Brand name: Mycamine
Drug 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

Medically reviewed by Drugs.com on Aug 25, 2023. Written by ASHP.

Introduction

Antifungal; echinocandin.

Uses for Micafungin

Candidemia and Other Invasive Candida Infections

Treatment of candidemia, acute disseminated candidiasis, and certain other invasive Candida infections (peritonitis, abscesses). A drug of choice.

Manufacturer states safety and efficacy not established for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida.

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in nonneutropenic patients in intensive care units (ICUs), IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial therapy; IV or oral fluconazole is an acceptable alternative for initial therapy in selected patients, including those who are not critically ill and unlikely to have infections caused by fluconazole-resistant Candida. IV amphotericin B recommended if echinocandin- and azole-resistant Candida suspected and is an alternative when echinocandins and fluconazole have been ineffective or cannot be used. Consider transition from the echinocandin to fluconazole (usually within 5–7 days) in clinically stable patients if strain susceptible to fluconazole (e.g., C. albicans) and initial treatment resulted in negative repeat blood cultures.

For treatment of candidemia in neutropenic patients, IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) or, alternatively, IV amphotericin B for initial therapy. Fluconazole is an alternative in those who are not critically ill and have had no prior exposure to azole antifungals; also can be used for step-down therapy in clinically stable patients who have fluconazole-susceptible isolates and documented bloodstream clearance. Voriconazole can be used as an alternative for initial therapy when broader antifungal coverage is required and also can be used as step-down therapy during neutropenia in clinically stable patients who have voriconazole-susceptible isolates and documented bloodstream clearance. An echinocandin, amphotericin B, or voriconazole recommended for infections known to be caused by C. krusei.

For treatment of osteoarticular infections^{† [off-label]} (e.g., osteomyelitis, septic arthritis) caused by Candida, IDSA recommends initial treatment with fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If septic arthritis involves a prosthetic device that cannot be removed, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended if isolate is susceptible.

For treatment of endocarditis^{† [off-label]} (native or prosthetic valve) or implantable cardiac device infections caused by Candida, IDSA recommends initial treatment with IV amphotericin B (with or without flucytosine) or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If isolate is susceptible, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended to prevent recurrence in those with native valve endocarditis who cannot undergo valve replacement and in those with prosthetic valve endocarditis.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of candidemia and disseminated candida infections.

Esophageal Candidiasis

Treatment of esophageal candidiasis. A drug of choice.

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).

IDSA recommends oral fluconazole as the preferred drug of choice for treatment of esophageal candidiasis; if oral therapy not tolerated, IV fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) recommended. For fluconazole-refractory infections, IDSA recommends itraconazole oral solution or IV or oral voriconazole; alternatives are an IV echinocandin (anidulafungin, caspofungin, micafungin) or IV amphotericin B. IDSA states oral posaconazole (oral suspension or delayed-release tablets) is another possible alternative for treatment of fluconazole-refractory esophageal candidiasis.

For treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral or IV fluconazole or itraconazole oral solution. Alternatives include oral or IV voriconazole, an IV echinocandin (anidulafungin, caspofungin, micafungin), or IV amphotericin B. For refractory esophageal candidiasis, including fluconazole-refractory infections, in HIV-infected adults and adolescents, itraconazole oral solution or posaconazole oral suspension is recommended; alternatives are IV amphotericin B, an IV echinocandin (anidulafungin, caspofungin, micafungin), or oral or IV voriconazole.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for esophageal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of esophageal candidiasis may benefit from secondary prophylaxis with oral fluconazole or posaconazole oral suspension; however, consider potential for development of azole resistance.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of esophageal candidiasis.

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis^{† [off-label]}. Considered an alternative, not a drug of choice.

For mild oropharyngeal candidiasis, IDSA recommends topical treatment with clotrimazole lozenges or miconazole buccal tablets; nystatin (oral suspension or tablets) is an alternative. For moderate to severe oropharyngeal candidiasis, IDSA recommends oral fluconazole. For fluconazole-refractory oropharyngeal candidiasis, IDSA recommends itraconazole oral solution or posaconazole oral suspension; oral voriconazole or amphotericin B oral suspension (not commercially available in US) recommended as alternatives. Other alternatives for refractory oropharyngeal candidiasis are IV echinocandins (anidulafungin, caspofungin, micafungin) or IV amphotericin B.

