Vismodegib - Uses, Dosage, Side Effects, Interaction

Vismodegib is an orally bioavailable, small molecule inhibitor of SMO and the Hedgehog (Hh) pathway, with potential antineoplastic activity. Upon oral administration, vismodegib targets binds to, and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. SMO is activated upon binding of the Hh ligand to the cell surface receptor Patched (PTCH); inappropriate activation of Hh signaling and uncontrolled cellular proliferation may be associated with SMO mutations.

Vismodegib is a kinase inhibitor actively used in the therapy of unresectable or metastatic basal cell carcinoma. Vismodegib therapy is associated with a low rate of transient elevations in serum aminotransferase during therapy and has been linked to rare cases of clinically apparent acute liver injury.

Vismodegib is a benzamide obtained by formal condensation between the carboxy group of 2-chloro-4-(methylsulfonyl)benzoic acid and the aniline group of 4-chloro-3-(pyridine-2-yl)aniline. Used for the treatment of metastatic basal cell carcinoma. It has a role as an antineoplastic agent, an SMO receptor antagonist, a Hedgehog signaling pathway inhibitor, and a teratogenic agent. It is a sulfone, a member of benzamides, a member of pyridines, and a member of monochlorobenzenes.

Mechanism of Action

Mutations of the Hedgehog pathway may results in uncontrolled proliferation of skin basal cells. Vismodegib binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway. Vismodegib is an inhibitor of the Hedgehog pathway. Vismodegib binds to and inhibits Smoothened, a transmembrane protein involved in Hedgehog signal transduction.

Recent evidence from in vitro and in vivo studies has demonstrated that aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway regulates genes that promote cellular proliferation in various human cancer stem cells (CSCs). Therefore, the chemotherapeutic agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for pancreatic cancer. GDC-0449 (Vismodegib), orally administrable molecule belonging to the 2-arylpyridine class, inhibits SHH signaling pathway by blocking the activities of Smoothened. The objectives of this study were to examine the molecular mechanisms by which GDC-0449 regulates human pancreatic CSC characteristics in vitro. GDC-0499 inhibited cell viability and induced apoptosis in three pancreatic cancer cell lines and pancreatic CSCs. This inhibitor also suppressed cell viability, Gli-DNA binding and transcriptional activities, and induced apoptosis through caspase-3 activation and PARP cleavage in pancreatic CSCs. GDC-0449-induced apoptosis in CSCs showed increased Fas expression and decreased expression of PDGFRa. Furthermore, Bcl-2 was down-regulated whereas TRAIL-R1/DR4 and TRAIL-R2/DR5 expression was increased following the treatment of CSCs with GDC-0449. Suppression of both Gli1 plus Gli2 by shRNA mimicked the changes in cell viability, spheroid formation, apoptosis and gene expression observed in GDC-0449-treated pancreatic CSCs. Thus, activated Gli genes repress DRs and Fas expressions, up-regulate the expressions of Bcl-2 and PDGFRa and facilitate cell survival. These data suggest that GDC-0499 can be used for the management of pancreatic cancer by targeting pancreatic CSCs.

Hedgehog (Hh) signaling is involved in the pathogenesis of liver fibrosis. It has been previously shown that Hh-inhibitor cyclopamine (CYA) can reduce liver fibrosis in rats. However, CYA is not stable in vivo, which limits its clinical application. This study compares the antifibrotic potential of two known Hh antagonists, vismodegib (GDC-0449, abbreviated to GDC) and CYA. GDC is a synthetic molecule presently in clinical cancer trials and has been reported to be safe and efficacious. These drugs attenuated early liver fibrosis in common bile duct ligated rats, improved liver function, and prevented hepatic stellate cell (HSC) activation, thereby suppressing epithelial to mesenchymal transition (EMT). While both CYA and GDC increased the number of proliferating cell nuclear antigen positive liver cells in vivo, only CYA increased Caspase-3 expression in HSCs in rat livers, suggesting that while GDC and CYA effectively attenuate early liver fibrosis, their hepatoprotective effects may be mediated through different modes of action. Thus, GDC has the potential to serve as a new therapeutic agent for treating early liver fibrosis.

Indications

Vismodegib is used for treating locally advanced or metastatic basal cell carcinoma in patients whose carcinoma has recurred after surgery, and in patients who are not candidates for surgery or radiation.
Erivedge is indicated for the treatment of adult patients with: symptomatic metastatic basal cell carcinoma locally advanced basal cell carcinoma inappropriate for surgery or radiotherapy
Vismodegib is a kinase inhibitor active used in the therapy of unresectable or metastatic basal cell carcinoma.
Erivedge capsule is indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.
Vismodegib is indicated for patients with basal cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.
Vismodegib is a hedgehog pathway inhibitor used to treat patients with locally advanced or metastatic basal cell carcinoma.
Vismodegib is used for treating locally advanced or metastatic basal cell carcinoma in patients whose carcinoma has recurred after surgery, and in patients who are not candidates for surgery or radiation.
Locally Advanced Basal Cell Carcinoma
Metastatic Basal cell carcinoma

Use in Cancer

Vismodegib is approved to treat:

Basal cell carcinoma (a type of skin cancer). It is used in adults whose disease has metastasized (spread to other parts of the body). It is also used in adults with locally advanced disease that has recurred (come back) after surgery or who cannot be treated with surgery or radiation.

Vismodegib is also being studied in the treatment of other types of cancer.

Contraindications

Vismodegib is contraindicated in pregnant women or women who may become pregnant.

Boxed Warning of Embryofetal Toxicity

Embryotoxic effects include:

Craniofacial abnormalities
Anorectal defects
Fused or absent digits

Blood Donations – Patients should be advised not to donate blood or blood products during vismodegib treatment and at least 24 months after the last dose.

Important Special Warnings – Counseling of both males and females on vismodegib is necessary.

Women- Following a negative pregnancy test, initiate highly effective contraception before the first dose of vismodegib and continue for seven months after treatment.

Men – During treatment, and for three months following treatment, men should not donate sperm and should use condoms with spermicide (even after vasectomy) as vismodegib may be present in seminal fluid. This precaution is to avoid exposure to patients that may be pregnant.

