General

Possible histamine-mediated symptoms have been reported with Mycamine, including rash, pruritus, facial swelling, and vasodilatation.

Injection site reactions, including phlebitis and thrombophlebitis have been reported, at Mycamine doses of 50-150 mg/day. These reactions tended to occur more often in patients receiving Mycamine via peripheral intravenous administration.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of Mycamine cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does provide a basis for identifying adverse events that appear to be related to drug use and for approximating rates.

Candidemia and Other Candida Infections

In a randomized, double-blind study for treatment of candidemia and other Candida infections, treatment emergent adverse events occurred in 183/200 (91.5%), 187/202 (92.6%) and 171/193 (88.6%) patients in the Mycamine 100 mg/day, Mycamine 150mg/day, and caspofungin (70/50mg/day) treatment groups, respectively. Treatment emergent adverse events occurring in ≥ 5% of the patients in any treatment study groups are shown in Table 2.

Table 2. *Treatment Emergent Adverse Events in Patients with Candidemia and Other Candida Infections

In a second, supportive, randomized, double-blind study for treatment of candidemia and other Candida infections, treatment emergent adverse events occurred in 245/264 (92.8%) and 250/265 (94.3%) patients in the Mycamine (100 mg/day) and AmBisome (3 mg/kg/day) treatment groups, respectively. The most common treatment emergent adverse events occurring in ≥ 5% of the Mycamine-treated patients at least 16 years of age were: pyrexia (15.2% vs. 17%); hypokalemia (16.7% vs. 20.8%); nausea (9.5% vs. 8.3%); diarrhea (10.6% vs. 11.3%) and vomiting (12.9% vs. 9.4%), in the Mycamine and AmBisome treatment groups, respectively. Other important treatment emergent adverse events that occurred at < 5% frequency were abnormal liver function tests (4.2% vs. 3%); increased aspartate aminotransferase (2.7% vs. 1.9%), and increased blood alkaline phosphatase (3% vs. 2.3%), in the Mycamine and AmBisome treatment groups, respectively.

Esophageal Candidiasis

In a randomized, double-blind study for treatment of esophageal candidiasis, a total of 202/260 (77.7%) patients who received Mycamine 150 mg/day and 186/258 (72.1%) patients who received intravenous fluconazole 200 mg/day experienced an adverse event. Treatment emergent adverse events resulting in discontinuation were reported in 17 (6.5%) Mycamine treated patients; and in 12 (4.7%) fluconazole treated patients. Treatment emergent adverse events occurring in ≥ 5% of the patients in either treatment group are shown in Table 3.

Table 3. *Treatment Emergent Adverse Events in Patients with Esophageal Candidiasis

Prophylaxis of Candida Infections in Hematopoietic Stem Cell Transplant Recipients

A double-blind study was conducted in a total of 882 patients scheduled to undergo an autologous or allogeneic hematopoietic stem cell transplant. The median duration of treatment was 18 days (range 1 to 51 days) in both treatment arms.

All patients who received Mycamine (425) and all patients who received fluconazole (457) experienced at least one adverse event during the study. Treatment emergent adverse events resulting in Mycamine discontinuation were reported in 18 (4.2%) patients; while those resulting in fluconazole discontinuation were reported in 33 (7.2%). Treatment emergent adverse events occurring in ≥ 15% of the patients in either treatment group are shown in Table 4.

Table 4. *Treatment Emergent Adverse Events During Prophylaxis of Candida Infection in Hematopoietic Stem Cell Transplant Recipients

Overall Mycamine Safety Experience in Clinical Trials

The overall safety of Mycamine was assessed in 3083 patients and 501 volunteers in 41 clinical studies, including the invasive candidiasis, esophageal candidiasis and prophylaxis studies, who received single or multiple doses of Mycamine, ranging from 12.5 mg to ≥ 150 mg/day. Treatment emergent adverse events which occurred in ≥ 5% of all patients who received Mycamine in these trials are shown in Table 5.

Overall, 2810 of 3083 (91.1%) patients who received Mycamine experienced an adverse event.

Clinically significant adverse events regardless of causality or incidence which occurred in these trials are listed below:

• Blood and lymphatic system disorders: coagulopathy, febrile neutropenia, hemolysis, hemolyric anemia, pancytopenia, thrombotic thrombocytopenia purpura
• Cardiac disorders: arrhythmia, atrial fibrillation, cardiac arrest, cyanosis, hypotension, myocardial infarction, tachycardia
• Gastrointestinal disorders: abdominal pain upper, dyspepsia
• General disorders and administration site conditions: injection site thrombosis
• Hepatobiliary disorders: hepatocellular damage, hepatomegaly, jaundice, hepatic failure
• Infections and infestations: infection, pneumonia, sepsis
• Metabolism and nutrition disorders: acidosis, anorexia, hyponatremia
• Musculoskeletal, connective tissue and bone disorders: arthralgia
• Nervous system disorders: convulsions, encephalopathy, intracranial hemorrhage
• Psychiatric disorders: delirium
• Renal and urinary disorders: anuria, hemoglobinuria, oliguria, renal failure acute, renal tubular necrosis
• Respiratory, thoracic and mediastinal disorders: apnea, dyspnea, hypoxia, pulmonary embolism
• Skin and subcutaneous tissue disorders: erythema multiforme, skin necrosis, urticaria
• Vascular disorders: deep venous thrombosis, hypertension

Table 5. *Treatment Emergent Adverse Events in Patients Who Received Mycamine in Clinical Trials

Postmarketing Adverse Reactions

The following adverse reactions have been identified during the post-approval use of micafungin sodium for injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency. A causal relationship to micafungin sodium for injection could not be excluded for these adverse reactions, which included:

• Blood and lymphatic system disorders: white blood cell count decreased, hemolytic anemia, disseminated intravascular coagulation
• Hepatobiliary disorders: hyperbilirubinemia, hepatic function abnormal, hepatic disorder, hepatocellular damage
• Renal and urinary disorders: acute renal failure and renal impairment
• Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis
• Vascular disorders: shock

Read the Mycamine (micafungin sodium) Side Effects Center for a complete guide to possible side effects »

A total of 14 clinical drug-drug interaction studies were conducted in healthy volunteers to evaluate the potential for interaction between Mycamine and amphotericin B, mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, sirolimus, nifedipine, fluconazole, itraconazole, voriconazole, ritonavir, and rifampin. In these studies, no interaction that altered the pharmacokinetics of micafungin was observed.

There was no effect of a single dose or multiple doses of Mycamine on mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, fluconazole, and voriconazole pharmacokinetics.

Sirolimus AUC was increased by 21% with no effect on Cmax in the presence of steady-state Mycamine compared with sirolimus alone. Nifedipine AUC and Cmax were increased by 18% and 42%, respectively, in the presence of steady-state Mycamine compared with nifedipine alone. Itraconazole AUC and Cmax were increased by 22% and 11%, respectively.

Patients receiving sirolimus, nifedipine or itraconazole in combination with Mycamine should be monitored for sirolimus, nifedipine or itraconazole toxicity and the sirolimus, nifedipine or itraconazole dosage should be reduced if necessary [see CLINICAL PHARMACOLOGY].

Micafungin is neither a substrate nor an inhibitor of P-glycoprotein and, therefore, would not be expected to alter P-glycoprotein-mediated drug transport activity.

Drug Abuse And Dependence

There has been no evidence of either psychological or physical dependence or withdrawal or rebound effects with Mycamine.

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.