micafungin sodium
Dosage Form: injection, powder, lyophilized, for solution
FULL PRESCRIBING INFORMATION
Indications and Usage for Mycamine
Mycamine® is indicated for:
Treatment of Patients with Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses
[see Clinical Studies (14.1)]
Mycamine has not been adequately studied in patients with endocarditis, osteomyelitis
and meningitis due to Candida infections.
Treatment of Patients with Esophageal Candidiasis
[see Clinical Studies (14.2)]
Prophylaxis of Candida Infections in Patients Undergoing Hematopoietic Stem Cell Transplantation
[see Clinical Studies (14.3)]
NOTE: The efficacy of Mycamine against infections caused by fungi other than Candida has not been established.
Mycamine Dosage and Administration
Do not mix or co-infuse Mycamine with other medications. Mycamine has been shown to precipitate when mixed directly with a number of other commonly used medications.
| |
| Indication | Recommended Reconstituted Dose Once Daily |
| Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses* | 100 mg |
| Treatment of Esophageal Candidiasis† | 150 mg |
| Prophylaxis of Candida Infections in HSCT Recipients‡ | 50 mg |
A loading dose is not required. Typically, 85% of the steady-state concentration is achieved after three daily Mycamine doses.
No dosing adjustments are required based on race, gender, or in patients with severe renal impairment or in patients with mild, moderate, or severe hepatic impairment [see Use in Specific Populations (8)].
No dose adjustment for Mycamine is required with concomitant use of mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, sirolimus, nifedipine, fluconazole, voriconazole, itraconazole, amphotericin B, ritonavir, or rifampin [see Drug Interactions (7)].
Directions for Reconstitution and Dilution
Please read this entire section carefully before beginning reconstitution.
The diluent to be used for reconstitution and dilution is 0.9% Sodium Chloride Injection, USP (without a bacteriostatic agent). Alternatively, 5% Dextrose Injection, USP, may be used for reconstitution and dilution of Mycamine. Solutions for infusion are prepared as follows:
Reconstitution
Mycamine 50 mg vial
Aseptically add 5 mL of 0.9% Sodium Chloride Injection, USP (without a bacteriostatic agent) to each 50 mg vial to yield a preparation containing approximately 10 mg micafungin/mL.
Mycamine 100 mg vial
Aseptically add 5 mL of 0.9% Sodium Chloride Injection, USP (without a bacteriostatic agent) to each 100 mg vial to yield a preparation containing approximately 20 mg micafungin/mL.
As with all parenteral drug products, reconstituted Mycamine should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use material if there is any evidence of precipitation or foreign matter. Aseptic technique must be strictly observed in all handling since no preservative or bacteriostatic agent is present in Mycamine or in the materials specified for reconstitution and dilution.
Dissolution
To minimize excessive foaming, GENTLY dissolve the Mycamine powder by swirling the vial. DO NOT VIGOROUSLY SHAKE THE VIAL. Visually inspect the vial for particulate matter.
Dilution
The diluted solution should be protected from light. It is not necessary to cover the infusion drip chamber or the tubing.
- For treatment of candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses: add 100 mg of reconstituted Mycamine [see Dosage and Administration (2.1)] into 100 mL of 0.9% Sodium Chloride Injection, USP or 100 mL of 5% Dextrose Injection, USP.
- For treatment of esophageal candidiasis: add 150 mg of reconstituted Mycamine [see Dosage and Administration (2.1)] into 100 mL of 0.9% Sodium Chloride Injection, USP or 100 mL of 5% Dextrose Injection, USP.
- For prophylaxis of Candida infections: add 50 mg of reconstituted Mycamine [see Dosage and Administration (2.1)] into 100 mL of 0.9% Sodium Chloride Injection, USP or 100 mL of 5% Dextrose Injection, USP.
Mycamine is preservative-free. Discard partially used vials.
Infusion Volume and Duration
Mycamine should be administered by intravenous infusion only. Infuse over one hour. More rapid infusions may result in more frequent histamine mediated reactions.
