ADVERSE REACTIONS
Adverse Reactions from Clinical Trials
Because clinical trials are conducted from widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The adverse reactions and frequencies below are based on 30 publications describing clinical experience with fractionated administration of ifosfamide as monotherapy with a total dose of 4 to 12 g/m2 per course.
System Organ Class (SOC)
|
Adverse Reaction
|
Percentage (Ratio)
|
INFECTIONS AND INFESTATIONS
|
Infection
|
9.9%
(112/1128)
|
BLOOD AND LYMPHATIC SYSTEM DISORDERS
|
Leukopenia
(any)
|
--
|
Leukopenia
<1 x 103/µL
|
43.5%
(267/614)
|
Thrombocytopenia
(any)
|
--
|
Thrombocytopenia,
50 x 103/µL
|
4.8%
(35/729)
|
Anemia
|
37.9%
(202/533)
|
METABOLISM AND NUTRITION DISORDERS
|
Anorexia
|
1.1%
(15/1317)
|
NERVOUS SYSTEM DISORDERS
|
Central nervous system toxicity
,
|
15.4%
(154/1001)
|
Peripheral neuropathy
|
0.4%
(5/1317)
|
CARDIAC DISORDERS
|
Cardiotoxicity
|
0.5%
(7/1317)
|
VASCULAR DISORDERS
|
Hypotention
|
0.3%
(4/1317)
|
GASTROINTESTINAL DISORDERS
|
Nausea/Vomiting
|
46.8%
(443/964)
|
Diarrhea
|
0.7%
(9/1317)
|
Stomatitis
|
0.3%
(4/1317)
|
HEPATOBILIARY DISORDERS
|
Hepatotoxicity
|
1.8%
(22/1190)
|
SKIN AND SUBCUTANEOUS TISSUES DISORDERS
|
Alopecia
|
89.6%
(540/603)
|
Dermatitis
|
0.08%
(1/1317)
|
Papular rash
|
0.08%
(1/1317)
|
RENAL AND URINARY DISORDERS
|
Hemorrhagic cystitis
|
--
|
Hematuria
|
- without mesna
|
44.1%
(282/640)
|
- with mesna
|
21.3%
(33/155)
|
Macrohematuria
|
- without mesna
|
11.1%
(66/594)
|
- with mesna
|
5.2%
(5/97)
|
Renal dysfunction
|
--
|
Renal structural damage
|
--
|
GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS
|
Phlebitis
|
2.8%
(37/1317)
|
Neutropenic fever
|
1.0%
(13/1317)
|
Fatigue
|
0.3%
(4/1317)
|
Malaise
|
Unable to calculate
|
Postmarketing Experience
The following adverse reactions have been reported in the post-marketing experience, listed by MedDRA System Organ Class (SOC), then by Preferred Term in order of severity, where feasible. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
INFECTIONS AND INFESTATIONS:
The following manifestations have been associated with myelosuppression and immunosuppression caused by ifosfamide: increased risk for and severity of infections†, pneumonias†, sepsis and septic shock (including fatal outcomes), as well as reactivation of latent infections, including viral hepatitis†, Pneumocystis jiroveci†, herpes zoster, Strongyloides, progressive multifocal leukoencephalopathy†, and other viral and fungal infections.
† Severe immunosuppression has led to serious, sometimes fatal, infections.
