rebound growth hormone insensitivity and protects pubertal bone maturation.
Key Takeaway: Somatropin is a highly effective, physiologic GH replacement that, when titrated with IGF‑1 and height metrics, offers significant growth and metabolic benefits while minimizing serious adverse outcomes.