Dosage

Strengths: 150 mg

Basal Cell Carcinoma

150 mg orally once a day until disease progression or unacceptable toxicity
Withhold therapy for up to 8 weeks for intolerable adverse reactions until improvement or resolution.
Treatment durations shorter than 8 weeks prior to interruptions have not been studied.

EMBRYOFETAL TOXICITY:

This drug can cause embryofetal death or severe birth defects when administered to a pregnant woman.
This drug is embryotoxic, fetotoxic, and teratogenic in animals.
Teratogenic effects include severe midline defects, missing digits, and other irreversible malformations.
Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating therapy.
Advise pregnant women of the potential risks to a fetus.
Advise females of reproductive potential to use effective contraception during and after therapy.
Advise males of the potential risk of drug exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential.

Administration advice:

This drug may be taken with or without food.
Swallow capsules whole; do not open or crush.
If a dose of is missed, do not make it up; resume with the next scheduled dose.
Verify pregnancy status of females of reproductive potential within 7 days prior to initiating this drug.

Side Effects

The Most Common

muscle spasms
joint pain
tiredness
hair loss
change in how things taste or loss of taste
decreased appetite
weight loss
nausea
vomiting
diarrhea
constipation
missed menstrual periods
Absent, missed, or irregular menstrual periods
change in taste
constipation
decreased appetite
diarrhea
difficulty having a bowel movement
difficulty with moving
hair loss or thinning
loss of taste
muscle spasm or stiffness
pain in the joints
stopping of menstrual bleeding
weight loss

More Common

Bloody or cloudy urine
confusion
decreased urine output
dizziness
dry mouth
fast or irregular heartbeat
headache
increased thirst
loss of consciousness
muscle pain or cramps
nausea
pain in the lower back or side
seizures
swelling of the face, ankles, or hands
thirst
unusual tiredness or weakness
vomiting

Rare

Black, tarry stools
blistering, peeling, loosening of the skin
chest pain
chills
cough
diarrhea
itching skin
joint or muscle pain
painful or difficult urination
red irritated eyes
red skin lesions, often with a purple center
sores, ulcers, or white spots in the mouth or on the lips
sore throat
swollen glands
trouble breathing
unusual bleeding or bruising
yellow eyes or skin

