CRESEMBA

Azole Antifungals

 
NOTE: The oral capsule and intravenous infusion formulations are bioequivalent. Dosage adjustment is not required when switching between formulations.

renal failure (unspecified) / Delayed / 10.1-10.1
thrombosis / Delayed / 0-5.0
hepatic failure / Delayed / 0-5.0
cholecystitis / Delayed / 0-5.0
cardiac arrest / Early / 0-5.0
bradycardia / Rapid / 0-5.0
atrial fibrillation / Early / 0-5.0
atrial flutter / Early / 0-5.0
bronchospasm / Rapid / 0-5.0
exfoliative dermatitis / Delayed / 0-5.0
pancytopenia / Delayed / 0-5.0
agranulocytosis / Delayed / 0-5.0
anaphylactoid reactions / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known

hypokalemia / Delayed / 19.1-19.1
elevated hepatic enzymes / Delayed / 17.1-17.1
dyspnea / Early / 17.1-17.1
peripheral edema / Delayed / 15.2-15.2
constipation / Delayed / 14.0-14.0
chest pain (unspecified) / Early / 8.9-8.9
delirium / Early / 8.6-8.6
confusion / Early / 8.6-8.6
hypotension / Rapid / 8.2-8.2
hypomagnesemia / Delayed / 5.4-5.4
hepatitis / Delayed / 0-5.0
cholelithiasis / Delayed / 0-5.0
hepatomegaly / Delayed / 0-5.0
supraventricular tachycardia (SVT) / Early / 0-5.0
shortened QT interval / Delayed / 0-5.0
palpitations / Early / 0-5.0
phlebitis / Rapid / 0-5.0
stomatitis / Delayed / 0-5.0
gastritis / Delayed / 0-5.0
hypoglycemia / Early / 0-5.0
hypoalbuminemia / Delayed / 0-5.0
hyponatremia / Delayed / 0-5.0
hematuria / Delayed / 0-5.0
proteinuria / Delayed / 0-5.0
peripheral neuropathy / Delayed / 0-5.0
hallucinations / Early / 0-5.0
encephalopathy / Delayed / 0-5.0
migraine / Early / 0-5.0
depression / Delayed / 0-5.0
tachypnea / Early / 0-5.0
erythema / Early / 0-5.0
bone pain / Delayed / 0-5.0
leukopenia / Delayed / 0-5.0
infusion-related reactions / Rapid / Incidence not known
secondary malignancy / Delayed / Incidence not known

nausea / Early / 27.6-27.6
vomiting / Early / 24.9-24.9
diarrhea / Early / 23.7-23.7
abdominal pain / Early / 16.7-16.7
headache / Early / 16.7-16.7
cough / Delayed / 12.0-12.0
fatigue / Early / 10.5-10.5
insomnia / Early / 10.5-10.5
back pain / Delayed / 10.1-10.1
anorexia / Delayed / 8.6-8.6
agitation / Early / 8.6-8.6
rash / Early / 8.6-8.6
anxiety / Delayed / 8.2-8.2
pruritus / Rapid / 8.2-8.2
injection site reaction / Rapid / 6.2-6.2
dyspepsia / Early / 6.2-6.2
chills / Rapid / 0-5.0
gingivitis / Delayed / 0-5.0
dysgeusia / Early / 0-5.0
tremor / Early / 0-5.0
malaise / Early / 0-5.0
paresthesias / Delayed / 0-5.0
hypoesthesia / Delayed / 0-5.0
syncope / Early / 0-5.0
petechiae / Delayed / 0-5.0
alopecia / Delayed / 0-5.0
urticaria / Rapid / 0-5.0
tinnitus / Delayed / 0-5.0
vertigo / Early / 0-5.0
dizziness / Early / Incidence not known

CRESEMBA

Rx

Oral and injectable azole antifungal
Used for the treatment of invasive aspergillosis or invasive mucormycosis
Bioequivalence between oral and intravenous formulations established

