6 ADVERSE REACTIONS The most common adverse reactions are (incidence ≥ 5%) chromaturia, nausea, vomiting and abdominal pain, alanine aminotransferase increased, arthralgia and neutropenia. (5.1, 6) To report SUSPECTED ADVERSE REACTIONS, contact ApoPharma Inc. at: Telephone: 1-866-949-0995 Email: [email protected]
or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trial Experience The following adverse reactions are also discussed in other sections of the labeling: Agranulocytosis/Neutropenia [see Warnings and Precautions (5.1)]. Elevated ALT (5.3), Decreased plasma zinc concentrations (5.3). 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. Adverse reaction information for Ferriprox represents the pooled data collected from 642 patients who participated in single arm or active-controlled clinical studies. The most serious adverse reaction reported in clinical trials with Ferriprox was agranulocytosis [see Warnings and Precautions (5.1)]. The most common adverse reactions reported during clinical trials were chromaturia, nausea, vomiting, abdominal pain, alanine aminotransferase increased, arthralgia and neutropenia. The table below lists the adverse drug reactions that occurred in at least 1% of patients treated with Ferriprox in clinical trials. Table 2: Adverse drug reactions occurring in ≥ 1% of 642 Ferriprox-treated patients Body System % Subjects Preferred Term BLOOD AND LYMPHATIC SYSTEM DISORDERS Neutropenia 6.2 Agranulocytosis 1.7 GASTROINTESTINAL DISORDERS Nausea 12.6 Abdominal pain/discomfort 10.4 Vomiting 9.8 Diarrhea 3.0 Dyspepsia 2.0 INVESTIGATIONS Alanine Aminotransferase increased 7.5 Neutrophil count decreased 7.3 Weight increased 1.9 Aspartate Aminotransferase increased 1.2 METABOLISM AND NUTRITION DISORDERS Increased appetite 4.0 Decreased appetite 1.1 MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS Arthralgia 9.8 Back pain 2.0 Pain in extremity 1.9 Arthropathy 1.4 NERVOUS SYSTEM DISORDERS Headache 2.5 URINARY DISORDERS Chromaturia 14.6 Gastrointestinal symptoms such as nausea, vomiting, and abdominal pain were the most frequent adverse reactions reported by patients participating in clinical trials and led to the discontinuation of Ferriprox therapy in 1.6% of patients. Chromaturia (reddish/brown discoloration of the urine) is a result of the excretion of the iron in the urine. 6.2 Postmarketing Experience The following additional adverse reactions have been reported in patients receiving Ferriprox. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Blood and lymphatic system disorders: thrombocytosis, pancytopenia. Cardiac disorders: atrial fibrillation, cardiac failure. Congenital, familial and genetic disorders: hypospadias. Eye disorders: diplopia, papilledema, retinal toxicity. Gastrointestinal disorders: enterocolitis, rectal hemorrhage, gastric ulcer, pancreatitis, parotid gland enlargement. General disorders and administration site conditions: chills, pyrexia, edema peripheral, multi-organ failure. Hepatobiliary disorders : jaundice, hepatomegaly. Immune system disorders: anaphylactic shock, hypersensitivity. Infections and infestations: cryptococcal cutaneous infection, enteroviral encephalitis, pharyngitis, pneumonia, sepsis, furuncle, infectious hepatitis, rash pustular, subcutaneous abscess. Investigations: blood bilirubin increased, blood creatinine phosphokinase increased. Metabolism and nutrition disorders: metabolic acidosis, dehydration. Musculoskeletal and connective tissue disorders: myositis, chondropathy, trismus. Nervous system disorders: cerebellar syndrome, cerebral hemorrhage, convulsion, gait disturbance, intracranial pressure increased, psychomotor skills impaired, pyramidal tract syndrome, somnolence. Psychiatric disorders: bruxism, depression, obsessive-compulsive disorder. Renal disorders: glycosuria, hemoglobinuria. Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome, epistaxis, hemoptysis, pulmonary embolism. Skin, subcutaneous tissue disorders: hyperhidrosis, periorbital edema, photosensitivity reaction, pruritis, urticaria, rash, Henoch-Schönlein purpura. Vascular disorders: hypotension, hypertension.