Class: Echinocandins
VA Class: AM700
Chemical Name: Pneumocandin A0, 1-[(4R,5R)-4,5-dihydroxy-N2-[4-[5-[4-(pentyloxy)phenyl]-3-isoxazolyl]benzoyl]- L-ornithine]-4-[(4S)-4-hydroxy-4-[4-hydroxy-3-(sulfooxy)phenyl]-L-threonine]-, monosodium salt
Molecular Formula: C56H70N9NaO23S
CAS Number: CAS-208538-73-2; CAS-235114-32-6
Brands: Mycamine
Introduction
Antifungal; echinocandin; lipopeptide synthesized from a fermentation product of Coleophoma empetri.1 2 3 4 5 8
Uses for Micafungin Sodium
Candidemia and Other Invasive Candida Infections
Treatment of candidemia, acute disseminated candidiasis, and certain other invasive Candida infections (peritonitis, abscesses).1 10 29 A drug of choice.10 23
For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in such patients, IDSA recommends fluconazole or an echinocandin (caspofungin, micafungin, anidulafungin) for initial therapy;23 amphotericin B (conventional or lipid formulation) is the preferred alternative.23 An echinocandin may be preferred for initial treatment in those who have moderately severe to severe candidemia, are allergic to or intolerant of azole antifungals, have recently received an azole, or have or are likely to have infections caused by C. glabrata or C. krusei.23 Fluconazole may be preferred for initial treatment in those who are less critically ill and have not recently received an azole and for infections caused by C. parapsilosis.23 If an echinocandin is used initially, transition to fluconazole is recommended for patients who are clinically stable and have isolates likely to be susceptible to fluconazole (e.g., C. albicans).23
For treatment of candidemia in neutropenic patients, IDSA recommends an echinocandin (caspofungin, micafungin, anidulafungin) or amphotericin B (a lipid formulation) for initial therapy;23 fluconazole is the preferred alternative in those who are less critically ill or have not recently received an azole;23 voriconazole can be used as an alternative when broader antifungal coverage is required.23 An echinocandin is preferred for C. glabrata infections;23 fluconazole or amphotericin B (a lipid formulation) is preferred for C. parapsilosis infections;23 an echinocandin, amphotericin B (a lipid formulation), or voriconazole is recommended for C. krusei infections.23 For initial empiric treatment of suspected invasive candidiasis in neutropenic patients, amphotericin B (a lipid formulation), caspofungin, or voriconazole is recommended;23 alternatives are fluconazole or itraconazole.23
Safety and efficacy not established for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida.1
Esophageal Candidiasis
Treatment of esophageal candidiasis.1 2 3 4 7 10 23 43 A drug of choice.10 23
Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).23 43 44
IDSA recommends oral fluconazole as the preferred drug of choice for treatment of esophageal candidiasis;23 if oral therapy is not tolerated, IV fluconazole, IV amphotericin B (conventional formulation), or an IV echinocandin (caspofungin, micafungin, anidulafungin) is recommended.23 For fluconazole-refractory infections, preferred alternatives are itraconazole oral solution, oral posaconazole, or IV or oral voriconazole;23 other alternatives are an IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B (conventional formulation).23
For treatment of esophageal candidiasis in HIV-infected adults and adolescents†, CDC, National Institutes of Health (NIH), and IDSA recommend IV or oral fluconazole as the preferred drug of choice and itraconazole oral solution as the preferred alternative.43 Other alternatives include an IV echinocandin (caspofungin, micafungin, anidulafungin), oral or IV voriconazole, oral posaconazole, or IV amphotericin B (conventional formulation).43 For refractory esophageal candidiasis, including fluconazole-refractory infections, itraconazole oral solution or oral posaconazole is preferred;43 alternatives include IV amphotericin B (conventional or lipid formulation), an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.43