†Indicates off-label use

No dosage adjustments are needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B). Isavuconazonium has not been studied in patients with severe hepatic impairment (Child-Pugh C); give considerable consideration to risks and benefits before administering to patients with severe hepatic impairment.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abacavir; Dolutegravir; Lamivudine: (Moderate) Concomitant use of isavuconazonium with dolutegravir may result in increased serum concentrations of dolutegravir. Dolutegravir is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with isavuconazonium is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with isavuconazonium. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
Acetaminophen: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Aspirin: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Caffeine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with isavuconazonium may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isavuconazonium is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4. (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Dextromethorphan: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Diphenhydramine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isavuconazonium is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Ibuprofen: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. If isavuconazonium is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like isavuconazonium can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If isavuconazonium is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Phenylephrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Acetaminophen; Pseudoephedrine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Adagrasib: (Contraindicated) Coadministration of isavuconazonium with adagrasib is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased isavuconazole exposure by 422%.
Albuterol; Budesonide: (Moderate) Concomitant use of isavuconazonium with budesonide may result in increased serum concentrations of budesonide. Budesonide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Aldesleukin, IL-2: (Moderate) Concomitant use of isavuconazonium with aldesleukin, IL-2 may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of CYP3A4; aldesleukin is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Alfentanil: (Moderate) Concomitant use of isavuconazonium with alfentanil may result in increased serum concentrations of alfentanil. Alfentanil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Alfuzosin: (Moderate) Concomitant use of isavuconazonium with alfuzosin may result in increased serum concentrations of alfuzosin. Alfuzosin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Aliskiren: (Moderate) Concomitant use of isavuconazonium with aliskiren may result in increased serum concentrations of aliskiren. Aliskiren is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of isavuconazonium with aliskiren may result in increased serum concentrations of aliskiren. Aliskiren is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Almotriptan: (Moderate) Concomitant use of isavuconazonium with almotriptan may result in increased serum concentrations of almotriptan. Almotriptan is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Alprazolam: (Major) Avoid coadministration of alprazolam and isavuconazonium due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with isavuconazonium, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate. Isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4. Coadministration with other moderate CYP3A4 inhibitors increased alprazolam exposure by 1.6- to 1.98-fold.
Amiodarone: (Major) Concomitant use of isavuconazonium with amiodarone may result in increased serum concentrations of both drugs. Amiodarone is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amitriptyline: (Moderate) Concomitant use of isavuconazonium with amitriptyline may result in increased serum concentrations of amitriptyline. Amitriptyline is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amlodipine: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amlodipine; Atorvastatin: (Major) Use caution and the lowest atorvastatin dose necessary if coadministration with isavuconazonium is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Isavuconazole, the active moiety of isavuconazonium, inhibits the CYP3A4-mediated metabolism and P-glycoprotein (P-gp)-mediated transport of atorvastatin. (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amlodipine; Benazepril: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amlodipine; Celecoxib: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amlodipine; Olmesartan: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amlodipine; Valsartan: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Concomitant use of isavuconazonium with clarithromycin may result in increased serum concentrations of both drugs. Clarithromycin is a substrate and moderate inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with omeprazole may result in increased serum concentrations of omeprazole. Omeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Apalutamide: (Contraindicated) Concomitant use of isavuconazonium with apalutamide is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; apalutamide is a strong inducer of this enzyme. Coadministration with another strong CYP3A4 inducer decreased isavuconazole serum concentrations by 97%.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of isavuconazonium with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant; increased isavuconazonium exposure may also occur. If coadministration cannot be avoided, use caution and monitor for an increase in isavuconazonium- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Isavuconazonium is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur. Isavuconazonium is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of isavuconazonium. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of isavuconazonium. Patients receiving both a CYP2D6 inhibitor plus isavuconazonium may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; isavuconazonium is a moderate CYP3A inhibitor.
Armodafinil: (Major) Coadministration of isavuconazonium with armodafinil is not recommended as there is a potential for elevated armodafinil concentrations and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Armodafinil is a CYP3A4 substrate/inducer. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4.
Artemether; Lumefantrine: (Moderate) Concomitant use of isavuconazonium with artemether; lumefantrine may result in increased serum concentrations of artemether; lumefantrine. Artemether and lumefantrine are substrates of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Asenapine: (Moderate) Concomitant use of isavuconazonium with asenapine may result in increased serum concentrations of asenapine. Asenapine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Aspirin, ASA; Omeprazole: (Moderate) Concomitant use of isavuconazonium with omeprazole may result in increased serum concentrations of omeprazole. Omeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. If isavuconazonium is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like isavuconazonium can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If isavuconazonium is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Contraindicated) Concomitant use of isavuconazonium with atazanavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; atazanavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated atazanavir concentrations would also be expected with coadministration, as atazanavir is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Atazanavir; Cobicistat: (Contraindicated) Coadministration of isavuconazonium with cobicistat is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%. (Contraindicated) Concomitant use of isavuconazonium with atazanavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; atazanavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated atazanavir concentrations would also be expected with coadministration, as atazanavir is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Atorvastatin: (Major) Use caution and the lowest atorvastatin dose necessary if coadministration with isavuconazonium is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Isavuconazole, the active moiety of isavuconazonium, inhibits the CYP3A4-mediated metabolism and P-glycoprotein (P-gp)-mediated transport of atorvastatin.
Atorvastatin; Ezetimibe: (Major) Use caution and the lowest atorvastatin dose necessary if coadministration with isavuconazonium is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Isavuconazole, the active moiety of isavuconazonium, inhibits the CYP3A4-mediated metabolism and P-glycoprotein (P-gp)-mediated transport of atorvastatin.
Avanafil: (Moderate) Concomitant use of isavuconazonium with avanafil may result in increased serum concentrations of avanafil. Avanafil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Avapritinib: (Major) Avoid coadministration of avapritinib with isavuconazonium due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration of avapritinib 300 mg PO once daily with a moderate CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 210% at steady-state.
Bedaquiline: (Major) Concurrent use of bedaquiline and isavuconazonium should be avoided due to the potential risk of adverse reactions. Isavuconazole, the active moiety of isavuconazonium may inhibit the CYP3A4 metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concurrent use of benzhydrocodone with isavuconazonium may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of isavuconazonium in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Isavuconazonium is an inhibitor of CYP3A4.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking isavuconazonium. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp substrate and isavuconazonium is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving isavuconazonium. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving isavuconazonium. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; isavuconazonium inhibits P-gp.
Bexarotene: (Major) Concomitant use of isavuconazonium with bexarotene may result in decreased concentrations of isavuconazonium. Caution and close monitoring are advised if these drugs are used together. Bexarotene is an inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Bortezomib: (Moderate) Concomitant use of isavuconazonium with bortezomib may result in increased serum concentrations of bortezomib. Bortezomib is metabolized by the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Bosentan: (Major) Concomitant use of isavuconazonium with bosentan may result in increased serum concentrations of bosentan and decreased concentrations of isavuconazonium. Bosentan is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Bosutinib: (Major) Avoid concomitant use of bosutinib and isavuconazonium; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor.
Brentuximab vedotin: (Moderate) Concomitant use of isavuconazonium with brentuximab vedotin may result in increased serum concentrations of brentuximab. Brentuximab is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Isavuconazonium is a moderate inhibitor of CYP3A4. If isavuconazonium is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, the brexpiprazole dose should be reduced and the patient should be carefully monitored for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a moderate CYP3A4 inhibitor.
Brigatinib: (Major) Avoid coadministration of brigatinib with isavuconazonium if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of isavuconazonium, resume the brigatinib dose that was tolerated prior to initiation of isavuconazonium. Brigatinib is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of isavuconazonium. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Budesonide: (Moderate) Concomitant use of isavuconazonium with budesonide may result in increased serum concentrations of budesonide. Budesonide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Budesonide; Formoterol: (Moderate) Concomitant use of isavuconazonium with budesonide may result in increased serum concentrations of budesonide. Budesonide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Concomitant use of isavuconazonium with budesonide may result in increased serum concentrations of budesonide. Budesonide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Bupivacaine Liposomal: (Moderate) Concomitant use of isavuconazonium with bupivacaine may result in increased serum concentrations of bupivacaine. Bupivacaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Bupivacaine: (Moderate) Concomitant use of isavuconazonium with bupivacaine may result in increased serum concentrations of bupivacaine. Bupivacaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Bupivacaine; Epinephrine: (Moderate) Concomitant use of isavuconazonium with bupivacaine may result in increased serum concentrations of bupivacaine. Bupivacaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of isavuconazonium with bupivacaine may result in increased serum concentrations of bupivacaine. Bupivacaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with lidocaine may result in increased serum concentrations of lidocaine. Lidocaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Bupivacaine; Meloxicam: (Moderate) Concomitant use of isavuconazonium with bupivacaine may result in increased serum concentrations of bupivacaine. Bupivacaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with meloxicam may result in increased serum concentrations of meloxicam. Meloxicam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Buprenorphine: (Moderate) Concomitant use of isavuconazonium with buprenorphine may result in increased serum concentrations of buprenorphine. Buprenorphine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Buprenorphine; Naloxone: (Moderate) Concomitant use of isavuconazonium with buprenorphine may result in increased serum concentrations of buprenorphine. Buprenorphine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Bupropion: (Moderate) Caution and close monitoring are advised when administering isavuconazonium concurrently with buproprion, as decreased buproprion serum concentrations may result. If decreased bupropion efficacy is noted, it may be necessary to increase the dose (not to exceed the maximum recommended dose). Isavuconazole, the active moiety of isavuconazonium, is an inducer of hepatic isoenzyme CYP2B6; bupropion is metabolized by this enzyme.
Bupropion; Naltrexone: (Moderate) Caution and close monitoring are advised when administering isavuconazonium concurrently with buproprion, as decreased buproprion serum concentrations may result. If decreased bupropion efficacy is noted, it may be necessary to increase the dose (not to exceed the maximum recommended dose). Isavuconazole, the active moiety of isavuconazonium, is an inducer of hepatic isoenzyme CYP2B6; bupropion is metabolized by this enzyme.
Buspirone: (Moderate) Concomitant use of isavuconazonium with buspirone may result in increased serum concentrations of buspirone. Buspirone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Butalbital; Acetaminophen: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4. (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of isavuconazonium with rilpivirine may result in increased serum concentrations of rilpivirine. Rilpivirine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Carbamazepine: (Contraindicated) Concomitant use of isavuconazonium with carbamazepine is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; carbamazepine is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer. Elevated carbamazepine concentrations would also be expected with coadministration, as carbamazepine is a substrate and isavuconazole is a moderate inhibitor of CYP3A4.
Cariprazine: (Moderate) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Isavuconazonium is a moderate inhibitor of CYP3A4 and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
Celecoxib; Tramadol: (Moderate) Concomitant use of isavuconazonium with tramadol may result in increased serum concentrations of tramadol. Tramadol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Cenobamate: (Moderate) Use caution when administering cenobamate and isavuconazonium due to the potential for a synergistic effect on the QT interval that would increase the QT shortening risk. Both cenobamate and isavuconazonium are associated with QT shortening. Nonclinical data indicate that QT shortening is associated with ventricular fibrillation.
Ceritinib: (Contraindicated) Coadministration of isavuconazonium with ceritinib is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%.
Chloramphenicol: (Contraindicated) Concomitant use of isavuconazonium with chloramphenicol is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor.
