Vismodegib (Erivedge) is a Hedgehog signal transduction pathway inhibitor that is used in the treatment of locally advanced or metastatic basal cell carcinoma. It may be used following surgery or adult patients who are not candidates of radiotherapy or a surgical procedure.

Vismodegib (Erivedge) Dose in Adults

Vismodegib (Erivedge) Dose in the treatment of metastatic or locally advanced Basal cell carcinoma:

• 150 mg orally once a day until toxicity develops or the disease progresses.
• If a dose is missed, resume with the next scheduled dose. Do not double the dose.

Vismodegib (Erivedge) Dose in Childrens

It should not be used in children less than 18 years of age. [

Pregnancy Risk Category: X

[US Boxed Warning]

• It is extremely toxic to the embryo, and can cause severe adverse reactions including death in pregnant women.
• It is possible for severe fetal malformations to occur. This includes severe midline defects, missing digits, and other irreversible malformations.

[US Boxed Warning]

• Before starting treatment, a pregnancy test must be done within seven days.
• Effective contraception should be used during and after treatment for females with reproductive potential.
• Effective barrier contraceptive methods should be used by males who have a female partner with reproductive potential. The drug is also excreted in the sperm.
• It is important to use a highly effective contraceptive method for 24 months after the last drug dose.

Use Vismodegib (Erivedge), while breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• Breastfeeding is not recommended for infants after receiving the last dose Erivedge.

Dose adjustment in patients with kidney disease:

• Adjustment in the dose is not necessary.

Dose adjustment in patients with liver disease:

• Adjustment in the dose is not necessary.

Side Effects of Vismodegib (Erivedge):

• Cardiovascular:

  • Increased Serum Creatine Phosphokinase

• Central Nervous System:

  • Fatigue

• Dermatologic:

  • Alopecia

• Endocrine & Metabolic:

  • Amenorrhea

• Gastrointestinal:

  • Dysgeusia
  • Weight Loss
  • Nausea
  • Diarrhea
  • Decreased Appetite
  • Constipation
  • Vomiting
  • Ageusia

• Neuromuscular & Skeletal:

  • Muscle Spasm
  • Arthralgia

Side Effects of Vismodegib (Erivedge) (Less common):

• Endocrine & metabolic:

  • Hyponatremia

• Genitourinary:

  • Azotemia

Contraindication to Vismodegib (Erivedge) Include:

• Allergy reactions to any component of the formulation or the drug
• Females who are pregnant
• Breastfeeding mothers
• Female partners may have male patients who do not agree with the Erivedge pregnancy prevention plan.
• Children younger than 18 years old.

Warnings and precautions

• Gastrointestinal toxicities:
  • Treatment may cause mild (Grade 1 and 2) gastrointestinal toxicities.
  • These symptoms include nausea and vomiting, constipation or diarrhea, as well as a decreased appetite.

Monitor:

• Monitor adherence to the treatment.
• A pregnancy test should be done one week before the initiation of treatment in women of reproductive potential.

How to administer Vismodegib (Erivedge)?

• It may be taken orally with or without food.
• The capsules must be swallowed whole.
• They should not be opened or crushed.

Mechanism of action of Vismodegib:

• Vismodegib inhibits Smoothened homologue, (SMO), which is a transmembrane transmembrane proteins that is involved with Hedgehog signal transduction.
• It acts as an indirect Hedgehog pathway inhibitor by binding to the SMO and inducing it.
• The Hedgehog signal transduction pathway, which regulates cell growth and differentiation, is active in fetal development.
• Although it is inactive in adulthood, basal cell carcinoma patients develop mutations in Hedgehog pathway components which result in unrestricted basal cell proliferation.
• Vismodegib is effective in inhibiting cellular growth in Hedgehog signal transduction pathway mutations. More than 99% of the drug's ingredients are natural

Protein-boundIt is mainly metabolized by albumin and alpha-acid glycoprotein. It is processed by glucuronidation and oxidation.

It has been abioavailability32%

Eliminating half-life About 4 days of continuous daily dosing, and approximately 7 days after one dose.

It takes time to get there Peak serum concentration It takes approximately 2.4 days.

It is Excreted It is found mainly in the feces (82%), and approximately 4% in the urine.

Vismodegib Brand Names (International):

• Erivedge

Vismodegib Brand Names in Pakistan:

It is not available in Pakistan.