Eraxis

Echinocandins Antifungals

For storage information, see the specific product information in the How Supplied section.

Visually inspect prepared infusions for particulate matter and discoloration prior to administration when solution and container permit. Discard solution if particulate matter or discoloration is identified.
Administer by intravenous infusion only, after appropriate dilution for IV infusion.

Reconstitution
Reconstitute each 50 mg or 100 mg vial with 15 mL or 30 mL of Sterile Water for Injection, respectively, for a resultant concentration of 3.33 mg/mL.
Storage: Reconstituted solutions are stable for up to 24 hours at temperatures up to 25 degrees C (77 degrees F).
 
Dilution
Do not use any diluent other than 5% Dextrose Injection or 0.9% Sodium Chloride Injection.
For preparation of 50 mg, 100 mg, or 200 mg doses:
50 mg dose: Withdraw the contents of one 50 mg reconstituted vial and add to an IV infusion bag or bottle containing 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection to give a total infusion volume of 65 mL.
100 mg dose: Withdraw the contents of one 100 mg reconstituted vial OR two 50 mg reconstituted vials and add to an IV infusion bag or bottle containing 100 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection to give a total infusion volume of 130 mL.
200 mg dose: Withdraw the contents of either four 50 mg reconstituted vials OR two 100 mg reconstituted vials and add to an IV infusion bag or bottle containing 200 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection to give a total infusion volume of 260 mL.
For preparation of pediatric doses below 50 mg:
Withdraw appropriate dose from the reconstituted vial (3.33 mg/mL) and dilute to a final concentration of 0.77 mg/mL.
Storage: Diluted solutions are stable for up to 48 hours at temperatures up to 25 degrees C (77 degrees F); do NOT freeze diluted solution.
 
Intermittent IV Infusion
Do not mix or infuse with other medications.
Administer as a slow infusion at a rate no greater than 1.1 mg/minute (equivalent to 1.4 mL/minute or 84 mL/hour when reconstituted and diluted per instructions). The minimum duration of infusion is 45 minutes for a 50 mg dose, 90 minutes for a 100 mg dose, and 180 minutes for a 200 mg dose.

thrombosis / Delayed / 10.0-10.0
pleural effusion / Delayed / 10.0-10.0
hyperkalemia / Delayed / 6.0-6.0
pancytopenia / Delayed / 0-5.0
seizures / Delayed / 0-5.0
hepatic necrosis / Delayed / 0-2.0
angioedema / Rapid / 0-2.0
coagulopathy / Delayed / 0-2.0
arrhythmia exacerbation / Early / 0-2.0
atrial fibrillation / Early / 0-2.0
visual impairment / Early / 0-2.0
hepatic failure / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known

hypokalemia / Delayed / 0-25.0
hypotension / Rapid / 15.0-15.0
hypomagnesemia / Delayed / 12.0-12.0
hypertension / Early / 12.0-12.0
dyspnea / Early / 12.0-12.0
peripheral edema / Delayed / 0-11.0
anemia / Delayed / 8.0-10.0
elevated hepatic enzymes / Delayed / 5.0-9.0
constipation / Delayed / 8.0-8.0
confusion / Early / 8.0-8.0
hypoglycemia / Early / 6.0-7.0
thrombocytopenia / Delayed / 0-6.0
thrombocytosis / Delayed / 0-6.0
dehydration / Delayed / 6.0-6.0
hyperglycemia / Delayed / 6.0-6.0
depression / Delayed / 6.0-6.0
stomatitis / Delayed / 0-5.0
skin ulcer / Delayed / 5.0-5.0
leukopenia / Delayed / 0-5.0
neutropenia / Delayed / 0-5.0
hyponatremia / Delayed / 0-5.0
hypocalcemia / Delayed / 0-5.0
chest pain (unspecified) / Early / 0-5.0
ocular inflammation / Early / 0-5.0
candidiasis / Delayed / 5.0-5.0
hemoptysis / Delayed / 0-5.0
cholestasis / Delayed / 0-2.0
hyperbilirubinemia / Delayed / 0-2.0
infusion-related reactions / Rapid / 0-2.0
hot flashes / Early / 0-2.0
erythema / Early / 0-2.0
phlebitis / Rapid / 0-2.0
QT prolongation / Rapid / 0-2.0
bundle-branch block / Early / 0-2.0
blurred vision / Early / 0-2.0
hyperamylasemia / Delayed / 0-2.0
hepatitis / Delayed / Incidence not known