An existing intravenous line should be flushed with 0.9% Sodium Chloride Injection, USP, prior to infusion of Mycamine.
Dosage Forms and Strengths
50 mg and 100 mg single-use vials
Contraindications
Mycamine is contraindicated in persons with known hypersensitivity to micafungin, any component of Mycamine, or other echinocandins.
Warnings and Precautions
Hypersensitivity Reactions
Isolated cases of serious hypersensitivity (anaphylaxis and anaphylactoid) reactions (including shock) have been reported in patients receiving Mycamine. If these reactions occur, Mycamine infusion should be discontinued and appropriate treatment administered.
Hematological Effects
Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of Mycamine (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia. Isolated cases of significant hemolysis and hemolytic anemia have also been reported in patients treated with Mycamine. Patients who develop clinical or laboratory evidence of hemolysis or hemolytic anemia during Mycamine therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/benefit of continuing Mycamine therapy.
Hepatic Effects
Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with Mycamine. In some patients with serious underlying conditions who were receiving Mycamine along with multiple concomitant medications, clinical hepatic abnormalities have occurred, and isolated cases of significant hepatic impairment, hepatitis, and hepatic failure have been reported. Patients who develop abnormal liver function tests during Mycamine therapy should be monitored for evidence of worsening hepatic function and evaluated for the risk/benefit of continuing Mycamine therapy.
Renal Effects
Elevations in BUN and creatinine, and isolated cases of significant renal impairment or acute renal failure have been reported in patients who received Mycamine. In fluconazole-controlled trials, the incidence of drug-related renal adverse events was 0.4% for Mycamine treated patients and 0.5% for fluconazole treated patients. Patients who develop abnormal renal function tests during Mycamine therapy should be monitored for evidence of worsening renal function.
Adverse Reactions
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 150 mg/day, and caspofungin (70/50 mg/day) treatment groups, respectively. Treatment emergent adverse events occurring in ≥5% of the patients in any treatment study groups are shown in Table 2.
Patient base: all randomized patients who received at least 1 dose of trial drug Common: ≥5% in any treatment arm | |||
| |||
| MedDRA v 5.0 System Organ Class Preferred Term† | Micafungin 100 mg (n = 200) | Micafungin 150 mg (n = 202) | Caspofungin‡ (n = 193) |
| All Systems, Any Adverse Event | 183 (91.5) | 187 (92.6) | 171 (88.6) |
| Gastrointestinal Disorders | 81 (40.5) | 89 (44.1) | 76 (39.4) |
| Diarrhea NOS | 15 (7.5) | 26 (12.9) | 14 (7.3) |
| Nausea | 19 (9.5) | 15 (7.4) | 20 (10.4) |
| Vomiting NOS | 18 (9) | 15 (7.4) | 16 (8.3) |
| Abdominal Pain NOS | 5 (2.5) | 4 (2) | 10 (5.2) |
