6 ADVERSE REACTIONS
The most clinically significant adverse reactions are anaphylaxis, infection, thrombocytopenia, leukopenia, arthralgia, edema, bradycardia, and abnormal renal and liver function tests.
6.1 Clinical Trials 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 clinical practice.
The safety of ATGAM has been evaluated in 367 patients with renal transplant and 109 patients with aplastic anemia.
The renal transplantation and aplastic anemia patients received a similar dosing regimen, and these data were pooled to obtain the frequencies listed in Tables 1 and 2 below.
The most commonly reported adverse reactions (occurring in greater than 10% of patients) are pyrexia, chills, rash, thrombocytopenia, leukopenia and arthralgia.
| Adverse Reaction*,† | ATGAM |
|---|---|
| Frequency (%) | |
| (N = 476) | |
| Pyrexia | 39.5 |
| Chills | 26.5 |
| Rash | 25.6 |
| Thrombocytopenia | 21.6 |
| Leukopenia | 17.9 |
| Arthralgia | 17.2 |
| Urticaria | 9.2 |
| Headache | 5.3 |
| Pruritus | 4.6 |
| Nausea | 4.2 |
| Infection | 3.4 |
| Vomiting | 3.4 |
| Thrombophlebitis | 3.2 |
| Hypertension | 2.9 |
| Hypotension | 2.9 |
| Diarrhea | 2.9 |
| Abdominal pain upper | 2.7 |
| Chest pain | 2.7 |
| Infusion site pain | 2.1 |
| Edema | 2.1 |
| Bradycardia | 1.5 |
| Back pain | 1.5 |
| Lymphadenopathy | 1.3 |
| Arteriovenous fistula thrombosis | 1.3 |
| Dizziness | 1.1 |
| Dyspnea | 1.1 |
| Tachycardia | 1.1 |
| Liver function test abnormal | 1.0 |
| Adverse Reaction*,† | ATGAM |
|---|---|
| Frequency (%) | |
| (N = 476) | |
| Convulsion | 0.8 |
| Pleural effusion | 0.8 |
| Night sweats | 0.8 |
| Serum sickness | 0.6 |
| Hyperglycemia | 0.6 |
| Stomatitis | 0.6 |
| Renal function test abnormal | 0.6 |
| Herpes simplex | 0.4 |
| Agitation | 0.4 |
| Hiccups | 0.4 |
| Proteinuria | 0.4 |
| Asthenia | 0.4 |
| Malaise | 0.4 |
| Wound dehiscence | 0.4 |
| Anaphylactic reaction | 0.2 |
| Encephalitis | 0.2 |
| Paresthesia | 0.2 |
| Renal artery thrombosis | 0.2 |
| Iliac vein occlusion | 0.2 |
| Laryngospasm | 0.2 |
| Pulmonary edema | 0.2 |
| Dermatitis allergic | 0.2 |
| Periorbital edema | 0.2 |
| Toxic epidermal necrolysis | 0.2 |
6.2 Post-Marketing Experience
The following adverse reactions have been identified during post approval use of ATGAM. Because 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: Hepatitis viral, Localized infection, Systemic infection
Blood and lymphatic system disorders: Anemia, Eosinophilia, Granulocytopenia, Hemolysis, Hemolytic anemia, Neutropenia, Pancytopenia
Psychiatric disorders: Confusional state, Disorientation
Nervous system disorders: Dyskinesia, Syncope, Tremor
Cardiac disorders: Cardiac failure congestive
Vascular disorders: Deep vein thrombosis, Vasculitis
Respiratory, thoracic and mediastinal disorders: Apnea, Cough, Epistaxis, Oropharyngeal pain
Gastrointestinal disorders: Abdominal pain, Gastrointestinal hemorrhage, Gastrointestinal perforation, Oral pain
Skin and subcutaneous tissue disorders: Hyperhidrosis
Musculoskeletal and connective tissue disorders: Flank pain, Muscle rigidity, Myalgia, Pain in extremity
Renal and urinary disorders: Kidney enlargement, Kidney rupture, Renal failure acute
Congenital, familial and genetic disorders: Aplasia
General disorders and administration site conditions: Infusion site erythema, Infusion site swelling, Pain