nausea / Early / 0-24.0
diarrhea / Early / 9.0-18.0
vomiting / Early / 7.0-18.0
fever / Early / 9.0-18.0
insomnia / Early / 15.0-15.0
abdominal pain / Early / 6.0-9.0
epistaxis / Delayed / 9.0-9.0
headache / Early / 0-8.0
dyspepsia / Early / 7.0-7.0
cough / Delayed / 7.0-7.0
xerostomia / Early / 0-5.0
leukocytosis / Delayed / 5.0-5.0
infection / Delayed / 0-5.0
tremor / Early / 0-5.0
agitation / Early / 0-5.0
back pain / Delayed / 0-5.0
musculoskeletal pain / Early / 0-5.0
urticaria / Rapid / 0-2.0
hyperhidrosis / Delayed / 0-2.0
flushing / Rapid / 0-2.0
pruritus / Rapid / 0-2.0
ocular pain / Early / 0-2.0
dizziness / Early / 0-2.0
rash / Early / Incidence not known

Eraxis

Rx

IV echinocandin antifungal drug
Used for candidemia and other invasive candidiasis infections and esophageal and oropharyngeal candidiasis
Efficacy for treatment of infections caused by fungi other than Candida has not been established

200 mg IV loading dose on day 1, then 100 mg IV once daily for several weeks and followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate.

Limited data are available. A 3 mg/kg/dose (Max: 200 mg/dose) IV loading dose, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily appears to provide comparable exposure to that seen in adults receiving a 200 mg IV loading dose, followed by 100 mg IV once daily. Treat for several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate.

200 mg IV loading dose on day 1, then 100 mg IV once daily for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.

3 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complication.

Very limited data are available. A 3 mg/kg/dose IV loading dose, then 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in children receiving similar weight-based dosing and adults receiving a 200 mg IV loading dose, followed by 100 mg IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts suggest that if an echinocandin is used in neonates, micafungin is the preferred agent.

100 mg IV loading dose on day 1, then 50 mg IV once daily. Alternatively, 200 mg IV once daily. Treat for 14 to 21 days as an alternative.

100 mg IV loading dose on day 1, then 50 mg IV once daily. Alternatively, 200 mg IV once daily. Treat for 14 to 21 days as an alternative.

1.5 mg/kg/dose (Max: 100 mg/dose) IV loading dose on day 1, then 0.75 mg/kg/dose (Max: 50 mg/dose) IV once daily. Alternatively, 3 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily. Treat for 14 to 21 days as an alternative.

200 mg IV loading dose on day 1, then 100 mg IV once daily for 14 days. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic persons; therefore, candiduria should be treated as disseminated candidiasis in these persons.

3 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 14 days. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic persons; therefore, candiduria should be treated as disseminated candidiasis in these persons.

200 mg IV loading dose on day 1, then 100 mg IV once daily for up to 28 days as an alternative.[60487]

3 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for up to 28 days as an alternative.

200 mg IV once daily. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

Limited data are available. A 3 mg/kg IV loading dose, then 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in adults receiving a 200 mg IV loading dose, followed by 100 mg IV daily. Doses should not exceed 200 mg for the loading dose and 100 mg for the maintenance dose; however, 200 mg IV once daily is recommended for adults with cardiac infections. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

Very limited data are available. A 3 mg/kg IV loading dose, then 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in children receiving similar weight-based dosing and adults receiving a 200 mg IV loading dose, followed by 100 mg IV daily. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts suggest that if an echinocandin is used in neonates, micafungin is the preferred agent. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, 200 mg IV loading dose on day 1, then 100 mg IV once daily.

Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Restrict treatment to pneumonia associated with disseminated infection. Limited data are available. A 3 mg/kg IV loading dose, then 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in adults receiving a 200 mg IV loading dose, followed by 100 mg IV daily. Doses should not exceed 200 mg for the loading dose and 100 mg for the maintenance dose.

Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Restrict treatment to pneumonia associated with disseminated infection. Very limited data are available. A 3 mg/kg IV loading dose, then 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in children receiving similar weight-based dosing and adults receiving a 200 mg IV loading dose, followed by 100 mg IV daily. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts suggest that if an echinocandin is used in neonates, micafungin is the preferred agent.

