8.1 Adverse Reaction Overview
The following adverse reactions have been reported in association with ALDACTONE (spironolactone):
Blood and lymphatic system disorders: Leukopenia (including agranulocytosis), thrombocytopenia, anemia.
Gastrointestinal disorders: Diarrhea and cramping, gastric bleeding, gastritis, nausea, ulceration, vomiting.
General disorders and administration site conditions: Malaise, ataxia.
Hepatobiliary disorders: Abnormal hepatic function. A few cases of mixed cholestatic/hepatocellular toxicity, with one reported fatality, have been reported with spironolactone administration.
Immune system disorders: Drug fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis, pruritus, rash.
Metabolism and nutrition disorders: Electrolyte disturbances, hyperkalemia.
Musculoskeletal and connective tissue disorders: Leg cramps, muscle spasms, rhabdomyolysis, myalgia, weakness
Nervous system/psychiatric disorders: Mental confusion, ataxia, headache, drowsiness, lethargy, dizziness, change in libido.
Renal and urinary disorders: Renal dysfunction (including acute renal failure).
Reproductive system and breast disorders: gynecomastia* (see 7 WARNINGS and PRECAUTIONS-, Carcinogenesis and Mutagenesis), erectile dysfunction (inability to achieve or maintain erection), abnormal semen (decreased motility and sperm count), irregular menses or amenorrhea, postmenopausal bleeding, benign breast neoplasm, breast pain, breast carcinoma (including male patients)
Respiratory, thoracic and mediastinal disorders: Dysphonia, dyspnea.
Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, hypertrichosis.
*Gynecomastia may develop with the use of spironolactone, and physicians should be advised of its possible occurrence. Development of gynecomastia is related to both dose and duration of therapy. If gynecomastia develops, discontinue the drug. Gynecomastia is usually reversible when spironolactone is discontinued, although in rare instances some breast enlargement may persist.
Adverse reactions are usually reversible upon discontinuation of the drug.
8.5 Post-Market Adverse Reactions
The frequency of the event listed in Table 3 are evaluated as very rare: (<1/10,000; <0.01%)
Blood and lymphatic system disorders |
Disseminated intravascular coagulation, Bone marrow failure, Lymphadenopathy Neutropenia Pancytopenia, Lymphopenia, Splenomegaly, Coagulopathy Eosinophilia |
Cardiac disorders |
Cardiac arrest, Cardio-respiratory/Sinus arrest, Torsade de pointes, Atrioventricular block (1st/2nd degree, complete), Bundle branch block (left), Sinoatrial block, Myocardial infarction, Myocardial ischaemia, Defect conduction intraventricular, Ventricular/Supraventricular tachycardia, Ventricular/Supraventricular extrasystoles, Cardiomegaly, Cardiomyopathy Cardiogenic shock, Sick sinus syndrome, Cardiac failure, Ventricular fibrillation, Atrial fibrillation/flutter, Tachycardia, Coronary artery disease, Cardiovascular disorder, Sinus bradycardia, Angina unstable, Angina pectoris, Tricuspid valve incompetence, Mitral valve incompetence, Palpitations, Arrhythmia, Pericardial effusion, Cyanosis, Coronary artery occlusion |
Ear and labyrinth disorders |
Deafness, Hypoacusis, Vertigo, Ear disorder, Ear pain, Tinnitus |
Endocrine disorders |
Hyperthyroidism, Hypothyroidism, Inappropriate antidiuretic hormone secretion |
Eye disorders |
Diabetic retinopathy, Cataract, Vision blurred, Visual impairment |
Gastrointestinal disorders |
Pancreatitis, GI haemorrhage, Varices oesophageal, Intestinal obstruction, Large intestine polyp, Diverticulum, Hiatus hernia, Ileus paralytic, Melaena, Coeliac disease, Gastrooesophageal reflux disease, Haemorrhoids, Duodenitis, Retching, Gastric disorder, Gastrointestinal disorder, Abdominal distension, Dyspepsia, Dysphagia, Constipation |
General disorders and administration site conditions |
Sudden death, Multi-organ failure, Hypothermia, Peripheral swelling, Face oedema, Chest pain/discomfort, General physical health deterioration, Gait disturbance, Swelling, Chills, Pain, Asthenia, Fatigue |
Hepatobiliary disorders |
Hepatitis, Hepatic failure/necrosis/cirrhosis/steatosis Portal hypertension, Hepatorenal syndrome, Portal vein thrombosis Jaundice cholestatic, Hepatic Hepatomegaly, Cholecystitis, Cholelithiasis Jaundice, Hyperbilirubinaemia, Gallbladder disorder |
Immune system |
Anaphylactic shock |
Infections and infestations |
