Central precocious puberty: Children ≥2 years: Supprelin LA: SubQ: 50 mg implant surgically inserted every 12 months; discontinue at the appropriate time for the onset of puberty
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Supprelin LA: Children ≥2 years: There are no dosage adjustments provided in the manufacturer's labeling.
All patients: There are no dosage adjustments provided in manufacturer's labeling; has not been adequately studied.
(For additional information see "Histrelin: Drug information")
Prostate cancer, advanced (Vantas): SubQ: 50 mg implant surgically inserted every 12 months.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Vantas: CrCl ≥15 mL/minute: No dosage adjustment necessary.
Supprelin LA: There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Kit, Subcutaneous:
Supprelin LA: 50 mg
Vantas: 50 mg [DSC]
No
An FDA-approved patient medication guide, which is available with the product information, and as follows, must be dispensed with this medication:
Supprelin LA https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022058s016lbl.pdf#page=20
SubQ: Surgical implantation within a sterile field using provided implantation device is required. Insert into the inner portion of the upper arm; it is preferable to use the patient's nondominant arm for placement; implant should be placed halfway between the shoulder and the elbow at the crease between the tricep and the bicep. Implant removal should occur after ~12 months; a replacement implant may be inserted if therapy is to be continued. For removal, palpate area of incision to locate implant; if not readily palpated, ultrasound, CT, or MRI may be necessary to locate implant; plain films are not recommended because the implant is not radiopaque. Refer to manufacturer's labeling for full insertion and removal details.
SubQ: Surgical implantation (using a sterile field) into the inner portion of the upper arm requires the use of the implantation device provided. Do not bend or pinch the implant. Use the patient's nondominant arm for placement; implant should be placed halfway between the shoulder and the elbow at the crease between the tricep and the bicep. Implant removal should occur after ~12 months; a replacement implant may be inserted if therapy is to be continued. Palpate area of incision to locate implant for removal. If not readily palpated, ultrasound, CT, or MRI may be used to locate implant; plain films are not recommended because the implant is not radiopaque. Refer to manufacturer's labeling for full insertion and removal details.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and (when dosage form allows) closed system transfer devices (CSTDs) for compounding. Double gloving and a protective gown are recommended during administration (NIOSH 2016).
Upon delivery, separate contents of implant carton. Store implant (small carton containing amber plastic pouch and glass vial) under refrigeration at 2°C to 8°C (36°F to 46°F) until the day of insertion; excursions permitted to 25°C (77°F) for 7 days (if unused within 7 days, may return to proper refrigeration until product expiration date). Keep implant wrapped in the amber pouch for protection from light; do not freeze. Do not open implant vial until just before the time of insertion. The implantation insertion kit should be stored at room temperature (do not refrigerate insertion kit).
Supprelin LA: Treatment of central precocious puberty (CPP) (FDA approved in children ages ≥2 years)
Vantas: Palliative treatment of advanced prostate cancer (FDA approved in adults)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
CPP:
>10%: Dermatologic: Dermatological reaction (51%; insertion site reaction includes bruise, discomfort, erythema, pain, protrusion of implant area, pruritus, soreness, swelling, tingling)
1% to 10%:
Central nervous system: Emotional lability (≤2%), headache (≤2%), migraine (≤2%), sensation of cold (≤2%)
Dermatologic: Cicatrix of skin (6%), pruritus (≤2%)
Endocrine & metabolic: Gynecomastia (≤2%), heavy menstrual bleeding (≤2%), weight gain (≤2%)
Genitourinary: Uterine hemorrhage (4%), breast tenderness (≤2%), dysmenorrhea (≤2%), precocious puberty (≤2%; progression of central precocious puberty)
Hematologic & oncologic: Pituitary neoplasm (≤2%)
Infection: Localized infection (≤2%; implant site)
Local: Application site pain (4%)
Neuromuscular & skeletal: Keloid-like scar (6%)
Respiratory: Epistaxis (≤2%), flu-like symptoms (≤2%)
Miscellaneous: Procedural complications (6%; suture-related), postoperative pain (4%)
Frequency not defined: Endocrine & metabolic: Altered hormone levels