200 mg IV loading dose on day 1, then 100 mg IV once daily. In general, antifungal therapy should continue for at least 14 days after the last positive culture.

3 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily. In general, antifungal therapy should continue for at least 14 days after the last positive culture.

Very limited data are available. A 3 mg/kg IV loading dose, then 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in children receiving similar weight-based dosing and adults receiving a 200 mg IV loading dose, followed by 100 mg IV daily. A dose of 1.5 mg/kg/day IV as add-on therapy was successfully used in a case report in a neonate with peritoneal candidiasis. In general, antifungal therapy should continue for at least 14 days after the last positive culture.

200 mg IV loading dose on day 1, then 100 mg IV once daily for at least 14 days after catheter removal for Candida and as salvage therapy for Aspergillus.

3 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for at least 14 days after catheter removal for Candida and as salvage therapy for Aspergillus.

100 mg IV once daily. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Recommended as an alternative to fluconazole as initial therapy. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.

Limited data are available. 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in adults receiving 100 mg IV daily. Doses should not exceed 100 mg. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Recommended as an alternative to fluconazole as initial therapy. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.

Very limited data are available. 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in children receiving similar weight-based dosing and adults receiving 100 mg IV daily. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts suggest that if an echinocandin is used in neonates, micafungin is the preferred agent. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis.

200 mg IV loading dose on day 1, then 100 mg IV once daily as an alternative therapy to fluconazole for high risk patients in intensive care units with a high rate (more than 5%) of invasive candidasis.

Very limited data are available. Doses of 1.5 mg/kg IV loading dose (Max: 100 mg/dose) on day 1 then 0.75 mg/kg/day IV (Max: 50 mg/day) or 3 mg/kg IV loading dose (Max: 200 mg/dose) on day 1 then 1.5 mg/kg/day IV (Max: 100 mg/day) were studied in a small trial of 25 children and adolescents (2 to 17 years) with neutropenia. Duration of therapy ranged from 4 to 23 days (median 8.7 days). A multicenter, open-label, dose-escalating study evaluated the safety, tolerability, and pharmacokinetics of anidulafungin given as empirical treatment for preventing invasive fungal infections in children with neutropenia due to cytotoxic chemotherapy or aplastic anemia. Although efficacy was not assessed, no patient developed a fungal infection during the study. An echinocandin, such as anidulafungin, is recommended as an alternative therapy to fluconazole for candidiasis prophylaxis in high risk patients in intensive care units with a high rate (more than 5%) of invasive candidiasis.

†Indicates off-label use

No dosage adjustment is needed. However, monitor patients for worsening hepatic function; consider risk/benefit of continuing treatment if further worsening of hepatic function occurs during anidulafungin treatment.

No dosage adjustment is needed in patients with renal impairment.[32019]
 
Intermittent hemodialysis
Anidulafungin is not dialyzable and may be administered without regard to the timing of hemodialysis. Supplemental dosing is not required.[32019]
 
Continuous renal replacement therapy
Anidulafungin is not dialyzable and may be administered without regard to the timing of hemodialysis. Supplemental dosing is not required.[32019]
 
Extracorporeal Membrane Oxygenation (ECMO)
Lower anidulafungin exposures have been noted in patients supported by ECMO. Higher anidulafungin doses may be necessary in these patients to achieve adequate drug concentrations.[54479]

Dichlorphenamide: (Moderate) Use dichlorphenamide and antifungals 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 dose or discontinuing dichlorphenamide therapy.
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.

Eraxis Intravenous Inj Pwd F/Sol: 50mg, 100mg

200 mg/day IV for loading dose; 100 mg/day IV for maintenance.

200 mg/day IV for loading dose; 100 mg/day IV for maintenance.

3 mg/kg IV (Max: 200 mg/dose) for loading dose; 1.5 mg/kg/day IV (Max: 100 mg/day) for maintenance dose.

3 mg/kg IV (Max: 200 mg/dose) for loading dose; 1.5 mg/kg/day IV (Max: 100 mg/day) for maintenance dose.

3 mg/kg IV for loading dose; 1.5 mg/kg/day IV for maintenance dose.

Safety and efficacy have not been established; however, 3 mg/kg IV as a loading dose and 1.5 mg/kg/day IV as a maintenance dose have been used off-label.

