ZOMACTON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOMACTON (ZOMACTON).
ZOMACTON is a recombinant human growth hormone that binds to growth hormone receptors on cell surfaces, activating intracellular signaling cascades (primarily JAK-STAT pathway) leading to increased IGF-1 production, which mediates growth and metabolic effects including linear growth, protein synthesis, and lipolysis.
| Metabolism | Growth hormone is metabolized in the liver and kidney via proteolysis; no specific CYP450 enzymes involved. |
| Excretion | Renal: nearly 100% of absorbed dose, mostly as intact hormone; negligible biliary/fecal elimination. |
| Half-life | Terminal elimination half-life: 2-3 hours after subcutaneous administration; clinically, this necessitates daily or more frequent dosing. |
| Protein binding | Approximately 30-40%, primarily bound to growth hormone binding protein (GHBP) and low-affinity binding proteins. |
| Volume of Distribution | 0.07-0.1 L/kg, indicating limited extravascular distribution; primarily confined to plasma volume. |
| Bioavailability | Subcutaneous: 75-85%; intramuscular: 80-90%; intravenous: 100%. |
| Onset of Action | Subcutaneous: 2-4 hours; intravenous: 15-30 minutes; intramuscular: 2-4 hours. |
| Duration of Action | Subcutaneous: 12-24 hours; intravenous: 8-12 hours; clinical effect duration shorter than metabolic clearance. |
| Molecular Weight | 22124 |
| Action Class | Growth hormone agonist |
Intramuscular or subcutaneous injection: 0.1-0.3 mg/kg/day (up to 0.6 mg/kg/day) divided into 1-2 doses. Typical adult dose for growth hormone deficiency: 0.2 mg/kg/day subcutaneously.
| Dosage form | INJECTABLE |
| Renal impairment | No specific guidelines. Somatropin may be used in patients with renal impairment; however, monitoring for fluid retention and electrolyte imbalances is advised. GFR-based dose reduction is not established. |
| Liver impairment | No specific Child-Pugh based adjustments. Caution in severe hepatic impairment due to potential for decreased clearance; monitor for adverse effects. |
| Pediatric use | Growth hormone deficiency: 0.025-0.05 mg/kg/day subcutaneously once daily; maximum 0.1 mg/kg/day. For Turner syndrome: 0.05 mg/kg/day. For chronic renal insufficiency: 0.045-0.05 mg/kg/day. |
| Geriatric use | Use lowest effective dose. May require lower doses due to age-related changes in metabolism and increased risk of adverse effects such as fluid retention, arthralgia, and glucose intolerance. Regular monitoring of IGF-1 levels recommended. |
| 1st trimester | Somatropin (ZOMACTON) should not be used during pregnancy unless clearly needed. No adequate human data in first trimester; animal studies show fetal abnormalities at high doses. |
| 2nd trimester | Limited human data; avoid use unless potential benefit outweighs risk. Somatropin may affect maternal glucose metabolism. |
| 3rd trimester | Avoid use; somatropin may cause maternal hyperglycemia and potential fetal macrosomia. Excreted in milk (see breastfeeding). |
Clinical note
Comprehensive clinical and safety monograph for ZOMACTON (ZOMACTON).
| Placental transfer | Minimal placental transfer; molecular weight >20 kDa limits crossing. Data from animal studies indicate low transfer. |
| Breastfeeding | Somatropin is detected in breast milk at low levels; theoretical risk of growth promotion in infant. Caution advised; benefits of breastfeeding vs. risk of infant exposure should be considered. |
■ FDA Black Box Warning
Increased risk of mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery, or multiple accidental trauma, or those with acute respiratory failure. ZOMACTON should not be used for such conditions.
| Serious Effects |
Active malignancyDiabetic retinopathyAcute critical illness due to complications following open heart surgery, abdominal surgery, or multiple accidental traumaChildren with Prader-Willi syndrome who are severely obese or have severe respiratory impairmentHypersensitivity to somatropin or any excipient
| Precautions | Risk of neoplasms (active malignancy), Intracranial hypertension (pseudotumor cerebri), Slipped capital femoral epiphysis, Pancreatitis, Glucose intolerance/diabetes mellitus, Fluid retention (edema, arthralgias), Hypoadrenalism in patients with ACTH deficiency, Thyroid dysfunction (monitor thyroid function), Progression of scoliosis, Lipoatrophy at injection site, Antibody formation to growth hormone |
| Food/Dietary | No specific food interactions. Maintain balanced diet to support growth. Avoid high-sugar meals if glucose intolerance develops. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | No well-controlled studies in pregnant women. Animal studies are inadequate or inconclusive. Somatropin is not recommended during pregnancy unless clearly needed. First trimester: limited data suggests no increased malformation risk; second/third trimester: theoretical risk of maternal glucose intolerance and fetal growth acceleration. |
| Fetal Monitoring | Monitor maternal glucose tolerance (HbA1c, glucose levels) due to potential insulin resistance. Fetal growth via ultrasound if used in pregnancy. Monitor for signs of fetal macrosomia or growth restriction. |
| Fertility Effects | No direct data on fertility impairment; somatropin is used to treat growth hormone deficiency which may be associated with subfertility. In women with GH deficiency, replacement therapy may improve ovulatory function and fertility. |
| Clinical Pearls | Rotate injection sites to prevent lipoatrophy; monitor for signs of intracranial hypertension; assess growth velocity quarterly; screen for hypothyroidism and glucose intolerance. Dosing should be individualized based on growth response. |
| Patient Advice | Inject exactly as prescribed, rotating sites each time. · Store reconstituted solution in refrigerator, do not freeze. · Report severe headache, vision changes, nausea (signs of intracranial hypertension). · Attend regular growth checks and blood tests. · Do not discontinue without consulting physician. |