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; if topical therapy used (e.g., mild to moderate episodes), drugs of choice are clotrimazole lozenges or miconazole buccal tablets. Alternatives for systemic treatment are itraconazole oral solution or posaconazole oral suspension; nystatin oral suspension is an alternative for topical treatment. For fluconazole-refractory infections in HIV-infected adults and adolescents, posaconazole oral suspension is preferred; itraconazole oral solution is an alternative.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for oropharyngeal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of oropharyngeal candidiasis may benefit from secondary prophylaxis with oral fluconazole; however, consider potential for development of azole resistance.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of oropharyngeal candidiasis.

Candida auris Infections

Treatment of infections caused by C. auris, an emerging pathogen associated with potentially fatal candidemia or other invasive infections.

First identified in 2009, C. auris has now been reported as the cause of serious invasive infections (including fatalities) in multiple countries worldwide (e.g., Japan, South Korea, India, Kuwait, South Africa, Pakistan, United Kingdom, Venezuela, Colombia, US). As of May 2017, a total of 77 clinical cases of C. auris had been reported to CDC from 7 different US states. May be difficult to identify using standard in vitro methods. Large percentage of C. auris clinical isolates are resistant to fluconazole; multidrug-resistant isolates with reduced susceptibility or resistance to all 3 major classes of antifungal agents (azoles, polyenes, echinocandins) reported.

CDC issued interim recommendations regarding laboratory diagnosis, treatment, and infection control measures for suspected or known C. auris infections. Based on limited data available to date, CDC recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial treatment of invasive C. auris infections (e.g., bloodstream or intra-abdominal infections) in adults. CDC states a switch to IV amphotericin B (lipid formulation) could be considered if patient is clinically unresponsive to the echinocandin or fungemia persists >5 days. Consultation with an infectious disease specialist highly recommended.

CDC recommends that infection control measures be observed for all patients with cultures yielding C. auris, including those with positive cultures only from noninvasive body sites.

If C. auris infection is suspected, immediately contact state or local public health authorities and the CDC (candidaauris@cdc.gov) for guidance. Consult interim recommendations and most recent information from CDC available at [Web] for additional information on diagnosis and management of C. auris infections.

Prevention of Candida Infections in Hematopoietic Stem Cell Transplant Recipients

Prophylaxis of Candida infections in hematopoietic stem cell transplant (HSCT) recipients. A drug of choice.

Aspergillosis

Has been used with some success as primary or salvage therapy, alone or in conjunction with other antifungals, for treatment of invasive aspergillosis^{† [off-label]}.

IDSA and other clinicians consider IV voriconazole the drug of choice for primary treatment of invasive aspergillosis in adult and pediatric patients, including HIV-infected patients; IV amphotericin B or isavuconazonium (prodrug of isavuconazole) usually recommended as alternatives for primary treatment.

For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends IV amphotericin B, an IV echinocandin (caspofungin, micafungin), oral or IV posaconazole, or itraconazole oral suspension. IDSA states that echinocandins (either alone or in conjunction with other antifungals) may be effective for salvage therapy of invasive aspergillosis; however, routine use of echinocandin monotherapy not recommended for primary treatment of invasive aspergillosis.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of aspergillosis.

Related/similar drugs

fluconazole, Diflucan, itraconazole, voriconazole, amphotericin b, posaconazole, Sporanox

Micafungin Dosage and Administration

Administration

IV Administration

Administer by slow IV infusion. Do not administer by rapid IV injection.

Do not admix or infuse concomitantly with other drugs.

If administered via an existing IV line; flush line with 0.9% sodium chloride injection prior to infusing micafungin.

To minimize risk of infusion reactions, administer micafungin solutions with concentrations >1.5 mg/mL IV via a central catheter.

Must be reconstituted and diluted prior to administration. Use strict aseptic technique since the drug contains no preservatives.

Protect diluted solution from light during storage; no need to protect IV tubing or infusion drip chamber during administration.

Reconstitution

Reconstitute 50- or 100-mg vials of lyophilized micafungin by adding 5 mL of 0.9% sodium chloride injection (or 5% dextrose injection) to provide a solution containing approximately 10 or 20 mg/mL, respectively. Gently swirl to avoid foam formation; do not shake.