Drug interactions

DRUG	INTERACTION
Abametapir	The serum concentration of Vismodegib can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Vismodegib can be increased when combined with Abatacept.
Abemaciclib	Vismodegib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Abrocitinib	The metabolism of Abrocitinib can be decreased when combined with Vismodegib.
Acenocoumarol	The metabolism of Vismodegib can be decreased when combined with Acenocoumarol.
Acetohexamide	The metabolism of Vismodegib can be decreased when combined with Acetohexamide.
Acetyl sulfisoxazole	The metabolism of Vismodegib can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acid	The metabolism of Vismodegib can be decreased when combined with Acetylsalicylic acid.
Adalimumab	The metabolism of Vismodegib can be increased when combined with Adalimumab.
Afatinib	Vismodegib may decrease the excretion rate of Afatinib which could result in a higher serum level.
Agomelatine	The metabolism of Vismodegib can be decreased when combined with Agomelatine.
Allopurinol	Vismodegib may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Alosetron	The metabolism of Vismodegib can be decreased when combined with Alosetron.
Alpelisib	The serum concentration of Alpelisib can be increased when it is combined with Vismodegib.
Aminophenazone	The metabolism of Vismodegib can be decreased when combined with Aminophenazone.
Amiodarone	The metabolism of Vismodegib can be decreased when combined with Amiodarone.
Amitriptyline	The metabolism of Vismodegib can be decreased when combined with Amitriptyline.
Amodiaquine	The metabolism of Vismodegib can be decreased when combined with Amodiaquine.
Amprenavir	The metabolism of Vismodegib can be decreased when combined with Amprenavir.
Anakinra	The metabolism of Vismodegib can be increased when combined with Anakinra.
Antipyrine	The metabolism of Vismodegib can be decreased when combined with Antipyrine.
Apalutamide	The metabolism of Vismodegib can be increased when combined with Apalutamide.
Apixaban	Vismodegib may decrease the excretion rate of Apixaban which could result in a higher serum level.
Apremilast	The metabolism of Vismodegib can be increased when combined with Apremilast.
Aprepitant	The metabolism of Vismodegib can be decreased when combined with Aprepitant.
Arformoterol	The metabolism of Vismodegib can be decreased when combined with Arformoterol.
Armodafinil	The metabolism of Vismodegib can be decreased when combined with Armodafinil.
Artemether	The metabolism of Vismodegib can be decreased when combined with Artemether.
Articaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Articaine.
Asciminib	The metabolism of Vismodegib can be decreased when combined with Asciminib.
Asunaprevir	The metabolism of Asunaprevir can be decreased when combined with Vismodegib.
Atazanavir	The metabolism of Vismodegib can be decreased when combined with Atazanavir.
Atovaquone	The metabolism of Vismodegib can be decreased when combined with Atovaquone.
Avanafil	The serum concentration of Avanafil can be increased when it is combined with Vismodegib.
Avapritinib	The metabolism of Vismodegib can be decreased when combined with Avapritinib.
Avatrombopag	The metabolism of Vismodegib can be increased when combined with Avatrombopag.
Azelastine	The metabolism of Vismodegib can be decreased when combined with Azelastine.
Belzutifan	The serum concentration of Belzutifan can be increased when it is combined with Vismodegib.
Benzocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Benzocaine.
Benzyl alcohol	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Benzyl alcohol.
Berotralstat	The serum concentration of Berotralstat can be increased when it is combined with Vismodegib.
Bexarotene	The metabolism of Vismodegib can be decreased when combined with Bexarotene.
Bimekizumab	The metabolism of Vismodegib can be increased when combined with Bimekizumab.
Boceprevir	The metabolism of Vismodegib can be decreased when combined with Boceprevir.
Bortezomib	The metabolism of Vismodegib can be decreased when combined with Bortezomib.
Bosentan	The metabolism of Vismodegib can be increased when combined with Bosentan.
Brigatinib	Vismodegib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Brivaracetam	The metabolism of Vismodegib can be decreased when combined with Brivaracetam.
Bupivacaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Bupivacaine.
Buprenorphine	The metabolism of Vismodegib can be decreased when combined with Buprenorphine.
Bupropion	The metabolism of Vismodegib can be decreased when combined with Bupropion.
Butacaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Butacaine.
Butamben	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Butamben.
Cabozantinib	The metabolism of Cabozantinib can be decreased when combined with Vismodegib.
Canakinumab	The metabolism of Vismodegib can be increased when combined with Canakinumab.
Candesartan	The metabolism of Vismodegib can be decreased when combined with Candesartan cilexetil.
Cannabidiol	The metabolism of Vismodegib can be decreased when combined with Cannabidiol.
Capecitabine	The metabolism of Vismodegib can be decreased when combined with Capecitabine.
Capsaicin	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Capsaicin.
Carbamazepine	The metabolism of Vismodegib can be increased when combined with Carbamazepine.
Carvedilol	The metabolism of Vismodegib can be decreased when combined with Carvedilol.
Celecoxib	Vismodegib may decrease the excretion rate of Celecoxib which could result in a higher serum level.
Cenobamate	The serum concentration of Vismodegib can be decreased when it is combined with Cenobamate.
Ceritinib	The metabolism of Vismodegib can be decreased when combined with Ceritinib.
Cerivastatin	Vismodegib may decrease the excretion rate of Cerivastatin which could result in a higher serum level.
Certolizumab pegol	The metabolism of Vismodegib can be increased when combined with Certolizumab pegol.
Chloroprocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Chloroprocaine.
Chlorpropamide	The metabolism of Vismodegib can be decreased when combined with Chlorpropamide.
Cilostazol	The serum concentration of Cilostazol can be increased when it is combined with Vismodegib.
Cimetidine	The metabolism of Vismodegib can be decreased when combined with Cimetidine.
Cinchocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Cinchocaine.
Cinnarizine	The metabolism of Vismodegib can be decreased when combined with Cinnarizine.
Ciprofloxacin	The metabolism of Vismodegib can be decreased when combined with Ciprofloxacin.
Cladribine	Vismodegib may decrease the excretion rate of Cladribine which could result in a higher serum level.
Clarithromycin	The metabolism of Vismodegib can be decreased when combined with Clarithromycin.
Clevidipine	The metabolism of Vismodegib can be decreased when combined with Clevidipine.
Clofarabine	Vismodegib may decrease the excretion rate of Clofarabine which could result in a higher serum level.
Clopidogrel	The metabolism of Vismodegib can be decreased when combined with Clopidogrel.
Clozapine	The metabolism of Vismodegib can be decreased when combined with Clozapine.
Cobicistat	The metabolism of Vismodegib can be decreased when combined with Cobicistat.
Cocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Cocaine.
Conivaptan	The metabolism of Vismodegib can be decreased when combined with Conivaptan.
Conjugated	Vismodegib may decrease the excretion rate of Conjugated estrogens which could result in a higher serum level.
Copanlisib	Vismodegib may decrease the excretion rate of Copanlisib which could result in a higher serum level.
Crizotinib	The metabolism of Vismodegib can be decreased when combined with Crizotinib.
Curcumin	The metabolism of Vismodegib can be decreased when combined with Curcumin.
Cyclizine	The metabolism of Vismodegib can be decreased when combined with Cyclizine.
Cyclophosphamide	The metabolism of Vismodegib can be decreased when combined with Cyclophosphamide.
Cyclosporine	The metabolism of Vismodegib can be decreased when combined with Cyclosporine.
Dabrafenib	The serum concentration of Vismodegib can be decreased when it is combined with Dabrafenib.
Dacomitinib	Vismodegib may decrease the excretion rate of Dacomitinib which could result in a higher serum level.
Dactinomycin	Vismodegib may decrease the excretion rate of Dactinomycin which could result in a higher serum level.
Danazol	The metabolism of Vismodegib can be decreased when combined with Danazol.
Dapagliflozin	The metabolism of Vismodegib can be decreased when combined with Dapagliflozin.
Dapsone	The metabolism of Vismodegib can be decreased when combined with Dapsone.
Darbepoetin alfa	The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Vismodegib.
Darolutamide	Vismodegib may decrease the excretion rate of Darolutamide which could result in a higher serum level.
Darunavir	The metabolism of Vismodegib can be decreased when combined with Darunavir.
Dasatinib	Vismodegib may decrease the excretion rate of Dasatinib which could result in a higher serum level.
Daunorubicin	Vismodegib may decrease the excretion rate of Daunorubicin which could result in a higher serum level