1%, postmarketing, and/or case reports: Aggressive behavior, amblyopia, crying, hostility, irritability, seizure, suicidal ideation
Prostate cancer:
>10%:
Dermatologic: Dermatological reaction (3% to 14%)
Endocrine & metabolic: Hot flash (66%)
1% to 10%:
Cardiovascular: Flushing (<2%), palpitations (<2%), peripheral edema (<2%), ventricular premature contractions (<2%)
Central nervous system: Fatigue (10%), headache (3%), insomnia (3%), depression (<2%), dizziness (<2%), irritability (<2%), lethargy (<2%), malaise (<2%), pain (<2%), sensation of cold (<2%)
Dermatologic: Diaphoresis (<2%), genital pruritus (<2%), hypotrichosis (<2%), night sweats (<2%), pruritus (<2%)
Endocrine & metabolic: Gynecomastia (4%), decreased libido (2%), weight gain (2%), fluid retention (<2%), hypercalcemia (<2%), hypercholesterolemia (<2%), increased lactate dehydrogenase (<2%), increased prostatic acid phosphatase (<2%), increased serum glucose (<2%), weight loss (<2%)
Gastrointestinal: Constipation (4%), abdominal distress (<2%), food cravings (<2%), increased appetite (<2%), nausea (<2%)
Genitourinary: Testicular atrophy (5%; expected pharmacological consequence of testosterone suppression), erectile dysfunction (4%), breast tenderness (<2%), dysuria (<2%), exacerbation of gynecomastia (<2%), exacerbation of hematuria (<2%), exacerbation of urinary frequency (<2%), hematuria (<2%), mastalgia (<2%), urinary frequency (<2%), urinary retention (<2%)
Hematologic & oncologic: Anemia (<2%), bruise (<2%), hematoma (<2%)
Hepatic: Hepatic disease (<2%), increased serum AST (<2%)
Local: Bruising at injection site (7%), pain at injection site (≤4%), tenderness at injection site (≤4%), erythema at injection site (3%), inflammation at injection site (1%), injection site infection (1%)
Neuromuscular & skeletal: Arthralgia (<2%), asthenia (<2%), back pain (<2%), exacerbation of back pain (<2%), limb pain (<2%), muscle twitching (<2%), myalgia (<2%), neck pain (<2%), ostealgia (<2%), tremor (<2%)
Renal: Renal insufficiency (5%), decreased creatinine clearance (<2%), exacerbation of renal failure (<2%), nephrolithiasis (<2%)
Respiratory: Dyspnea on exertion (<2%)
Miscellaneous: Stent occlusion (<2%)
<1%, postmarketing, and/or case reports: Decreased bone mineral density, hepatic injury (severe), increased testosterone level, swelling at injection site
Hypersensitivity to gonadotropin-releasing hormone (GnRH) or GnRH-agonist analogs; females who are or may become pregnant (Supprelin LA).
Concerns related to adverse effects:
• Cardiovascular effects: Androgen-deprivation therapy (ADT) may increase the risk for cardiovascular disease (Levine 2010). An increased risk of MI, sudden cardiac death, and stroke has been reported with gonadotropin-releasing hormone (GnRH) agonist use in men; monitor for symptoms associated with cardiovascular disease. ADT may prolong the QT/QTc interval; consider the benefits of ADT versus the risk for QT prolongation in patients with a history of QTc prolongation, congenital long QT syndrome, heart failure, frequent electrolyte abnormalities, and in patients with medications known to prolong the QT interval, or with pre-existing cardiac disease. Consider periodic monitoring of electrocardiograms and electrolytes in at-risk patients.
• Hyperglycemia: Hyperglycemia has been reported with androgen deprivation therapy (in prostate cancer) and may manifest as diabetes or worsening of preexisting diabetes. Monitor blood glucose and/or HbA1c.
• Pituitary apoplexy: Rare cases of pituitary apoplexy (frequently secondary to pituitary adenoma) have been observed with GnRH agonist administration (onset from 1 hour to usually <2 weeks); may present as sudden headache, vomiting, visual or mental status changes, and infrequently, cardiovascular collapse; immediate medical attention required.
• Psychiatric events: Psychiatric events have been described with GnRH agonists, including histrelin; symptoms of emotional lability, irritability, impatience, anger, and aggression have been reported in postmarketing accounts. Monitor for development or worsening of psychiatric symptoms.
• Seizures: Seizures have been reported in patients receiving GnRH agonists, including histrelin. Reports have occurred in patients with a history of seizures, epilepsy, cerebrovascular disorders, CNS anomalies, or tumors, and patients on concomitant medications associated with seizures (eg, bupropion, SSRIs). Seizures have also been reported in patients without underlying conditions.
• Spinal cord compression: Has been reported, may contribute to paralysis when used for prostate cancer; closely observe patients with metastatic vertebral lesions for weakness and paresthesias in first few weeks of therapy.
