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 events tended to occur more often in patients receiving MYCAMINE via peripheral intravenous administration.
Clinical Adverse Experiences
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.
Esophageal Candidiasis
In a phase 3, 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. Adverse events considered to be drug-related occurred in 72 (27.7%) and 55 (21.3%) patients in the MYCAMINE and fluconazole treatment groups, respectively. Drug-related adverse events resulting in discontinuation were reported in 6 (2.3%) MYCAMINE treated patients; and in 2 (0.8%) fluconazole treated patients. Rash and delirium were the most common drug-related adverse events resulting in MYCAMINE discontinuation. Drug-related adverse experiences occurring in ≥0.5% of the patients in either treatment group are shown in Table 2.
Table 2: Common Drug-Related Relationship to drug was determined by the investigator to be possibly, probably, or definitely drug-related. Adverse Events Among Patients with Esophageal Candidiasis |
Adverse Events Within a system organ class patients may experience more than 1 adverse event.
(MedDRA System Organ Class and Preferred Term) |
MYCAMINE
150 mg/day
n (%) |
Fluconazole
200 mg/day
n (%) |
| | |
Number of Patients Patient base: all randomized patients who received at least 1 dose of trial drug
Common: ≥0.5% in either treatment arm. | 260 | 258 |
| | |
| Blood and Lymphatic System Disorders |
| Leukopenia | 7 (2.7) | 2 (0.8) |
| Neutropenia | 3 (1.2) | 1 (0.4) |
| Thrombocytopenia | 3 (1.2) | 4 (1.6) |
| Anemia | 3 (1.2) | 4 (1.6) |
| Lymphopenia | 2 (0.8) | 1 (0.4) |
| Eosinophilia | 0 | 2 (0.8) |
|
| Gastrointestinal Disorders |
| Nausea | 6 (2.3) | 7 (2.7) |
| Abdominal Pain | 5 (1.9) | 4 (1.6) |
| Vomiting | 3 (1.2) | 4 (1.6) |
|
| General Disorders and Administration Site Conditions |
| Rigors | 6 (2.3) | 0 |
| Pyrexia | 5 (1.9) | 1 (0.4) |
| Infusion Site Inflammation | 4 (1.5) | 3 (1.2) |
|
| Laboratory Tests |
| Blood Alkaline Phosphatase Increased | 4 (1.5) | 4 (1.6) |
| Aspartate Aminotransferase Increased | 2 (0.8) | 4 (1.6) |
| Blood Lactate Dehydrogenase Increased | 2 (0.8) | 3 (1.2) |
| Transaminases Increased | 2 (0.8) | 1 (0.4) |
| Alanine Aminotransferase Increased | 1 (0.4) | 5 (1.9) |
|
| Metabolism and Nutrition Disorders |
| Hypomagnesemia | 0 | 3 (1.2) |
|
| Nervous System Disorders |
| Headache | 7 (2.7) | 3 (1.2) |
| Dizziness | 1 (0.4) | 2 (0.8) |
| Somnolence | 1 (0.4) | 7 (2.7) |
|
| Psychiatric Disorders |
| Delirium | 2 (0.8) | 2 (0.8) |
|
| Skin and Subcutaneous Tissue Disorders |
| Rash | 8 (3.1) | 5 (1.9) |
| Pruritus | 3 (1.2) | 3 (1.2) |
| | |
| Vascular Disorders | | |
| Phlebitis | 11 (4.2) | 6 (2.3) |
Prophylaxis of Candida Infections in Hematopoietic Stem Cell Transplant Recipients
A double-blind, phase 3 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. Drug-related adverse events occurred in 64/425 (15.1%) and 77/457 (16.8%) patients in the MYCAMINE and fluconazole treatment groups, respectively. Drug-related adverse events resulting in MYCAMINE discontinuation were reported in 11 (2.6%) patients; while those resulting in fluconazole discontinuation were reported in 16 (3.5%). Drug-related adverse experiences occurring in ≥0.5% of the patients in either treatment group are shown in Table 3.
Table 3: Common Adverse Events RelatedRelationship to drug was determined by the investigator to be possibly, probably, or definitely drug-related. to Study Drug in Clinical Study of Prophylaxis of Candida Infection in Hematopoietic Stem Cell Transplant Recipients |
Adverse Events Within a system organ class patients may experience more than 1 adverse event.
