Serious and Otherwise Important Adverse Reactions
The following serious and otherwise important adverse reactions are discussed in greater detail in the WARNINGS AND PRECAUTIONS section of the label:
- Tendinopathy and Tendon Rupture [see WARNINGS AND PRECAUTIONS]
- QT Prolongation [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Other Serious and Sometimes Fatal Reactions [see WARNINGS AND PRECAUTIONS]
- Central Nervous System Effects [see WARNINGS AND PRECAUTIONS]
- Clostridium Difficile-Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
- Peripheral Neuropathy that may be irreversible [see WARNINGS AND PRECAUTIONS]
- Photosensitivity/Phototoxicity [see WARNINGS AND PRECAUTIONS]
- Development of Drug Resistant Bacteria [see WARNINGS AND PRECAUTIONS]
Clinical Trial Experience
Because clinical trials are conducted under 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 practice.
The data described below reflect exposure to AVELOX in 14981 patients in 71 active controlled Phase II-IV clinical trials in different indications [see INDICATIONS AND USAGE]. The population studied had a mean age of 50 years (approximately 73% of the population was <65 years of age), 50% were male, 63% were Caucasian, 12% were Asian and 9% were Black. Patients received AVELOX 400 mg once daily PO, IV, or sequentially (IV followed by PO). Treatment duration was usually 6-10 days, and the mean number of days on therapy was 9 days.
Discontinuation of AVELOX due to adverse events occurred in 5.0% of patients overall, 4.1% of patients treated with 400 mg PO, 3.9% with 400 mg IV and 8.2% with sequential therapy 400 mg PO/IV. The most common adverse events leading to discontinuation with the 400 mg PO doses were nausea (0.8%), diarrhea (0.5%), dizziness (0.5%), and vomiting (0.4%). The most common adverse event leading to discontinuation with the 400 mg IV dose was rash (0.5%). The most common adverse events leading to discontinuation with the 400 mg IV/PO sequential dose were diarrhea (0.5%), pyrexia (0.4%).
Adverse reactions occurring in ≥1% of AVELOX-treated patients and less common adverse reactions, occurring in 0.1 to <1% of AVELOX-treated patients, are shown in Tables 2 and Table 3, respectively. The most common adverse drug reactions (≥3%) are nausea, diarrhea, headache, and dizziness.
Table 2 : Common (≥ 1.0%) Adverse Reactions Reported in Active-Controlled Clinical Trials with AVELOX
System Organ Class | Adverse Reactionsa | % (N=14,981) |
Blood and Lymphatic System Disorders | Anemia | 1.1 |
Gastrointestinal Disorders | Nausea | 6.9 |
Diarrhea | 6.0 | |
Vomiting | 2.4 | |
Constipation | 1.9 | |
Abdominal pain | 1.5 | |
Abdominal pain upper | 1.1 | |
Dyspepsia | 1.0 | |
General Disorders and Administration Site Conditions | Pyrexia | 1.1 |
Investigations | Alanine aminotransferase increased | 1.1 |
Metabolism and Nutritional Disorder | Hypokalemia | 1 |
Nervous System Disorders | Headache | 4.2 |
Dizziness | 3.0 | |
Psychiatric Disorders | Insomnia | 1.9 |
a MedDRA Version 12.0 |
Table 3 : Less Common (0.1 to <1.0%) Adverse Reactions Reported in Active-Controlled Clinical Trials with AVELOX (N=14,981)
System Organ Class | Adverse Reactionsa |
Blood and Lymphatic System Disorders | Thrombocythemia Eosinophilia Neutropenia Thrombocytopenia Leukopenia Leukocytosis |
Cardiac Disorders | Atrial fibrillation Palpitations Tachycardia Cardiac failure congestive Angina pectoris Cardiac failure Cardiac arrest Bradycardia |
Ear and Labyrinth Disorders | Vertigo Tinnitus |
Eye Disorders | Vision blurred |
Gastrointestinal Disorders | Dry mouth Abdominal discomfort Flatulence Abdominal distention Gastritis Gastroesophageal reflux disease |
General Disorders and Administration Site Conditions | Fatigue Chest pain Asthenia Edema peripheral Pain Malaise Infusion site extravasation Edema Chills Chest discomfort Facial pain |
Hepatobiliary disorders | Hepatic function abnormal |
Infections and Infestations | Vulvovaginal candidiasis Oral candidiasis Vulvovaginal mycotic infection Candidiasis Vaginal infection Oral fungal infection Fungal infection Gastroenteritis |
