Mycamine

Dosage Forms & Strengths

powder for injection

• 50mg/vial
• 100mg/vial

Candidiasis

Treatment (esophageal): 150 mg/day IV infusion x10-30 days (mean 15 days)

Prophylaxis in hematopoietic stem cell transfer (HSCT) patients: 50 mg/day IV infusion x6-51 days (mean 19 days)

Candidemia, Disseminated Candidiasis, Candida Peritonitis & Abscesses

100 mg/day IV infusion x10-47 days (mean 15 days)

Candida auris (Off-label)

Based on the limited data, an echinocandin drug (eg, anidulafungin, caspofungin, micafungin) is recommended by the CDC as initial therapy for treatment of C auris infections

100 mg IV qDay

Dosage Forms & Strengths

powder for injection

• 50mg/vial
• 100mg/vial

Candida Infections

Indicated for candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses, esophageal candidiasis, and prophylaxis of Candida infections in hematopoietic stem cell transplants (HSCT) recipients

<4 months: Safety and efficacy not established

≥4 months: See specific Candida infection below

Treatment of Candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses

• 2 mg/kg IV qDay; not to exceed 100 mg/day

Treatment of esophageal candidiasis

• ≤30 kg: 3 mg/kg IV qDay
• >30 kg: 2.5 mg/kg IV qDay; not to exceed 150 mg/day

Prophylaxis of Candida infections in HSCT recipients

• 1 mg/kg IV qDay; not to exceed 50 mg/day

Candida auris (Off-label)

Neonates and infants <2 months

• In exceptional circumstances, where CNS involvement has been definitively ruled out, may consider use of caspofungin or micafungin with caution; the CDC recommends amphotericin B deoxycholate as initial treatment of choice
• 10 mg/kg/day IV

≥2 months

• Based on the limited data, an echinocandin drug (eg, anidulafungin, caspofungin, micafungin) is recommended by the CDC as initial therapy for treatment of C auris infections in adults and children aged ≥2 months
• 2 mg/kg/day IV; option to increase to 4 mg/kg/day IV if body weight at least 40 kg

1-10%

Abd pain

Anemia

Headache

Diarrhea

Increased LFTs

Leukopenia

Nausea

Neutropenia

Phlebitis

Pruritus

Pyrexia

Rash

Rigors

Thrombocytopenia

Vomiting

Facial swelling

Vasodilation

<1%

Delirium

Dizziness

Somnolence

Postmarketing Reports

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

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• pale or yellowed skin, dark colored urine, fever, confusion or weakness;

• swelling, rapid weight gain, little or no urinating; or

• upper stomach pain, itching, loss of appetite, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• nausea, vomiting, diarrhea;

• flushing (warmth, redness, or tingly feeling); or

• mild itching or rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other drugs may interact with micafungin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

50 mg single-dose vial is equivalent to 50.86 mg micafungin sodium
100 mg single-dose vial is equivalent to 101.73 mg micafungin sodium

Pregnancy

Pregnancy Category C. There are no adequate and well-controlled studies of Mycamine in pregnant women. Animal reproduction studies in rabbits showed visceral abnormalities and increased abortion at 4 times the recommended human dose. However, animal studies are not always predictive of human response. Mycamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

When pregnant rabbits were given 4 times the recommended human dose, there were increased abortion and visceral abnormalities including abnormal lobation of the lung, levocardia, retrocaval ureter, anomalous right subclavian artery, and dilatation of the ureter [see Nonclinical Toxicology (13.2)].

Nursing Mothers

It is not known whether micafungin is excreted in human milk. Caution should be exercised when Mycamine is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients younger than 4 months of age have not been established.

Safety and effectiveness of Mycamine in pediatric patients 4 months of age and older have been demonstrated based on the evidence from adequate and well-controlled studies in adult and pediatric patients and additional pediatric pharmacokinetic and safety data.Two randomized, double-blind, active-control studies investigated the safety and efficacy of Mycamine in both adult and pediatric patients: one for the treatment of invasive candidiasis and candidemia and the other for prophylaxis of Candida infections in patients undergoing HSCT [see Dosage and Administration (2), Adverse Reactions (6.3), Clinical Pharmacology (12.3), Clinical Studies (14)].

