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 ?
Vismodegib was the first Hh pathway inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of adults with metastatic or locally advanced BCC.
The global sales of the first targeted drug approved by US FDA for metastatic or locally advanced BCC, Erivedge (vismodegib), has generated the sales revenue of USD253m in 2017 (according to GlobalData) and is expected to peak at USD533m by 2022 (forecasted by Coven & Co's).
Yoo et al., "Efficacy and safety of the hedgehog pathway inhibitor vismodegib in patients with advanced basal cell carcinoma (BCC): ERIVANCE BCC study update," Journal of Clinical Oncology, vol.
The third one relapsed in transit disease and parothid and is currently on Vismodegib. They were both diagnosed with sclerodermiform BCC with perineural invasion.
Grob et al., "Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial," Lancet Oncology, vol.
Caption: FIGURE 2: Lesions of the right thorax before (left) and six months after (right) radiation showing excellent response to radiation (66-76 Gy) with concurrent and adjuvant vismodegib: (anterior upper (a); anterior lower (b); lower neck (c); and back (d)).
Caption: Figure 2: Computer tomography demonstrating pulmonary metastases two months before treatment (t = -2M), with partial regression after 3 months of vismodegib treatment (t = 3 M, arrow 1) and with progressive disease after 11 and 14 months (arrow 1).
(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).
Oro et al., "Efficacy and safety of vismodegib in advanced basal-cell carcinoma," The New England Journal of Medicine, vol.
Gores, "Vismodegib suppresses TRAIL-mediated liver injury in a mouse model of nonalcoholic steatohepatitis," PLoS One, vol.