Micafungin sodium

1. Health Canada Product Monograph — Micafungin sodium

• Micafungin is used to treat candidemia (a Candida yeast infection in the bloodstream), acute disseminated candidiasis, and Candida peritonitis and abscesses in adults and children 4 months of age and older.
• Micafungin is used to treat esophageal candidiasis (a Candida yeast infection of the esophagus).
• Micafungin is used to prevent Candida infections in patients undergoing hematopoietic stem cell transplantation.
• Micafungin has not been adequately studied for Candida infections of the heart valves, bone, or central nervous system, and its effectiveness against fungi other than Candida has not been established.

• No adequate, well-controlled studies of micafungin have been conducted in pregnant women.
• Animal studies in pregnant rabbits showed abnormalities in internal organs and pregnancy loss at high doses of micafungin.
• Micafungin should be used during pregnancy only if the potential benefits outweigh the potential risks.

• It is not known whether micafungin passes into human breast milk, though it has been found in the milk of nursing rats given the drug.
• Caution should be used when giving micafungin to a breastfeeding woman.

• No overall differences in safety or effectiveness have been observed between older adults (over 65) and younger adults in clinical studies of micafungin, and no dose adjustment is needed based on age alone.

• Micafungin is approved for use in children 4 months of age and older, with dosing based on body weight.
• Safety and effectiveness of micafungin have not been established in infants under 4 months of age, and it should not be used in this age group.

• Micafungin is given only by slow intravenous infusion over about 1 hour; more rapid infusion can increase the risk of histamine-related reactions.
• For treatment of candidemia and other invasive Candida infections, the usual adult dose is 100 mg once daily.
• For prevention of Candida infections in stem cell transplant patients, the usual adult dose is 50 mg once daily.
• For treatment of esophageal candidiasis, the usual adult dose is 150 mg once daily.
• In children 4 months of age and older, dosing is calculated by body weight and indication, with a maximum daily dose based on the adult dose for each indication.
• No loading dose is needed; steady drug levels are generally reached after about three daily doses.
• No dose adjustment is required for kidney impairment, including patients on hemodialysis, or for mild, moderate, or severe liver impairment.
• No dose adjustment is required based on gender or race.
• An existing intravenous line should be flushed with saline before infusing micafungin, and micafungin should never be mixed or co-infused with other medications in the same line.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• No cases of micafungin overdose have been reported in humans.
• Repeated daily doses well above the highest recommended adult and pediatric doses have been given in clinical studies without reported dose-limiting toxicity.
• Because micafungin is highly bound to blood proteins, it is not removed by dialysis.
• Management of a suspected overdose would be supportive, since there is no specific antidote.

• Diarrhea may occur.
• Nausea may occur.
• Vomiting may occur.
• Low blood sugar (hypoglycemia) may occur.
• Electrolyte disturbances, such as high sodium or high potassium levels, may occur.
• Fever may occur.
• Elevated liver enzymes, such as alkaline phosphatase, may occur.
• Irregular heartbeat, including atrial fibrillation, may occur.
• Headache may occur.
• Rash or itching may occur.
• Swelling of the face may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Serious allergic (anaphylactic and anaphylactoid) reactions, including shock, have been reported with micafungin.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, have been reported.
• Serious liver problems, including hepatitis and worsening liver failure, have been reported, especially in patients with serious underlying illness taking multiple medications.
• Kidney problems, including acute kidney failure, have been reported.
• Hemolysis (breakdown of red blood cells) and hemolytic anemia have been reported.
• A drop in white blood cell count has been reported.
• Disseminated intravascular coagulation, a serious blood clotting disorder, has been reported.
• Liver tumours (adenomas and carcinomas) developed in long-term animal studies, so micafungin should not be used at higher-than-recommended doses or for longer than needed.
• Injection site reactions, including inflammation and clot formation in the vein (phlebitis), can occur, especially when the drug is given through a vein in the arm rather than a central line.
• Seek urgent medical attention for signs of a severe allergic reaction, a blistering or peeling skin rash, yellowing of the skin or eyes, unusual bleeding or bruising, or a significant decrease in urination.

• Use with caution in patients with pre-existing liver disease or abnormal liver function tests, with monitoring for worsening liver function during treatment.
• Use with caution in patients with kidney impairment, with monitoring of kidney function during treatment.
• Use with caution in patients receiving other medications known to affect the liver.
• Use with caution and monitor closely if signs of hemolysis or hemolytic anemia develop during treatment.
• Use with caution in patients receiving sirolimus, itraconazole, or nifedipine together with micafungin, since blood levels of these drugs can increase; watch for signs of toxicity and reduce the dose of these drugs if needed.
• Use with caution when co-administering amphotericin B deoxycholate, since micafungin can increase amphotericin B levels and its associated toxicity.

• Contraindicated in patients with known hypersensitivity to micafungin, other echinocandin antifungals, or any component of the product.

• Combining micafungin with amphotericin B deoxycholate increases amphotericin B blood levels, so this combination should only be used when the benefits outweigh the risks, with close monitoring for amphotericin B toxicity.
• Micafungin increases blood levels of sirolimus, so patients on this combination should be monitored for sirolimus toxicity.
• Micafungin increases blood levels of nifedipine, so patients on this combination should be monitored for nifedipine toxicity, such as low blood pressure or flushing.
• Micafungin increases blood levels of itraconazole, so patients on this combination should be monitored for itraconazole toxicity.
• No clinically important interaction affecting micafungin's own levels was found with mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, voriconazole, fluconazole, ritonavir, or rifampin.
• Micafungin does not inhibit P-glycoprotein, so it is not expected to alter the transport of drugs that rely on this pathway.

• Micafungin is given only by intravenous infusion, so it has no interaction with food or meals.

• Each dose of micafungin is given as a slow intravenous infusion over about 1 hour, usually once daily, at a time scheduled by the treating hospital or clinic rather than in relation to meals.

• Store unopened micafungin vials at controlled room temperature (15°C to 30°C), protected from light.
• After reconstitution, the concentrate may be stored in the original vial, protected from light, for up to 24 hours at room temperature.
• After dilution for infusion, the solution may be stored protected from light for up to 24 hours at room temperature.
• Micafungin contains no preservative, so any partially used vial should be discarded.

• Micafungin is an antifungal medicine given only through an intravenous line in a hospital or clinic; it is not a medication you take at home.
• Tell your healthcare team about any liver or kidney problems and all other medications you take before starting this medicine.
• Tell your nurse or doctor right away if you notice itching, rash, facial swelling, or trouble breathing during your infusion.
• Report yellowing of your skin or eyes, unusual bruising or bleeding, or a significant decrease in urination to your healthcare team.
• Your healthcare team will monitor your liver function, kidney function, and blood counts during treatment.