Investigations | Aspartate aminotransferase increased Gamma-glutamyltransferase increased Blood alkaline phosphatase increased Hepatic enzyme increased Electrocardiogram QT prolonged Blood lactate dehydrogenase increased Platelet count increased Blood amylase increased Blood glucose increased Lipase increased Hemoglobin decreased Blood creatinine increased Transaminases increased White blood cell count increased Blood urea increased Liver function test abnormal Hematocrit decreased Prothrombin time prolonged Eosinophil count increased Activated partial thromboplastin time prolonged Blood bilirubin increased Blood triglycerides increased Blood uric acid increased Blood pressure increased |
Metabolism and Nutrition Disorders | Hyperglycemia Anorexia Hypoglycemia Hyperlipidemia Decreased appetite Dehydration |
Musculoskeletal and Connective Tissue Disorders | Back pain Pain in extremity Arthralgia Myalgia Muscle spasms Musculoskeletal chest pain Musculoskeletal pain |
Nervous System Disorders | Dysgeusia Somnolence Tremor Lethargy Paresthesia Tension headache Hypoesthesia Syncope |
Psychiatric Disorders | Anxiety Confusional state Agitation Depression Nervousness Restlessness Hallucination Disorientation |
Renal and Urinary Disorders | Renal failure Dysuria Renal failure acute |
Reproductive System and Breast Disorders | Vulvovaginal pruritus |
Respiratory, Thoracic, and Mediastinal Disorders | Dyspnea Asthma Wheezing Bronchospasm |
Skin and Subcutaneous Tissue Disorders | Rash Pruritus Hyperhidrosis Erythema Urticaria Dermatitis allergic Night sweats |
Vascular disorders | Hypertension Hypotension Phlebitis |
a MedDRA Version 12.0 |
Laboratory Changes
Changes in laboratory parameters, without regard to drug relationship, which are not listed above and which occurred in ≥ 2% of patients and at an incidence greater than in controls included: increases in MCH, neutrophils, WBCs, PT ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreases in hemoglobin, RBCs, neutrophils, eosinophils, basophils, PT ratio, glucose, pO2, bilirubin, and amylase. It cannot be determined if any of the above laboratory abnormalities were caused by the drug or the underlying condition being treated.
Postmarketing Experience
Table 4 lists adverse reactions that have been identified during post-approval use of AVELOX. Because these events 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.
Table 4: Postmarketing Reports of Adverse Drug Reactions
System/Organ Class | Adverse Reaction |
Blood and Lymphatic System Disorders | Agranulocytosis Pancytopenia [see WARNINGS AND PRECAUTIONS] |
Cardiac Disorders | Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions) |
Ear and Labyrinth Disorders | Hearing impairment, including deafness (reversible in majority of cases) |
Eye Disorders | Vision loss (especially in the course of CNS reactions, transient in majority of cases) |
Hepatobiliary Disorders | Hepatitis (predominantly cholestatic) Hepatic failure (including fatal cases) Jaundice Acute hepatic necrosis [see WARNINGS AND PRECAUTIONS] |
Immune System Disorders | Anaphylactic reaction Anaphylactic shock Angioedema (including laryngeal edema) [see WARNINGS AND PRECAUTIONS] |
Musculoskeletal and Connective Tissue Disorders | Tendon rupture [see WARNINGS AND PRECAUTIONS] |
Nervous System Disorders | Altered coordination Abnormal gait [see WARNINGS AND PRECAUTIONS] Myasthenia gravis (exacerbation of) [see WARNINGS AND PRECAUTIONS] Muscle weakness Peripheral neuropathy (that may be irreversible), polyneuropathy [see WARNINGS AND PRECAUTIONS] |
Psychiatric Disorders | Psychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts [see WARNINGS AND PRECAUTIONS] |
Renal and Urinary Disorders | Renal dysfunction Interstitial nephritis [see WARNINGS AND PRECAUTIONS] |
Respiratory, Thoracic and Mediastinal Disorders | Allergic pneumonitis [see WARNINGS AND PRECAUTIONS] |
Skin and Subcutaneous Tissue Disorders | Photosensitivity/phototoxicity reaction [see WARNINGS AND PRECAUTIONS] Stevens-Johnson syndrome Toxic epidermal necrolysis [see WARNINGS AND PRECAUTIONS] |