Version May 2024
Note: Vantas has been discontinued in the United States for >1 year.
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).
Refer to adult dosing.
(For additional information see "Histrelin: Pediatric drug information")
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. Extended use of a single histrelin implant for 24 months or until pubertal escape has been shown to be effective for pubertal suppression. A prospective study of 33 children (26 female and 7 male) showed continued suppression of puberty in the majority of patients for up to 24 months (Ref). An additional retrospective study evaluated prolonged use in 8 patients. Implants were not removed until hormonal or physical signs of puberty were seen; removal took place at an average of 27.5 months (17 to 50 months) (Ref).
Gender incongruence ; suppression of puberty: Limited data available: Note: Treatment should not be initiated until patient has reached Tanner stage 2 of puberty (Ref).
Pubertal children and adolescents: SUBQ: 50 mg implant surgically inserted at a minimum of every 12 months; however, data show that active effect extends beyond 12 months, allowing for a longer use of each implant; monitor patient for biochemical or clinical signs of pubertal escape to determine time for redose (Ref). A retrospective review of 42 transgender or nonbinary adolescents showed continued use of single implant for an average of 40.3 (24 to 62) months with histrelin as monotherapy or for an average of 27.6 (24 to 36) months when combined with gender-affirming hormone therapy (Ref).
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions in central precocious puberty are for children and adolescents. Reported adverse reactions in prostate cancer are for adults.
Central precocious puberty:
>10%: Local: Injection-site reaction (implant site: including bruise at injection site, discomfort at injection site, erythema at injection site, injection-site pruritus, local soreness/soreness at injection site, pain at injections site, protrusion of implant area, swelling at injections site, tingling sensation [implant site])
1% to 10%:
Dermatologic: Cicatrix of skin, erythema of skin, keloid-like scar, pruritus
Endocrine & metabolic: Gynecomastia, heavy menstrual bleeding, pituitary neoplasm (benign), weight gain
Genitourinary: Abnormal uterine bleeding, breast tenderness, dysmenorrhea
Infection: Wound infection (implant site)
Nervous system: Emotional lability, headache, migraine, sensation of cold
Respiratory: Epistaxis, flu-like symptoms
Postmarketing:
Nervous system: Aggressive behavior, depression, irritability (including impatience), outbursts of anger, seizure, suicidal ideation, suicidal tendencies
Miscellaneous: Crying
Prostate cancer:
>10%:
Endocrine & metabolic: Hot flash (66%)
Local: Injection-site reaction (implant site: 6% to 14%; including bruising at injection site [7%], erythema at injection site [3%], inflammation at injection site [<1%], injection-site infection [<1%], local soreness/soreness at injection site [≤4%], pain at injection site [≤4%], swelling at injection site [<1%], tenderness at injection site [≤4%])
1% to 10%:
Cardiovascular: Flushing (<2%), palpitations (<2%), peripheral edema (<2%), ventricular premature contractions (<2%)
Dermatologic: Diaphoresis (<2%), hypotrichosis (<2%), night sweats (<2%), pruritus (<2%)
Endocrine & metabolic: Decreased libido (2%), fluid retention (<2%), gynecomastia (4%), hypercalcemia (<2%), hypercholesterolemia (<2%), increased lactate dehydrogenase (<2%), increased serum glucose (<2%), weight gain (2%), weight loss (<2%)
Gastrointestinal: Abdominal distress (<2%), constipation (4%), food craving (<2%), increased appetite (<2%), nausea (<2%)
Genitourinary: Breast tenderness (<2%), dysuria (<2%), erectile dysfunction (4%), exacerbation of gynecomastia (<2%), exacerbation of hematuria (<2%), exacerbation of urinary frequency (<2%), genital pruritus (<2%), increased prostatic acid phosphatase (<2%), mastalgia (<2%), sexual disorder (<2%), testicular atrophy (5%), urinary frequency (<2%), urinary retention (<2%)
Hematologic & oncologic: Anemia (<2%), bruise (<2%), hematoma (<2%)
Hepatic: Hepatic disease (<2%; including severe hepatic insufficiency), increased serum aspartate aminotransferase (<2%)
Nervous system: Asthenia (<2%), depression (<2%), dizziness (<2%), fatigue (10%), headache (3%), insomnia (3%), irritability (<2%), lethargy (<2%), malaise (<2%), pain (<2%), sensation of cold (<2%), tremor (<2%)
Neuromuscular & skeletal: Arthralgia (<2%), back pain (<2%), exacerbation of back pain (<2%), limb pain (<2%), muscle twitching (<2%), myalgia (<2%), neck pain (<2%), ostealgia (<2%)
Renal: Decreased creatinine clearance (<2%), exacerbation of renal failure (<2%), nephrolithiasis (<2%), renal insufficiency (5%)
Respiratory: Dyspnea on exertion (<2%)
Postmarketing:
Nervous system: Seizure
Neuromuscular & skeletal: Decreased bone mineral density
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.
• Pseudotumor cerebri: Pseudotumor cerebri (idiopathic intracranial hypertension) has been reported in pediatric patients receiving GnRH agonists.
• 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).
Vantas has been discontinued in the United States for >1 year.
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
Kit (Supprelin LA Subcutaneous)
50 mg (per each): $56,871.56
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.
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.
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. The manufacturer recommends that implant removal (and replacement if necessary) should occur after ~12 months; however, some studies have reported retaining implant for as long as 2 to 5 years (Lewis 2013; Pine-Twaddell 2023; manufacturer's labeling). 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.
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).
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/2022/022058s017lbl.pdf#page=20
Central precocious puberty (Supprelin LA): Treatment of children with central precocious puberty
Prostate cancer, advanced (Vantas): Palliative treatment of advanced prostate cancer
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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
Flotufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Flotufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of ADT on the performance of flotufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
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 (gozetotide) 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.
It is not known if histrelin is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Central precocious puberty (CPP): Luteinizing hormone, follicle-stimulating hormone, estradiol, or testosterone (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; monitor for development or worsening of psychiatric symptoms, including depression; monitor for signs and symptoms of pseudotumor cerebri.
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. Consider periodic monitoring of electrocardiograms and electrolytes.
Prostate cancer:
Testosterone level: Expected to rise during the first few days and decline to below initiation level by week 2 before reaching ≤50 ng/dL (castrate level)
PSA: Expected to decrease to normal levels after 6 months of therapy
Note: Lack of response (testosterone and PSA decreases) should prompt suspicion that the implant has been expelled.
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
Altered kidney function: Average serum histrelin concentrations are approximately 50% higher in patients with renal function impairment.
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