Patients with frequent or severe recurrences of esophageal candidiasis, including HIV-infected patients, may benefit from long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral posaconazole;23 43 however, the potential for azole resistance should be considered.23 43 Echinocandins not in recommendations for secondary prophylaxis of esophageal candidiasis.23 43 44 Patients with fluconazole-refractory esophageal candidiasis who responded to an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.43
Oropharyngeal Candidiasis
Treatment of oropharyngeal candidiasis†.10 23 43 Considered an alternative, not a drug of choice.23 43
IDSA recommends topical clotrimazole or topical nystatin for mild oropharyngeal candidiasis;23 oral fluconazole is recommended for moderate to severe disease.23 For refractory oropharyngeal candidiasis, including fluconazole-refractory infections, itraconazole oral solution, oral posaconazole, or oral voriconazole is recommended.23 An IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B (conventional formulation) also are recommended as alternatives for refractory infections.23
For treatment of oropharyngeal candidiasis in HIV-infected adults and adolescents†, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes;43 alternatives for initial episodes include topical clotrimazole or topical nystatin.43 For fluconazole-refractory infections, itraconazole oral solution or oral posaconazole is preferred;43 alternatives include IV amphotericin B (conventional or a lipid formulation), an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.43
Patients with frequent or severe recurrences of oropharyngeal candidiasis, including HIV-infected patients, may benefit from long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or itraconazole oral solution;23 43 however, the potential for azole resistance should be considered.23 43 Echinocandins not included in recommendations for secondary prophylaxis of oropharyngeal candidiasis.23 43 Patients with fluconazole-refractory oropharyngeal candidiasis who responded to an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.43
Prevention of Candida Infections in Hematopoietic Stem Cell Transplant Recipients
Prophylaxis of Candida infections in hematopoietic stem cell transplant (HSCT) recipients.1 2 3 4 6 23 A drug of choice.23
For antifungal prophylaxis in HSCT recipients with neutropenia, IDSA recommends fluconazole, posaconazole, or micafungin.23
Aspergillosis
Has been used with some success as primary or salvage therapy, alone or in conjunction with other antifungals, for treatment of invasive aspergillosis†.2 5 12 25 27 30 31 32 33 34 39 40 The role of micafungin in treatment of invasive aspergillosis remains to be defined.2 3 4 5 11 25 37
IDSA and other clinicians consider voriconazole the drug of choice for treatment of invasive aspergillosis and amphotericin B (a lipid formulation) the preferred alternative for initial treatment.10 45 For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA and others recommend amphotericin B (a lipid formulation), caspofungin, micafungin, posaconazole, or itraconazole.10 45 For empiric or preemptive therapy, IDSA recommends amphotericin B (a lipid formulation), caspofungin, itraconazole, or voriconazole as drugs of choice.45
Micafungin Sodium Dosage and Administration
Administration
IV Administration
Administer by slow IV infusion.1 Do not administer by rapid IV injection.1
Do not admix or infuse concomitantly with other drugs.1
If administered via an existing IV line; flush line with 0.9% sodium chloride injection prior to infusing micafungin.1
Reconstituted and diluted solutions should be protected from light, but covering the IV tubing or infusion drip chamber not necessary.1
Reconstitution
Reconstitute 50- or 100-mg vials of lyophilized micafungin by adding 5 mL of 0.9% sodium chloride injection to provide a solution containing approximately 10 or 20 mg/mL, respectively.1 Alternatively, 5 mL of 5% dextrose injection can be used.1 Gently swirl to avoid foam formation; do not shake.1
Use strict aseptic technique since drug contains no preservative.1
Dilution
Add contents of appropriate number of reconstituted 50- or 100-mg vials to 100 mL of 0.9% sodium chloride injection or, alternatively, 100 mL of 5% dextrose injection.1 Discard partially used vials.1
Rate of Administration
IV infusions are given over 1 hour.1 More rapid infusion may increase risk of histamine-mediated reactions.1 (See Hypersensitivity Reactions under Cautions.)