Chlordiazepoxide: (Moderate) Concomitant use of isavuconazonium with chlordiazepoxide may result in increased serum concentrations of chlordiazepoxide. Chlordiazepoxide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Chlordiazepoxide; Amitriptyline: (Moderate) Concomitant use of isavuconazonium with amitriptyline may result in increased serum concentrations of amitriptyline. Amitriptyline is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with chlordiazepoxide may result in increased serum concentrations of chlordiazepoxide. Chlordiazepoxide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Chlordiazepoxide; Clidinium: (Moderate) Concomitant use of isavuconazonium with chlordiazepoxide may result in increased serum concentrations of chlordiazepoxide. Chlordiazepoxide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with isavuconazonium may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isavuconazonium is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isavuconazonium is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Cilostazol: (Moderate) Concomitant use of isavuconazonium with cilostazol may result in increased serum concentrations of cilostazol. Cilostazol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Cimetidine: (Moderate) Concomitant use of isavuconazonium with cimetidine may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; cimetidine is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Ciprofloxacin: (Moderate) Concomitant use of isavuconazonium with ciprofloxacin may result in increased serum concentrations of isavuconazonium. Caution and close monitoring for adverse effects, such as hepatotoxicity, are advised if these drugs are used together. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate CYP3A4; ciprofloxacin is an inhibitor of this enzyme.
Cisapride: (Major) Do not use isavuconazonium and cisapride concurrently. Isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4. Co-administration of isavuconazole with CYP3A4 substrates, such as cisapride, can increase cisapride exposure leading to toxicity, specifically an increased risk for QT prolongation.
Clarithromycin: (Moderate) Concomitant use of isavuconazonium with clarithromycin may result in increased serum concentrations of both drugs. Clarithromycin is a substrate and moderate inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Clobazam: (Moderate) Coadministration of isavuconazonium with clobazam may decrease isavuconazonium concentrations. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Clobazam is a weak inducer of CYP3A4. Isavuconazole, the active moiety of isavuconazonium, is a sensitive CYP3A4 substrate.
Clomipramine: (Moderate) Concomitant use of isavuconazonium with clomipramine may result in increased serum concentrations of clomipramine. Clomipramine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Clonazepam: (Moderate) Use isavuconazonium cautiously and carefully monitor patients receiving concurrent clonazepam due to impaired metabolism of clonazepam leading to exaggerated concentrations and adverse effects, such as CNS and/or respiratory depression. Clonazepam is a CYP3A4 substrate. Isavuconazole, the active moiety of isavuconazonium, is a CYP3A4 inhibitor.
Clorazepate: (Moderate) Concomitant use of isavuconazonium with clorazepate may result in increased serum concentrations of clorazepate. Clorazepate is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with isavuconazonium and monitor for adverse reactions. If isavuconazonium is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A. Isavuconazonium is a moderate CYP3A inhibitor.
Cobicistat: (Contraindicated) Coadministration of isavuconazonium with cobicistat is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic isavuconazonium therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of isavuconazonium is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of isavuconazonium, resume cobimetinib at the previous dose. Use an alternative to isavuconazonium in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; isavuconazonium is a moderate inhibitor of CYP3A and a weak P-gp inhibitor. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Cocaine: (Moderate) Concomitant use of isavuconazonium with cocaine may result in increased serum concentrations of both drugs. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of the hepatic isoenzyme CYP3A4; cocaine is a substrate and inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Codeine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Isavuconazonium is a moderate inhibitor of CYP3A4.
Colchicine: (Major) Avoid concomitant use of colchicine and isavuconazonium due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and isavuconazonium is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Crizotinib: (Moderate) Monitor for an increase in crizotinib-related adverse reactions if coadministration with isavuconazonium is necessary. Crizotinib is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Cyclosporine: (Moderate) Use caution and closely monitor cyclosporine serum concentrations when administered concurrently with isavuconazonium. Use of these drugs together results in elevated cyclosporine serum concentrations and an increased risk for adverse reactions, such as renal toxicity. Cyclosporine dose adjustments may be necessary and should be guided by serum concentrations during coadministration. Isavuconazole, the active moiety of isavuconazonium, is an inhibitor of hepatic isoenzyme CYP3A4 as well as the drug transporter P-glycoprotein (P-gp); cyclosporine is a substrate of CYP3A4 and P-gp. Additionally, isavuconazole is a sensitive substrate of CYP3A4 while cyclosporine is an inhibitor of this enzyme; elevated isavuconazole serum concentrations may also occur.
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with isavuconazonium, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like isavuconazonium in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with isavuconazonium, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Dabrafenib: (Major) The concomitant use of dabrafenib and isavuconazonium may lead to decreased isavuconazonium concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of isavuconazonium efficacy. Dabrafenib is a CYP3A4 substrate and a moderate CYP3A4 inducer; isavuconazonium is a sensitive CYP3A4 substrate and a moderate inhibitor of CYP3A4. The use of isavuconazonium is contraindicated with strong CYP3A4 inducers; however, the manufacturer does not provide guidance for moderate inducers. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with isavuconazonium, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Danazol: (Moderate) Concomitant use of isavuconazonium with danazol may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; danazol is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Dapagliflozin; Saxagliptin: (Moderate) Concomitant use of isavuconazonium with saxagliptin may result in increased serum concentrations of saxagliptin. Saxagliptin is a substrate of the hepatic isoenzyme CYP3A4); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring for adverse effects, such as hypoglycemia, are advised if these drugs are used together.
Dapsone: (Moderate) Concomitant use of isavuconazonium with dapsone may result in increased serum concentrations of dapsone. Dapsone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Daridorexant: (Major) Limit the daridorexant dose to 25 mg if coadministered with isavuconazonium. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Concomitant use of another moderate CYP3A inhibitor increased daridorexant overall exposure 2.4-fold.
Darifenacin: (Moderate) Concomitant use of isavuconazonium with darifenacin may result in increased serum concentrations of darifenacin. Darifenacin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Darunavir: (Contraindicated) Concomitant use of isavuconazonium with darunavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; darunavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated darunavir concentrations would also be expected with coadministration, as darunavir is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Darunavir; Cobicistat: (Contraindicated) Coadministration of isavuconazonium with cobicistat is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%. (Contraindicated) Concomitant use of isavuconazonium with darunavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; darunavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated darunavir concentrations would also be expected with coadministration, as darunavir is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of isavuconazonium with cobicistat is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%. (Contraindicated) Concomitant use of isavuconazonium with darunavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; darunavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated darunavir concentrations would also be expected with coadministration, as darunavir is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor. (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Deferasirox: (Major) Concomitant use of isavuconazonium with deferasirox may result in decreased serum concentrations of isavuconazonium and the potential for treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of CYP3A4; deferasirox is an inducer of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with isavuconazonium. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Delavirdine: (Contraindicated) Concomitant use of isavuconazonium with delavirdine is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; delavirdine is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated delavirdine concentrations would also be expected with coadministration, as delavirdine is a substrate and isavuconazole is a moderate inhibitor of CYP3A4.
Desogestrel; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Dextromethorphan; Bupropion: (Moderate) Caution and close monitoring are advised when administering isavuconazonium concurrently with buproprion, as decreased buproprion serum concentrations may result. If decreased bupropion efficacy is noted, it may be necessary to increase the dose (not to exceed the maximum recommended dose). Isavuconazole, the active moiety of isavuconazonium, is an inducer of hepatic isoenzyme CYP2B6; bupropion is metabolized by this enzyme.
Dextromethorphan; Quinidine: (Moderate) Caution and therapeutic drug concentration monitoring, if available, are recommended during coadministration of quinidine with isavuconazonium. Quinidine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Concurrent use may result in elevated quinidine plasma concentrations.
Diazepam: (Moderate) Concomitant use of isavuconazonium with diazepam may result in increased serum concentrations of diazepam. Diazepam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Dichlorphenamide: (Moderate) Use dichlorphenamide and isavuconazonium together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dichlorphenamide dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) Concomitant use of isavuconazonium with diclofenac may result in increased serum concentrations of diclofenac. Diclofenac is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Diclofenac; Misoprostol: (Moderate) Concomitant use of isavuconazonium with diclofenac may result in increased serum concentrations of diclofenac. Diclofenac is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Digoxin: (Moderate) Use caution and closely monitor digoxin serum concentrations when using digoxin and isavuconazonium concurrently. Coadministration results in increased digoxin exposure, and serum concentrations should guide digoxin dose titration. Isavuconazole, the active moiety of isavuconazonium, is an inhibitor of the drug transporter P-glycoprotein (P-gp); digoxin is a substrate for this transporter.
Dihydroergotamine: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and isavuconazonium. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A inhibitor.
Diltiazem: (Moderate) Concomitant use of isavuconazonium with diltiazem may result in increased serum concentrations of both drugs. Diltiazem is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Disopyramide: (Moderate) Concomitant use of isavuconazonium with disopyramide may result in increased serum concentrations of disopyramide. Disopyramide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Disulfiram: (Moderate) Concomitant use of isavuconazonium with disulfiram may result in increased serum concentrations of disulfiram. Disulfiram is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Docetaxel: (Moderate) Concomitant use of isavuconazonium with docetaxel may result in increased serum concentrations of docetaxel. Docetaxel is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Dofetilide: (Contraindicated) Concurrent use of isavuconazonium with dofetilide is contraindicated due to the potential for increased dofetilide exposure resulting in serious and life-threatening adverse events, such as QT prolongation and torsade de pointes (TdP). Isavuconazonium inhibits the renal organic cation transporter OCT2, and dofetilide is eliminated via this transporter.
Dolasetron: (Moderate) Concomitant use of isavuconazonium with dolasetron may result in increased serum concentrations of dolasetron. Dolasetron is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Dolutegravir: (Moderate) Concomitant use of isavuconazonium with dolutegravir may result in increased serum concentrations of dolutegravir. Dolutegravir is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Dolutegravir; Lamivudine: (Moderate) Concomitant use of isavuconazonium with dolutegravir may result in increased serum concentrations of dolutegravir. Dolutegravir is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of isavuconazonium with dolutegravir may result in increased serum concentrations of dolutegravir. Dolutegravir is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with rilpivirine may result in increased serum concentrations of rilpivirine. Rilpivirine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Donepezil: (Moderate) Concomitant use of isavuconazonium with donepezil may result in increased serum concentrations of donepezil. Donepezil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Donepezil; Memantine: (Moderate) Concomitant use of isavuconazonium with donepezil may result in increased serum concentrations of donepezil. Donepezil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Doxorubicin Liposomal: (Moderate) Concomitant use of isavuconazonium with doxorubicin may result in increased serum concentrations of doxorubicin. Doxorubicin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of isavuconazonium and doxorubicin if possible. If avoidance is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Moderate) Concomitant use of isavuconazonium with doxorubicin may result in increased serum concentrations of doxorubicin. Doxorubicin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of isavuconazonium and doxorubicin if possible. If avoidance is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Major) Use caution if coadministration of dronabinol with isavuconazonium is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; isavuconazonium is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Moderate) Concomitant use of isavuconazonium with dronedarone may result in increased serum concentrations of both drugs. Dronedarone is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Drospirenone; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Dutasteride; Tamsulosin: (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Tamsulosin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp.
Duvelisib: (Moderate) Monitor for increased toxicity of duvelisib and isavuconazonium during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; isavuconazonium is a sensitive substrate and moderate inhibitor of CYP3A.
Efavirenz: (Major) Coadministration of isavuconazonium with efavirenz is not recommended as there is a potential for elevated efavirenz concentrations and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Efavirenz is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of isavuconazonium with efavirenz is not recommended as there is a potential for elevated efavirenz concentrations and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Efavirenz is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of isavuconazonium with efavirenz is not recommended as there is a potential for elevated efavirenz concentrations and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Efavirenz is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme.
Elacestrant: (Major) Avoid concomitant use of elacestrant and isavuconazonium due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Elagolix: (Major) The concomitant use of elagolix and isavuconazonium may lead to decreased isavuconazonium concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of isavuconazonium efficacy. Elagolix is a weak to moderate CYP3A4 inducer; isavuconazonium is a sensitive CYP3A4 substrate. The use of isavuconazonium is contraindicated with strong CYP3A4 inducers; however, the manufacturer does not provide guidance for moderate inducers.