(MedDRA System Organ Class and Preferred Term) |
MYCAMINE
50 mg/day
n (%) |
Fluconazole
400 mg/day
n (%) |
| | |
Number of Patients Patient base: all randomized patients who received at least 1 dose of trial drug
Common: ≥0.5% in either treatment arm. | 425 | 457 |
| | |
| Blood and Lymphatic System Disorders |
| Neutropenia | 5 (1.2) | 4 (0.9) |
| Anemia | 4 (0.9) | 3 (0.7) |
| Febrile neutropenia | 4 (0.9) | 1 (0.2) |
| Leukopenia | 4 (0.9) | 2 (0.4) |
| Thrombocytopenia | 4 (0.9) | 5 (1.1) |
|
| Gastrointestinal Disorders |
| Nausea | 10 (2.4) | 12 (2.6) |
| Diarrhea | 9 (2.1) | 14 (3.1) |
| Vomiting | 7 (1.6) | 5 (1.1) |
| Abdominal pain | 4 (0.9) | 3 (0.7) |
| Dyspepsia | 3 (0.7) | 1 (0.2) |
| Constipation | 1 (0.2) | 3 (0.7) |
| Hiccups | 1 (0.2) | 3 (0.7) |
| Abdominal pain upper | 0 | 3 (0.7) |
|
| General Disorders and Administrative Site Conditions |
| Pyrexia | 4 (0.9) | 5 (1.1) |
| Mycosal inflammation | 1 (0.2) | 3 (0.7) |
| Rigors | 1 (0.2) | 5 (1.1) |
| Fatigue | 0 | 5 (1.1) |
|
| Hepatobiliary Disorders |
| Hyperbilirubinemia | 12 (2.8) | 11 (2.4) |
|
| Laboratory Tests |
| Alanine aminotransferase increased | 4 (0.9) | 9 (2.0) |
| Aspartate aminotransferase increased | 3 (0.7) | 9 (2.0) |
| Liver function tests abnormal | 3 (0.7) | 6 (1.3) |
| Blood creatinine increased | 1 (0.2) | 3 (0.7) |
| Drug level increased | 1 (0.2) | 3 (0.7) |
| Transaminases increased | 1 (0.2) | 4 (0.9) |
|
| Metabolism and Nutrition Disorders |
| Hypokalemia | 8 (1.9) | 8 (1.8) |
| Hypophosphatemia | 6 (1.4) | 4 (0.9) |
| Hypomagnesemia | 5 (1.2) | 6 (1.3) |
| Hypocalcemia | 4 (0.9) | 4 (0.9) |
| Appetite decreased | 3 (0.7) | 0 |
|
| Nervous System Disorders |
| Headache | 4 (0.9) | 4 (0.9) |
| Dysgeusia | 3 (0.7) | 1 (0.2) |
| Dizziness | 0 | 5 (1.1) |
|
| Skin and Subcutaneous Tissue Disorders |
| Rash | 6 (1.4) | 4 (0.9) |
| Pruritus | 4 (0.9) | 3 (0.7) |
|
| Vascular Disorders |
| Flushing | 1 (0.2) | 6 (1.3) |
| Hypotension | 1 (0.2) | 4 (0.9) |
Overall MYCAMINE Safety Experience
The overall safety of MYCAMINE was assessed in 1980 patients and 422 volunteers in 32 clinical studies, including the esophageal candidiasis and prophylaxis studies, who received single or multiple doses of MYCAMINE, ranging from 12.5 mg to ≥150 mg/day.
A total of 606 subjects (patients and volunteers) received at least 150 mg/day MYCAMINE for a minimum of 10 days.
Overall, 2028 of 2402 (84.4%) subjects who received MYCAMINE experienced an adverse event. Adverse events considered to be drug-related were reported in 717 (29.9%) subjects. Drug-related adverse events which occurred in ≥ 0.5% of all subjects who received MYCAMINE in these trials are shown in Table 4.