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Delafloxacin	Vismodegib may decrease the excretion rate of Delafloxacin which could result in a higher serum level.
Delavirdine	The metabolism of Vismodegib can be decreased when combined with Delavirdine.
Desogestrel	The metabolism of Vismodegib can be decreased when combined with Desogestrel.
Desvenlafaxine	The metabolism of Vismodegib can be decreased when combined with Desvenlafaxine.
Dexamethasone	The metabolism of Vismodegib can be increased when combined with Dexamethasone.
Dexibuprofen	The metabolism of Dexibuprofen can be decreased when combined with Vismodegib.
Dextromethorphan	The metabolism of Vismodegib can be decreased when combined with Dextromethorphan.
Diacerein	The metabolism of Vismodegib can be decreased when combined with Diacerein.
Diazepam	The metabolism of Vismodegib can be decreased when combined with Diazepam.
Diclofenac	The metabolism of Vismodegib can be decreased when combined with Diclofenac.
Dicoumarol	The metabolism of Vismodegib can be decreased when combined with Dicoumarol.
Diethylstilbestrol	The metabolism of Vismodegib can be decreased when combined with Diethylstilbestrol.
Diltiazem	The metabolism of Vismodegib can be decreased when combined with Diltiazem.
Diosmin	The metabolism of Vismodegib can be decreased when combined with Diosmin.
Diphenhydramine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Diphenhydramine.
Doconexent	The metabolism of Vismodegib can be decreased when combined with Doconexent.
Dolutegravir	Vismodegib may decrease the excretion rate of Dolutegravir which could result in a higher serum level.
Donepezil	Vismodegib may decrease the excretion rate of Donepezil which could result in a higher serum level.
Doxazosin	The metabolism of Vismodegib can be decreased when combined with Doxazosin.
Doxepin	The metabolism of Vismodegib can be decreased when combined with Doxepin.
Doxorubicin	Vismodegib may decrease the excretion rate of Doxorubicin which could result in a higher serum level.
Dronabinol	The metabolism of Vismodegib can be decreased when combined with Dronabinol.
Dronedarone	The metabolism of Vismodegib can be decreased when combined with Dronedarone.
Duloxetine	The metabolism of Vismodegib can be decreased when combined with Duloxetine.
Duvelisib	Vismodegib may decrease the excretion rate of Duvelisib which could result in a higher serum level.
Dyclonine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Dyclonine.
Efavirenz	The metabolism of Vismodegib can be decreased when combined with Efavirenz.
Eletriptan	The metabolism of Vismodegib can be decreased when combined with Eletriptan.
Elvitegravir	The metabolism of Vismodegib can be decreased when combined with Elvitegravir.
Emapalumab	The metabolism of Vismodegib can be increased when combined with Emapalumab.
Enasidenib	Vismodegib may decrease the excretion rate of Enasidenib which could result in a higher serum level.
Enzalutamide	The serum concentration of Vismodegib can be decreased when it is combined with Enzalutamide.
Epinephrine	The metabolism of Vismodegib can be decreased when combined with Epinephrine.
Erdafitinib	The metabolism of Erdafitinib can be decreased when combined with Vismodegib.
Ergotamine	The metabolism of Vismodegib can be decreased when combined with Ergotamine.
Ertugliflozin	Vismodegib may decrease the excretion rate of Ertugliflozin which could result in a higher serum level.
Erythromycin	The metabolism of Vismodegib can be decreased when combined with Erythromycin.
Erythropoietin	The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Vismodegib.
Esketamine	The metabolism of Esketamine can be decreased when combined with Vismodegib.
Estradiol	The metabolism of Vismodegib can be decreased when combined with Estradiol.
Estradiol acetate	The metabolism of Estradiol acetate can be decreased when combined with Vismodegib.
Estradiol benzoate	The metabolism of Estradiol benzoate can be decreased when combined with Vismodegib.
Estradiol cypionate	The metabolism of Estradiol cypionate can be decreased when combined with Vismodegib.
Estradiol dienant	The metabolism of Estradiol dienanthate can be decreased when combined with Vismodegib.
Estradiol valerate	The metabolism of Estradiol valerate can be decreased when combined with Vismodegib.
Estrone sulfate	The metabolism of Vismodegib can be decreased when combined with Estrone sulfate.
Etanercept	The metabolism of Vismodegib can be increased when combined with Etanercept.
Ethambutol	The metabolism of Vismodegib can be decreased when combined with Ethambutol.
Ethanol	The metabolism of Vismodegib can be decreased when combined with Ethanol.
Ethinylestradiol	The metabolism of Vismodegib can be decreased when combined with Ethinylestradiol.
Ethyl chloride	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Ethyl chloride.
Etidocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Etidocaine.
Etodolac	The metabolism of Vismodegib can be decreased when combined with Etodolac.
Etoposide	Vismodegib may decrease the excretion rate of Etoposide which could result in a higher serum level.
Etoricoxib	The metabolism of Vismodegib can be decreased when combined with Etoricoxib.
Etravirine	The metabolism of Vismodegib can be decreased when combined with Etravirine.
Ezetimibe	Vismodegib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Felbamate	The metabolism of Vismodegib can be decreased when combined with Felbamate.
Felodipine	The metabolism of Vismodegib can be decreased when combined with Felodipine.
Fenofibrate	The metabolism of Vismodegib can be decreased when combined with Fenofibrate.
Flecainide	The metabolism of Vismodegib can be decreased when combined with Flecainide.
Floxuridine	The metabolism of Vismodegib can be decreased when combined with Floxuridine.
Fluconazole	The metabolism of Vismodegib can be decreased when combined with Fluconazole.
Fluindione	The metabolism of Fluindione can be decreased when combined with Vismodegib.
Flunarizine	The metabolism of Vismodegib can be decreased when combined with Flunarizine.
Flunitrazepam	The metabolism of Vismodegib can be decreased when combined with Flunitrazepam.
Fluorouracil	Vismodegib may decrease the excretion rate of Fluorouracil which could result in a higher serum level.
Fluoxetine	The metabolism of Vismodegib can be decreased when combined with Fluoxetine.
Flurbiprofen	The metabolism of Vismodegib can be decreased when combined with Flurbiprofen.
Fluvastatin	The metabolism of Vismodegib can be decreased when combined with Fluvastatin.
Fluvoxamine	The metabolism of Vismodegib can be decreased when combined with Fluvoxamine.
Folic acid	Vismodegib may decrease the excretion rate of Folic acid which could result in a higher serum level.
Formoterol	The metabolism of Vismodegib can be decreased when combined with Formoterol.
Fosnetupitant	The metabolism of Vismodegib can be decreased when combined with Fosnetupitant.
Fosphenytoin	The metabolism of Vismodegib can be increased when combined with Fosphenytoin.
Fostemsavir	Vismodegib may decrease the excretion rate of Fostemsavir which could result in a higher serum level.
Fusidic acid	The metabolism of Vismodegib can be decreased when combined with Fusidic acid.
Gefitinib	Vismodegib may decrease the excretion rate of Gefitinib which could result in a higher serum level.
Gemfibrozil	The metabolism of Vismodegib can be decreased when combined with Gemfibrozil.
Ginkgo biloba	The metabolism of Vismodegib can be decreased when combined with Ginkgo biloba.
Glasdegib	Vismodegib may decrease the excretion rate of Glasdegib which could result in a higher serum level.
Glecaprevir	Vismodegib may decrease the excretion rate of Glecaprevir which could result in a higher serum level.
Gliclazide	The metabolism of Vismodegib can be decreased when combined with Gliclazide.
Glimepiride	The metabolism of Vismodegib can be decreased when combined with Glimepiride.
Glipizide	The metabolism of Vismodegib can be decreased when combined with Glipizide.
Gliquidone	The metabolism of Vismodegib can be decreased when combined with Gliquidone.
Glyburide	Vismodegib may decrease the excretion rate of Glyburide which could result in a higher serum level.
Golimumab	The metabolism of Vismodegib can be increased when combined with Golimumab.
Haloperidol	The serum concentration of Haloperidol can be increased when it is combined with Vismodegib.
Halothane	The metabolism of Vismodegib can be decreased when combined with Halothane.
Hydromorphone	The metabolism of Vismodegib can be decreased when combined with Hydromorphone.
Ibuprofen	The metabolism of Vismodegib can be decreased when combined with Ibuprofen.
Idarubicin	The metabolism of Vismodegib can be decreased when combined with Idarubicin.
Idelalisib	Vismodegib may decrease the excretion rate of Idelalisib which could result in a higher serum level.
Ifosfamide	The metabolism of Vismodegib can be decreased when combined with Ifosfamide.
Imatinib	The metabolism of Vismodegib can be decreased when combined with Imatinib.
Indinavir	The metabolism of Vismodegib can be decreased when combined with Indinavir.
Indomethacin	The metabolism of Vismodegib can be decreased when combined with Indomethacin.
Infliximab	The metabolism of Vismodegib can be increased when combined with Infliximab.
Irbesartan	The metabolism of Vismodegib can be decreased when combined with Irbesartan.