Elagolix; Estradiol; Norethindrone acetate: (Major) The concomitant use of elagolix and isavuconazonium may lead to decreased isavuconazonium concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of isavuconazonium efficacy. Elagolix is a weak to moderate CYP3A4 inducer; isavuconazonium is a sensitive CYP3A4 substrate. The use of isavuconazonium is contraindicated with strong CYP3A4 inducers; however, the manufacturer does not provide guidance for moderate inducers.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with isavuconazonium may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Isavuconazonium is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eletriptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with isavuconazonium. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
Elexacaftor; tezacaftor; ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with isavuconazonium; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); isavuconazonium is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If isavuconazonium and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to every other day in the morning when coadministered with isavuconazonium; omit the ivacaftor evening dose and administer in the morning every other day alternating with elexacaftor; tezacaftor; ivacaftor (i.e., recommended dose of elexacaftor; tezacaftor; ivacaftor on day 1 in the morning and recommended dose of ivacaftor on day 2 in the morning). Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; isavuconazonium is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure by 2.9-fold. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2.1-fold, respectively.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of isavuconazonium with eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of isavuconazonium and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both isavuconazonium and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as isavuconazole, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Coadministration of isavuconazonium with cobicistat is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%. (Moderate) Concomitant use of isavuconazonium with elvitegravir may result in increased concentrations of elvitegravir. Isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of the hepatic isoenzyme CYP3A4; elvitegravir is a substrate of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of isavuconazonium with cobicistat is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%. (Moderate) Concomitant use of isavuconazonium with elvitegravir may result in increased concentrations of elvitegravir. Isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of the hepatic isoenzyme CYP3A4; elvitegravir is a substrate of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of isavuconazonium with rilpivirine may result in increased serum concentrations of rilpivirine. Rilpivirine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of isavuconazonium with rilpivirine may result in increased serum concentrations of rilpivirine. Rilpivirine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Emtricitabine; Tenofovir alafenamide: (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Encorafenib: (Major) Avoid coadministration of encorafenib and isavuconazonium due to increased encorafenib exposure. Concurrent use may also result in increased toxicity or decreased efficacy of isavuconazonium. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of isavuconazonium. If isavuconazonium is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of isavuconazonium. Encorafenib is a CYP3A4 substrate; in vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established. Isavuconazonium is a moderate CYP3A4 inhibitor and sensitive CYP3A4 substrate. Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respectively.
Entrectinib: (Major) Avoid coadministration of entrectinib with isavuconazonium due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If isavuconazonium is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of isavuconazonium. Entrectinib is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Enzalutamide: (Contraindicated) Concomitant use of isavuconazonium with enzalutamide is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; enzalutamide is a strong inducer of this enzyme. There was a 97% decrease in isavuconazole serum concentrations when coadministered with another strong CYP3A4 inducer.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Isavuconazonium is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Ergotamine: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and isavuconazonium. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A inhibitor.
Ergotamine; Caffeine: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and isavuconazonium. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A inhibitor.
Erythromycin: (Moderate) Caution is warranted as concomitant use of isavuconazonium and erythromycin may result in increased isavuconazonium serum concentrations. Erythromycin is an inhibitor of CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of CYP3A4.
Escitalopram: (Moderate) Concomitant use of isavuconazonium with escitalopram may result in increased serum concentrations of escitalopram. Escitalopram is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Eslicarbazepine: (Major) Concomitant use of isavuconazonium with eslicarbazepine may result in decreased serum concentrations of isavuconazonium and the potential for treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; eslicarbazepine is an inducer of this enzyme. Caution and close monitoring for decreased antifungal efficacy are advised if these drugs are used together.
Esomeprazole: (Moderate) Concomitant use of isavuconazonium with esomeprazole may result in increased concentrations of esomeprazole. Esomeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Estazolam: (Moderate) Concomitant use of isavuconazonium with estazolam may result in increased serum concentrations of estazolam. Estazolam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Ethinyl Estradiol; Norelgestromin: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Ethinyl Estradiol; Norgestrel: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Ethosuximide: (Moderate) Concomitant use of isavuconazonium with ethosuximide may result in increased serum concentrations of ethosuximide. Ethosuximide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as isavuconazonium may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together. (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as isavuconazonium may increase the serum concentration of etonogestrel.
Etravirine: (Major) Concomitant use of isavuconazonium with etravirine may result in increased serum concentrations of etravirine and decreased serum concentrations of isavuconazonium. Etravirine is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Everolimus: (Major) Coadministration of everolimus with isavuconazonium requires a dose reduction for some indications and close monitoring for others. For patients with oncology indications and tuberous sclerosis complex (TSC)-associated renal angiomyolipoma, reduce the initial dose of everolimus to 2.5 mg PO once daily; the dose may be increased to 5 mg PO once daily if the 2.5 mg dose is tolerated. For patients with TSC-associated subependymal giant cell astrocytoma (SEGA) and TSC-associated partial-onset seizures, reduce the daily dose of everolimus by 50%, changing to every-other-day dosing if the reduced dose is lower than the lowest available strength; assess the everolimus whole blood trough concentration 2 weeks after initiation of isavuconazonium and adjust the dose as necessary to remain in the recommended therapeutic range. Also monitor everolimus whole blood trough concentrations for patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Isavuconazonium is a moderate CYP3A4 and P-gp inhibitor. Coadministration with other moderate CYP3A4/P-gp inhibitors increased the AUC of everolimus by 3.5 to 4.4-fold.
Ezetimibe; Simvastatin: (Moderate) Closely monitor for evidence of myopathy, including rhabdomyolysis if simvastatin and isavuconazonium are coadministered. Concomitant use of isavuconazonium with simvastatin may result in increased serum concentrations of simvastatin. Simvastatin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4.
Felbamate: (Major) Avoid coadministration of isavuconazonium with felbamate. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; felbamate is an inducer of this enzyme. Coadministration may decrease the plasma concentrations of isavuconazole resulting in the potential for treatment failure.
Felodipine: (Moderate) Concomitant use of isavuconazonium with felodipine may result in increased serum concentrations of felodipine. Felodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. If isavuconazonium is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If isavuconazonium is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finasteride; Tadalafil: (Moderate) Concomitant use of isavuconazonium with tadalafil may result in increased serum concentrations of tadalafil. Tadalafil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or isavuconazole; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and isavuconazole is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased overall exposure to finerenone by 248%.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as isavuconazonium, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluconazole: (Moderate) Concomitant use of isavuconazonium with fluconazole may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; fluconazole is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Fluoxetine: (Moderate) Concomitant use of isavuconazonium with fluoxetine may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; fluoxetine is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Flurazepam: (Moderate) Concomitant use of isavuconazonium with flurazepam may result in increased serum concentrations of flurazepam. Flurazepam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Flutamide: (Major) Concomitant use of isavuconazonium with flutamide may result in increased serum concentrations of flutamide and decreased serum concentrations of isavuconazonium. Flutamide is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant use of isavuconazonium with umeclidinium; vilanterol may result in increased serum concentrations of umeclidinium; vilanterol. Umeclidinium; vilanterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Fluticasone; Vilanterol: (Moderate) Concomitant use of isavuconazonium with umeclidinium; vilanterol may result in increased serum concentrations of umeclidinium; vilanterol. Umeclidinium; vilanterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Fluvoxamine: (Moderate) Concomitant use of isavuconazonium with fluvoxamine may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; fluvoxamine is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Fosamprenavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with isavuconazonium. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Fosphenytoin: (Contraindicated) Concomitant use of isavuconazonium with phenytoin or fosphenytoin is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; phenytoin is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer. Elevated phenytoin concentrations would also be expected with coadministration, as phenytoin is a substrate and isavuconazole is moderate inhibitor of CYP3A4.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of g lecaprevir and isavuconazonium as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); isavuconazonium is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and isavuconazonium as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); isavuconazonium is an inhibitor of P-gp.
Granisetron: (Minor) Concomitant use of isavuconazonium with granisetron may result in increased serum concentrations of granisetron. Granisetron is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Grapefruit juice: (Contraindicated) Concomitant use of isavuconazonium with grapefruit juice is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; grapefruit juice is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isavuconazonium is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Isavuconazonium may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Upon isavuconazonium discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and isavuconazonium is a moderate CYP3A4 inhibitor.
Haloperidol: (Moderate) Concomitant use of isavuconazonium with haloperidol may result in increased serum concentrations of haloperidol. Haloperidol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isavuconazonium is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isavuconazonium is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isavuconazonium is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like isavuconazonium can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If isavuconazonium is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Ibrutinib: (Major) If ibrutinib is coadministered with isavuconazonium, reduce the initial ibrutinib dosage to 280 mg/day PO in patients receiving ibrutinib for B-cell malignancy. Resume ibrutinib at the previous dosage if isavuconazonium is discontinued. No initial ibrutinib dosage adjustment is necessary in patients receiving ibrutinib for chronic graft-versus-host disease. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection);modify the ibrutinib dosage as recommended if toxicity occurs. Ibrutinib is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A4 inhibitor, the AUC value of ibrutinib was increased by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. If isavuconazonium is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like isavuconazonium can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If isavuconazonium is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Idelalisib: (Contraindicated) Concomitant use of isavuconazonium with idelalisib is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; idelalisib is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with isavuconazonium is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) Concomitant use of isavuconazonium with iloperidone may result in increased serum concentrations of iloperidone. Iloperidone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Imatinib: (Moderate) Concomitant use of isavuconazonium with imatinib, STI-571 may result in increased serum concentrations of both drugs. Imatinib is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Imipramine: (Moderate) Concomitant use of isavuconazonium with imipramine may result in increased serum concentrations of imipramine. Imipramine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Indacaterol: (Moderate) Concomitant use of isavuconazonium with indacaterol may result in increased serum concentrations of indacaterol. Indacaterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Indacaterol; Glycopyrrolate: (Moderate) Concomitant use of isavuconazonium with indacaterol may result in increased serum concentrations of indacaterol. Indacaterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Indinavir: (Contraindicated) Concomitant use of isavuconazonium with indinavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; indinavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated indinavir concentrations would also be expected with coadministration, as indinavir is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp).
Infigratinib: (Major) Avoid concomitant use of infigratinib and isavuconazonium. Coadministration may increase infigratinib exposure, increasing the risk of adverse effects. Infigratinib is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Concomitant use of isavuconazonium with rifampin is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; rifampin is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin.
Isoniazid, INH; Rifampin: (Contraindicated) Concomitant use of isavuconazonium with rifampin is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; rifampin is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin.
Isradipine: (Moderate) Concomitant use of isavuconazonium with isradipine may result in increased serum concentrations of isradipine. Isradipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Itraconazole: (Contraindicated) Isavuconazonium is contraindicated for use with and for 2 weeks after itraconazole therapy, due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; itraconazole is a strong inhibitor of this enzyme. Isavuconazole serum concentrations were increased 5-fold when coadministered with another strong CYP3A4 inhibitor. Elevated itraconazole concentrations would also be expected with coadministration, as itraconazole is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp).