| Metabolism and Nutrition Disorders | 77 (38.5) | 83 (41.1) | 73 (37.8) |
| Hypokalemia | 28 (14) | 34 (16.8) | 28 (14.5) |
| Hypomagnesaemia | 11 (5.5) | 17 (8.4) | 14 (7.3) |
| Hypoglycemia NOS | 12 (6) | 14 (6.9) | 9 (4.7) |
| Hypernatremia | 8 (4) | 13 (6.4) | 8 (4.1) |
| Hyperkalemia | 10 (5) | 8 (4) | 5 (2.6) |
| Infections and Infestations | 67 (33.5) | 81 (40.1) | 59 (30.6) |
| Bacteremia | 10 (5) | 18 (8.9) | 11 (5.7) |
| Septic Shock | 15 (7.5) | 9 (4.5) | 9 (4.7) |
| Sepsis NOS | 11 (5.5) | 10 (5) | 11 (5.7) |
| Pneumonia NOS | 3 (1.5) | 11 (5.4) | 4 (2.1) |
| General Disorders/ Administration Site Conditions | 59 (29.5) | 56 (27.7) | 51 (26.4) |
| Pyrexia | 14 (7) | 22 (10.9) | 15 (7.8) |
| Edema Peripheral | 11 (5.5) | 12 (5.9) | 14 (7.3) |
| Vascular Disorders | 43 (21.5) | 47 (23.3) | 36 (18.7) |
| Hypotension NOS | 20 (10) | 12 (5.9) | 15 (7.8) |
| Hypertension NOS | 6 (3) | 10 (5) | 12 (6.2) |
| Investigations | 36 (18) | 49 (24.3) | 37 (19.2) |
| Blood Alkaline Phosphatase NOS Increased | 11 (5.5) | 16 (7.9) | 8 (4.1) |
| Blood/Lymphatic System Disorders | 38 (19) | 45 (22.3) | 37 (19.2) |
| Thrombocytopenia | 8 (4) | 8 (4) | 11 (5.7) |
| Anemia NOS | 5 (2.5) | 6 (3) | 13 (6.7) |
| Anemia NOS Aggravated | 4 (2) | 10 (5) | 5 (2.6) |
| Cardiac Disorders | 35 (17.5) | 48 (23.8) | 36 (18.7) |
| Tachycardia NOS | 6 (3) | 7 (3.5) | 13 (6.7) |
| Bradycardia NOS | 5 (2.5) | 10 (5) | 8 (4.1) |
| Atrial Fibrillation | 5 (2.5) | 10 (5) | 0 |
| Nervous System Disorders | 21 (10.5) | 42 (20.8) | 32 (16.6) |
| Headache NOS | 4 (2) | 10 (5) | 11 (5.7) |
| Skin/Subcutaneous Tissue Disorders | 26 (13) | 34 (16.8) | 33 (17.1) |
| Decubitus Ulcer | 9 (4.5) | 12 (5.9) | 9 (4.7) |
| Psychiatric Disorders | 31 (15.5) | 27 (13.4) | 33 (17.1) |
| Insomnia | 11 (5.5) | 8 (4) | 16 (8.3) |
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.
Patient base: all randomized patients who received at least 1 dose of trial drug Common: ≥5% in either treatment arm. | ||
| ||
Adverse Events † (MedDRA System Organ Class and Preferred Term) | Mycamine 150 mg/day n (%) | Fluconazole 200 mg/day n (%) |
| Number of Patients | 260 | 258 |
| All Systems, Any Adverse Event | 202 (77.7) | 186 (72.1) |
| Gastrointestinal Disorders | 84 (32.3) | 93 (36) |
| Diarrhea NOS | 27 (10.4) | 29 (11.2) |
| Nausea | 20 (7.7) | 23 (8.9) |
| Vomiting NOS | 17 (6.5) | 17 (6.6) |
| Abdominal Pain NOS | 10 (3.8) | 15 (5.8) |
| General Disorders/Administration Site Conditions | 52 (20) | 45 (17.4) |
| Pyrexia | 34 (13.1) | 21 (8.1) |
| Nervous System Disorders | 42 (16.2) | 40 (15.5) |
| Headache NOS | 22 (8.5) | 20 (7.8) |
| Blood /Lymphatic System Disorders | 38 (14.6) | 43 (16.7) |
| Anemia NOS | 8 (3.1) | 16 (6.2) |
| Vascular Disorders | 54 (20.8) | 21 (8.1) |
| Phlebitis NOS | 49 (18.8) | 13 (5) |
| Skin and Subcutaneous Tissue Disorders | 36 (13.8) | 26 (10.1) |
| Rash NOS | 14 (5.4) | 6 (2.3) |
| Psychiatric Disorders | 20 (7.7) | 21 (8.1) |
| Insomnia | 9 (3.5) | 13 (5) |
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.