Dilution

Add contents of appropriate number of reconstituted 50- or 100-mg vials to 100 mL of 0.9% sodium chloride injection or 5% dextrose injection). Discard partially used vials.

Final solution for IV infusion should have a concentration of 0.5–4 mg/mL.

Rate of Administration

Administer by IV infusion over 1 hour. More rapid infusion may increase risk of histamine-mediated reactions. (See Hypersensitivity Reactions under Cautions.)

Dosage

Available as micafungin sodium; dosage expressed in terms of micafungin.

A loading dose is not required.

Pediatric Patients

General Pediatric Dosage

IV

AAP recommends 2–10 mg/kg (up to 200 mg) once daily.

Candidemia and Other Invasive Candida Infections

IV

Pediatric patients ≥4 months of age: Manufacturer recommends 2 mg/kg (up to 100 mg) once daily.

HIV-infected infants weighing <15 kg: 5–7 mg/kg daily.

HIV-infected children 2–8 years of age weighing ≤40 kg: 3–4 mg/kg daily.

HIV-infected children 9–17 years of age: 2–3 mg/kg daily in those weighing ≤40 kg and 100 mg daily in those weighing >40 kg.

IDSA recommends that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 2 weeks after documented clearance of Candida from the bloodstream, resolution of candidemia symptoms, and resolution of neutropenia.

Esophageal Candidiasis

IV

Pediatric patients ≥4 months of age: Manufacturer recommends 3 mg/kg once daily in those weighing ≤30 kg and 2.5 mg/kg (up to 150 mg) once daily in those weighing >30 kg.

HIV-infected infants weighing <15 kg: 5–7 mg/kg daily.

HIV-infected children 2–8 years of age weighing ≤40 kg: 3–4 mg/kg daily.

HIV-infected children 9–17 years of age: 2–3 mg/kg daily in those weighing ≤40 kg and 100 mg daily in those weighing >40 kg.

HIV-infected adolescents: 150 mg once daily.

IDSA and others recommend that antifungal treatment for esophageal candidiasis be continued for 14–21 days.

Prevention of Candida Infections in Hematopoietic Stem Cell Transplant Recipients

IV

Pediatric patients ≥4 months of age: 1 mg/kg (up to 50 mg) once daily.

Adults

Candidemia and Other Invasive Candida Infections

IV

100 mg once daily.

IDSA states consider a transition from the echinocandin to fluconazole (usually within 5–7 days) in patients who are clinically stable, have isolates susceptible to fluconazole (e.g., C. albicans), and have negative repeat blood cultures after initial antifungal treatment.

IDSA recommends that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 2 weeks after documented clearance of Candida from the bloodstream and resolution of candidemia symptoms and neutropenia. Mean duration of successful micafungin treatment in clinical trials was 15 days (range: 10–47 days).

Osteoarticular infections^{† [off-label]}: IDSA recommends 100 mg once daily. After ≥2 weeks, can switch to fluconazole.

Endocarditis^† (native or prosthetic valve) or implantable cardiac device infections^†: IDSA recommends 150 mg once daily. If infection caused by fluconazole-susceptible Candida, can switch to fluconazole after patient stabilized and Candida has been cleared from bloodstream.

Esophageal Candidiasis

IV

150 mg once daily.

HIV-infected adults: 150 mg once daily.

IDSA and others recommend that antifungal treatment be continued for 14–21 days. Mean duration of successful micafungin treatment in clinical trials was 15 days (range: 10–30 days).

Oropharyngeal Candidiasis†

IV

100 mg once daily for 7–14 days.

Candida auris Infections

IV

CDC recommends 100 mg once daily.

Prevention of Candida Infections in Hematopoietic Stem Cell Transplant Recipients

IV

50 mg once daily.

Mean duration of effective prophylaxis in clinical trials was 19 days (range: 6–51 days).

Aspergillosis†

IV

100–150 mg once daily.

Duration of treatment is based on severity of patient's underlying disease, recovery from immunosuppression, and clinical response. IDSA recommends that treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks.

Special Populations

Hepatic Impairment

Mild, moderate, or severe hepatic impairment (Child-Pugh score 7–12): Dosage adjustments not necessary.

Renal Impairment

Mild, moderate, or severe renal impairment: Dosage adjustments not necessary.

Not dialyzable; supplemental doses not required following dialysis.

Geriatric Patients

Adults ≥65 years of age: Dosage adjustments not necessary.