Ivabradine: (Major) Avoid coadministration of ivabradine and isavuconazonium. Ivabradine is primarily metabolized by CYP3A4; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration may increase the plasma concentrations of ivabradine further increasing the risk for bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If isavuconazonium and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with isavuconazonium due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation; isavuconazonium exposure may also decrease. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Monitor for loss of efficacy of isavuconazonium. Ivosidenib is a CYP3A4 substrate and inducer; isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor and sensitive substrate. Coadministration with another moderate CYP3A4 inhibitor is predicted to increase the ivosidenib single-dose AUC to 173% of control based on physiologically-based pharmacokinetic modeling, with no change in Cmax. Multiple doses of the moderate CYP3A4 inhibitor are predicted to increase the ivosidenib steady-state AUC to 152% of control and AUC to 190% of control.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of isavuconazonium is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Ketoconazole: (Contraindicated) Concomitant use of isavuconazonium with ketoconazole is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; ketoconazole is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when codadministered with ketoconazole. Elevated ketoconazole concentrations would also be expected with coadministration, as ketoconazole is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Lansoprazole: (Moderate) Concomitant use of isavuconazonium with lansoprazole may result in increased serum concentrations of lansoprazole. Lansoprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Concomitant use of isavuconazonium with clarithromycin may result in increased serum concentrations of both drugs. Clarithromycin is a substrate and moderate inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with lansoprazole may result in increased serum concentrations of lansoprazole. Lansoprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with isavuconazonium is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and isavuconazonium is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Larotrectinib: (Moderate) Monitor for an increase in larotrectinib-related adverse reactions if concomitant use with isavuconazonium is necessary. Concomitant use may increase larotrectinib exposure. Larotrectinib is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase larotrectinib exposure by 2.7-fold.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with isavuconazonium as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 and P-gp substrate; isavuconazonium is a P-gp and moderate CYP3A4 inhibitor. The effect of moderate inhibitors on lefamulin has not been studied; however, coadministration of a combined P-gp and strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and isavuconazonium as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Letermovir: (Moderate) Concurrent use of isavuconazonium and letermovir may result in elevated isavuconazonium plasma concentrations. Coadministration is contraindicated in patients also receiving cyclosporine, because the magnitude of this interaction may be amplified. Isavuconazonium is a sensitive CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent administration with a strong CYP3A4 inhibitor increased exposure of isavuconazole by more than 5-fold.
Levamlodipine: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Levoketoconazole: (Contraindicated) Concomitant use of isavuconazonium with ketoconazole is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; ketoconazole is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when codadministered with ketoconazole. Elevated ketoconazole concentrations would also be expected with coadministration, as ketoconazole is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Levomilnacipran: (Moderate) Concomitant use of isavuconazonium with levomilnacipran may result in increased serum concentrations of levomilnacipran. Levomilnacipran is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Lidocaine: (Moderate) Concomitant use of isavuconazonium with lidocaine may result in increased serum concentrations of lidocaine. Lidocaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Lidocaine; Epinephrine: (Moderate) Concomitant use of isavuconazonium with lidocaine may result in increased serum concentrations of lidocaine. Lidocaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Lidocaine; Prilocaine: (Moderate) Concomitant use of isavuconazonium with lidocaine may result in increased serum concentrations of lidocaine. Lidocaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Lomitapide: (Contraindicated) Concomitant use of isavuconazonium and lomitapide is contraindicated. If treatment with isavuconazonium is unavoidable, lomitapide should be stopped during the course of treatment. Isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and isavuconazonium is contraindicated; concurrent use may increase the exposure of both drugs and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitors; isavuconazonium is a sensitive CYP3A4 substrate and moderate CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with isavuconazonium. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and isavuconazonium is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with isavuconazonium. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and isavuconazonium is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Contraindicated) Concomitant use of isavuconazonium with high-dose ritonavir (i.e., 400 mg every 12 hours) is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; ritonavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated ritonavir concentrations may also be seen with coadministration, as ritonavir is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp). (Moderate) Caution is advised when administering isavuconazonium concurrently with lopinavir. Coadministration may result in a loss of antiviral efficacy due to decreased lopinavir plasma concentrations. During drug interaction studies in healthy adults, coadministration resulted in a 27% decrease in lopinavir concentrations.
Losartan: (Moderate) Concomitant use of isavuconazonium with losartan may result in increased serum concentrations of losartan. Losartan is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of isavuconazonium with losartan may result in increased serum concentrations of losartan. Losartan is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Lovastatin: (Moderate) Concomitant use of isavuconazonium with lovastatin may result in increased serum concentrations of lovastatin. Lovastatin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Lumacaftor; Ivacaftor: (Major) Concomitant use of isavuconazonium and lumacaftor; ivacaftor is not recommended because lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic effectiveness of isavuconazonium. If concurrent use cannot be avoided, monitor closely for antifungal efficacy and adjust the dose accordingly. Isavuconazole, the active moiety of isavuconazonium, is a sensitive CYP3A4 substrate, and lumacaftor is a strong CYP3A inducer. (Major) If isavuconazonium and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Lumacaftor; Ivacaftor: (Major) Concomitant use of isavuconazonium and lumacaftor; ivacaftor is not recommended because lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic effectiveness of isavuconazonium. If concurrent use cannot be avoided, monitor closely for antifungal efficacy and adjust the dose accordingly. Isavuconazole, the active moiety of isavuconazonium, is a sensitive CYP3A4 substrate, and lumacaftor is a strong CYP3A inducer.
Lumateperone: (Major) Reduce the dose of lumateperone to 21 mg once daily if concomitant use of isavuconazonium is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased lumateperone exposure by approximately 2-fold.
Lurasidone: (Moderate) Concomitant use of isavuconazonium with lurasidone may result in increased serum concentrations of lurasidone. Lurasidone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and isavuconazonium due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. Lurbinectedin is a CYP3A substrate and isavuconazonium is a strong CYP3A inhibitor.
Macitentan: (Moderate) Concomitant use of isavuconazonium with macitentan may result in increased serum concentrations of macitentan. Macitentan is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Maprotiline: (Moderate) Concomitant use of isavuconazonium with maprotiline may result in increased serum concentrations of maprotiline. Maprotiline is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with isavuconazonium is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A/P-glycoprotein (P-gp) substrate and isavuconazole, the active moiety of isavuconazonium, is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting isavuconazonium therapy. Avoid initiation of isavuconazonium in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable isavuconazonium therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Mefloquine: (Moderate) Concomitant use of isavuconazonium with mefloquine may result in increased serum concentrations of mefloquine. Mefloquine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Clinical monitoring for adverse effects, such as GI or neuropsychiatric effects, is recommended during coadministration.
Meloxicam: (Moderate) Concomitant use of isavuconazonium with meloxicam may result in increased serum concentrations of meloxicam. Meloxicam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Metformin; Repaglinide: (Moderate) Concomitant use of isavuconazonium with repaglinide may result in increased serum concentrations of repaglinide. Repaglinide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as hypoglycemia, are advised if these drugs are used together.
Metformin; Saxagliptin: (Moderate) Concomitant use of isavuconazonium with saxagliptin may result in increased serum concentrations of saxagliptin. Saxagliptin is a substrate of the hepatic isoenzyme CYP3A4); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring for adverse effects, such as hypoglycemia, are advised if these drugs are used together.
Methadone: (Moderate) Concomitant use of isavuconazonium with methadone may result in increased serum concentrations of methadone. Methadone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Methylprednisolone: (Moderate) Concomitant use of isavuconazonium with methylprednisolone may result in increased serum concentrations of methylprednisolone. Methylprednisolone is a substrate of CYP3A4 and isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring for adverse effects, such as corticosteroid-related adverse effects, are advised if these drugs are used together.
Midazolam: (Moderate) Concurrent administration of isavuconazonium and midazolam resulted in increased midazolam exposure. If these drugs are to be coadministered, use caution and consider reducing the midazolam dose in order to avoid the risk for serious adverse reactions such as excess sedation and/or cardiorespiratory depression. Isavuconazole, the active moiety of isavuconazonium, is an inhibitor of hepatic isoenzyme CYP3A4; midazolam is metabolized by this enzyme.
Mifepristone: (Moderate) Concomitant use of isavuconazonium with mifepristone may result in increased serum concentrations of both drugs. Mifepristone is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Mitapivat: (Moderate) Do not exceed mitapivat 20 mg PO twice daily during coadministration with isavuconazonium and monitor hemoglobin and for adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased mitapivat overall exposure by 2.6-fold.
Mitotane: (Contraindicated) Concomitant use of isavuconazonium with mitotane is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; mitotane is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and isavuconazonium/isavuconazole; reduce the dose of mobocertinib by approximately 50% and monitor the QT interval more frequently if use is necessary. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions. Mobocertinib is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Use of a moderate CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 100% to 200%.
Modafinil: (Major) Coadministration of isavuconazonium with modafinil is not recommended as there is a potential for elevated modafinil concentrations and decreased isavuconazonium concentrations. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Modafinil is a CYP3A4 substrate/inducer. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and inhibitor of CYP3A4.
Mycophenolate: (Moderate) Concomitant use of isavuconazonium with mycophenolate results in elevated mycophenolate serum concentrations. Patients receiving this drug combination should be closely monitored for mycophenolate-related adverse reactions and toxicities. The mechanism of the interaction is not completely understood, but is expected to be due to UDP-glucosyltransferase (UGT) metabolism; both isavuconazole, the active moiety of isavuconazonium, and mycophenolate are substrates for UGT, and isavuconazole may also inhibit UGT.
Nafcillin: (Major) Caution and close monitoring are warranted when isavuconazonium is administered with nafcillin as there is a potential for decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; nafcillin is an inducer of this enzyme.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with isavuconazonium. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a substrate of CYP3A4 and P-gp; isavuconazonium is a weak P-gp inhibitor and a moderate CYP3A4 inhibitor.
Naloxegol: (Major) Avoid concomitant administration of naloxegol and isavuconazonium due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with isavuconazonium is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and isavuconazonium. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and isavuconazonium is a moderate CYP3A and P-gp inhibitor.
Naproxen; Esomeprazole: (Moderate) Concomitant use of isavuconazonium with esomeprazole may result in increased concentrations of esomeprazole. Esomeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Nefazodone: (Contraindicated) Concomitant use of isavuconazonium with nefazodone is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; nefazodone is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when codadministered with another strong CYP3A4 inhibitor, ketoconazole. Elevated nefazodone concentrations would also be expected with coadministration, as nefazodone is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
Nelfinavir: (Contraindicated) Concomitant use of isavuconazonium with nelfinavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; nelfinavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated nelfinavir concentrations would also be expected with coadministration, as nelfinavir is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp).
Neratinib: (Major) Avoid concomitant use of isavuconazonium with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and isavuconazonium is a dual moderate CYP3A4/P-glycoprotein (P-gp) inhibitor. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another dual moderate CYP3A4/P-gp inhibitor may increase neratinib exposure by 299%.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Concomitant use of isavuconazonium with netupitant; palonosetron may result in increased serum concentrations of all 3 drugs. Netupitant and palonosetron are substrates of the hepatic isoenzyme CYP3A4 while netupitant is also an inhibitor of CYP344; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with palonosetron may result in increased serum concentrations of palonosetron. Palonosetron is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Nevirapine: (Moderate) Monitor for decreased efficacy of isavuconazonium if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease isavuconazonium exposure. Isavuconazonium is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Niacin; Simvastatin: (Moderate) Closely monitor for evidence of myopathy, including rhabdomyolysis if simvastatin and isavuconazonium are coadministered. Concomitant use of isavuconazonium with simvastatin may result in increased serum concentrations of simvastatin. Simvastatin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4.
Nicardipine: (Moderate) Concomitant use of isavuconazonium with nicardipine may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; nicardipine is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Nifedipine: (Moderate) Concomitant use of isavuconazonium with nifedipine may result in increased serum concentrations of nifedipine. Nifedipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Nimodipine: (Moderate) Concomitant use of isavuconazonium with nimodipine may result in increased serum concentrations of nimodipine. Nimodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Nintedanib: (Moderate) Dual inhibitors of P-glycoprotein (P-gp) and CYP3A4, such as isavuconazonium, are expected to increase the exposure and clinical effect of nintedanib. If use together is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain, loss of appetite), headache, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of nintedanib therapy may be necessary. Isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Nintedanib is a P-gp substrate and a minor CYP3A4 substrate. In drug interactions studies, administration of nintedanib with a dual P-gp and CYP3A4 inhibitor increased nintedanib AUC by 60%.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of isavuconazonium with high-dose ritonavir (i.e., 400 mg every 12 hours) is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; ritonavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated ritonavir concentrations may also be seen with coadministration, as ritonavir is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp).
