vismodegib

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
vis-moe-deg-ib

Trade Name(s)

• Erivedge

Ther. Class.

antineoplastics

Pharm. Class.

hedgehog pathway inhibitors

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 signaling pathway; binds/inhibits a transmembrane protein involved in hedgehog signal transduction.

Therapeutic Effect(s):

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))

Contraindication/Precautions

Contraindicated in:

• Blood donation;
• OB:  Pregnancy;
• Lactation:  Lactation.

Use Cautiously in:

• Rep:  Women of reproductive potential and men with female partners of reproductive potential;
• Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

Derm: alopecia, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

F and E: hypokalemia, hyponatremia

GI: constipation, ↓ appetite, diarrhea, impaired taste, nausea, vomiting

GU: amenorrhea, azotemia

Metabolic: weight loss

MS: arthralgia, ↑ creatine kinase, muscle spasm

Neuro: fatigue

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

PO (Adults): 150 mg once daily until disease progression or unacceptable toxicity.

Availability

Capsules: 150 mg

Assessment

• Monitor for diarrhea and vomiting. Maintain adequate hydration and electrolyte balance.
• Monitor for rash periodically during therapy. May cause life-threatening cutaneous reactions, including DRESS, SJS, and TEN. Permanently discontinue if symptoms occur.

Lab Test Considerations:

Obtain a pregnancy test within 7 days of starting vismodegib.

• Obtain serum creatinine and CK at baseline and if patient develops muscle pain/tenderness during therapy. Hold therapy for severe or intolerable muscle symptoms. Permanently discontinue if muscle symptoms recur after restarting therapy.
• May cause hyponatremia, hypokalemia, and azotemia.

Implementation

• If intolerable side effects occur, vismodegib may be held for up to 8 wk.
• PO Administer once daily without regard to food.  DNC: Swallow capsule whole; do not open, crush, or chew. 

Patient/Family Teaching

• Instruct patient to take as directed. If a dose is missed, skip missed dose. Do not make up dose. Resume dosing with next scheduled dose.
• Advise patient to notify health care professional if signs and symptoms of skin reactions (blisters or peeling of skin, high fever or flu-like symptoms, blisters on lip or around mouth or eyes, enlarged lymph nodes, mouth sores, genital sores, skin pain and burning) occur.
• 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 24 mo after last dose.
• Rep:  May can cause fetal harm. Advise females of reproductive potential to use a highly effective method (IUD, hormonal contraceptive, tubal ligation, partner's vasectomy) of contraception during and for at least 24 mo after therapy. Males with female partners of reproductive potential must always use condoms with spermicide, even if they have undergone a successful vasectomy during and for 3 mo after last dose, and may not donate sperm during and for 3 mo after completion of therapy. Instruct patient to notify health care professional promptly if pregnancy is suspected or if breastfeeding. Advise women to avoid breastfeeding during and for 24 mo after final dose of vismodegib. May cause amenorrhea with unknown reversibility.

Evaluation/Desired Outcomes

Decreased spread of basal cell carcinoma.