Antifungal Injection

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Drug Interactions and Contraindications

Drug-Drug Interactions and Contraindications as Listed in the Prescribing Information

CANCIDASa

Antibacterials/ Antimycotics: rifampin

Antiepileptics: carbamazepine, phenytoin

Antiretrovirals: efavirenz, nevirapine

Steroids/ Immunosuppressants: cyclosporine, dexamethasone, tacrolimus

Fluconazole16,a

Antiretrovirals: zidovudine

Bronchodilators: theophylline

Diuretics: hydrochlorothiazide

Gastric acid modifiers: cimetidine, cisapride

Oral contraceptives: ethinyl estradiol, levonorgestrel

Oral hypoglycemics: glipizide, glyburide, tolbutamide

Psychotropic agents: phenytoin, short-acting benzodiazepines

Steroids/ Immunosuppressants: cyclosporine, tacrolimus

Others: rifabutin, rifampin, terfenadine, warfarin

Voriconazole17,a

Antiarrhythmics: quinidine

Antineoplastics: vinblastine, vincristine

Antiretrovirals: amprenavir, delavirdine, efavirenz, nelfinavir, nevirapine, ritonavir, saquinavir

Gastric acid modifiers: cisapride, omeprazole

Long-acting barbiturates: mephobarbital, phenobarbital

Oral hypoglycemics: sulfonylureas

Psychotropic agents: alprazolam, carbamazepine, midazolam, phenytoin, pimozide, triazolam

Statins: atorvastatin

Steroids/ Immunosuppressants: cyclosporine, sirolimus, tacrolimus

Others: astemizole, ergot alkaloids (ergotamine, dihydroergotamine), rifabutin, rifampin, terfenadine, warfarin

AmBisome18,b

No formal clinical studies of drug interactions have been conducted with AmBisome. However, the following drugs are known to interact with amphotericin B and may interact with AmBisome:

Antifungals: azoles (clotrimazole, fluconazole, ketoconazole, miconazole, etc), flucytosine

Antineoplastic agents

Corticosteroids

Digitalis glycosides

Leukocyte transfusions

Other nephrotoxic medications

Skeletal muscle relaxants


Contraindications
CANCIDAS is contraindicated in patients with hypersensitivity to any component of this product.

Contraindications
Fluconazole is contraindicated in patients who have shown hypersensitivity to fluconazole or to any of its excipients. Coadministration of terfenadine is contraindicated in patients receiving fluconazole at multiple doses of 400 mg or higher. The combined use of fluconazole with cisapride is contraindicated.

Contraindications
Voriconazole is contraindicated in patients with known hypersensitivity to voriconazole or to any of its excipients. The combined use of voriconazole with CYP3A4 substrates, astemizole, carbamazepine, cisapride, dihydroergotamine, efavirenz, ergotamine, long-acting barbiturates, pimozide, quinidine, rifabutin, rifampin, ritonavir, sirolimus, or terfenadine is contraindicated.

Contraindications
AmBisome is contraindicated in patients who have demonstrated or have known hypersensitivity to amphotericin B deoxycholate or any other constituents of the product unless, in the opinion of the treating physician, the benefit of therapy outweighs the risk.

a Drug categories that are derived from Gubbins et al do not necessarily indicate that the products listed interact with all the drugs in this category.19

 

b Drug categories as listed in AmBisome Prescribing Information.

 

Concomitant use of CANCIDAS with cyclosporine should be limited to patients for whom the potential benefit outweighs the potential risk of increased hepatic enzyme abnormalities. See the Warning in the Prescribing Information.

Unlike Azoles, CANCIDAS Is Not an Inhibitor of the Cytochrome P450 System16,17

  • In vitro studies demonstrate that CANCIDAS is not an inhibitor of any enzyme in the cytochrome P450 system, is not a substrate for P-glycoprotein, and is a poor substrate for cytochrome P450 enzymes.

References

16.
Diflucan [package insert]. New York, NY: Pfizer Inc; 2004.
17.
Vfend [package insert]. New York, NY: Pfizer Inc; 2005.
18.
AmBisome [package insert]. Deerfield, Ill: Astellas Pharma US Inc; 2005.
19.
Gubbins PO, Anaissie E. Overview of antifungal agents. Infectious Disease Special Edition. 2002;5:65–70.


See All References

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Selected Important Risk Information

CANCIDAS is contraindicated in patients with hypersensitivity to any component of this product.

Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with CANCIDAS. In some patients with serious underlying conditions who were receiving multiple concomitant medications with CANCIDAS, isolated cases of clinically significant hepatic dysfunction, hepatitis, and hepatic failure have been reported; a causal relationship to CANCIDAS has not been established. Patients who develop abnormal liver function tests during therapy with CANCIDAS should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing therapy with CANCIDAS.

For patients receiving CANCIDAS and tacrolimus, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended.

Adult patients on rifampin should receive 70 mg of CANCIDAS daily. When CANCIDAS is co-administered to adult patients with inducers of drug clearance, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, use of a daily dose of 70 mg of CANCIDAS should be considered.

When CANCIDAS is co-administered to pediatric patients with inducers of drug clearance, such as rifampin, efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a dose of 70 mg/m2 daily (not to exceed an actual daily dose of 70 mg) should be considered.

Possible histamine-mediated symptoms have been reported including rash, facial swelling, pruritus, sensation of warmth, or bronchospasm. Anaphylaxis has been reported during administration of CANCIDAS.

The most common adverse reactions in adult patients treated with CANCIDAS (≥10%), regardless of causality, are: diarrhea, pyrexia, chills, ALT/AST increase, blood alkaline phosphatase increase, and decrease of blood potassium.

The most common adverse reactions in pediatric patients treated with CANCIDAS, regardless of causality, were pyrexia (29.2%), blood potassium decreased (15.2%), diarrhea (14%), increased aspartate aminotransferase (11.7%), rash (11.7%), increased alanine aminotransferase (11.1%), hypotension (11.1%), and chills (11.1%).

There is no clinical experience in adult patients with severe hepatic insufficiency (Child-Pugh score >9) and in pediatric patients with any degree of hepatic insufficiency.

Administer by slow intravenous infusion (IV) over approximately 1 hour. Not for IV bolus administration.

 

Before prescribing CANCIDAS, please read the Prescribing Information.

CANCIDAS® (caspofungin acetate)

 
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