Nisoldipine: (Major) Avoid coadministration of nisoldipine with isavuconazonium due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and isavuconazonium is a CYP3A4 inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Norethindrone; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Norgestimate; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Nortriptyline: (Moderate) Concomitant use of isavuconazonium with nortriptyline may result in increased serum concentrations of nortriptyline. Nortriptyline is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of isavuconazonium with fluoxetine may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; fluoxetine is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Olaparib: (Major) Avoid coadministration of olaparib with isavuconazonium due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after isavuconazonium is discontinued. Olaparib is a CYP3A substrate and isavuconazonium is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and isavuconazonium is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and isavuconazonium may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If isavuconazonium is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and isavuconazonium. If concomitant use is necessary, decrease omaveloxolone dose to 100 mg once daily; additional dosage reductions may be necessary. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased omaveloxolone overall exposure by 1.25-fold.
Omeprazole: (Moderate) Concomitant use of isavuconazonium with omeprazole may result in increased serum concentrations of omeprazole. Omeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Omeprazole; Amoxicillin; Rifabutin: (Major) Caution and close monitoring are warranted when isavuconazonium is administered with rifabutin as there is a potential for elevated rifabutin concentrations and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Rifabutin is a substrate and inducer of the hepatic isoenzyme CYP3A4. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. (Moderate) Concomitant use of isavuconazonium with omeprazole may result in increased serum concentrations of omeprazole. Omeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Omeprazole; Sodium Bicarbonate: (Moderate) Concomitant use of isavuconazonium with omeprazole may result in increased serum concentrations of omeprazole. Omeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Ondansetron: (Moderate) Concomitant use of isavuconazonium with ondansetron may result in increased serum concentrations of ondansetron. Ondansetron is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Oritavancin: (Major) Caution and close monitoring are warranted when isavuconazonium is administered with oritavancin as there is a potential for decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; oritavancin is an inducer of this enzyme.
Oxcarbazepine: (Major) Caution and close monitoring are warranted when isavuconazonium is administered with oxcarbazepine as there is a potential for decreased concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; oxcarbazepine is an inducer of this enzyme.
Oxybutynin: (Moderate) Concomitant use of isavuconazonium with oxybutynin may result in increased serum concentrations of oxybutynin. Oxybutynin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. If isavuconazonium is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like isavuconazonium can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If isavuconazonium is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Paclitaxel: (Moderate) Concomitant use of isavuconazonium with paclitaxel may result in increased serum concentrations of paclitaxel. Paclitaxel is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Pacritinib: (Major) Avoid concurrent use of pacritinib with isavuconazonium due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Palonosetron: (Moderate) Concomitant use of isavuconazonium with palonosetron may result in increased serum concentrations of palonosetron. Palonosetron is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Palovarotene: (Major) Avoid concomitant use of palovarotene and isavuconazonium due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. If concomitant use is necessary, decrease the palovarotene dose by half. Palovarotene is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased palovarotene overall exposure by 2.5-fold.
Paricalcitol: (Moderate) Concomitant use of isavuconazonium with paricalcitol may result in increased serum concentrations of paricalcitol. Paricalcitol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as GI effects, are advised if these drugs are used together.
Pazopanib: (Moderate) Concomitant use of isavuconazonium with pazopanib may result in increased serum concentrations of both drugs. Pazopanib is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and isavuconazonium due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If isavuconazonium is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of isavuconazonium. Pemigatinib is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase pemigatinib exposure by approximately 50% to 80%.
Pentobarbital: (Major) Concomitant use of isavuconazonium with pentobarbital should be undertaken with great caution due to the potential for treatment failure. Coadministration may result in reduced systemic exposure to isavucaonazole, the active moiety of isavuconazoium. Isavuconazole is a sensitive substrate of hepatic isoenzyme CYP3A4. Barbituates are known to induce hepatic CYP isoenzymes; phenobarbital, a potent inducer of CYP3A4, is contraindicated for use with isavuconazole.
Perampanel: (Major) Caut ion and close monitoring are warranted when isavuconazonium is administered with perampanel as there is a potential for elevated perampanel concentrations and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Perampanel is a substrate and inducer of the hepatic isoenzyme CYP3A4. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme.
Perindopril; Amlodipine: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Perphenazine; Amitriptyline: (Moderate) Concomitant use of isavuconazonium with amitriptyline may result in increased serum concentrations of amitriptyline. Amitriptyline is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and isavuconazonium due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If isavuconazonium is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of isavuconazonium. Pexidartinib is a CYP3A substrate; isavuconazonium is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Phenobarbital: (Contraindicated) Concomitant use of isavuconazonium with phenobarbital is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; phenobarbital is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Contraindicated) Concomitant use of isavuconazonium with phenobarbital is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; phenobarbital is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer.
Phentermine; Topiramate: (Moderate) Caution and close monitoring are warranted when isavuconazonium is administered with topiramate as there is a potential for decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of this enzyme.
Phenytoin: (Contraindicated) Concomitant use of isavuconazonium with phenytoin or fosphenytoin is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; phenytoin is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer. Elevated phenytoin concentrations would also be expected with coadministration, as phenytoin is a substrate and isavuconazole is moderate inhibitor of CYP3A4.
Pimozide: (Major) Concomitant use of isavuconazonium with pimozide should be avoided. Pimozide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Posaconazole: (Contraindicated) Concomitant use of isavuconazonium with posaconazole is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; posaconazole is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated posaconazole concentrations may also be seen with coadministration, as posaconazole is a substrate and isavuconazole is an inhibitor of the drug transporter P-glycoprotein (P-gp).
Pralsetinib: (Major) Avoid concomitant use of isavuconazonium with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and isavuconazonium is a combined moderate CYP3A and P-gp inhibitor. Coadministration with another combined moderate CYP3A and P-gp inhibitor increased the overall exposure of pralsetinib by 108%.
Prasugrel: (Moderate) Concomitant use of isavuconazonium with prasugrel may result in increased serum concentrations of prasugrel. Prasugrel is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Prednisolone: (Moderate) Concomitant use of isavuconazonium with prednisolone may result in increased serum concentrations of prednisolone. Prednisolone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as corticosteroid-related side effects, are advised if these drugs are used together.
Prednisone: (Moderate) Concomitant use of isavuconazonium with prednisone may result in increased serum concentrations of prednisone. Prednisolone, the active metabolite of prednisone, is a substrate of the hepatic isoenzyme CYP3A4; additionally prednisone is a substrate of the drug transporter P-glycoprotein (P-gp). Isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring for adverse effects, such as corticosteroid-related side effects, are advised if these drugs are used together.
Primidone: (Contraindicated) Concomitant use of isavuconazonium with primidone is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; primidone is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and isavuconazonium due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and isavuconazonium is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Propafenone: (Moderate) Concomitant use of isavuconazonium with propafenone may result in increased serum concentrations of propafenone. Propafenone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Quazepam: (Moderate) Concomitant use of isavuconazonium with quazepam may result in increased serum concentrations of quazepam. Quazepam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as CNS depression, are advised if these drugs are used together.
Quetiapine: (Moderate) Concomitant use of isavuconazonium with quetiapine may result in increased serum concentrations of quetiapine. Quetiapine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Quinidine: (Moderate) Caution and therapeutic drug concentration monitoring, if available, are recommended during coadministration of quinidine with isavuconazonium. Quinidine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Concurrent use may result in elevated quinidine plasma concentrations.
Quinine: (Major) Concomitant use of isavuconazonium with quinine may result in increased serum concentrations of quinine and altered concentrations of isavuconazonium. Quinine is a substrate/inhibitor/inducer of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Rabeprazole: (Moderate) Concomitant use of isavuconazonium with rabeprazole may result in increased serum concentrations of rabeprazole. Rabeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Ramelteon: (Moderate) Concomitant use of isavuconazonium with ramelteon may result in increased serum concentrations of ramelteon. Ramelteon is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Ranolazine: (Major) The dose of ranolazine, a CYP3A4 and P-glycoprotein (P-gp) substrate, should be limited to 500 mg PO twice daily when coadministered with isavuconazonium. Isavuconazole, the active moiety of isavuconazonium is a moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Inhibition of ranolazine CYP3A4 metabolism could lead to increased ranolazine plasma concentrations. Serum concentrations of isavuconazole may also be increased as ranolazine is a CYP3A4 inhibitor, while isavuconazole is a sensitive substrate of CYP3A4.
Relugolix: (Major) Avoid concomitant use of relugolix and oral isavuconazonium. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer isavuconazonium at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of isavuconazonium is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and isavuconazonium is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral isavuconazonium. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer isavuconazonium at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of isavuconazonium is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and isavuconazonium is a P-gp inhibitor.
Repaglinide: (Moderate) Concomitant use of isavuconazonium with repaglinide may result in increased serum concentrations of repaglinide. Repaglinide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as hypoglycemia, are advised if these drugs are used together.
Ribociclib: (Contraindicated) Coadministration of isavuconazonium with ribociclib is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%.
Ribociclib; Letrozole: (Contraindicated) Coadministration of isavuconazonium with ribociclib is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%.
Rifabutin: (Major) Caution and close monitoring are warranted when isavuconazonium is administered with rifabutin as there is a potential for elevated rifabutin concentrations and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Rifabutin is a substrate and inducer of the hepatic isoenzyme CYP3A4. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme.
Rifampin: (Contraindicated) Concomitant use of isavuconazonium with rifampin is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; rifampin is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin.
Rifapentine: (Contraindicated) Concomitant use of isavuconazonium with rifapentine is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; rifapentine is a strong inducer of this enzyme. Coadministration with another strong CYP3A4 inducer decreased isavuconazole serum concentrations by 97%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with isavuconazonium is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and isavuconazonium is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Moderate) Concomitant use of isavuconazonium with rilpivirine may result in increased serum concentrations of rilpivirine. Rilpivirine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with isavuconazonium; concurrent use may increase rimegepant exposure. Rimegepant is a CYP3A4 and P-gp substrate; isavuconazonium is a moderate CYP3A4 inhibitor and a P-gp inhibitor.
Riociguat: (Moderate) Concomitant use of isavuconazonium with riociguat may result in increased serum concentrations of riociguat. Riociguat is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring for adverse effects, such as hypotension, are advised if these drugs are used together.
Ritonavir: (Contraindicated) Concomitant use of isavuconazonium with high-dose ritonavir (i.e., 400 mg every 12 hours) is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; ritonavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated ritonavir concentrations may also be seen with coadministration, as ritonavir is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp).
Rivaroxaban: (Moderate) Concomitant use of isavuconazonium with rivaroxaban may result in increased serum concentrations of rivaroxaban which may increase the bleeding risk. Rivaroxaban is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Romidepsin: (Moderate) Caution is warranted when isavuconazonium is administered with romidepsin as there is a potential for elevated romidepsin concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Romidepsin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp.
Rufinamide: (Moderate) Use caution when administering rufinamide and isavuconazonium due to the potential for a synergistic effect on the QT interval that would increase the QT shortening risk. Both rufinamide and isavuconazonium are associated with QT shortening. Nonclinical data indicate that QT shortening is associated with ventricular fibrillation.
Ruxolitinib: (Moderate) The plasma concentrations of ruxolitinib may be elevated when administered concurrently with isavuconazonium. Ruxolitinib is a CYP3A4 substrate; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Although a dose adjustment is not necessary when used with drugs that are mild or moderate inhibitors of CYP3A4 such as isavuconazole, monitoring patients for ruxolitinib toxicity may be prudent when these drugs are given concurrently. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days (another moderate CYP3A4 inhibitor). The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure.
Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the fungal or yeast infection is completely treated.
Saquinavir: (Contraindicated) Concomitant use of isavuconazonium with saquinavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; saquinavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated saquinavir concentrations may also be seen with coadministration, as saquinavir is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp).
