rezafungin (Rx)

>10%

Hypokalemia (15%)

Pyrexia (12%)

Diarrhea (11%)

1-10%

Anemia (10%)

Vomiting (9%)

Nausea (9%)

Hypomagnesemia (8%)

Abdominal pain (7%)

Constipation (5%)

Hypophosphatemia (5%)

Infusion-related reactions (<5%)

Disseminated intravascular coagulation (<5%)

Dysphagia (<5%)

Gastrointestinal hemorrhage (<5%)

Fluid overload (<5%)

Insomnia (<5%)

Erythema (<5%)

Headache (<5%)

Dizziness (<5%)

Acute kidney injury (<5%)

Abnormal liver tests (including hypertransaminasemia and increased gamma-glutamyl transferase) (<5%)

Peripheral neuropathy (includes neuropathy peripheral, polyneuropathy, and peroneal nerve palsy) (<5%)

Tremors (2.6%)

Contraindications

Hypersensitivity to rezafungin or other echinocandins

Cautions

Infusion-related reactions (eg, flushing, sensation of warmth, urticaria, nausea, chest tightness) observed; if these reactions occur, slow or pause infusion, and restart at a lower rate

May cause photosensitivity; advise patient to use protection from sun exposure and other sources of UV radiation during treatment

Abnormal liver tests observed; monitor patients who develop abnormal liver tests during therapy and evaluate the risk/benefit of continuing therapy

Pregnancy & Lactation

Pregnancy

No data are available on use of rezafungin during pregnancy to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

Infertility

• Based on rat studies, rezafungin could lead to decreased sperm motility, decreased sperm numbers, and increased incidence of sperm with abnormal morphology
• Effect on human fertility is unknown

Animal data

• No adverse embryofetal outcomes observed when IV rezafungin was administered to rat pups or pregnant rabbits during organogenesis at doses up to 5x or 3x, respectively, clinical exposure based on AUC comparisons

Lactation

There are no data on presence of rezafungin or its metabolite in human milk, effects on breastfed infants, or effects on milk production

Rezafungin was present in rat milk

Drug is likely to present in human milk since it is present in animal milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Echinocandin antifungal drug that inhibits synthesis of 1,3-beta-D-glucan, which is an essential component of fungal cell walls

Shown to have antifungal activity against the following

• Candida albicans
• Candida glabrata
• Candida parapsilosis
• Candida tropicalis

Absorption

Peak plasma concentration

• Day 1: 19.2 mcg/mL
• Day 15: 11.8 mcg/mL

Minimum plasma concentration

• Day 1: 2.4 mcg/mL
• Day 15: 2.2 mcg/mL

AUC

• Day 1: 827 mcg·hr/mL
• Day 15: 667 mcg·hr/mL

Distribution

Vd: 67 L

Protein bound

• Patients: 87.5-93.6%
• Healthy adults: 95.6->98.6%

Metabolism

Hepatic metabolism not observed; unlikely it is a clinically relevant substrate of CYP450 enzymes

Elimination

Clearance: 0.35 L/hr

Half-life: 152 hr

Excretion

• Feces: 74.3% (primarily as rezafungin)
• Urine: 25.7% (primarily as inactive metabolites)

IV Compatibilities

0.9% NaCl

0.45% NaCl

Dextrose 5% (D5W)

IV Preparation

Reconstitution

• Aseptically reconstitute each 200 mg-vial with 9.5 mL of sterile water for injection, concentration of 20 mg/mL in each vial
• For loading 400-mg dose, use 2 vials
• For 200-mg dose, use 1 vial
• Swirl gently to dissolve the white to pale yellow cake or powder
• Avoid shaking to minimize foaming; solution should be clear to pale yellow after dissolution
• Visually inspect parenteral drug products for particulate matter and discoloration before administration, whenever solution and container permit; discard if reconstituted solution is cloudy or has precipitated
• NOTE: Reconstituted solution is not for direct injection and must dilute before IV infusion

Preparation of IV infusion solution

• Further dilution required with 0.9% NaCl, 0.45% NaCl, or D5W
• Aseptically withdraw volume from 250-mL IV bag that equals dosage volume

• 400-mg dose

  • Total reconstituted volume required: 20 mL
  • Infusion diluent volume discarded: 20 mL
  • Infusion diluent volume use: 230 mL
  • Total infusion volume: 250 mL (final concentration = 1.6 mg/mL)

• 200-mg dose

  • Total reconstituted volume required: 10 mL
  • Infusion diluent volume discarded: 10 mL
  • Infusion diluent volume use: 240 mL
  • Total infusion volume: 250 mL (final concentration = 0.8 mg/mL)
• Aseptically transfer indicated volume of reconstituted solution (10 mL per vial) into IV bag

IV Administration

• Administer IV only
• Infuse over ~1 hr (~250 mL/hr)
• If infusion-related reactions occur, may slow, or pause infusion and restart at lower rate
• Infusion bag must not be frozen

Missed doses

• Missed dose (not taken on the assigned day): Administer missed dose as soon as possible
• Missed dose ≤3 days of assigned day: May give next weekly dose on schedule
• Missed dose >3 days after assigned day: Revise dosing schedule to ensure there are at least 4 days before the next dose
• Restarting ≥2 weeks after missed dose: Start dosing again at 400-mg loading dose

Storage

Unopened vials

• Store at 20-25°C (68-77°F); brief excursions to 15-30°C (59-86°F)

Reconstituted solution

• May store at 5-25°C (41-77°F) for up to 24 hr

Diluted IV infusion bags

• Store at 5-25°C (41-77°F) for up to 48 hr
• Infusion solution must not be frozen