DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Ifex (Ifosfamide) - Side Effects and Adverse Reactions

 
 



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 1 (any)

-- 2

Leukopenia

<1 x 103/µL

43.5%

(267/614)

Thrombocytopenia 3 (any)

-- 4

Thrombocytopenia, 

50 x 103/µL

4.8%

(35/729)

Anemia 5

37.9%

(202/533)

METABOLISM AND NUTRITION DISORDERS

Anorexia

1.1%

(15/1317)

NERVOUS SYSTEM DISORDERS

Central nervous system toxicity 6 , 7

15.4%

(154/1001)

Peripheral neuropathy

0.4%

(5/1317)

CARDIAC DISORDERS

Cardiotoxicity 8

0.5%

(7/1317)

VASCULAR DISORDERS

Hypotention 9

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 10

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

-- 11

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 12

--

Renal structural damage

--

GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS

Phlebitis 13

2.8%

(37/1317)

Neutropenic fever 14

1.0%

(13/1317)

Fatigue

0.3%

(4/1317)

Malaise

Unable to calculate

1 The following adverse reaction terms have been reported for leukopenia: neutropenia, granulocytopenia, lymphopenia, and pancytopenia. For neutropenic fever, see below.
2 The frequency category of leukopenia is based on the frequency of leukopenia <3 x 103/µL [42.5% (150/353) not shown in table] and <1 x 103/µL; a relevant percentage ratio cannot be calculated for the pooled data and thus the conservative frequency category of “Very common” was included in the table.
3 Thrombocytopenia may also be complicated by bleeding. Bleeding with fatal outcome has been reported.
4 Frequency of thrombocytopenia is based on the frequency of thrombocytopenia <100 x 103/µL [12.2% (24/196) not shown in table] and <50 x 103/µL; a relevant percentage ratio cannot be calculated from the pooled data and thus the conservative frequency of “Very common” was included in the table.
5 Includes cases reported as anemia and decrease in hemoglobin/hematocrit.
6 Encephalopathy with coma and death has been reported.
7 Central nervous system toxicity was reported to be manifested by the following signs and symptoms: Abnormal behavior, Affect lability Aggression, Agitation, Anxiety, Aphasia, Asthenia, Ataxia, Cerebellar syndrome, Cerebral function deficiency, Cognitive disorder, Coma, Confusional state, Convulsions, Cranial nerve dysfunction, Depressed state of consciousness, Depression, Disorientation, Dizziness, Electroencephalogram abnormal, Encephalopathy, Flat affect. Hallucinations, Headache, Ideation, Lethargy, Memory impairment, Mood change, Motor dysfunction, Muscle spasms, Myoclonus, Progressive loss of brainstem reflexes, Psychotic reaction, Restlessness, Somnolence, Tremor, Urinary incontinence.
8 Cardiotoxicity was reported as congestive heart failure, tachycardia, pulmonary edema. Fatal outcome has been reported.
9 Hypotension leading to shock and fatal outcome has been reported.
10 Hepatotoxicity was reported as increases in liver enzymes, i.e., serum alanine aminotransferase, serum aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase and lactate dehydrogenase, increased bilirubin, jaundice, hepatorenal syndrome.
11 Frequency of hemorrhagic cystitis is estimated based on the frequency of hematuria. Reported symptoms of hemorrhagic cystitis included dysuria and pollakiuria. See also Post-marketing Adverse Reactions (6.2).
12 Renal dysfunction was reported to be manifested as: Renal failure (including acute renal failure, irreversible renal failure; fatal outcomes have been reported), Serum creatinine increased, BUN increased, Creatinine clearance decreased, Metabolic acidosis, Anuria, Oliguria, Glycosuria, Hyponatremia, Uremia, Creatinine clearance increased. Renal structural damage was reported to be manifested as: Acute tubular necrosis, renal parenchymal damage, Enzymuria, Cylindruria, Proteinuria.
13 Includes cases reported as phlebitis and irritation of the venous walls.
14 Frequency of neutropenic fever: Includes cases reported as granulocytopenic fever.

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

Drug label data at the top of this Page last updated: 2014-08-28

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017