Dosage
Available as micafungin sodium; dosage expressed in terms of the salt.1
A loading dose is not required.1
Adults
Candidemia and Other Invasive Candida Infections (Acute Disseminated Candidiasis, Peritonitis, Abscesses)
IV
100 mg once daily by slow IV infusion.1 10 43
IDSA and others recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia.10 23 Mean duration of successful micafungin treatment in clinical trials was 15 days (range: 10–47 days).1
Esophageal Candidiasis
IV
150 mg once daily by slow IV infusion.1 10
HIV-infected adults: 150 mg once daily by slow IV infusion.43
IDSA and others recommend that antifungal treatment be continued for 14–21 days.10 23 43 Mean duration of successful micafungin treatment in clinical trials was 15 days (range: 10–30 days).1
Oropharyngeal Candidiasis†
IV
100 or 150 mg once daily by slow IV infusion.10 23
HIV-infected adults: 150 mg once daily by slow IV infusion.43
IDSA and others recommended that antifungal treatment be continued for 7–14 days.23 43
Prevention of Candida Infections in Hematopoietic Stem Cell Transplant Recipients
IV
50 mg once daily by slow IV infusion.1 23
Optimum duration of antifungal prophylaxis not known;23 continue prophylaxis throughout the period of risk of neutropenia.23 Mean duration of effective prophylaxis in clinical trials was 19 days (range: 6–51 days).1
Invasive Aspergillosis†
IV
100 or 150 mg once daily by slow IV infusion has been recommended as salvage therapy;45 optimum dosage and duration of antifungal treatment not established.45
Special Populations
Hepatic Impairment
Dosage adjustment not required in adults with mild to moderate hepatic impairment (Child-Pugh score 7–9).1 2 5
Data not available regarding use in adults with severe hepatic impairment (Child-Pugh score >9);1 select dosage with caution.20
Renal Impairment
Dosage adjustment not required.1 3 5 Not dialyzable; supplemental doses not required following dialysis.1 3 5
Geriatric Patients
Dosage adjustment not required in adults ≥65 years of age.1 3 5
Cautions for Micafungin Sodium
Contraindications
Known hypersensitivity to micafungin, other echinocandin antifungals (e.g., anidulafungin, caspofungin), or any ingredient in the formulation.1
Warnings/Precautions
Sensitivity Reactions
Hypersensitivity Reactions
Serious hypersensitivity reactions (e.g., anaphylaxis and anaphylactoid reactions, including shock) have occurred.1 4 6 7 8
Possible histamine-mediated symptoms (e.g., rash, pruritus, facial swelling) have occurred.1 Rapid IV infusion may increase risk of histamine-mediated reactions.1 (See Rate of Administration under Dosage and Administration.)
If serious hypersensitivity reaction occurs, discontinue infusion and initiate appropriate therapy as indicated.1
Hematologic Effects
Clinically important hemolysis and hemolytic anemia reported rarely.1 Transient acute intravascular hemolysis and hemoglobinuria (without clinically important anemia) reported in a healthy volunteer receiving micafungin and prednisolone concomitantly.1 20
If clinical or laboratory evidence of hemolysis or hemolytic anemia occurs, monitor closely for evidence of worsening of these conditions and evaluate benefits versus risks of continuing micafungin.1
Hepatic Effects
Abnormal liver function test results reported.1 Clinically important hepatic dysfunction, hepatitis, and hepatic failure reported in patients with serious underlying conditions receiving multiple drugs concomitantly.1
If abnormal liver function test results occur, monitor for development of worsening hepatic function and evaluate benefits versus risks of continuing micafungin.1
Renal Effects
Increased BUN and Scr reported.1 Clinically important renal dysfunction or acute renal failure reported rarely.1
If abnormal renal function test results occur, monitor for development of worsening renal function.1
Selection and Use of Antifungals
The manufacturer states that efficacy not established for treatment of infections caused by fungi other than Candida.1
Specific Populations
Pregnancy
Category C.1
Lactation
Distributed into milk in rats;21 not known whether distributed into human milk.1 Use caution.1