Patient base: all randomized patients who received at least 1 dose of trial drug Common: ≥15% in either treatment arm. | ||
| ||
Adverse Events† (MedDRA System Organ Class and Preferred Term) | Mycamine 50 mg/day n (%) | Fluconazole 400 mg/day n (%) |
| Number of Patients | 425 | 457 |
| All Systems, Any Adverse Events | 425 (100) | 457 (100) |
| Gastrointestinal Disorders | 421 (99.1) | 449 (98.2) |
| Diarrhea NOS | 302 (71.1) | 348 (76.1) |
| Nausea | 296 (69.6) | 309 (67.6) |
| Vomiting NOS | 281 (66.1) | 307 (67.2) |
| Constipation | 129 (30.4) | 143 (31.3) |
| Dyspepsia | 104 (24.5) | 122 (26.7) |
| Abdominal Pain NOS | 115 (27.1) | 107 (23.4) |
| General Disorders/Administration Site Conditions | 410 (96.5) | 440 (96.3) |
| Mucosal Inflammation NOS | 322 (75.8) | 360 (78.8) |
| Pyrexia | 191 (44.9) | 218 (47.7) |
| Fatigue | 126 (29.6) | 145 (31.7) |
| Rigors | 112 (26.4) | 118 (25.8) |
| Edema Peripheral | 88 (20.7) | 100 (21.9) |
| Blood and Lymphatic System Disorders | 408 (96) | 429 (93.9) |
| Neutropenia | 320 (75.3) | 327 (71.6) |
| Thrombocytopenia | 307 (72.2) | 304 (66.5) |
| Anemia NOS | 151 (35.5) | 173 (37.9) |
| Febrile Neutropenia | 155 (36.5) | 166 (36.3) |
| Metabolism and Nutrition Disorders | 385 (90.6) | 428 (93.7) |
| Hypomagnesaemia | 214 (50.4) | 256 (56) |
| Hypokalemia | 209 (49.2) | 232 (50.8) |
| Anorexia | 116 (27.3) | 121 (26.5) |
| Appetite Decreased NOS | 87 (20.5) | 93 (20.4) |
| Fluid Overload | 74 (17.4) | 96 (21) |
| Hyperglycemia NOS | 68 (16) | 92 (20.1) |
| Hypocalcemia | 72 (16.9) | 82 (17.9) |
| Fluid Retention | 69 (16.2) | 66 (14.4) |
| Respiratory, Thoracic and Mediastinal Disorders | 291 (68.5) | 336 (73.5) |
| Cough | 98 (23.1) | 112 (24.5) |
| Epistaxis | 49 (11.5) | 84 (18.4) |
| Dyspnea NOS | 54 (12.7) | 64 (14) |
| Skin and Subcutaneous Tissue Disorders | 290 (68.2) | 316 (69.1) |
| Rash NOS | 110 (25.9) | 102 (22.3) |
| Pruritus NOS | 75 (17.6) | 87 (19) |
| Erythema | 48 (11.3) | 71 (15.5) |
| Nervous System Disorders | 261 (61.4) | 268 (58.6) |
| Headache NOS | 179 (42.1) | 165 (36.1) |
| Dizziness | 55 (12.9) | 83 (18.2) |
| Psychiatric Disorders | 257 (60.5) | 249 (54.5) |
| Insomnia | 152 (35.8) | 146 (31.9) |
| Anxiety | 95 (22.4) | 92 (20.1) |
| Vascular Disorders | 224 (52.7) | 267 (58.4) |
| Hypertension NOS | 91 (21.4) | 113 (24.7) |
| Hypotension NOS | 79 (18.6) | 89 (19.5) |
| Flushing | 47 (11.1) | 70 (15.3) |
| Infections and Infestations | 178 (41.9) | 208 (45.5) |
| Bacteremia | 66 (15.5) | 86 (18.8) |
| Cardiac Disorders | 147 (34.6) | 162 (35.4) |
| Tachycardia NOS | 105 (24.7) | 102 (22.3) |
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, hemolytic anemia, pancytopenia, thrombotic thrombocytopenic 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
| Patient base: all randomized patients who received at least 1 dose of trial drug Common: Incidence of adverse event ≥5%. | |
| |
Adverse Events† (MedDRA System Organ Class and Preferred Term) | Mycamine n (%) |
| Number of Patients | 3083 |
| All Systems, Any Adverse Event | 2810 (91.1) |
| Gastrointestinal Disorders | 1764 (57.2) |
| Diarrhea NOS | 718 (23.3) |
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