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Vismodegib: Drug information

Vismodegib: Drug information
(For additional information see "Vismodegib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Embryofetal toxicity:

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 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.

Brand Names: US
  • Erivedge
Brand Names: Canada
  • Erivedge
Pharmacologic Category
  • Antineoplastic Agent, Hedgehog Pathway Inhibitor
Dosing: Adult
Basal cell carcinoma, metastatic or locally advanced

Basal cell carcinoma, metastatic or locally advanced: Oral: 150 mg once daily until disease progression or unacceptable toxicity (Sekulic 2012; Sekulic 2017).

Missed doses: If a dose is missed, resume dosing with the next scheduled dose.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Adjustment for Toxicity: Adult

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Erivedge: 150 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Erivedge: 150 mg

Prescribing and Access Restrictions

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.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203388s016lbl.pdf#page=14, must be dispensed with this medication.

Administration: Adult

Oral: May be administered with or without food. Swallow capsules whole; do not open or crush.

Hazardous Drugs Handling Considerations

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).

Use: Labeled Indications

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Vismodegib may be confused with glasdegib, sonidegib, vandetanib, vemurafenib, venetoclax

High alert medication:

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.

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

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Contraindications

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; breast-feeding; 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.

Warnings/Precautions

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.

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.

• Pregnancy: [US Boxed Warning]: 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. Advise pregnant women of the potential risks to a fetus. Verify pregnancy status of females of reproductive potential within 7 days prior to initiating vismodegib. 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.

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).

Metabolism/Transport Effects

Substrate of CYP2C9 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

There are no known significant interactions.

Reproductive Considerations

[US Boxed Warning]: Verify pregnancy status of females of reproductive potential within 7 days prior to initiating vismodegib. Advise females of reproductive potential to use effective contraception during and after vismodegib. After a negative pregnancy test, initiate highly effective contraception prior to the first vismodegib dose and continue during treatment and for 24 months after the final vismodegib dose.

Amenorrhea may occur in females.

[US Boxed Warning]: 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. It is not known if the presence of vismodegib in semen can cause embryotoxicity and/or fetotoxicity.

Male patients should not donate sperm during vismodegib treatment and for 3 months after the last vismodegib dose.

Male patients with female partners of childbearing potential should use condoms (even after vasectomy) during vismodegib treatment and for 3 months after the last vismodegib dose.

Pregnancy Considerations

[US Boxed Warning]: 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. Advise pregnant women of the potential risks to a fetus.

Women exposed to vismodegib during pregnancy (directly or via seminal fluid) are encouraged to contact the Pregnancy Exposure Registry (1-888-835-2555).

Breastfeeding Considerations

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.

Monitoring Parameters

Pregnancy test within 1 week prior to treatment initiation (in females of reproductive potential). 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.

Mechanism of Action

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.

Pharmacokinetics

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%)

Pricing: US

Capsules (Erivedge Oral)

150 mg (per each): $529.76

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.

Brand Names: International
  • Erivedge (AR, AT, AU, BB, BE, BH, CH, CL, CR, CU, CY, CZ, DE, DK, DO, EE, FR, GB, GT, HK, HN, HR, HU, IE, IL, IS, KR, LB, LT, LU, LV, MT, NI, NL, NO, NZ, PA, PL, RO, SE, SI, SK, SV, TH, TR, UA)


For country code abbreviations (show table)
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Erivedge (vismodegib) [prescribing information]. South San Francisco, CA: Genentech USA; July 2020.
  3. Erivedge (vismodegib) [product monograph]. Mississauga, Ontario, Canada: Hoffmann-La Roche Limited; May 2020.
  4. Graham RA, Lum BL, Cheeti S, et al, “Pharmacokinetics of Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Patients With Locally Advanced or Metastatic Solid Tumors: The Role of Alpha-1-Acid Glycoprotein Binding,” Clin Cancer Res, 2011, 17(8):2512-20. [PubMed 21300760]
  5. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  6. Sekulic A, Migden MR, Basset-Seguin N, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer. 2017;17(1):332. doi: 10.1186/s12885-017-3286-5. [PubMed 28511673]
  7. Sekulic A, Migden M, Oro AE, et al, “Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma,” New Engl J Med, 2012, 366(23):2171-9. [PubMed 22670903]
  8. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al, “Inhibiting the Hedgehog Pathway in Patients With the Basal-Cell Nevus Syndrome,” New Engl J Med, 2012, 366(23):2180-8. [PubMed 22670904]
  9. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.
  10. Von Hoff DD, LoRusso PM, Rudin CM, et al, “Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma,” N Engl J Med, 2009, 361(12):1164-72. [PubMed 19726763]
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