Anidulafungin inhibits glucan synthase, an enzyme important in the formation of beta (1,3)-D-glucan, a major fungal cell wall component. Glucan synthase is not present in mammalian cells and therefore is an attractive target for antifungal activity. Inhibition of glucan synthase results in morphological changes in fungi cell walls resulting in osmotic instability and fungal cell death.
 
Anidulafungin has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections: Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. In addition, at least 90% of Candida guilliermondii and Candida krusei isolates have minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoint for anidulafungin in vitro; however, the effectiveness of anidulafungin in treating clinical infections due to C. guilliermondii or C. krusei has not been established. The Clinical and Laboratory Standards Institute (CLSI) defines MICs for C. albicans, C. krusei, and C. tropicalis as susceptible if 0.25 mcg/mL or less, intermediate if 0.5 mcg/mL, and resistant if 1 mcg/mL or more. For C. glabrata, the MICs for susceptible, intermediate, and resistant are 0.12 mcg/mL or less, 0.25 mcg/mL, and 0.5 mcg/mL or more, respectively. C. parapsilosis and C. guilliermondii have the highest MIC break-points, susceptible if 2 mcg/mL or less, intermediate if 4 mcg/mL, and resistant if 8 mcg/mL or more. Decreased susceptibility has been reported among Candida isolates, suggesting the potential for resistance. Activity against Aspergillus sp. is not well defined; currently there are no established interpretive breakpoints for Aspergillus sp. Because of its unique mechanism of action, cross-resistance with amphotericin B and the azoles is not expected.

Anidulafungin is administered by intravenous infusion. After administration, anidulafungin has a short distribution half-life of 0.5 to 1 hour and a volume of distribution similar to total body fluid volume (approximately 30 to 50 L in adults). Anidulafungin is greater than 99% bound to human plasma proteins. It has excellent tissue penetration into tissues such as lung, liver, kidney, and spleen.[54502] Systemic exposure is dose-proportional with low intersubject variability (coefficient of variation less than 25%). Anidulafungin is not hepatically metabolized and is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 enzymes. Metabolism occurs through slow chemical degradation to a ring-opened peptide that does not have antifungal activity; this degradation occurs at physiologic temperature and pH with a half-life of about 24 hours. The resultant degradation product is further converted to peptide degradants and eliminated. Elimination data for anidulafungin are based on radiolabeled single-dose studies in healthy subjects. Approximately 30% of an administered dose is eliminated in the feces over 9 days; less than 10% is intact drug. Less than 1% of an administered dose is excreted in the urine. Anidulafungin concentrations fell below detectable levels 6 days post-dose; negligible amounts of drug-derived radioactivity were recovered in blood, urine, and feces 8 weeks post-dose. In adults, the clearance of anidulafungin is approximately 1 L/hour and the terminal elimination half-life is about 40 to 50 hours.[32019] [54502] Anidulafungin has the longest elimination half-life of all of the echinocandins.[54502]
 
Affected cytochrome P450 isoenzymes: none
Pre-clinical in vitro and in vivo and clinical studies demonstrate that anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of any clinically important CYP enzymes (1A2, 2C9, 2D6, 3A4). Drug interaction studies report that no dosage adjustments of either drug are necessary when administered with tacrolimus or voriconazole and that no dosage adjustments of anidulafungin are required when administered with rifampin or liposomal amphotericin B.

Peak concentrations are achieved immediately after IV administration. Anidulafungin steady-state plasma concentrations are reached on the first day after an intravenous loading dose and the estimated plasma accumulation factor at steady state is approximately 2.

There are no available human data on the use of anidulafungin in pregnancy to inform a drug-associated risk of adverse developmental outcomes. Based on animal studies, anidulafungin can cause fetal harm. Reduced fetal weights and incomplete ossification were observed in rabbits following maternal exposure to drug concentrations 4-times more than the recommended human maintenance dose. In addition, anidulafungin was detected in fetal plasma, indicating the drug crosses the placental barrier. Inform a pregnant woman of the risk to the fetus.

There are no data on the presence of anidulafungin in breast milk, the effects on the breast-fed infant, or the effects on breast milk. Anidulafungin was found in the milk of lactating rats. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for anidulafungin and any potential adverse effects on the breast-fed infant from anidulafungin or the underlying maternal condition.