Cautions for Micafungin

Contraindications

• Known hypersensitivity to micafungin, other echinocandin antifungals (e.g., anidulafungin, caspofungin), or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions (e.g., anaphylaxis and anaphylactoid reactions, including shock) have occurred.

Possible histamine-mediated symptoms (e.g., rash, pruritus, facial swelling, vasodilation) have occurred. Rapid IV infusion may increase risk of histamine-mediated reactions. (See Rate of Administration under Dosage and Administration.)

If serious hypersensitivity reaction occurs, discontinue infusion and initiate appropriate therapy as indicated.

Hematologic Effects

Clinically important hemolysis and hemolytic anemia reported rarely. Transient acute intravascular hemolysis and hemoglobinuria (without clinically important anemia) reported in a healthy volunteer receiving micafungin and prednisolone concomitantly.

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.

Hepatic Effects

Abnormal liver function test results reported. Clinically important hepatic dysfunction, hepatitis, and hepatic failure reported in patients with serious underlying conditions receiving multiple drugs concomitantly.

If abnormal liver function test results occur, monitor for development of worsening hepatic function and evaluate benefits versus risks of continuing micafungin.

Renal Effects

Increased BUN and S_cr reported. Clinically important renal dysfunction or acute renal failure reported rarely.

If abnormal renal function test results occur, monitor for development of worsening renal function.

Infusion Reactions

Possible histamine-mediated symptoms reported. (See Hypersensitivity Reactions under Cautions.)

Injection site reactions, including phlebitis and thrombophlebitis, reported in patients receiving micafungin dosages of 50–150 mg daily; these reactions tend to occur more often when IV infusions given using a peripheral vein. To minimize risk of infusion reactions, give micafungin solutions with concentrations >1.5 mg/mL via a central catheter. (See Dosage and Administration.)

Selection and Use of Antifungals

Manufacturer states efficacy not established for treatment of infections caused by fungi other than Candida.

Specific Populations

Pregnancy

Category C.

No adequate and well-controlled studies in pregnant women; use during pregnancy only if potential benefits outweigh potential risks to fetus.

In rabbits, increased abortions and visceral abnormalities (abnormal lobation of the lung, levocardia, retrocaval ureter, anomalous right subclavian artery, dilatation of the ureter) reported with dosage about 4 times the recommended human dosage (based on body surface area comparisons).

Lactation

Distributed into milk in rats; not known whether distributed into human milk.

Use with caution in nursing women.

Pediatric Use

Safety and efficacy not established in pediatric patients <4 months of age.

Safety and efficacy in pediatric patients ≥4 months of age demonstrated based on evidence from adequate and well-controlled studies in adults and pediatric patients and additional pediatric pharmacokinetic and safety data.

Although data limited, some experts state micafungin can be considered for first-line treatment of invasive candidiasis or for alternative treatment of esophageal candidiasis in HIV-infected children.

Geriatric Use

No overall differences in safety and efficacy were observed between adults ≥65 years of age and younger adults, but possibility that some older patients may have increased sensitivity to the drug cannot be ruled out.

Hepatic Impairment

Moderate hepatic impairment (Child-Pugh score 7–9): Peak plasma concentration and AUC of micafungin decreased by approximately 22%; dosage adjustments not necessary.

Severe hepatic impairment (Child-Pugh score 10–12): Peak plasma concentration and AUC of micafungin decreased by approximately 30%; dosage adjustments not necessary.

Renal Impairment

Severe renal impairment (creatinine clearance <30 mL/minute): Peak plasma concentrations and AUC not altered; dosage adjustments not necessary.

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, abdominal pain, abdominal distention ), pyrexia, infusion-related reactions, hypoglycemia, hypomagnesemia, hypernatremia, hyperkalemia, epistaxis, hematologic effects (thrombocytopenia, neutropenia, anemia, febrile neutropenia ), increased AST, increased ALT, increased alkaline phosphatase, rash, pruritus, urticaria, headache, insomnia, anxiety, decreased urine output, hematuria, atrial fibrillation, tachycardia, injection site reactions (inflammation, phlebitis, thrombophlebitis).

Drug Interactions

Substrate for and weak inhibitor of CYP3A in vitro; CYP3A plays minor role in metabolism in vivo.

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely with drugs metabolized by CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4.

