Summary of the safety profile The safety of bexarotene has been examined in clinical studies of 193 patients with CTCL who received bexarotene for up to 118 weeks and in 420 non-CTCL cancer patients in other studies. In 109 patients with CTCL treated at the recommended initial dose of 300 mg/m2/day, the most commonly reported adverse reactions to Targretin were hyperlipaemia ((primarily elevated triglycerides) 74%), hypothyroidism (29%), hypercholesterolaemia (28%), headache (27%), leucopenia (20%), pruritus (20%), asthenia (19%), rash (16%), exfoliative dermatitis (15%), and pain (12%).
Tabulated list of adverse reactions The following Targretin-related adverse reactions were reported during clinical studies in patients with CTCL (N=109) treated at the recommended initial dose of 300 mg/m2/day. The frequencies of adverse reactions are classified as very common (>1/10), common (>1/100, <1/10), uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000), and very rare (<1/10,000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table 2 Adverse reactions reported in patients in clinical trials System Organ Class (MedDRA terminology*) Very Common Common Uncommon Blood and lymphatic system disorders Leucopenia Lymphoma Like Reaction Lymphadenopathy Hypochromic Anaemia1,2,3 Blood Dyscrasia Purpura Coagulation Disorder Coagulation Time Increased2,3 Anaemia1 Thrombocytopenia3 Thrombocythemia Eosinophilia1 Leukocytosis2 Lymphocytosis Endocrine disorders Hypothyroidism Thyroid Disorder Hyperthyroidism Metabolism and nutrition disorders Hyperlipaemia Hypercholesterolaemia Weight Gain SGOT Increased SGPT Increased Lactic Dehydrogenase Increased Creatinine Increased Hypoproteinaemia Gout Bilirubinemia1,3 BUN Increased1 High Density Lipoprotein Decreased Nervous system disorders Dizziness Hypesthesia Insomnia Ataxia Neuropathy Vertigo Hyperaesthesia Depression1,2,3 Agitation Eye disorders Dry Eyes Eye Disorder Cataract Specified1,2,3 Amblyopia3 Visual Field Defect Corneal Lesion Abnormal Vision1,2,3 Blepharitis Conjunctivitis3 8 System Organ Class (MedDRA terminology*) Very Common Common Uncommon Ear and labyrinth disorders Deafness Ear disorder Cardiac disorders Tachycardia Vascular disorders Peripheral Oedema Haemorrhage Hypertension Oedema3 Vasodilatation1,2,3 Varicose Vein Gastrointestinal disorders Vomiting Diarrhoea1,3 Nausea3 Anorexia1 Liver Function Tests Abnormal Cheilitis2 Dry Mouth2,3 Constipation Flatulence Pancreatitis1,3 Hepatic Failure Gastrointestinal Disorder1 Skin and subcutaneous tissue disorders Exfoliative Dermatitis Pruritus Rash Skin Ulcer Alopecia1 Skin Hypertrophy Skin Nodule Acne Sweating Dry Skin2,3 Skin Disorder Serous Drainage1 Herpes Simplex Pustular Rash Skin Discoloration3 Hair Disorder1 Nail Disorder1,3 Musculoskeletal and connective tissue disorders Bone Pain Arthralgia Myalgia Myasthaenia1 Renal and urinary disorders Albuminuria1,3 Kidney Function Abnormal General disorders and administration site conditions Pain Headache Asthaenia Allergic Reaction Infection Chills1 Abdominal Pain Hormone Level Altered1 Neoplasm Fever1,2,3 Cellulitis Infection Parasitic Mucous Membrane Disorder3 Back Pain1,2,3 Lab Test Abnormal 1: adverse reactions noted with increased frequency when bexarotene was administered at a dose >300mg/m2/day.
2: adverse reactions noted with increased frequency when bexarotene was administered at a dose of 300 mg/m2/day in non-CTCL cancer patients. 3: adverse reactions noted with increased frequency when bexarotene was administered at a dose of >300 mg/m2/day (compared to administration to CTCL patients at 300 mg/m2/day) in non-CTCL cancer patients.
e. used in CTCL at an initial dose >300mg/m2/day or in non-CTCL cancer indications): 9 Newly observed adverse reactions Ecchymosis, petechia, abnormal white blood cells, thromboplastin decreased, abnormal erythrocytes, dehydration, increased gonadotrophic luteinizing hormone, weight loss, increased alkaline phosphatase, increased creatinine phosphokinase, lipase increased, hypercalcaemia, migraine, peripheral neuritis, paraesthesia, hypertonia, confusion, anxiety, emotional lability, somnolence, decreased libido, nervousness, night blindness, nystagmus, lacrimation disorder, tinnitus, taste perversion, chest pain, arrhythmia, peripheral vascular disorder, generalized oedema, haemoptysis, dyspnoea, increased cough, sinusitis, pharyngitis, dysphagia, mouth ulceration, oral moniliasis, stomatitis, dyspepsia, thirst, abnormal stools, eructation, vesicobullous rash, maculopapular rash, leg cramps, haematuria, flu syndrome, pelvic pain, and body odour.
Single observations of the following were also reported: bone marrow depression, decreased prothrombin, decreased gonadotrophic luteinizing hormone, increased amylase, hyponatraemia, hypokalaemia, hyperuricaemia, hypocholesterolaemia, hypolipaemia, hypomagnesaemia, abnormal gait, stupor, circumoral paraesthesia, abnormal thinking, eye pain, hypovolaemia, subdural haematoma, congestive heart failure, palpitation, epistaxis, vascular anomaly, vascular disorder, pallor, pneumonia, respiratory disorder, lung disorder, pleural disorder, cholecystitis, liver damage, jaundice, cholestatic jaundice, melaena, vomiting, laryngismus, tenesmus, rhinitis, increased appetite, gingivitis, herpes zoster, psoriasis, furunculosis, contact dermatitis, seborrhoea, lichenoid dermatitis, arthritis, joint disorder, urinary retention, impaired urination, polyuria, nocturia, impotence, urine abnormality, breast enlargement, carcinoma, photosensitivity reaction, face oedema, malaise, viral infection, enlarged abdomen.
The majority of adverse reactions were noted at a higher incidence at doses greater than 300 mg/m2/day. Generally, these resolved without sequelae on dose reduction or withdrawal of treatment. However, among a total of 810 patients, […]