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Irinotecan	Vismodegib may decrease the excretion rate of Irinotecan which could result in a higher serum level.
Isavuconazole	The metabolism of Vismodegib can be decreased when combined with Isavuconazole.
Isavuconazonium	The metabolism of Vismodegib can be decreased when combined with Isavuconazonium.
Isoniazid	The metabolism of Vismodegib can be decreased when combined with Isoniazid.
Isradipine	The metabolism of Vismodegib can be decreased when combined with Isradipine.
Istradefylline	The metabolism of Istradefylline can be decreased when combined with Vismodegib.
Itraconazole	The metabolism of Vismodegib can be decreased when combined with Itraconazole.
Ivermectin	Vismodegib may decrease the excretion rate of Ivermectin which could result in a higher serum level.
Ivosidenib	The metabolism of Vismodegib can be increased when combined with Ivosidenib.
Ketamine	The metabolism of Vismodegib can be decreased when combined with Ketamine.
Ketoconazole	The metabolism of Vismodegib can be decreased when combined with Ketoconazole.
Ketorolac	The metabolism of Vismodegib can be decreased when combined with Ketorolac.
Lacosamide	The metabolism of Vismodegib can be decreased when combined with Lacosamide.
Lamivudine	Vismodegib may decrease the excretion rate of Lamivudine which could result in a higher serum level.
Lansoprazole	The metabolism of Vismodegib can be decreased when combined with Lansoprazole.
Leflunomide	Vismodegib may decrease the excretion rate of Leflunomide which could result in a higher serum level.
Lenvatinib	Vismodegib may decrease the excretion rate of Lenvatinib which could result in a higher serum level.
Lesinurad	The metabolism of Lesinurad can be decreased when combined with Vismodegib.
Levobupivacaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Levobupivacaine.
Levoketoconazole	The metabolism of Vismodegib can be decreased when combined with Levoketoconazole.
Lidocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Lidocaine.
Linagliptin	The metabolism of Vismodegib can be decreased when combined with Linagliptin.
Lonafarnib	The metabolism of Vismodegib can be decreased when combined with Lonafarnib.
Lopinavir	The metabolism of Vismodegib can be decreased when combined with Lopinavir.
Lornoxicam	The metabolism of Vismodegib can be decreased when combined with Lornoxicam.
Losartan	The metabolism of Vismodegib can be decreased when combined with Losartan.
Lovastatin	The metabolism of Vismodegib can be decreased when combined with Lovastatin.
Lumacaftor	The metabolism of Vismodegib can be increased when combined with Lumacaftor.
Lumiracoxib	The metabolism of Vismodegib can be decreased when combined with Lumiracoxib.
Lusutrombopag	Vismodegib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Lynestrenol	The metabolism of Lynestrenol can be decreased when combined with Vismodegib.
Manidipine	The metabolism of Vismodegib can be decreased when combined with Manidipine.
Mavacamten	The serum concentration of Vismodegib can be decreased when it is combined with Mavacamten.
Medroxyprogester	The metabolism of Vismodegib can be decreased when combined with Medroxyprogesterone acetate.
Mefenamic acid	The metabolism of Vismodegib can be decreased when combined with Mefenamic acid.
Meloxicam	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Meloxicam.
Mephenytoin	The metabolism of Vismodegib can be decreased when combined with Mephenytoin.
Mepivacaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Mepivacaine.
Mestranol	The metabolism of Vismodegib can be decreased when combined with Mestranol.
Methadone	The metabolism of Vismodegib can be decreased when combined with Methadone.
Methimazole	The metabolism of Vismodegib can be decreased when combined with Methimazole.
Methotrexate	Vismodegib may decrease the excretion rate of Methotrexate which could result in a higher serum level.
Methoxy	The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Vismodegib.
Methoxyflurane	The metabolism of Vismodegib can be decreased when combined with Methoxyflurane.
Methylene blue	The metabolism of Vismodegib can be decreased when combined with Methylene blue.
Metreleptin	The metabolism of Vismodegib can be increased when combined with Metreleptin.
Metronidazole	The metabolism of Vismodegib can be decreased when combined with Metronidazole.
Miconazole	The metabolism of Vismodegib can be decreased when combined with Miconazole.
Midostaurin	The metabolism of Vismodegib can be decreased when combined with Midostaurin.
Mifepristone	The metabolism of Vismodegib can be decreased when combined with Mifepristone.
Milnacipran	The metabolism of Vismodegib can be decreased when combined with Milnacipran.
Mitotane	The metabolism of Vismodegib can be increased when combined with Mitotane.
Mitoxantrone	Vismodegib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level.
Modafinil	The metabolism of Vismodegib can be decreased when combined with Modafinil.
Montelukast	The metabolism of Vismodegib can be decreased when combined with Montelukast.
Mycophenolate	Vismodegib may decrease the excretion rate of Mycophenolate mofetil which could result in a higher serum level.
Nabilone	The metabolism of Vismodegib can be decreased when combined with Nabilone.
Nabumetone	The metabolism of Vismodegib can be decreased when combined with Nabumetone.
Naloxone	The metabolism of Vismodegib can be decreased when combined with Naloxone.
Naproxen	The metabolism of Vismodegib can be decreased when combined with Naproxen.
Nateglinide	The metabolism of Vismodegib can be decreased when combined with Nateglinide.
Nefazodone	The metabolism of Vismodegib can be decreased when combined with Nefazodone.
Nelfinavir	The metabolism of Vismodegib can be decreased when combined with Nelfinavir.
Netupitant	The metabolism of Vismodegib can be decreased when combined with Netupitant.
Nevirapine	The metabolism of Vismodegib can be decreased when combined with Nevirapine.
Nicardipine	The metabolism of Vismodegib can be decreased when combined with Nicardipine.
Niclosamide	The metabolism of Vismodegib can be decreased when combined with Niclosamide.
Nilotinib	The metabolism of Vismodegib can be decreased when combined with Nilotinib.
Nilutamide	The metabolism of Vismodegib can be decreased when combined with Nilutamide.
Nilvadipine	The metabolism of Vismodegib can be decreased when combined with Nilvadipine.
Nitrofurantoin	Vismodegib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Norgestimate	The metabolism of Vismodegib can be decreased when combined with Norgestimate.
Noscapine	The metabolism of Vismodegib can be decreased when combined with Noscapine.
Olanzapine	The metabolism of Vismodegib can be decreased when combined with Olanzapine.
Olodaterol	The metabolism of Olodaterol can be decreased when combined with Vismodegib.
Ombitasvir	Vismodegib may decrease the excretion rate of Ombitasvir which could result in a higher serum level.
Omeprazole	The metabolism of Vismodegib can be decreased when combined with Omeprazole.
Ondansetron	The metabolism of Vismodegib can be decreased when combined with Ondansetron.
Oritavancin	The metabolism of Vismodegib can be decreased when combined with Oritavancin.
Osimertinib	Vismodegib may decrease the excretion rate of Osimertinib which could result in a higher serum level.
Ospemifene	The metabolism of Vismodegib can be decreased when combined with Ospemifene.
Oxaliplatin	Vismodegib may decrease the excretion rate of Oxaliplatin which could result in a higher serum level.
Oxandrolone	The metabolism of Vismodegib can be decreased when combined with Oxandrolone.
Oxetacaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Oxetacaine.
Oxybuprocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Oxybuprocaine.
Ozanimod	Vismodegib may decrease the excretion rate of Ozanimod which could result in a higher serum level.
Palbociclib	Vismodegib may decrease the excretion rate of Palbociclib which could result in a higher serum level.
Paramethadione	The metabolism of Vismodegib can be decreased when combined with Paramethadione.
Parecoxib	The metabolism of Vismodegib can be decreased when combined with Parecoxib.
Paroxetine	The metabolism of Vismodegib can be decreased when combined with Paroxetine.
Pazopanib	Vismodegib may decrease the excretion rate of Pazopanib which could result in a higher serum level.
Peginesatide	The risk or severity of Thrombosis can be increased when Peginesatide is combined with Vismodegib.
Peginterferon	The metabolism of Vismodegib can be increased when combined with Peginterferon alfa-2b.
Pentobarbital	The metabolism of Vismodegib can be increased when combined with Pentobarbital.
Phenobarbital	The metabolism of Vismodegib can be increased when combined with Phenobarbital.
Phenol	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Phenol.
Phenprocoumon	The metabolism of Vismodegib can be decreased when combined with Phenprocoumon.
Phenylbutazone	The metabolism of Vismodegib can be decreased when combined with Phenylbutazone.
Phenytoin	The metabolism of Vismodegib can be increased when combined with Phenytoin.
Pibrentasvir	Vismodegib may decrease the excretion rate of Pibrentasvir which could result in a higher serum level.

