FDA label 3fbb8494-fe79-242a-e054-00144ff88e88

WARNINGS

ADVERSE REACTIONS ULTRAM ER was administered to a total of 3108 patients during studies conducted in the U.S. These included four double-blind studies in patients with osteoarthritis and/or chronic low back pain and one open-label study in patients with chronic non-malignant pain. A total of 901 patients were 65 years or older. The frequency of adverse events generally increased with doses from 100 mg to 400 mg in the two pooled, twelve-week, randomized, double-blind, placebo-controlled studies in patients with chronic non-malignant pain (see Table 2 ). Table 2: Incidence (%) of patients with adverse event rates5% from two 12-week placebo-controlled studies in patients with moderate to moderately severe chronic pain by dose (N=1811). ULTRAM ER PlaceboMedDRA Preferred Term100 mg (N=403) n (%)200 mg (N=400) n (%)300 mg (N=400) n (%)400 mg (N=202) n (%)(N=406) n (%) Dizziness (not vertigo)64 (15.9)81 (20.3)90 (22.5)57 (28.2)28 (6.9)Nausea61 (15.1)90 (22.5)102 (25.5)53 (26.2)32 (7.9)Constipation49 (12.2)68 (17.0)85 (21.3)60 (29.7)17 (4.2)Headache49 (12.2)62 (15.5)46 (11.5)32 (15.8)43 (10.6)Somnolence33 (8.2)45 (11.3)29 (7.3)41 (20.3)7 (1.7)Flushing31 (7.7)40 (10.0)35 (8.8)32 (15.8)18 (4.4)Pruritus25 (6.2)34 (8.5)30 (7.5)24 (11.9)4 (1.0)Vomiting20 (5.0)29 (7.3)34 (8.5)19 (9.4)11 (2.7)Insomnia26 (6.5)32 (8.0)36 (9.0)22 (10.9)13 (3.2)Dry Mouth20 (5.0)29 (7.3)39 (9.8)18 (8.9)6 (1.5)Diarrhea15 (3.7)27 (6.8)37 (8.5)10 (5.0)17 (4.2)Asthenia14 (3.5)24 (6.0)26 (6.5)13 (6.4)7 (1.7)Postural hypotension7 (1.7)17 (4.3)8 (2.0)11 (5.4)9 (2.2)Sweating increased6 (1.5)8 (2.0)15 (3.8)13 (6.4)1 (0.2)Anorexia3 (0.7)7 (1.8)21 (5.3)12 (5.9)1 (0.2)The following adverse events were reported from all the chronic pain studies (N=3108). The lists below include adverse events not otherwise noted in Table 2. Adverse events with incidence rates of 1.0% to <5.0% Eye disorders: vision blurred Gastrointestinal disorders: abdominal pain upper, dyspepsia, abdominal pain, sore throat General disorders: weakness, pain, feeling hot, influenza like illness, fall, rigors, lethargy, pyrexia, chest pain Infections and infestations: nasopharyngitis, upper respiratory tract infection, sinusitis, influenza, gastroenteritis viral, urinary tract infection, bronchitis Investigations: blood creatine phosphokinase increased, weight decreased Metabolism and nutrition disorders: appetite decreased Musculoskeletal, connective tissue and bone disorders: arthralgia, back pain, pain in limb, neck pain Nervous system disorders: tremor, paresthesia, hypoesthesia Psychiatric disorders: nervousness, anxiety, depression, restlessness Respiratory, thoracic and mediastinal disorders: sneezing, cough, rhinorrhea, nasal congestion, dyspnea, sinus congestion Skin and subcutaneous tissue disorders: sweating increased, dermatitis Vascular disorders: hot flushes, vasodilatation Adverse events with incidence rates of 0.5% to <1.0% and serious adverse events reported in at least 2 patients. Cardiac disorders: palpitations, myocardial infarction Ear and labyrinth disorders: tinnitus, vertigo Gastrointestinal disorders: flatulence, toothache, constipation aggravated, appendicitis, pancreatitis General disorders: feeling jittery, edema lower limb, shivering, joint swelling, malaise, drug withdrawal syndrome, peripheral swelling Hepato-biliary disorders: cholelithiasis, cholecystitis Infections and infestations: cellulitis, ear infection, gastroenteritis, pneumonia, viral infection Injury and poisoning: joint sprain, muscle injury Investigations: alanine aminotransferase increased, blood pressure increased, aspartate aminotransferase increased, heart rate increased, blood glucose increased, liver function tests abnormal , Musculoskeletal, connective tissue and bone disorders: muscle cramps, muscle spasms, joint stiffness, muscle twitching, myalgia, osteoarthritis aggravated Nervous system disorders: migraine, sedation, syncope, disturbance in attention, dizziness aggravated Psychiatric disorders: euphoric mood, irritability, libido decreased, sleep disorder, agitation, disorientation, abnormal dreams Renal and urinary disorders: difficulty in micturition, urinary frequency, hematuria, dysuria, urinary retention Respiratory, thoracic and mediastinal disorders: yawning Skin and subcutaneous tissue disorders: contusion, piloerection, clamminess, night sweats, urticaria Vascular disorders: hypertension aggravated, hypertension, peripheral ischemia