ZOLADEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOLADEX (ZOLADEX).
Gonadotropin-releasing hormone (GnRH) agonist; initially stimulates and then suppresses luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, leading to reduced sex steroid production.
| Metabolism | Primarily metabolized via hydrolysis of the peptide bonds; not significantly metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily renal (approximately 20% as unchanged drug); remainder as metabolites via biliary/fecal (approximately 80%). |
| Half-life | Approximately 4.2 hours (subcutaneous); due to continuous release from depot formulation, effective half-life is extended to ~28 days. |
| Protein binding | Approximately 30% bound to albumin; no specific binding to sex hormone-binding globulin. |
| Volume of Distribution | Approximately 20 L/kg (large, indicating extensive tissue distribution). |
| Bioavailability | Subcutaneous: ~90% (relative to intravenous); oral: negligible (not orally bioavailable). |
| Onset of Action | Subcutaneous: Suppression of LH and FSH occurs within 2-4 weeks; a transient initial surge (flare) in testosterone occurs in the first week. |
| Duration of Action | Subcutaneous depot (3.6 mg): Sustained suppression of testosterone to castrate levels for 28 days; clinical effect persists for the duration of therapy. |
3.6 mg subcutaneously every 28 days (prostate cancer, endometriosis) or 10.8 mg subcutaneously every 12 weeks (prostate cancer).
| Dosage form | IMPLANT |
| Renal impairment | No dose adjustment required for renal impairment based on GFR; pharmacokinetics are not significantly altered. |
| Liver impairment | No dose adjustment required for hepatic impairment; Child-Pugh classification does not affect goserelin elimination. |
| Pediatric use | Not recommended for use in pediatric patients; safety and efficacy have not been established. |
| Geriatric use | No specific dose adjustment; same dosing as for younger adults. Monitor for bone density loss and cardiovascular events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOLADEX (ZOLADEX).
| Breastfeeding | M/P ratio unknown. Goserelin is not indicated during breastfeeding due to potential for hormonal effects in the infant and lack of safety data. Not recommended. |
| Teratogenic Risk | Zoladex (goserelin) is a GnRH agonist. Pregnancy category D. First trimester: Risk of miscarriage and congenital anomalies based on hormonal disruption. Second/third trimesters: Potential for fetal gonadotropin suppression and genitourinary tract abnormalities. Avoid use during pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Not applicable; ZOLADEX does not have a black box warning.
| Serious Effects |
Hypersensitivity to goserelin or any component; pregnancy and possibility of pregnancy (category X); lactation (not recommended); undiagnosed abnormal vaginal bleeding.
| Precautions | Transient worsening of symptoms (tumor flare) upon initial administration; hyperglycemia and increased risk of diabetes; cardiovascular risks (QT prolongation); bone density loss; injection site injury risk. |
Loading safety data…
| Pregnancy test before initiation; rule out pregnancy monthly during therapy; monitor for signs of ectopic pregnancy if used for assisted reproduction; ultrasound for fetal development if inadvertent exposure. |
| Fertility Effects | Reversible suppression of pituitary-ovarian axis; inhibits ovulation and causes amenorrhea. Fertility returns after discontinuation. Use for controlled ovarian hyperstimulation requires careful monitoring. |