Geriatric Use

A total of 418 subjects in clinical studies of Mycamine were 65 years of age and older, and 124 subjects were 75 years of age and older. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The exposure and disposition of a 50 mg Mycamine dose administered as a single 1-hour infusion to 10 healthy subjects aged 66-78 years were not significantly different from those in 10 healthy subjects aged 20-24 years. No dose adjustment is necessary for the elderly.

Use in Patients with Renal Impairment

Mycamine does not require dose adjustment in patients with renal impairment. Supplementary dosing should not be required following hemodialysis [see Clinical Pharmacology (12.3)].

Use in Patients with Hepatic Impairment

Dose adjustment of Mycamine is not required in patients with mild, moderate, or severe hepatic impairment [see Clinical Pharmacology (12.3)].

Race and Gender

No dose adjustment of Mycamine is required based on gender or race. After 14 daily doses of 150 mg to healthy subjects, micafungin AUC in women was greater by approximately 23% compared with men, due to smaller body weight. No notable differences among white, black, and Hispanic subjects were seen. The micafungin AUC was greater by 19% in Japanese subjects compared to blacks, due to smaller body weight.

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

Adult Treatment of Candidemia and Other Candida Infections

Two dose levels of Mycamine were evaluated in a randomized, double-blind study to determine the efficacy and safety versus caspofungin in patients with invasive candidiasis and candidemia. Patients were randomized to receive once daily intravenous infusions (IV) of Mycamine, either 100 mg/day or 150 mg/day or caspofungin (70 mg loading dose followed by 50 mg maintenance dose). Patients in both study arms were permitted to switch to oral fluconazole after at least 10 days of intravenous therapy, provided they were non-neutropenic, had improvement or resolution of clinical signs and symptoms, had a Candida isolate which was susceptible to fluconazole, and had documentation of 2 negative cultures drawn at least 24 hours apart. Patients were stratified by APACHE II score (20 or less or greater than 20) and by geographic region. Patients with Candida endocarditis were excluded from this analysis. Outcome was assessed by overall treatment success based on clinical (complete resolution or improvement in attributable signs and symptoms and radiographic abnormalities of the Candida infection and no additional antifungal therapy) and mycological (eradication or presumed eradication) response at the end of IV therapy. Deaths that occurred during IV study drug therapy were treated as failures.

In this study, 111/578 (19.2%) of the patients had baseline APACHE II scores of greater than 20, and 50/578 (8.7%) were neutropenic at baseline (absolute neutrophil count less than 500 cells/mm3). Outcome, relapse and mortality data are shown for the recommended dose of Mycamine (100 mg/day) and caspofungin in Table 11.

In two cases of ophthalmic involvement assessed as failures in the above table due to missing evaluation at the end of IV treatment with Mycamine, therapeutic success was documented during protocol-defined oral fluconazole therapy.

Adult Treatment of Esophageal Candidiasis

In two controlled trials involving 763 patients with esophageal candidiasis, 445 adults with endoscopically-proven candidiasis received Mycamine, and 318 received fluconazole for a median duration of 14 days (range 1-33 days).

Mycamine was evaluated in a randomized, double-blind study which compared Mycamine 150 mg/day (n = 260) to intravenous fluconazole 200 mg/day (n = 258) in adults with endoscopically-proven esophageal candidiasis. Most patients in this study had HIV infection, with CD4 cell counts less than 100 cells/mm3. Outcome was assessed by endoscopy and by clinical response at the end of treatment. Endoscopic cure was defined as endoscopic grade 0, based on a scale of 0-3. Clinical cure was defined as complete resolution in clinical symptoms of esophageal candidiasis (dysphagia, odynophagia, and retrosternal pain). Overall therapeutic cure was defined as both clinical and endoscopic cure. Mycological eradication was determined by culture, and by histological or cytological evaluation of esophageal biopsy or brushings obtained endoscopically at the end of treatment. As shown in Table 12, endoscopic cure, clinical cure, overall therapeutic cure, and mycological eradication were comparable for patients in the Mycamine and fluconazole treatment groups.

Most patients (96%) in this study had Candida albicans isolated at baseline. The efficacy of Mycamine was evaluated in less than 10 patients with Candida species other than C. albicans, most of which were isolated concurrently with C. albicans.