Piperaquine	The metabolism of Piperaquine can be decreased when combined with Vismodegib.
Pirfenidone	The metabolism of Vismodegib can be decreased when combined with Pirfenidone.
Piroxicam	The metabolism of Vismodegib can be decreased when combined with Piroxicam.
Pitavastatin	Vismodegib may decrease the excretion rate of Pitavastatin which could result in a higher serum level.
Pitolisant	The serum concentration of Vismodegib can be decreased when it is combined with Pitolisant.
Ponatinib	Vismodegib may decrease the excretion rate of Ponatinib which could result in a higher serum level.
Posaconazole	The metabolism of Vismodegib can be decreased when combined with Posaconazole.
Pralatrexate	Vismodegib may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
Pralsetinib	Vismodegib may decrease the excretion rate of Pralsetinib which could result in a higher serum level.
Pramocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Pramocaine.
Prasugrel	The metabolism of Vismodegib can be decreased when combined with Prasugrel.
Pravastatin	Vismodegib may decrease the excretion rate of Pravastatin which could result in a higher serum level.
Prazosin	Vismodegib may decrease the excretion rate of Prazosin which could result in a higher serum level.
Prilocaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Prilocaine.
Primaquine	The metabolism of Vismodegib can be decreased when combined with Primaquine.
Primidone	The metabolism of Vismodegib can be increased when combined with Primidone.
Probenecid	The metabolism of Vismodegib can be decreased when combined with Probenecid.
Procaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Procaine.
Progesterone	The metabolism of Vismodegib can be decreased when combined with Progesterone.
Proguanil	The metabolism of Vismodegib can be decreased when combined with Proguanil.
Promazine	The metabolism of Vismodegib can be decreased when combined with Promazine.
Promethazine	The metabolism of Vismodegib can be decreased when combined with Promethazine.
Proparacaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Proparacaine.
Propofol	The metabolism of Vismodegib can be decreased when combined with Propofol.
Propoxycaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Propoxycaine.
Propranolol	The serum concentration of Propranolol can be increased when it is combined with Vismodegib.
Quazepam	The metabolism of Vismodegib can be decreased when combined with Quazepam.
Quinidine	The metabolism of Vismodegib can be decreased when combined with Quinidine.
Quinine	The metabolism of Vismodegib can be decreased when combined with Quinine.
Raloxifene	Vismodegib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
Ramelteon	The metabolism of Vismodegib can be decreased when combined with Ramelteon.
Regorafenib	The metabolism of Vismodegib can be decreased when combined with Regorafenib.
Revefenacin	Vismodegib may decrease the excretion rate of Revefenacin which could result in a higher serum level.
Ribociclib	The metabolism of Vismodegib can be decreased when combined with Ribociclib.
Rifampicin	The metabolism of Vismodegib can be increased when combined with Rifampicin.
Rifamycin	The metabolism of Vismodegib can be increased when combined with Rifamycin.
Rifapentine	The metabolism of Vismodegib can be increased when combined with Rifapentine.
Rilonacept	The metabolism of Vismodegib can be increased when combined with Rilonacept.
Rilpivirine	The metabolism of Vismodegib can be decreased when combined with Rilpivirine.
Riluzole	Vismodegib may decrease the excretion rate of Riluzole which could result in a higher serum level.
Rimegepant	The serum concentration of Rimegepant can be increased when it is combined with Vismodegib.
Riociguat	Vismodegib may decrease the excretion rate of Riociguat which could result in a higher serum level.
Ripretinib	Vismodegib may decrease the excretion rate of Ripretinib which could result in a higher serum level.
Ritonavir	The serum concentration of Vismodegib can be increased when it is combined with Ritonavir.
Rivaroxaban	Vismodegib may decrease the excretion rate of Rivaroxaban which could result in a higher serum level.
Rofecoxib	The metabolism of Vismodegib can be decreased when combined with Rofecoxib.
Ropivacaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Ropivacaine.
Rosiglitazone	The metabolism of Vismodegib can be decreased when combined with Rosiglitazone.
Rosuvastatin	Vismodegib may decrease the excretion rate of Rosuvastatin which could result in a higher serum level.
Rucaparib	Vismodegib may decrease the excretion rate of Rucaparib which could result in a higher serum level.
Rupatadine	The metabolism of Rupatadine can be decreased when combined with Vismodegib.
Ruxolitinib	The metabolism of Ruxolitinib can be decreased when combined with Vismodegib.
Salicylic acid	The metabolism of Vismodegib can be decreased when combined with Salicylic acid.
Saquinavir	The metabolism of Vismodegib can be decreased when combined with Saquinavir.
Satralizumab	The serum concentration of Vismodegib can be decreased when it is combined with Satralizumab.
Secukinumab	The metabolism of Vismodegib can be increased when combined with Secukinumab.
Selegiline	The metabolism of Vismodegib can be decreased when combined with Selegiline.
Selumetinib	Vismodegib may decrease the excretion rate of Selumetinib which could result in a higher serum level.
Sertraline	The metabolism of Vismodegib can be decreased when combined with Sertraline.
Sildenafil	The metabolism of Vismodegib can be decreased when combined with Sildenafil.
Siltuximab	The metabolism of Vismodegib can be increased when combined with Siltuximab.
Simeprevir	The metabolism of Vismodegib can be decreased when combined with Simeprevir.
Simvastatin	The metabolism of Vismodegib can be decreased when combined with Simvastatin.
Siponimod	The metabolism of Siponimod can be decreased when combined with Vismodegib.
Sitaxentan	The metabolism of Vismodegib can be decreased when combined with Sitaxentan.
Sofosbuvir	Vismodegib may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Somatrogon	The metabolism of Vismodegib can be increased when combined with Somatrogon.
Sorafenib	The metabolism of Vismodegib can be decreased when combined with Sorafenib.
Sotorasib	The serum concentration of Vismodegib can be decreased when it is combined with Sotorasib.
St. John’s Wort	The metabolism of Vismodegib can be increased when combined with St. John’s Wort.
Stiripentol	The metabolism of Vismodegib can be decreased when combined with Stiripentol.
Sulfadiazine	The metabolism of Vismodegib can be decreased when combined with Sulfadiazine.
Sulfamethizole	The metabolism of Vismodegib can be decreased when combined with Sulfamethizole.
Sulfamethoxazole	The metabolism of Vismodegib can be decreased when combined with Sulfamethoxazole.
Sulfaphenazole	The metabolism of Vismodegib can be decreased when combined with Sulfaphenazole.
Sulfapyridine	The metabolism of Vismodegib can be decreased when combined with Sulfapyridine.
Sulfasalazine	Vismodegib may decrease the excretion rate of Sulfasalazine which could result in a higher serum level.
Sulfinpyrazone	The metabolism of Vismodegib can be decreased when combined with Sulfinpyrazone.
Sulfisoxazole	The metabolism of Vismodegib can be decreased when combined with Sulfisoxazole.
Sumatriptan	Vismodegib may decrease the excretion rate of Sumatriptan which could result in a higher serum level.
Talazoparib	Vismodegib may decrease the excretion rate of Talazoparib which could result in a higher serum level.
Tamoxifen	Vismodegib may decrease the excretion rate of Tamoxifen which could result in a higher serum level.
Tazemetostat	Vismodegib may decrease the excretion rate of Tazemetostat which could result in a higher serum level.
Tegaserod	Vismodegib may decrease the excretion rate of Tegaserod which could result in a higher serum level.
Telaprevir	The metabolism of Vismodegib can be decreased when combined with Telaprevir.
Telithromycin	The metabolism of Vismodegib can be decreased when combined with Telithromycin.
Telotristat ethyl	The serum concentration of Vismodegib can be decreased when it is combined with Telotristat ethyl.
Teniposide	Vismodegib may decrease the excretion rate of Teniposide which could result in a higher serum level.
Tenofovir	The serum concentration of Tenofovir alafenamide can be increased when it is combined with Vismodegib.
Tenoxicam	The metabolism of Vismodegib can be decreased when combined with Tenoxicam.
Tepotinib	The metabolism of Vismodegib can be decreased when combined with Tepotinib.
Terbinafine	The metabolism of Vismodegib can be decreased when combined with Terbinafine.
Terfenadine	The metabolism of Vismodegib can be decreased when combined with Terfenadine.
Teriflunomide	Vismodegib may decrease the excretion rate of Teriflunomide which could result in a higher serum level.
Testosterone	Vismodegib may decrease the excretion rate of Testosterone which could result in a higher serum level.
Testosterone	Vismodegib may decrease the excretion rate of Testosterone cypionate which could result in a higher serum level.
Testosterone	Vismodegib may decrease the excretion rate of Testosterone enanthate which could result in a higher serum level.
Tetracaine	The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Tetracaine.
Thalidomide	The metabolism of Vismodegib can be decreased when combined with Thalidomide.
Thiamylal	The metabolism of Vismodegib can be decreased when combined with Thiamylal.