Septic shock, Pneumonia, Sepsis, Respiratory tract infection, Empyema, Bronchitis, Pyelonephritis, Bacterial/fungal/viral infection, Urinary tract infection, Herpes zoster, Diverticulitis, Gastroenteritis, Mastitis, Cystitis, Cellulitis, Sinusitis, Onychomycosis Infection |
Injury, poisoning and procedural complications |
Head injury, Fall, Ankle fracture, Lower limb fracture, Contusion, Road traffic accident, Injury |
Investigations |
Electrocardiogram QT prolonged, Electrocardiogram QRS complex prolonged, Electrocardiogram abnormal, Blood creatinine increased, Blood pressure increased/decreased, , Blood bilirubin increased, Transaminases increased, Aspartate aminotransferase increased, International normalised ratio increased, Alanine aminotransferase increased, Gamma-glutamyltransferase increased, Liver function test abnormal, Blood alkaline phosphatase increased, Haematocrit decreased, Blood glucose increased/decreased, Blood lactate dehydrogenase increased, Blood potassium decreased, Amylase increased, Blood chloride decreased, Occult blood positive, Blood aldosterone increased, Blood uric acid increased, Urine output decreased, White blood cell count increased, Eosinophil count increased, Weight decreased/increased |
Metabolism and nutrition disorders |
Diabetes mellitus, Hypo/hyperglycaemia, Fluid retention, Hypovolaemia Dehydration, Hypomagnesaemia, Hypo/hypercalcaemia, Metabolic alkalosis Hyperammonaemia, Gout, Malnutrition, Obesity, Decreased appetite |
Musculoskeletal and connective tissue disorders |
Rhabdomyolysis, Systemic lupus erythematosus/lupus like syndrome, Rheumatoid arthritis, Osteoarthritis, Muscle haemorrhage, Osteopenia, Osteoporosis, Muscle spasms/weakness/pain, Bursitis, Limb discomfort, Arthropathy, Myalgia, Arthralgia, Back pain, Pain in extremity |
Neoplasms benign, malignant and unspecified |
Pancreatic carcinoma, Lung neoplasm malignant, Hepatic cancer. Neoplasm malignant, Colon cancer, Gastrointestinal carcinoma, Lymphoma |
Nervous system disorders |
Cerebral haemorrhage, Cerebral infarction, Cerebrovascular accident, Coma, Depressed/altered level of consciousness, Transient ischaemic attack, Hepatic encephalopathy, Hydrocephalus, Encephalopathy, Cerebral atrophy, Paralysis, Convulsion, Parkinson's disease, VIIth nerve paralysis, Diabetic neuropathy, Neuropathy peripheral, Syncope, Presyncope, Dementia, Memory impairment, Cognitive disorder, Paraesthesia, Hypoaesthesia, Dysarthria, Stupor, Ageusia, Asterixis, Tremor, Disturbance in attention, Hypokinesia, Nystagmus, Speech disorder, Balance disorder |
Psychiatric disorders |
Suicide/Suicide attempt/suicidal ideation, Hallucination, Depression, Psychotic disorder, Abnormal behaviour, Apathy, Visual disorientation, Delirium, Insomnia, Anxiety, Agitation, Drug abuse |
Renal and urinary disorders |
Anuria, Chronic Renal failure, Renal tubular necrosis, Tubulointerstitial nephritis, Nephropathy toxic, Diabetic nephropathy, Prerenal failure, Proteinuria, Nephrolithiasis, Renal cyst, Urinary retention, Haematuria, Dysuria, Chromaturia, Pollakiuria, Oliguria, Polyuria |
Reproductive system and breast disorders |
Breast mass, Breast swelling Genital haemorrhage, Uterine disorder |
Respiratory, thoracic and mediastinal disorders |
Respiratory arrest/disorder/distress/failure Pulmonary embolism, Pulmonary oedema, Pulmonary hypertension Atelectasis, Bronchospasm, Pneumonitis, Interstitial lung disease, Pneumonia aspiration, Asthma, Wheezing, Pleural effusion, Chronic obstructive pulmonary disease, Haemoptysis, Sleep apnoea syndrome, Hypoxia, Lung disorder, Oropharyngeal pain, Epistaxis, Cough, Rales |
Skin and subcutaneous tissue disorders |
Toxic skin eruption, Angioedema, Skin necrosis/exfoliation, Lichenoid keratosis, Drug eruption, Dermatitis bullous/exfoliative, Erythema multiforme, Photosensitivity reaction, Hyperhidrosis, Lichen planus, Skin ulcer, Eczema, Pemphigoid, Dermatitis, Erythema, Purpura, Blister, Dry skin, Skin discolouration, Cold sweat |
Surgical and medical procedures |
Surgery, Hysterectomy, Knee arthroplasty |
Vascular disorders |
Circulatory collapse, Hypovolaemic shock, Shock haemorrhagic, Shock, Infarction, Haemorrhage, Thrombosis, Hypotension, Orthostatic hypotension, Peripheral arterial occlusive disease, Arteriosclerosis, Deep vein thrombosis, Peripheral vascular disorder, Peripheral venous disease, Phlebitis, Angiopathy, Lymphoedema, Haematoma, Flushing, Hot flush |