Relapse was assessed at 2 and 4 weeks post-treatment in patients with overall therapeutic cure at end of treatment. Relapse was defined as a recurrence of clinical symptoms or endoscopic lesions (endoscopic grade greater than 0). There was no statistically significant difference in relapse rates at either 2 weeks or through 4 weeks post-treatment for patients in the Mycamine and fluconazole treatment groups, as shown in Table 13.

In this study, 459 of 518 (88.6%) patients had oropharyngeal candidiasis in addition to esophageal candidiasis at baseline. At the end of treatment 192/230 (83.5%) Mycamine-treated patients and 188/229 (82.1%) of fluconazole-treated patients experienced resolution of signs and symptoms of oropharyngeal candidiasis. Of these, 32.3% in the Mycamine group, and 18.1% in the fluconazole group (treatment difference = 14.2%; 95% confidence interval [5.6, 22.8]) had symptomatic relapse at 2 weeks post-treatment. Relapse included patients who died or were lost to follow-up, and those who received systemic antifungal therapy during the post-treatment period. Cumulative relapse at 4 weeks post-treatment was 52.1% in the Mycamine group and 39.4% in the fluconazole group (treatment difference 12.7%, 95% confidence interval [2.8, 22.7]).

Prophylaxis of Candida Infections in Hematopoietic Stem Cell Transplant Recipients

In a randomized, double-blind study, Mycamine (50 mg IV once daily) was compared to fluconazole (400 mg IV once daily) in 882 [adult (791) and pediatric (91)] patients undergoing an autologous or syngeneic (46%) or allogeneic (54%) stem cell transplant. All pediatric patients, except 2 per group, received allogeneic transplants. The status of the patients’ underlying malignancy at the time of randomization was: 365 (41%) patients with active disease, 326 (37%) patients in remission, and 195 (22%) patients in relapse. The more common baseline underlying diseases in the 476 allogeneic transplant recipients were: chronic myelogenous leukemia (22%), acute myelogenous leukemia (21%), acute lymphocytic leukemia (13%), and non-Hodgkin’s lymphoma (13%). In the 404 autologous and syngeneic transplant recipients the more common baseline underlying diseases were: multiple myeloma (37.1%), non-Hodgkin's lymphoma (36.4%), and Hodgkin's disease (15.6%). During the study, 198 of 882 (22.4%) transplant recipients had proven graft-versus-host disease; and 475 of 882 (53.9%) recipients received immunosuppressive medications for treatment or prophylaxis of graft-versus-host disease.

Study drug was continued until the patient had neutrophil recovery to an absolute neutrophil count (ANC) of 500 cells/mm3 or greater or up to a maximum of 42 days after transplant. The average duration of drug administration was 18 days (range 1 to 51 days). Duration of therapy was slightly longer in the pediatric patients who received Mycamine (median duration 22 days) compared to the adult patients who received Mycamine (median duration 18 days).

Successful prophylaxis was defined as the absence of a proven, probable, or suspected systemic fungal infection through the end of therapy (usually 18 days), and the absence of a proven or probable systemic fungal infection through the end of the 4-week post-therapy period. A suspected systemic fungal infection was diagnosed in patients with neutropenia (ANC less than 500 cells/mm3); persistent or recurrent fever (while ANC less than 500 cells/mm3) of no known etiology; and failure to respond to at least 96 hours of broad spectrum antibacterial therapy. A persistent fever was defined as four consecutive days of fever greater than 38ºC. A recurrent fever was defined as having at least one day with temperatures 38.5ºC or higher after having at least one prior temperature higher than 38ºC; or having two days of temperatures higher than 38ºC after having at least one prior temperature higher than 38ºC. Transplant recipients who died or were lost to follow-up during the study were considered failures of prophylactic therapy.

Successful prophylaxis was documented in 80.7% of adult and pediatric Mycamine recipients, and in 73.7% of adult and pediatric patients who received fluconazole (7.0% difference [95% CI = 1.5, 12.5]), as shown in Table 14, along with other study endpoints. The use of systemic antifungal therapy post-treatment was 42% in both groups.

The number of proven breakthrough Candida infections was 4 in the Mycamine and 2 in the fluconazole group.

The efficacy of Mycamine against infections caused by fungi other than Candida has not been established.

Call your doctor for instructions if you miss a dose of Mycamine.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.