Table 4: Common Drug-RelatedRelationship to drug was determined by the investigator to be possibly, probably, or definitely drug-related. Adverse Events in Subjects Subjects included patients and volunteers Who Received MYCAMINE in Clinical Trials |
Adverse Events Within a system organ class, patients may experience more than 1 adverse event
(MedDRA System Organ Class and Preferred Term) |
MYCAMINE
n (%) |
| |
Number of Patients Patient base: all randomized patients who received at least 1 dose of trial drug
Common: Incidence of adverse event ≥0.5%. | 2402 |
| |
| Blood and Lymphatic System Disorders |
| Leukopenia | 38 (1.6) |
| Neutropenia | 29 (1.2) |
| Thrombocytopenia | 20 (0.8) |
| Anemia | 19 (0.8) |
|
| Gastrointestinal Disorders |
| Nausea | 67 (2.8) |
| Vomiting | 58 (2.4) |
| Diarrhea | 38 (1.6) |
| Abdominal pain | 23 (1.0) |
| Abdominal pain upper | 11 (0.5) |
|
| General Disorders and Administration Site Conditions |
| Pyrexia | 37 (1.5) |
| Rigors | 23 (1.0) |
| Injection site pain | 21 (0.9) |
|
| Hepatobiliary Disorders |
| Hyperbilirubinemia | 25 (1.0) |
|
| Laboratory Tests |
| Aspartate aminotransferase increased | 64 (2.7) |
| Alanine aminotransferase increased | 62 (2.6) |
| Blood alkaline phosphatase increased | 48 (2.0) |
| Liver function tests abnormal | 36 (1.5) |
| Blood creatinine increased | 14 (0.6) |
| Blood urea increased | 12 (0.5) |
| Blood lactate dehydrogenase increased | 11 (0.5) |
|
| Metabolism and Nutrition Disorders |
| Hypokalemia | 28 (1.2) |
| Hypocalcemia | 27 (1.1) |
| Hypomagnesemia | 27 (1.1) |
|
| Nervous System Disorders |
| Headache | 57 (2.4) |
| Dizziness | 16 (0.7) |
| Somnolence | 12 (0.5) |
|
| Skin and Subcutaneous Tissue Disorders |
| Rash | 38 (1.6) |
| Pruritus | 18 (0.7) |
| |
| Vascular Disorders | |
| Phlebitis | 39 (1.6) |
| Hypertension | 14 (0.6) |
| Flushing | 12 (0.5) |
Other clinically significant adverse events regardless of causality which occurred in these trials are listed below:
- Blood and lymphatic system disorders: coagulopathy, hemolysis, hemolytic anemia, pancytopenia, thrombotic thrombocytopenic purpura
- Cardiac disorders: arrhythmia, cardiac arrest, cyanosis, myocardial infarction, tachycardia
- Hepatobiliary disorders: hepatocellular damage, hepatomegaly, jaundice, hepatic failure
- General disorders and administration site conditions: injection site thrombosis
- 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
Postmarketing Adverse Events
The following adverse events have been identified during the post-approval use of micafungin sodium for injection in Japan. 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 events, which included:
- Hepatobiliary disorders: hyperbilirubinemia, hepatic function abnormal, hepatic disorder, hepatocellular damage
- Renal and urinary disorders: acute renal failure and renal impairment
- Blood and lymphatic system disorders: white blood cell count decreased, hemolytic anemia
- Vascular disorders: shock
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REPORTS OF SUSPECTED MYCAMINE SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Mycamine. The information is not vetted and should not be considered as verified clinical evidence.
Possible Mycamine side effects / adverse reactions in 58 year old male
Reported by a physician from Austria on 2011-11-17
Patient: 58 year old male
Reactions: Candidiasis
Adverse event resulted in: hospitalization
Suspect drug(s):
Mycamine
Possible Mycamine side effects / adverse reactions in 64 year old male
Reported by a physician from Poland on 2011-11-18
Patient: 64 year old male weighing 85.0 kg (187.0 pounds)
Reactions: Swelling Face, Rash
Suspect drug(s):
Mycamine
Other drugs received by patient: Metoclopramide; Caspofungin Acetate; Colistin; Metocard; Proxacin; Cefoperazone Sodium; Fraxiparin; Acetylocysteina
Possible Mycamine side effects / adverse reactions in 19 year old male
Reported by a physician from United States on 2011-11-29
Patient: 19 year old male
Reactions: Thrombotic Thrombocytopenic Purpura
Suspect drug(s):
Mycamine
Other drugs received by patient: Immune Globulin Intravenous (Human); Albuterol; Calcium Gluconate; Ondansetron; Fentanyl; Insulin; Furosemide; Propofol; Levofloxacin; Bacitracin (Bacitracin) Ointment; Vasopressors
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