Version May 2024
Vismodegib can cause embryofetal death or severe birth defects when administered to a pregnant woman. Vismodegib is embryotoxic, fetotoxic, and teratogenic in animals. Teratogenic effects included severe midline defects, missing digits, and other irreversible malformations.
Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating vismodegib. Advise pregnant women of the potential risks to a fetus. Advise females of reproductive potential to use effective contraception during and after vismodegib. Advise males of the potential risk of vismodegib exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential.
Note: Verify pregnancy status within 7 days prior to therapy initiation (in patients who could become pregnant).
Basal cell carcinoma, locally advanced or metastatic: Oral: 150 mg once daily until disease progression or unacceptable toxicity (Ref).
Missed doses: If a dose is missed, resume dosing with the next scheduled dose.
No dosage adjustment necessary.
No dosage adjustment necessary.
Intolerable adverse reactions: Withhold vismodegib treatment for up to 8 weeks until improvement or resolution.
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms: Permanently discontinue vismodegib.
Severe or intolerable musculoskeletal adverse reactions: Withhold vismodegib treatment. Permanently discontinue vismodegib for recurrent severe or intolerable musculoskeletal adverse reactions.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Alopecia (64%)
Endocrine & metabolic: Amenorrhea (premenopausal women: 30%), weight loss (45%)
Gastrointestinal: Ageusia (11%), constipation (21%), decreased appetite (25%), diarrhea (29%), dysgeusia (55%), nausea (30%), vomiting (14%)
Nervous system: Fatigue (40%)
Neuromuscular & skeletal: Arthralgia (16%), muscle spasm (72%)
1% to 10%:
Endocrine & metabolic: Hypokalemia (grade 3: 1%), hyponatremia (grade 3: 4%)
Genitourinary: Azotemia (grade 3: 2%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (grades 3/4: 2%)
Postmarketing:
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
Hepatic: Hepatic injury
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to vismodegib or any component of the formulation; pregnancy or females at risk of becoming pregnant; breastfeeding; male patients or female patients of childbearing potential who do not comply with the Erivedge Pregnancy Prevention Program; children and adolescents <18 years of age.
Concerns related to adverse effects:
• Dermatologic toxicity: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms, have been reported with vismodegib; may be life-threatening or fatal. Permanently discontinue vismodegib if severe cutaneous adverse reactions occur.
• Musculoskeletal effects: Musculoskeletal adverse reactions, which may be accompanied by CPK elevations, have occurred with vismodegib (and with other medications that inhibit the Hedgehog pathway). Musculoskeletal and connective tissue adverse reactions occurred in a majority of patients; grade 3 events have been reported. The most frequent manifestations (all grades) were muscle spasms and arthralgias. Grade 3 or 4 CPK elevations occurred in a small percentage of patients.
Special populations:
• Pediatrics: Premature fusion of the epiphyses has been reported in pediatric patients exposed to vismodegib; the fusion progressed after vismodegib discontinuation in some cases. Vismodegib is not indicated for use in pediatric patients.
Other warnings/precautions:
• Blood donations: Advise patients not to donate blood or blood products during vismodegib treatment and for at least 24 months after the last vismodegib dose.
• Toxicity duration: In a study of vismodegib in patients with basal cell nevus syndrome (not an approved use), with discontinuation of vismodegib treatment, taste alteration and muscle cramps abated within 1 month, and scalp and body hair began to regrow within 3 months (Tang 2012).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Erivedge: 150 mg
No
Capsules (Erivedge Oral)
150 mg (per each): $572.94
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Erivedge: 150 mg
US: Available at specialty pharmacies through the Erivedge Access Solutions program. Further information may be obtained from the manufacturer, Genentech, at 1-888-249-4918, or at www.ErivedgeAccessSolutions.com
Canada: Available through a controlled distribution program called Erivedge Pregnancy Prevention Program (EPPP). Registration with the program is required for participating prescribers and pharmacies. Patients must also be registered with the program and meet all necessary requirements to receive vismodegib. Consult product monograph for detailed information regarding program requirements. Further information may also be obtained at 1-888-748-8926.
Oral: May be administered with or without food. Swallow capsules whole; do not open or crush.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/203388s017lbl.pdf#page=15, must be dispensed with this medication.
Basal cell carcinoma, metastatic or locally advanced: Treatment (in adults) of metastatic basal cell carcinoma, or locally advanced basal cell carcinoma that has recurred following surgery or in patients who are not candidates for surgery and not candidates for radiation therapy.
Vismodegib may be confused with glasdegib, sonidegib, vandetanib, vemurafenib, venetoclax
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP2C9 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
There are no known significant interactions.
Evaluate pregnancy status prior to use; verify the patient is not pregnant within 7 days prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 24 months after the last vismodegib dose.
Patients with partners who are or who could become pregnant should use condoms to prevent potential vismodegib exposure via semen during therapy and for 3 months after the last vismodegib dose; condoms should be used even after vasectomy. Semen should not be donated during treatment and for 3 months after the last dose of vismodegib.
Amenorrhea may occur; consider discussions on fertility preservation prior to therapy.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to vismodegib may cause fetal harm. Vismodegib inhibits the Hedgehog pathway, which is critical to fetal development (Walterhouse 1999, Villavicencio 2000). Outcome data following inadvertent exposure to vismodegib during pregnancy are limited (Schnetzler 2022). Embryo-fetal death or severe birth defects may occur following exposure to vismodegib.
The European Society for Medical Oncology has published guidelines for the diagnosis, treatment, and follow up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]). Vismodegib is not recommended for use in pregnant patients.
Data collection to monitor pregnancy and infant outcomes following exposure to vismodegib is ongoing. Persons exposed to vismodegib during pregnancy (directly or via seminal fluid) are encouraged to contact the Pregnancy Exposure Registry (1-888-835-2555).
It is not known if vismodegib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 24 months after the last vismodegib dose.
Obtain CPK and creatinine levels at baseline and as clinically indicated (eg, if muscle symptoms are reported). Pregnancy test within 1 week prior to treatment initiation (in patients who could become pregnant). Monitor for signs/symptoms of cutaneous adverse reactions. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Basal cell cancer is associated with mutations in Hedgehog pathway components. Hedgehog regulates cell growth and differentiation in embryogenesis; while generally not active in adult tissue, Hedgehog mutations associated with basal cell cancer can activate the pathway resulting in unrestricted proliferation of skin basal cells. Vismodegib is a selective Hedgehog pathway inhibitor which binds to and inhibits Smoothened homologue (SMO), the transmembrane protein involved in Hedgehog signal transduction.
Distribution: Vd: 16.4 to 26.6 L
Males: The average vismodegib concentration in semen was 6.5% of the average steady state plasma concentration on day 8
Protein binding: >99%; primarily to serum albumin and alpha1 acid glycoprotein (AAG)
Metabolism: Metabolized by oxidation, glucuronidation, and pyridine ring cleavage, although >98% of circulating components are as the parent drug
Bioavailability: 32%
Half-life, elimination: Continuous daily dosing: ~4 days; Single dose: ~12 days
Time to peak: ~2.4 days (Graham 2011)
Excretion: Feces (82%); urine (~4%)
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