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 rates ≥ 5% from two 12-week placebo-controlled studies in patients with moderate to moderately severe chronic pain by dose (N=1811).
|
ULTRAM ER |
Placebo |
MedDRA Preferred Term |
100 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) |
Nausea |
61 (15.1) |
90 (22.5) |
102 (25.5) |
53 (26.2) |
32 (7.9) |
Constipation |
49 (12.2) |
68 (17.0) |
85 (21.3) |
60 (29.7) |
17 (4.2) |
Headache |
49 (12.2) |
62 (15.5) |
46 (11.5) |
32 (15.8) |
43 (10.6) |
Somnolence |
33 (8.2) |
45 (11.3) |
29 (7.3) |
41 (20.3) |
7 (1.7) |
Flushing |
31 (7.7) |
40 (10.0) |
35 (8.8) |
32 (15.8) |
18 (4.4) |
Pruritus |
25 (6.2) |
34 (8.5) |
30 (7.5) |
24 (11.9) |
4 (1.0) |
Vomiting |
20 (5.0) |
29 (7.3) |
34 (8.5) |
19 (9.4) |
11 (2.7) |
Insomnia |
26 (6.5) |
32 (8.0) |
36 (9.0) |
22 (10.9) |
13 (3.2) |
Dry Mouth |
20 (5.0) |
29 (7.3) |
39 (9.8) |
18 (8.9) |
6 (1.5) |
Diarrhea |
15 (3.7) |
27 (6.8) |
37 (8.5) |
10 (5.0) |
17 (4.2) |
Asthenia |
14 (3.5) |
24 (6.0) |
26 (6.5) |
13 (6.4) |
7 (1.7) |
Postural hypotension |
7 (1.7) |
17 (4.3) |
8 (2.0) |
11 (5.4) |
9 (2.2) |
Sweating increased |
6 (1.5) |
8 (2.0) |
15 (3.8) |
13 (6.4) |
1 (0.2) |
Anorexia |
3 (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
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