• Tumor flare: Transient increases in serum testosterone (in men with prostate cancer) occur during the first week of use and may result in a worsening of disease signs and symptoms (bone pain, neuropathy, hematuria, ureteral/bladder outlet obstruction, spinal cord compression) during the first week of treatment.
• Urinary tract obstruction: Ureteral obstruction may occur when used for prostate cancer; closely observe patients for urinary tract obstruction or poor urine output in first few weeks of therapy.
• Worsening of symptoms: Transient increases in estradiol serum levels (female) or testosterone levels (female and male) may occur during the first week of use for central precocious puberty (CPP); however, manifestations of puberty should decrease within 4 weeks.
Other warnings/precautions:
• Appropriate use: GnRH analog treatment is usually continued upon development of nonmetastatic and metastatic castration-resistant prostate cancer.
• Implant complications: Proper surgical insertion technique is essential to avoid complications. Patients should keep arm dry for 24 hours and avoid heavy lifting/strenuous exertion of insertion arm for 7 days after implantation. In prostate cancer studies, the implant was not recovered in a small number of patients. Serum testosterone rose above castrate level and the implant was not palpable or visualized (via ultrasound); it was believed to have been extruded. Some patients had continued testosterone levels below castration level even though the implant was not palpable. If the implant breaks during removal in children with CPP, the remaining pieces should be removed; confirm the removal of the entire implant (refer to manufacturer's instructions for removal procedure).
None known.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Choline C 11: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy
Corifollitropin Alfa: Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa. Risk X: Avoid combination
Gallium Ga 68 PSMA-11: Androgen Deprivation Therapy Agents may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of gallium Ga 68 PSMA-11 in prostate cancer. The impact of ADT on the performance of gallium Ga 68 PSMA-11 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Indium 111 Capromab Pendetide: Luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Piflufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Piflufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of ADT on the performance of piflufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Histrelin is contraindicated for use in patients who may become pregnant.
When used for central precocious puberty, the return of menses is variable (several months to years) once therapy is discontinued. Once menarche and normal menstrual cycles are achieved, fertility is not impaired due to previous treatment with a gonadotropin-releasing hormone agonist (Bangalore Krishna 2019).
Based on the mechanism of action and data from animal reproduction studies, male fertility may be impaired during treatment and is reversible following discontinuation.
Histrelin may cause fetal harm or spontaneous abortion if administered during pregnancy. Use is contraindicated in patients who are pregnant.
Central precocious puberty:
Manufacturer labeling: Luteinizing hormone, follicle-stimulating hormone, estradiol, or testosterone serum concentration (after 1 month then every 6 months); height, bone age (every 6 to 12 months); Tanner staging, monitor for clinical evidence of suppression of CPP manifestations
Consensus recommendation: Tanner stage and growth (growth velocity, height) every 3 to 6 months and bone age periodically. Routine or random stimulated measurements of gonadotropins or sex steroids may be used, particularly if suboptimal response; however, use of FSH levels not typically used (Carel 2009).
Prostate cancer: Serum testosterone levels, prostate specific antigen (PSA); bone mineral density; weakness, paresthesias, and urinary tract obstruction (especially during first few weeks of therapy); screen for diabetes; monitor for symptoms associated with cardiovascular disease
Potent inhibitor of gonadotropin secretion; continuous administration results in, after an initiation phase, the suppression of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and a subsequent decrease in testosterone and dihydrotestosterone (males) and estrone and estradiol (premenopausal females). Testosterone levels are reduced to castrate levels in males (treated for prostate cancer) within 2 to 4 weeks. Additionally, in patients with CPP, linear growth velocity is slowed (improves chance of attaining predicted adult height).
Onset of action: Prostate cancer: Chemical castration: Within 2 to 4 weeks; CPP: Progression of sexual development stops and growth is decreased within 1 month
Duration: 12 months (plus a few additional weeks of histrelin release)
Distribution: Adults: Vd: ~58.4 L ± 7.86 L
Protein binding: Adults: ~70% ± 9%
Metabolism: Hepatic via C-terminal dealkylation and hydrolysis
Bioavailability: Adults: SubQ: 92%
Half-life elimination: Adults: Terminal: ~4 hours
Time to peak, serum: Adults: 12 hours
Renal function impairment: Average serum histrelin concentrations are approximately 50% higher in patients with renal function impairment.
Kit (Supprelin LA Subcutaneous)
50 mg (per each): $51,682.58
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