NEOPLASMS, BENIGN AND MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS):
As treatment-related secondary malignancy*, Acute leukemia* (Acute myeloid leukemia)*, Acute promyelocytic leukemia*, Acute lymphocytic leukemia*, Myelodysplastic syndrome, Lymphoma (Non-Hodgkin’s lymphoma), Sarcomas*, Renal cell carcinoma, Thyroid cancer
BLOOD AND LYMPHATIC SYSTEM DISORDERS:
Hematotoxicity*, Myelosuppression manifested as Bone marrow failure, Agranulocytosis; Febrile bone marrow aplasia; Disseminated intravascular coagulation, Hemolytic uremic syndrome, Hemolytic anemia, Neonatal anemia, Methemoglobinemia
IMMUNE SYSTEM DISORDERS:
Angioedema*, Anaphylactic reaction, Immunosuppression, Urticaria, Hypersensitivity reaction
ENDOCRINE DISORDERS:
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
METABOLISM AND NUTRITION DISORDERS:
Tumor lysis syndrome, Metabolic acidosis, Hypokalemia, Hypocalcemia, Hypophosphatemia, Hyperglycemia, Polydipsia
PSYCHIATRIC DISORDERS:
Panic attack, Catatonia, Mania, Paranoia, Delusion, Delirium, Bradyphrenia, Mutism, Mental status change, Echolalia, Logorrhea, Perseveration, Amnesia
NERVOUS SYSTEM DISORDERS:
Convulsion*, Status epilepticus (convulsive and nonconvulsive), reversible posterior leukoencephalopathy syndrome, Leukoencephalopathy, Extrapyramidal disorder, Asterixis, Movement disorder, Polyneuropathy, Dysesthesia, Hypothesia, Paresthesia, Neuralgia, Gait disturbance, Fecal incontinence, Dysarthria
EYE DISORDERS:
Visual impairment, Vision blurred, Conjunctivitis, Eye irritation
EAR AND LABYRINTH DISORDERS:
Deafness, Hypoacusis, Vertigo, Tinnitus
CARDIAC DISORDERS:
Cardiotoxicity*, Cardiac arrest*, Ventricular fibrillation*, Ventricular tachycardia*, Cardiogenic shock*, Myocardial infarction*, Cardiac failure*, Bundle branch block left, Bundle branch block right, Pericardial effusion, Myocardial hemorrhage, Angina pectoris, Left ventricular failure, Cardiomyopathy*, Congestive cardiomyopathy, Myocarditis*, Arrhythmia*, Pericarditis, Atrial fibrillation, Atrial flutter, Bradycardia, Supraventricular extrasystoles, Premature atrial contractions, Ventricular extrasystoles, Myocardial depression, Palpitations, Ejection fraction decreased*, Electrocardiogram ST-segment abnormal, Electrocardiogram T-wave inversion, Electrocardiogram QRS complex abnormal
VASCULAR DISORDERS:
Pulmonary embolism, Deep vein thrombosis, Capillary leak syndrome, Vasculitis, Hypertension, Flushing, Blood pressure decreased
RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS:
Respiratory failure*, Acute respiratory distress syndrome*, Pulmonary hypertension*, Interstitial lung disease* as manifested by Pulmonary fibrosis*, Alveolitis allergic, Interstitial pneumonitis, Pneumonitis*, Pulmonary edema*, Pleural effusion, Bronchospasm, Dyspnea, Hypoxia, Cough
GASTROINTESTINAL DISORDERS:
Cecitis, Colitis, Enterocolitis, Pancreatitis, Ileus, Gastrointestinal hemorrhage, Mucosal ulceration, Constipation, Abdominal pain, Salivary hypersecretion
HEPATOBILIARY DISORDERS:
Hepatic failure*, Hepatitis fulminant*, Veno-occlusive liver disease, Portal vein thrombosis, Cytolytic hepatitis, Cholestasis
SKIN AND SUBCUTANEOUS TISSUE DISORDERS:
Toxic epidermal necrolysis, Stevens-Johnson syndrome, Palmar-plantar erythrodysesthesia syndrome, Radiation recall dermatitis, Skin necrosis, Facial swelling, Petechiae, Macular rash, Rash, Pruritus, Erythema, Skin hyperpigmentation, Hyperhidrosis, nail disorder
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER:
Rhabdomyolysis, Osteomalacia, Rickets, Growth retardation, Myalgia, Arthralgia, Pain in extremity, Muscle twitching
RENAL AND URINARY DISORDERS:
Fanconi syndrome, Tubulointerstitial nephritis, Nephrogenic diabetes insipidus, Phosphaturia, Aminoaciduria, Polyuria, Enuresis, Feeling of residual urine
Fatal outcomes from acute and chronic renal failure have been documented.
REPRODUCTIVE SYSTEM AND BREAST DISORDERS:
Infertility, Ovarian failure, Premature menopause, Amenorrhea, Ovarian disorder, Ovulation disorder, Azoospermia, Oligospermia, Impairment of spermatogenesis, Blood estrogen decreased, Blood gonadotrophin increased
CONGENITAL, FAMILIAL AND GENETIC DISORDERS:
Fetal growth retardation
GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS:
Multi-organ failure*, General physical deterioration, Injection/Infusion site reactions including swelling, inflammation, pain, erythema, tenderness, pruritus; Chest pain, Edema, Mucosal inflammation, Pain, Pyrexia, Chills
* Including fatal outcomes
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