Pediatric Use
Safety and efficacy not established in children ≤16 years of age.1
Has been used in some neonates and children <16 years of age† for treatment of candidemia or other invasive Candida infections and generally was well tolerated.20 35
Some experts state data are insufficient to date to recommend use of micafungin for first-line treatment of invasive candidiasis or for treatment of esophageal or oropharyngeal candidiasis in children (including HIV-infected children).44
Geriatric Use
Safety and efficacy in those ≥65 years of age similar to that reported in younger adults, but possibility of increased sensitivity cannot be ruled out.1
Hepatic Impairment
Moderate hepatic impairment (Child-Pugh score 7–9): Peak plasma concentration and AUC of micafungin decreased by approximately 22%;1 dosage adjustments not necessary.1
Severe hepatic impairment (Child-Pugh score >9): Pharmacokinetics not evaluated.1 Evaluate benefits versus risks of continued therapy if abnormal liver function test results occur.1
Common Adverse Effects
GI effects (diarrhea,1 42 nausea,1 vomiting,1 42 constipation,1 abdominal pain,1 dyspepsia,1 anorexia1 ), pyrexia,1 mucosal inflammation,1 rigors,1 peripheral edema,1 fatigue,1 hypokalemia,1 40 hypomagnesemia,1 42 hypocalcemia,1 hyperglycemia,1 fluid overload,1 bacteremia,1 sepsis,1 cough,1 dyspnea,1 epistaxis,1 hematologic effects (thrombocytopenia,1 neutropenia1 anemia,1 febrile neutropenia1 ), increased AST,1 42 increased ALT,1 42 increased alkaline phosphatase,1 42 rash,1 pruritus,1 headache,1 insomnia,1 anxiety,1 hypotension,1 hypertension,1 back pain,1 tachycardia,1 injection site reactions (inflammation, phlebitis, thrombophlebitis).1 2 4 6 42
Interactions for Micafungin Sodium
Substrate for and weak inhibitor of CYP3A in vitro; CYP3A plays minor role in metabolism in vivo.1 4 8
Drugs Metabolized by Hepatic Microsomal Enzymes
Pharmacokinetic interactions unlikely with drugs metabolized by CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4.1 4 5 18 19
Drugs Affecting or Affected by P-glycoprotein Transport
Not an inhibitor or substrate of the P-glycoprotein transport system; pharmacokinetic interactions unlikely.1 4
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Amphotericin
|
No effect on micafungin pharmacokinetics1
In vitro evidence of additive or synergistic antifungal effects against Aspergillus; no in vitro evidence of antagonism2
|
Micafungin dosage adjustment not necessary1
|
Corticosteroids (prednisolone)
|
No evidence of pharmacokinetic interactions 1
|
Micafungin dosage adjustment not necessary1
|
Fluconazole
|
No evidence of pharmacokinetic interactions with oral or IV fluconazole1 2
|
Micafungin dosage adjustment not necessary1
|
Immunosuppressive agents (cyclosporine, mycophenolate, sirolimus, tacrolimus)
|
Cyclosporine: Decreased oral clearance and increased half-life of cyclosporine; no effect on micafungin pharmacokinetics17
Mycophenolate: No evidence of pharmacokinetic interactions1
Sirolimus: Increased sirolimus AUC; no effect on peak sirolimus plasma concentrations; no effect on micafungin pharmacokinetics1
Tacrolimus: No evidence of pharmacokinetic interactions 1 16
|
Cyclosporine: Monitor cyclosporine concentrations when micafungin initiated or discontinued; adjust cyclosporine dosage as needed;17 20 40 micafungin dosage adjustment not necessary1
Mycophenolate: Micafungin dosage adjustment not necessary1
Sirolimus: Monitor for sirolimus toxicity and reduce sirolimus dosage if necessary;1 micafungin dosage adjustment not necessary1
Tacrolimus: Micafungin dosage adjustment not necessary1
|
Itraconazole
|
Increased itraconazole peak plasma concentration and AUC;1 no effect on micafungin pharmacokinetics1
|
Monitor for itraconazole toxicity and reduce itraconazole dosage if necessary;1 micafungin dosage adjustment not necessary1
|
Nifedipine
|
Increased nifedipine peak plasma concentration and AUC; no effect on micafungin pharmacokinetics1
|
Monitor for nifedipine toxicity and reduce nifedipine dosage if necessary; micafungin dosage adjustment not necessary1
