Names and pronunciation
(eye-sa-vue-koe-na-zoe′nee-um) Cresemba
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Drug reference
(eye-sa-vue-koe-na-zoe′nee-um) Cresemba
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Func. class.: Antifungal, systemic
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Chem. class.: Azole
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ACTION: Exerts antifungal activity by inhibiting the synthesis of ergos- terol, an essential component of the fungal cell membrane. The depletion of ergosterol within the fungal cell mem- brane results in increased cellular per- meability, causing leakage of cellular content
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USES: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Rhizopus oryzae, Mucormycetes species; do NOT use for infections of Candida, Blastomy ces, Histoplasma
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CONTRAINDICATIONS: Hyper- sensitivity, short QT syndrome Precautions: Azole hypersensitivity, pregnancy, breastfeeding, infusion- related reactions, hepatic disease
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SIDE EFFECTS CNS: Headache, paresthesias, periph- eral neuropathy, hallucinations, depres- sion, insomnia, dizziness, fever, vertigo, tremor, confusion CV: Tachypnea, supraventricular tachy- cardia, atrial fibrillation/flutter EENT: Tinnitus GI: Nausea, vomiting, anorexia, diarrhea, cramps, hepatitis, stomatitis GU: Hypokalemia, renal failure HEMA: Anemia, eosinophilia, hypomag- nesemia, thrombocytopenia, leukopenia INTEG: Burning, irritation, pain, necro- sis at inj site with extravasation, rash MISC: Cough
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INTERACTIONS Increase: effects of benzodiazepines, cal- cium channel blockers, cycloSPORINE, ergots, HMG-CoA reductase inhibitors, pimozide, quiNIDine, prednisoLONE, sirolimus, sulfonylureas, tacrolimus, vinca alkaloids, warfarin, rifabutin, pro- ton pump inhibitors, NNRTIs, protease inhibitors, phenytoin Increase: isavuconazonium effect— CYP3A4 substrates Decrease: isavuconazonium effect— CYP3A4 inhibitors Decrease: bupropion effect—dose may need to be increased Drug/Herb • Do not use with St. John’s wort Drug/Lab Test Increase: AST/ALT, alk phos, creatinine, bilirubin Decrease: HB/Hct, platelets, WBC
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DOSAGE AND ROUTES • Adult: PO loading dose of 2 caps (372 mg) q8hr × 6 doses. Then, 2 caps (372 mg) daily. Start maintenance dosing 12- 24 hr after the last loading dose; treat- ment may last 6-12 wk up to 6 mo. IV loading dose of 372 mg q8hr × 6 doses, then 372 mg/day, beginning 12-24 hr af- ter the last loading dose; use a 0.2- to 1.2-micron in-line filter and administer over a minimum of 1 hr; an additional loading dose is not needed when switch- ing to PO
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Administer: PO route • Swallow whole; do not chew, crush, dissolve, open the capsules; may be used without regard to food IV route • Visually inspect for particulate mat- ter and discoloration; diluted solution may contain translucent to white par- ticulates that will be removed by the in-line filter Reconstitution • Reconstitute the dry powder with 5 mL sterile water for injection, gently shake until dissolved • Storage: the reconstituted solution may be stored below 77°F (25°C) for a maximum of 1 hr before further dilution Dilution • Remove 5 mL of the reconstituted solu- tion and add it to 250 mL of either 0.9% NaCl or D5W (1.5 mg/mL) • Gently mix the solution or roll the bag. DO NOT shake. Do not place in a pneu- matic transport system • Apply an in-line filter (0.2-1.2 mi- crons), adhere an in-line filter reminder sticker to the infusion bag • Give within ≤6 hr of dilution • Storage: may be stored immediately after dilution at 36°F to 46°F (2°C to 8°C); ad- ministration MUST be completed within 24 hr of the time of dilution. Do NOT freeze • Product only after C&S confirms or- ganism, product needed to treat condi- tion; make sure product is used in life-threatening infections • Flush IV lines with 0.9% sodium chlo- ride or 5% dextrose in water before and after administration of the infusion • Must be administered through a 0.2- to 1.2-micron filter; give over ≥1 hr. Do not give by bolus • Do not admix
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Available forms: Caps 186 mg; powder for injection 382 mg
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Assess: • Short QT syndrome: do not use in this condition • VS q15-30min during first infusion; note changes in pulse, B/P • Blood studies: CBC, potassium, so- dium, calcium, magnesium, q2wk; ob- tain culture and sensitivity before starting first dose; may start treatment before re- sults are received • Hepatotoxicity: increases in AST, ALT, alk phos, bilirubin, baseline and periodically • Allergic reaction: dermatitis, rash; product should be discontinued, antihis- tamines (mild reaction) or epinephrine (severe reaction) administered • Hypokalemia: anorexia, drowsiness, weakness, decreased reflexes, dizziness, increased urinary output, increased thirst, paresthesias • Ototoxicity: tinnitus (ringing, roaring in ears), vertigo • Infusion-related reactions: dizziness, chills, fever, hypotension, dyspnea; dis- continue if these occur • Pregnancy/breastfeeding: test for pregnancy before starting treatment; do not use in or breastfeed
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Evaluate: I • Therapeutic response: resolution of fungal infection, negative C&S
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • That long-term therapy may be needed to clear infection (2 wk-3 mo, depending on type of infection); not to discontinue unless approved by pre- scriber • To notify prescriber of bleeding, bruis- ing, soft-tissue swelling, dark urine, per- sistent nausea or diarrhea, headache, rash, yellow skin/eyes • That women of childbearing age should use effective contraceptive; not to breast feed • To notify provider of all OTC, Rx, herbal products or supplements taken and to avoid new products unless ap- proved by prescriber • That lab exams will be required
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PHARMACOKINETICS Metabolized by CYP3A4, CYP3A5, UGT, P-gp, OCT2 enzymes; eliminated in urine/feces; peak 2 hr (PO), Chinese patients (levels 40% lower), protein binding >99%
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• Adult: PO loading dose of 2 caps (372 mg) q8hr × 6 doses. Then, 2 caps (372 mg) daily. Start maintenance dosing 12- 24 hr after the last loading dose; treat- ment may last 6-12 wk up to 6 mo. IV loading dose of 372 mg q8hr × 6 doses, then 372 mg/day, beginning 12-24 hr af- ter the last loading dose; use a 0.2- to 1.2-micron in-line filter and administer over a minimum of 1 hr; an additional loading dose is not needed when switch- ing to PO
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