Saxagliptin: (Moderate) Concomitant use of isavuconazonium with saxagliptin may result in increased serum concentrations of saxagliptin. Saxagliptin is a substrate of the hepatic isoenzyme CYP3A4); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring for adverse effects, such as hypoglycemia, are advised if these drugs are used together.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Concomitant use of isavuconazonium with ethinyl estradiol may result in increased serum concentrations of both drugs. Ethinyl estradiol is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together. (Minor) Coadministration of segesterone, a CYP3A4 substrate and a moderate CYP3A4 inhibitor, such as isavuconazonium may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and isavuconazonium due to the risk of increased selpercatinib exposure, which may increase the risk of adverse reactions, including QT prolongation. If coadministration is unavoidable, reduce the dose of selpercatinib to 80 mg PO twice daily if original dose was 120 mg twice daily, and to 120 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If isavuconazonium is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of isavuconazonium. Selpercatinib is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase selpercatinib exposure by 60% to 99%.
Selumetinib: (Major) Avoid coadministration of selumetinib and isavuconazonium due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If isavuconazonium is discontinued, resume the original selumetinib dose after 3 elimination half-lives of isavuconazonium. Selumetinib is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase selumetinib exposure by 41%.
Sildenafil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with isavuconazonium is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor.
Silodosin: (Moderate) The plasma concentrations of silodosin may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as hypotension or dizziness, is recommended during coadministration. Silodosin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp.
Simvastatin: (Moderate) Closely monitor for evidence of myopathy, including rhabdomyolysis if simvastatin and isavuconazonium are coadministered. Concomitant use of isavuconazonium with simvastatin may result in increased serum concentrations of simvastatin. Simvastatin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4.
Siponimod: (Moderate) Concomitant use of siponimod and isavuconazonium may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of isavuconazonium. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and isavuconazonium is a moderate CYP3A and P-gp inhibitor. Concomitant use of other moderate CYP3A and P-gp inhibitors increased sirolimus overall exposure by 2.2- to 4.2-fold.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with isavuconazonium. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazonium is a weak inhibitor of P-gp. Isavuconazonium is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with isavuconazonium. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazonium is a weak inhibitor of P-gp. Isavuconazonium is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Solifenacin: (Moderate) Concomitant use of isavuconazonium with solifenacin may result in increased serum concentrations of solifenacin. Solifenacin is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and isavuconazonium; sonidegib levels may be significantly increased resulting in increased risk of adverse events, particularly musculoskeletal toxicity. If concomitant use cannot be avoided, administer isavuconazonium for less than 14 days; monitor patients closely for adverse reactions (e.g., elevated serum creatine kinase and serum creatinine levels). Sonidegib is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Physiologic-based pharmacokinetic (PBPK) simulations indicate a moderate 3A4 inhibitor would increase the sonidegib AUC by 1.8-fold if administered for 14 days and by 2.8-fold if the moderate CYP3A inhibitor is administered with sonidegib for more than 14 days.
Sparsentan: (Moderate) Monitor for an increase in sparsentan-related adverse effects if concomitant use with isavuconazonium is necessary. Concomitant use may increase sparsentan exposure. Sparsentan is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sparsentan overall exposure by 70%.
St. John's Wort, Hypericum perforatum: (Contraindicated) Concomitant use of isavuconazonium with St. John's Wort is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; St. John's Wort is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer.
Stiripentol: (Moderate) Consider a dose adjustment of isavuconazonium when coadministered with stiripentol. Coadministration may alter plasma concentrations of isavuconazonium resulting in an increased risk of adverse reactions and/or decreased efficacy. Isavuconazonium is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if isavuconazonium must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of isavuconazonium is necessary. If isavuconazonium is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like isavuconazonium can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If isavuconazonium is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Suvorexant: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with isavuconazonium. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate. Isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4.
Tacrolimus: (Moderate) Use caution and closely monitor tacrolimus serum concentrations when administered concurrently with isavuconazonium. Use of these drugs together results in elevated tacrolimus serum concentrations and an increased risk for adverse reactions. Tacrolimus dose adjustments may be necessary and should be guided by serum concentrations during coadministration. Isavuconazole, the active moiety of isavuconazonium, is a inhibitor of hepatic isoenzyme CYP3A4; tacrolimus is metabolized by this enzyme.
Tadalafil: (Moderate) Concomitant use of isavuconazonium with tadalafil may result in increased serum concentrations of tadalafil. Tadalafil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with isavuconazonium is necessary. Talazoparib is a P-gp substrate and isavuconazonium is a P-gp inhibitor.
Tamsulosin: (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Tamsulosin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp.
Tasimelteon: (Moderate) Concomitant use of isavuconazonium with tasimelteon may result in increased serum concentrations of tasimelteon. Tasimelteon is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with isavuconazonium as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If isavuconazonium is discontinued, wait at least 3 half-lives of isavuconazonium before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telmisartan; Amlodipine: (Moderate) Concomitant use of isavuconazonium with amlodipine may result in increased serum concentrations of amlodipine. Amlodipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with isavuconazonium is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and isavuconazonium is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus.
Teniposide: (Major) Concomitant use of isavuconazonium with teniposide may result in increased serum concentrations of teniposide. Teniposide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring for adverse effects, such as myelosuppression, are advised if these drugs are used together.
Tenofovir Alafenamide: (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Tenofovir Alafenamide: (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering isavuconazonium. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Tezacaftor; Ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with isavuconazonium; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); isavuconazonium is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If isavuconazonium and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Theophylline, Aminophylline: (Moderate) Concomitant use of isavuconazonium with theophylline, aminophylline may result in increased serum concentrations of theophylline. Theophylline and aminophylline are substrates of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Tiagabine: (Moderate) The plasma concentrations of tiagabine may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Tiagabine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.
Ticagrelor: (Moderate) Coadministration of ticagrelor and isavuconazonium may result in increased exposure to ticagrelor which may increase the bleeding risk. In addition, the exposure to isavuconazonium may be increased resulting in potential adverse effects. Ticagrelor is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Tinidazole: (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Tinidazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.
Tipranavir: (Contraindicated) Concomitant use of isavuconazonium with tipranavir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; tipranavir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated tipranavir concentrations may also be seen with coadministration, as tipranavir is a substrate and isavuconazole is an inhibitor of CYP3A4 and the drug transporter P-glycoprotein (P-gp).
Tolterodine: (Moderate) The plasma concentrations of tolterodine may be elevated when administered concurrently with isavuconazonium, and a decreased dose may be warranted. Clinical monitoring for adverse effects, such as dry mouth or QT prolongation, is recommended during coadministration. Tolterodine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.
Tolvaptan: (Major) Avoid coadministration of isavuconazonium when tolvaptan is administered for hyponatremia. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with isavuconazonium. In ADPKD patients receiving tolvaptan 90mg every morning and 30 mg every evening, reduce the dose to 45 mg every morning and 15 mg every evening; for those receiving tolvaptan 60 mg every morning and 30 mg every evening, reduce the dose to 30 mg every morning and 15 mg every evening; for those receiving tolvaptan 45 mg every morning and 15 mg every evening, reduce the dose to 15 mg every morning and 15 mg every evening. Consider additional dosage reduction if the reduced dose is not tolerated. Interrupt tolvaptan in ADPKD patients if the recommended reduced doses are not available in patients requiring short-term therapy of isavuconazonium. Tolvaptan is a sensitive CYP3A4 substrate; isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased the tolvaptan AUC by 200%.
Topiramate: (Moderate) Caution and close monitoring are warranted when isavuconazonium is administered with topiramate as there is a potential for decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of this enzyme.
Topotecan: (Major) Avoid coadministration of isavuconazonium with oral topotecan due to increased topotecan exposure; isavuconazonium may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and isavuconazonium is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Tramadol: (Moderate) Concomitant use of isavuconazonium with tramadol may result in increased serum concentrations of tramadol. Tramadol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Tramadol; Acetaminophen: (Moderate) Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen. Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. (Moderate) Concomitant use of isavuconazonium with tramadol may result in increased serum concentrations of tramadol. Tramadol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Trandolapril; Verapamil: (Moderate) Concomitant use of isavuconazonium with verapamil may result in increased serum concentrations of both drugs. Verapamil is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Trazodone: (Moderate) Concomitant use of isavuconazonium with trazodone may result in increased serum concentrations of trazodone. Trazodone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with isavuconazonium and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Tucatinib: (Contraindicated) Coadministration of isavuconazonium with tucatinib is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%.
Ubrogepant: (Major) Limit the initial dose of ubrogepant to 50 mg and avoid a second dose within 24 hours if coadministered with isavuconazonium. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 and P-gp substrate; isavuconazonium is a moderate CYP3A4 inhibitor and a P-gp inhibitor. Coadministration with another moderate CYP3A4 inhibitor resulted in a 3.5-fold increase in the exposure of ubrogepant.
Umeclidinium: (Moderate) Concomitant use of isavuconazonium with umeclidinium; vilanterol may result in increased serum concentrations of umeclidinium; vilanterol. Umeclidinium; vilanterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Umeclidinium; Vilanterol: (Moderate) Concomitant use of isavuconazonium with umeclidinium; vilanterol may result in increased serum concentrations of umeclidinium; vilanterol. Umeclidinium; vilanterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with isavuconazonium due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; isavuconazoniium is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Vemurafenib: (Major) Concomitant use of isavuconazonium with vemurafenib may result in increased serum concentrations of vemurafenib and decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Vemurafenib is a substrate and inducer of the hepatic isoenzyme CYP3A4 and a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with isavuconazonium due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of isavuconazonium. Venetoclax is a CYP3A4 and P-glycoprotein (P-gp) substrate; isavuconazonium is a CYP3A4 (moderate) and P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Moderate) Concomitant use of isavuconazonium with venlafaxine may result in increased serum concentrations of venlafaxine. Venlafaxine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Verapamil: (Moderate) Concomitant use of isavuconazonium with verapamil may result in increased serum concentrations of both drugs. Verapamil is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with isavuconazonium is necessary. Vinblastine is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Vincristine Liposomal: (Moderate) Concomitant use of isavuconazonium with vincristine may result in increased serum concentrations of vincristine. Vincristine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Vincristine: (Moderate) Concomitant use of isavuconazonium with vincristine may result in increased serum concentrations of vincristine. Vincristine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with isavuconazonium is necessary. Vinorelbine is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor.
Voclosporin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with isavuconazonium. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Concomitant use of isavuconazonium with clarithromycin may result in increased serum concentrations of both drugs. Clarithromycin is a substrate and moderate inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Vorapaxar: (Major) Concomitant use of isavuconazonium with vorapaxar may result in increased serum concentrations of vorapaxar which may increase the risk of bleeding complications. Vorapaxar is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Voriconazole: (Contraindicated) Coadministration of isavuconazonium with voriconazole is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and voiconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%. Typically isavuconazonium would not be used in combination with other systemic azole antifungal agents, such as voriconazole, due to similar mechanisms of action and indications for use (duplicate therapies).
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with isavuconazonium is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Isavuconazonium is a moderate CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zafirlukast: (Moderate) Concomitant use of isavuconazonium with zafirlukast may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; zafirlukast is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with isavuconazonium. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of isavuconazonium, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Ziprasidone: (Moderate) Concomitant use of isavuconazonium with ziprasidone may result in increased serum concentrations of ziprasidone. Ziprasidone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, are advised if these drugs are used together.
Zolmitriptan: (Moderate) Concomitant use of isavuconazonium with zolmitriptan may result in increased serum concentrations of zolmitriptan. Zolmitriptan is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Zolpidem: (Moderate) It is advisable to closely monitor zolpidem tolerability and safety during concurrent use of isavuconazonium, a moderate CYP3A4 inhibitor, since CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism. There is evidence of an increase in pharmacodynamics effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4, such as azole antifungals.

