vismodegib

vismodegib

(vis-moe-deg-ib) ,

Erivedge

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: hedgehog pathway inhibitors
Pregnancy Category: D

Indications

Metastatic basal cell carcinoma or locally advanced basal cell carcinoma which has recurred in patients who are not candidates for further surgery or radiation.

Action

Inhibits the hedgehog (Hh) signaling pathway; binds/inhibits a transmembrane protein involved in Hedgehog signal transduction.

Therapeutic effects

Decreased spread of basal cell carcinoma.

Pharmacokinetics

Absorption: 31.8% absorbed following oral administration, absorption is saturable.
Distribution: Unknown.
Protein Binding: >99%.
Metabolism and Excretion: Mostly metabolized, eliminated by the liver; 83% excreted in feces, 4.4% in urine.
Half-life: 4 days (continuous once-daily dosing), 12 days (single dose).

Time/action profile (response))

ROUTEONSETPEAKDURATION
POunknownunknown7.6 mo
†Duration of response.

Contraindications/Precautions

Contraindicated in: Obstetric: Pregnancy (can cause embryo-fetal death or severe birth defects); Lactation: Recommend another feeding method; Blood donation (avoid for 7 mo following last dose).
Use Cautiously in: Patients with reproductive potential (females and males; pregnancy prevention is necessary); Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)

Gastrointestinal

  • ↓ appetite (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • impaired taste (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Genitourinary

  • amenorrhea
  • azotemia

Dermatologic

  • alopecia (most frequent)

Fluid and Electrolyte

  • hypokalemia
  • hyponatremia

Metabolic

  • weight loss (most frequent)

Musculoskeletal

  • arthralgias (most frequent)
  • muscle spasms (most frequent)

Interactions

Drug-Drug interaction

Blood levels and toxicity may be ↑ by inhibitors of P-glycoprotein (P-gp) including clarithromycin, erythromycin and azithromycin. Blood levels and effectiveness may be ↓ proton pump inhibitors, H2-receptor antagonists or antacids.

Route/Dosage

Oral (Adults) 150 mg once daily continued until disease progression or unacceptable toxicity.

Availability

Capsules: 150 mg

Nursing implications

Nursing assessment

  • Monitor for diarrhea and vomiting. Maintain adequate hydration and electrolyte balance.
  • Lab Test Considerations: Obtain a pregnancy test within 7 days of starting vismodegib.
    • May cause hyponatremia, hypokalemia, and azotemia.

Potential Nursing Diagnoses

Impaired skin integrity (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Oral: Administer once daily. Swallow capsule whole; do not open, crush, or chew.

Patient/Family Teaching

  • Instruct patient to take as directed. If a dose is missed, skip the missed dose. Do not make up dose. Resume dosing with next scheduled dose.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Discuss the possibility of hair loss with patient. Explore methods of coping.
  • Advise patient not to donate blood during therapy and for at least 7 mo after last dose.
  • Vismodegib can cause fetal harm. Advise male and female patient to use a highly effective method (IUD, hormonal contraceptive, tubal ligation, partner's vasectomy) of contraception during and for at least 7 mo after therapy. Male patients receiving vismodegib must always use condoms with spermicide during any contact with females with child-bearing potential, even if they have undergone a successful vasectomy during and for at least 2 months after completion of therapy. Instruct patient to notify health care professional promptly if pregnancy is suspected or if breastfeeding. Encourage women who have been exposed to vismodegib either directly or through seminal fluid, to participate in ERIVEDGE pregnancy pharmacovigilance program by contacting the Genentech Adverse Event Line at 1-888-835-2555.

Evaluation/Desired Outcomes

  • Decreased spread of basal cell carcinoma.
References in periodicals archive ?
Acquisition of medicines: Erlotinib, Pertuzumab, Trastuzumab emtansina, Vismodegib, Rituxumab and obinutuzumab
3,4) Metastatic or locally advanced tumors may be managed with vismodegib or other inhibitors of Hedgehog pathway signaling.
In addition, imiquimod cream 5%, topical 5-fluorouracil and vismodegib in locally-advanced and metastatic forms are other treatment options (9, 10).
The first such drug, vismodegib (Erivedge), was approved in 2012, and sonidegib (Odomzo) came on the market about 1 year ago.
Contributions with a detail focus then discuss predictive biomarkers in cancer, the drugs crizotinib and vemurafenib, the compound vismodegib in treatment of basal-cell carcinoma, and G-quadruplexes as therapeutic targets.
Clinical trials in Newcastle - one of only a handful that have taken place in the country - found that the treatment vismodegib was able to shrink visible lesions in 47% of patients with advanced basal cell carcinoma.
Vismodegib (Erivedge; basal cell cancer) is a miscellaneous antineoplastic that has been associated with amenorrhea in clinical trials.
From today patients with a particular type of skin cancer could be treated with vismodegib, which is available following European Medicines Agency approval for use in the UK and listing on the national Cancer Drugs Fund.
Finally, the researchers showed that an experimental drug called vismodegib, which blocks the Hhg pathway, inhibits the growth of tamoxifen-resistant human breast tumors in an animal model.
The first publication, entitled "Efficacy and Safety of Vismodegib in Advanced Basal Cell Carcinoma," reports on the results of the pivotal Phase II ERIVANCE BCC study in 104 patients with advanced basal cell carcinoma (BCC) conducted by Genentech.
And in January 2012, the FDA approved vismodegib (Erivedge) to treat advanced and metastatic basal cell carcinoma.
Vismodegib, an oral, once-daily medication for adults with locally advanced and metastatic advanced basal cell carcinoma was approved late last month.