Drugs Affecting or Affected by P-glycoprotein Transport

Not an inhibitor or substrate of the P-glycoprotein transport system; pharmacokinetic interactions unlikely.

Specific Drugs

Micafungin Pharmacokinetics

Absorption

Plasma Concentrations

Linear relationship between dose and AUC over dosage range of 50–150 mg daily and 3–8 mg/kg daily.

85% of steady-state concentration usually achieved after 3 once-daily doses.

AUC is approximately 23% larger in women compared with men, presumably because of lower body weight.

Distribution

Extent

Distributed into milk of lactating rats; not known whether distributed into human milk.

Plasma Protein Binding

>99%.

Binds principally to albumin and to a lesser extent to α₁-acid-glycoprotein; does not competitively displace bilirubin from albumin.

Elimination

Metabolism

Metabolized principally by arylsulfatase and catechol-O-methyltransferase; CYP3A plays only a minor role.

Elimination Route

Excreted principally in feces; 71% of a dose eliminated in feces within 28 days.

Half-life

Adults: 13.4–17.2 hours.

Pediatric patients 4 months through 16 years of age: Mean plasma half-life at steady state is 12.5 hours in those weighing ≤30 kg or 13.6 hours in those weighing >30 kg.

Special Populations

Geriatric adults: Pharmacokinetics in those 66–78 years of age similar to that reported in adults 20–24 years of age.

Adults with moderate hepatic impairment (Child-Pugh score 7–9): Peak plasma concentration and AUC 22% lower than those reported with normal hepatic function.

Adults with severe hepatic impairment (Child-Pugh score 10–12): Peak plasma concentration and AUC 30% lower than those reported with normal hepatic function.

Stability

Storage

Parenteral

Powder for Injection

25°C (may be exposed to 15–30°C).

Following reconstitution, may be stored in original vial for up to 24 hours at 25°C.

Following further dilution, may be stored for up to 24 hours at 25°C; protect from light.

Compatibility

Parenteral

Solution Compatibility1 HID

Drug CompatibilityHID

Actions and Spectrum

• Semisynthetic echinocandin antifungal; lipopeptide synthesized from a fermentation product of Coleophoma empetri F-11899.

• Echinocandins (e.g., anidulafungin, caspofungin, micafungin) differ structurally and pharmacologically from other available antifungals.

• Inhibits synthesis of β-D-glucan an essential component of fungal cell walls that is not present in mammalian cells.

• May be fungistatic or fungicidal in action. Depending on the concentration, may be fungicidal against some Candida, but usually fungistatic against Aspergillus.

• Active in vitro against Candida, including C. albicans, C. dubliniensis, C. glabrata, C. guilliermondii, C. krusei, C. lusitaniae, C. metapsilosis, C. orthopsilosis, C. parapsilosis, and C. tropicalis.

• Clinical isolates of C. auris (often misidentified as C. haemulonii, C. famata, or Rhodotorula glutinis) generally have been inhibited in vitro by micafungin concentrations of 0.03–2 mcg/mL.

• Active in vitro against Aspergillus, including A. fumigatus, A. flavis, A. niger, and A. terreus.

• Like other echinocandins, not active against Cryptococcus neoformans, Trichosporon, or zygomycetes.

• Resistance to micafungin has been reported. Resistance may be related to specific mutations in the FKS protein component of the glucan synthase enzyme.

• C. albicans with reduced susceptibility to micafungin reported after long-term treatment with the drug. Resistance also has developed in C. parapsilosis. Some clinical isolates of C. auris have reduced susceptibility or resistance to micafungin in vitro (i.e., MICs ≥4 mcg/mL).

• Some C. albicans with reduced susceptibility to micafungin also have reduced susceptibility to caspofungin.

Advice to Patients

• Inform patients about possible benefits and risks associated with micafungin.

• Inform patients about potential adverse effects associated with micafungin, including hypersensitivity reactions (anaphylaxis and anaphylactoid reactions including shock), hematologic effects (acute intravascular hemolysis, hemolytic anemia, hemoglobinuria), hepatic effects (abnormal liver function tests, hepatic impairment, hepatitis or worsening hepatic failure), and renal effects (elevated BUN and creatinine concentrations, renal impairment or acute renal failure).

• Importance of informing clinicians if any unusual symptoms develop or if any known symptoms persist or worsen.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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