CRESEMBA Intravenous Inj Pwd F/Sol: 372mg
CRESEMBA/Isavuconazonium sulfate Oral Cap: 74.5mg, 186mg

1116 mg/day isavuconazonium (equivalent to 600 mg/day isavuconazole) PO or IV.

1116 mg/day isavuconazonium (equivalent to 600 mg/day isavuconazole) PO or IV.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Like other azole antifungals, isavuconazole (the active metabolite of isavuconazonium) exerts its antifungal activity by inhibiting the synthesis of ergosterol, an essential component of fungal cell membrane. Azole antifungals block ergosterol synthesis by inhibiting 14-alpha demethylase, a cytochrome P450 dependent enzyme, which is needed to convert lanosterol to ergosterol. The depletion of ergosterol within the fungal cell membrane results in increased cellular permeability causing leakage of cellular contents.
 
Isavuconazole displays antifungal activity (both in vitro and in clinical infections) against most strains of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Rizopus oryzae, and Mucormycetes species. Unlike other azole antifungals, isavuconazonium is not indicated for the treatment of infections cause by other fungal species, such as Candida, Blastomyces, nor Histoplasma.
 
The mechanism of resistance to isavuconazonium is likely due to multiple mechanisms, including substitutions in the target gene CYP51. Changes in sterol profile and increased efflux pump activity have been observed; however, the clinical relevance of these findings is unclear. In vitro and animal studies suggest cross-resistance between isavuconazole and other azoles; patients failing prior azole therapy may require alternative antifungal therapy.

Isavuconazonium is administered orally, by nasogastric tube, or intravenously. Once in systemic circulation, esterases (primarily butylcholinesterase) present in the blood rapidly hydrolyze isavuconazonium to isavuconazole, the active drug component. Isavuconazole is highly protein bound (more than 99%, primarily to albumin) and has a mean steady-state Vd of about 450 L. Isavuconazole is initially metabolized in the liver by CYP3A4/5 enzymes, with subsequent metabolism involving uridine diphosphate-glucuronosyltransferases (UGT). It is excreted almost entirely as inactive metabolites. The mean plasma half-life is approximately 130 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP3A5, UGT, P-gp, OCT2
In vivo single- and multiple-dose drug interaction studies show that isavuconazole is both a substrate and moderate inhibitor of CYP3A4, a substrate of CYP3A5 and uridine diphosphate-glucuronosyltransferases (UGT), and a mild inhibitor of P-glycoprotein (P-gp) and organic cation transporter 2 (OCT2). In vitro, it inhibits CYP2C8, CYP2C9, CYP2C19, and CYP2D6, and induces CYP3A4, CYP2B6, CYP2C8, and CYP2C9; drug interaction studies did not display drug-drug effects specific to these isoenzymes in vivo.

Opportunistic infection guidelines recommend the use of an alternative antifungal agent during pregnancy, especially during the first trimester.[34362] There are no data available on the use of isavuconazonium in human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, based on findings from animal studies, isavuconazonium may cause fetal harm. Advise pregnant women of the potential risk to the fetus. In animal reproduction studies, perinatal mortality was increased in the offspring of pregnant rats given oral isavuconazonium 90 mg/kg/day (approximately 0.5 times the clinical exposure based on AUC comparisons) during pregnancy through the weaning period. Isavuconazonium use was associated with dose-related increases in the incidences of rudimentary cervical ribs in rats and rabbits at 30 and 45 mg/kg, respectively, doses equivalent to about 0.2 and 0.1 of the human maintenance dose based on AUC comparisons. In rats, dose-related increases in the incidences of zygomatic arch fusion and supernumerary ribs or rudimentary supernumerary ribs were also noted at 30 mg/kg and above, equivalent to one-fifth the maintenance human dose based on AUC comparison.[59042]

Discontinue breast-feeding during treatment with isavuconazonium. There are no data on the presence of isavuconazonium in human milk, the effects on the breast-fed infant, or the effects on milk production. Isavuconazonium was present in the milk of lactating rats after intravenous administration.