SUPPRELIN LA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SUPPRELIN LA (SUPPRELIN LA).
SUPPRELIN LA is a sterile, biodegradable, subcutaneous implant containing histrelin acetate, a synthetic nonapeptide agonist of gonadotropin-releasing hormone (GnRH). After an initial transient increase, continuous administration results in downregulation of pituitary GnRH receptors, leading to suppressed luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, thereby reducing gonadal sex steroid production (testosterone in males, estradiol in females) to castrate levels.
| Metabolism | Histrelin is primarily metabolized via hydrolysis of the C-terminal prolineamide bond and removal of the N-terminal pyroglutamyl residue; specific CYP enzymes are not involved. |
| Excretion | Renal: <5% unchanged; hepatic metabolism; fecal elimination of metabolites. |
| Half-life | Terminal half-life approximately 3-4 hours; clinical suppression of luteinizing hormone and testosterone sustained for 4 weeks due to depot formulation. |
| Protein binding | Approximately 43% bound to albumin; minimal binding to sex hormone-binding globulin. |
| Volume of Distribution | Vd approximately 10-15 L; not clinically significant due to small Vd. |
| Bioavailability | Subcutaneous implant: 100% (systemic delivery); oral: negligible (<1%). |
| Onset of Action | Subcutaneous implant: Suppression of testosterone to castrate levels achieved by week 4. |
| Duration of Action | Subcutaneous implant: Clinical effect (testosterone suppression) persists for 12 months; implant removal reverses effect. |
| Molecular Weight | 1323.5 |
50 mg subcutaneously once every 12 months (implant placed in inner upper arm).
| Dosage form | IMPLANT |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Not approved for use in pediatric patients (indicated for central precocious puberty in children, but not in standard dosing). |
| Geriatric use | No specific dose adjustment recommended; use with caution due to limited data in elderly. |
| 1st trimester | Histrelin is an GnRH agonist; caution is advised in first trimester. Animal studies showed fetal resorptions and reduced litter size at high doses. There is no adequate human data; potential fetal harm cannot be excluded. |
| 2nd trimester | Similar caution: continued use in second trimester may interfere with normal fetal development due to hormonal suppression. Risk vs benefit should be considered. |
| 3rd trimester | Use in third trimester is not recommended as it may affect maternal hormonal status and potentially impact fetal development; lack of human data. |
Clinical note
Comprehensive clinical and safety monograph for SUPPRELIN LA (SUPPRELIN LA).
| Placental transfer | Limited data; as a synthetic decapeptide with molecular weight ~1323 Da, it is expected to cross the placenta to some extent. Animal studies suggest placental transfer occurs. |
| Breastfeeding | It is unknown whether histrelin is excreted in human milk. However, due to its low oral bioavailability and peptide structure, systemic absorption by the infant is unlikely. Caution should be exercised when administered to a nursing woman. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to histrelin or any component of the formulationPregnancy (may cause fetal harm)
| Precautions | Monitor for transient increase in serum estradiol or testosterone during initial treatment, which may cause transient exacerbation of signs of puberty including vaginal bleeding or breast enlargement; monitor bone mineral density loss with prolonged use; risk of psychiatric events including emotional lability and aggression; insertion site reactions including infection, implant extrusion, and granuloma formation; implant removal must be performed by a trained healthcare provider; pseudotumor cerebri has been reported. |
| Food/Dietary | No known food interactions. Take with or without food. Avoid grapefruit juice as it may theoretically affect hormone metabolism but clinical significance is unknown. No specific dietary restrictions. |
Loading safety data…
| Lactation Rating | L3 (Limited Data) |
| Teratogenic Risk | Pregnancy Category X. Contraindicated in pregnancy. Histrelin acetate (GnRH agonist) causes fetal harm in animal studies, including increased resorptions and skeletal abnormalities. Risk in all trimesters; use in early pregnancy may disrupt implantation. Avoid in women of childbearing potential unless using effective contraception. |
| Fetal Monitoring | Monitor serum estradiol or testosterone levels to confirm suppression. Rule out pregnancy with sensitive test before initiation and monthly during treatment. Monitor bone mineral density with DEXA scan if prolonged use. No specific fetal monitoring required if pregnancy avoided. |
| Fertility Effects | Reversible suppression of pituitary-gonadal axis. In females, inhibits ovulation; in males, suppresses spermatogenesis. Fertility returns after discontinuation, typically within weeks to months. Use may cause temporary infertility during treatment. |
| Clinical Pearls | Supprelin LA (histrelin acetate) is a subcutaneous implant indicated for central precocious puberty (CPP). Implant is inserted in the inner upper arm and removed after 12 months; replacement is needed annually. Monitor for initial LH and FSH surge which may transiently worsen symptoms; concomitant administration of a GnRH antagonist is not required. Monitor bone age advancement suppression; if inadequate, consider replacement. Implant may be palpable but should not be visible; infection at insertion site is rare. Avoid MRI or diathermy near implant site. Non-biodegradable; must be removed. |
| Patient Advice | The implant is placed under the skin of the upper arm and releases medication for 12 months; it must be removed after one year and a new one placed if needed. · During the first few weeks, you may notice a temporary increase in puberty symptoms (e.g., breast development, menstrual bleeding) due to initial hormone stimulation. · Keep the implant site clean and dry; avoid soaking in water (baths, swimming) for 24 hours after insertion. · Do not apply heat or cold packs directly over the implant; avoid rough contact sports that could damage the arm. · Tell all healthcare providers you have this implant, especially before MRI or any procedure using diathermy (heat therapy). · If the implant breaks, falls out, or you have signs of infection (redness, swelling, pus), contact your doctor immediately. · Regular follow-up appointments including bone age X-rays and hormone tests are necessary to monitor treatment response. · Missed doses cannot be made up; if you suspect the implant is not working, consult your specialist. |