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Ticagrelor	The metabolism of Vismodegib can be decreased when combined with Ticagrelor.
Ticlopidine	The metabolism of Vismodegib can be decreased when combined with Ticlopidine.
Tipranavir	The metabolism of Vismodegib can be decreased when combined with Tipranavir.
Tocilizumab	The metabolism of Vismodegib can be increased when combined with Tocilizumab.
Tolazamide	The metabolism of Vismodegib can be decreased when combined with Tolazamide.
Tolbutamide	The metabolism of Vismodegib can be decreased when combined with Tolbutamide.
Tolterodine	The metabolism of Vismodegib can be decreased when combined with Tolterodine.
Topotecan	Vismodegib may decrease the excretion rate of Topotecan which could result in a higher serum level.
Torasemide	The metabolism of Vismodegib can be decreased when combined with Torasemide.
Trabectedin	The metabolism of Vismodegib can be decreased when combined with Trabectedin.
Tranylcypromine	The metabolism of Vismodegib can be decreased when combined with Tranylcypromine.
Treprostinil	The metabolism of Vismodegib can be decreased when combined with Treprostinil.
Tretinoin	The metabolism of Vismodegib can be decreased when combined with Tretinoin.
Triclabendazole	The metabolism of Vismodegib can be decreased when combined with Triclabendazole.
Trilaciclib	Vismodegib may decrease the excretion rate of Trilaciclib which could result in a higher serum level.
Trimethadione	The metabolism of Vismodegib can be decreased when combined with Trimethadione.
Trimethoprim	The metabolism of Vismodegib can be decreased when combined with Trimethoprim.
Trimipramine	The metabolism of Vismodegib can be decreased when combined with Trimipramine.
Troglitazone	The metabolism of Vismodegib can be decreased when combined with Troglitazone.
Troleandomycin	The metabolism of Vismodegib can be decreased when combined with Troleandomycin.
Tucatinib	The metabolism of Tucatinib can be decreased when combined with Vismodegib.
Ubrogepant	The serum concentration of Ubrogepant can be increased when it is combined with Vismodegib.
Valdecoxib	The metabolism of Vismodegib can be decreased when combined with Valdecoxib.
Valproic acid	The metabolism of Vismodegib can be decreased when combined with Valproic acid.
Valsartan	The metabolism of Vismodegib can be decreased when combined with Valsartan.
Velpatasvir	Vismodegib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Vemurafenib	Vismodegib may decrease the excretion rate of Vemurafenib which could result in a higher serum level.
Venetoclax	The metabolism of Vismodegib can be decreased when combined with Venetoclax.
Verapamil	The metabolism of Vismodegib can be decreased when combined with Verapamil.
Viloxazine	The metabolism of Vismodegib can be decreased when combined with Viloxazine.
Vincristine	Vismodegib may decrease the excretion rate of Vincristine which could result in a higher serum level.
Voriconazole	The metabolism of Vismodegib can be decreased when combined with Voriconazole.
Vortioxetine	The metabolism of Vortioxetine can be decreased when combined with Vismodegib.
Voxelotor	The metabolism of Voxelotor can be decreased when combined with Vismodegib.
Voxilaprevir	Vismodegib may decrease the excretion rate of Voxilaprevir which could result in a higher serum level.
Warfarin	The metabolism of Vismodegib can be increased when combined with Warfarin.
Ximelagatran	The metabolism of Vismodegib can be decreased when combined with Ximelagatran.
Zafirlukast	The metabolism of Vismodegib can be decreased when combined with Zafirlukast.
Zidovudine	Vismodegib may decrease the excretion rate of Zidovudine which could result in a higher serum level.
Zileuton	The metabolism of Vismodegib can be decreased when combined with Zileuton.
Zimelidine	The metabolism of Vismodegib can be decreased when combined with Zimelidine.
Ziprasidone	The metabolism of Vismodegib can be decreased when combined with Ziprasidone.
Zolpidem	The metabolism of Vismodegib can be decreased when combined with Zolpidem.
Zopiclone	The metabolism of Vismodegib can be decreased when combined with Zopiclone.