|
Rifampin
|
No effect on micafungin pharmacokinetics1
|
Micafungin dosage adjustment not necessary1
|
Ritonavir
|
No effect on micafungin pharmacokinetics1
|
Micafungin dosage adjustment not necessary1
|
Voriconazole
|
No effect on pharmacokinetics of voriconazole or micafungin1
In vitro evidence of additive antifungal effects against Aspergillus;2 indifferent antifungal effects reported against Candida46
|
Micafungin dosage adjustment not necessary1
|
Micafungin Sodium Pharmacokinetics
Absorption
Plasma Concentrations
Linear relationship between dose and AUC over dosage range of 50–150 mg daily and 3–8 mg/kg daily.1
85% of steady-state concentration usually achieved after 3 once-daily doses.1
AUC is approximately 23% larger in women compared with men, presumably because of lower body weight.1
Distribution
Extent
Distributed into milk of lactating rats;21 not known whether distributed into human milk.1
Plasma Protein Binding
>99%.1
Binds principally to albumin and to a lesser extent to α1-acid-glycoprotein; does not competitively displace bilirubin from albumin.1
Elimination
Metabolism
Metabolized principally by arylsulfatase and catechol-O-methyltransferase;1 CYP3A plays only a minor role.1
Elimination Route
Excreted principally in feces;1 71% of a dose eliminated in feces within 28 days.1
Half-life
Adults: 13.4–17.2 hours.1
Special Populations
Geriatric adults: Pharmacokinetics in those 66–78 years of age similar to that reported in adults 20–24 years of age.1
Adults with moderate hepatic impairment (Child-Pugh score 7–9): Peak plasma concentration and AUC 22% lower than those reported with normal hepatic function.1 Pharmacokinetics not evaluated in patients with severe hepatic impairment.1
Stability
Storage
Parenteral
Powder for Injection
25°C (may be exposed to 15–30°C).1
Reconstituted solution may be stored in original vial for up to 24 hours at 25°C.1 Following dilution, protect from light and store for up to 24 hours at 25°C.1
Actions and SpectrumActions
Echinocandins (e.g., anidulafungin, caspofungin, micafungin) differ structurally and pharmacologically from other available antifungals.1 2 3 4
Inhibits synthesis of β-D-glucan an essential component of fungal cell walls that is not present in mammalian cells.1 2 3 5 6
May be fungistatic or fungicidal in action.2 3 4 24 27 28 36 37 38 39 40 41 Depending on the concentration, may be fungicidal against some Candida, but usually fungistatic against Aspergillus.24 27 28 36 37 38 39 40 41
Active in vitro against Candida, including C. albicans,1 2 27 28 C. dubliniensis,2 27 28 C. glabrata,1 2 27 28 C. guilliermondii,1 2 27 28 C. krusei,1 2 27 28 C. lusitaniae,2 27 28 C. metapsilosis,48 C. orthopsilosis,48 C. parapsilosis,1 2 27 28 47 48 and C. tropicalis.1 2 27 28
Active in vitro against Aspergillus, including A. fumigatus, A. flavis, A. niger, and A. terreus.2 3 4 5 8 14 25 27 28
Like other echinocandins, not active against Cryptococcus neoformans, Trichosporon, or zygomycetes.24 27 28 36 39 40 41
Potential for development of resistance not known.1 5 C. albicans with reduced susceptibility to micafungin reported after long-term treatment with the drug.1 22 27 41 Resistance also has developed in C. parapsilosis.47
Some C. albicans with reduced susceptibility to micafungin also have reduced susceptibility to caspofungin.22
Advice to Patients
Importance of informing patients about the possible benefits and risks associated with micafungin.1
Importance of informing patients about adverse potential effects associated with micafungin, including hypersensitivity reactions, hematologic effects, hepatic effects, and renal effects.1
Importance of informing the clinician if any unusual symptoms develop or if known symptoms persist or worsen.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Micafungin Sodium
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Parenteral
|
For injection, for IV infusion
|
50 mg
|
Mycamine
|
Astellas
|
|
|
100 mg
|
Mycamine
|
Astellas
|
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
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