Pregnancy and Lactation

FDA Pregnancy Category D

Pregnancy

Vismodegib capsule can cause fetal harm when administered to a pregnant female based on its mechanism of action. Vismodegib is teratogenic in rats at doses corresponding to an exposure of 20% of the exposure at the recommended human dose (estimated AUC0-24hr steady-state exposure). In rats, malformations included craniofacial anomalies, open perineum, and absent or fused digits. Fetal retardations and variations were also observed. Vismodegib is embryolethal in rats at exposures within the range achieved at the recommended human dose. If vismodegib is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the embryo or fetus. Encourage women who may have been exposed to vismodegib during pregnancy, either directly or through seminal fluid, to participate in the vismodegib pregnancy pharmacovigilance program by contacting the Genentech

Lactation

No information is available on the clinical use of vismodegib during breastfeeding. Because vismodegib is more than 99% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is 4 days and it might accumulate in the infant. The manufacturer recommends that breastfeeding be discontinued during vismodegib therapy and for 24 months after the final dose.

How should this medicine be used?

Vismodegib comes as a capsule to take by mouth. It is usually taken once a day with or without food. To help you remember to take vismodegib, take it at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take vismodegib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Swallow the capsules whole; do not split, chew, or crush them.

What special precautions should I follow?

Before taking vismodegib,

tell your doctor and pharmacist if you are allergic to vismodegib, any other medications, or any of the ingredients in vismodegib capsules. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antacids; certain antibiotics such as azithromycin (Z-Pak, Zithromax), clarithromycin (Biaxin, in Prevpac), and erythromycin (E.E.S., Eryc, Ery-Tab, Erythrocin, PCE); a medication for indigestion, heartburn, or ulcers such as cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac); and proton-pump inhibitors such as dexlansoprazole (Dexilant), lansoprazole (Prevacid, in Prevpac), omeprazole (Prilosec, Zegerid), pantoprazole (Protonix), and rabeprazole (AcipHex). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with vismodegib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
do not breastfeed while you are taking vismodegib and for 7 months after your treatment.

References