TRAMADOL HYDROCHLORIDE
Generic: TRAMADOL HYDROCHLORIDE
Basic Information
Manufacturer
Medsource Pharmaceuticals
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
1278980b-4068-df57-e063-6394a90a8742
Indications & Usage
1 INDICATIONS AND USAGE Tramadol hydrochloride extended-release tablet is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.
Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosages or duration, and because of the greater risks of overdose and death with extended-release opioid formulations [see Warnings and Precautions ( 5.1 )] , reserve tramadol hydrochloride extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
Tramadol hydrochloride extended-release tablet is not indicated as an as-needed (prn) analgesic.
Tramadol hydrochloride extended-release tablets are an opioid agonist indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.
( 1 ) Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosages or duration, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve tramadol hydrochloride extended-release tablet for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain.
( 1 ) Tramadol hydrochloride extended-release tablets is not indicated as an as-needed (prn) analgesic.
( 1 )
Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosages or duration, and because of the greater risks of overdose and death with extended-release opioid formulations [see Warnings and Precautions ( 5.1 )] , reserve tramadol hydrochloride extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
Tramadol hydrochloride extended-release tablet is not indicated as an as-needed (prn) analgesic.
Tramadol hydrochloride extended-release tablets are an opioid agonist indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.
( 1 ) Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosages or duration, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve tramadol hydrochloride extended-release tablet for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain.
( 1 ) Tramadol hydrochloride extended-release tablets is not indicated as an as-needed (prn) analgesic.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions ( 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children [see Warnings and Precautions ( 5.6 )] Opioid-Induced Hyperalgesia and Allodynia [See Warnings and Precautions ( 5.8 )] Serotonin Syndrome [see Warnings and Precautions ( 5.9 )] Seizures [see Warnings and Precautions ( 5.10 )] Suicide [see Warnings and Precautions ( 5.11 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.13 )] Severe Hypotension [see Warnings and Precautions ( 5.14 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.16 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.17 )] Withdrawal [see Warnings and Precautions ( 5.18 )] Most common adverse reactions (≥10% and ≥2 x placebo rate): Dizziness, constipation, nausea, headache, somnolence, flushing, pruritus, vomiting, insomnia, dry mouth.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc.
at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 practice.
Tramadol hydrochloride extended-release tablet 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 reactions 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 1).
The most common adverse reactions from Table 1 occurring in ≥10% and ≥2 x placebo rate of the patients treated with tramadol hydrochloride extended-release tablets are dizziness (not vertigo), nausea, constipation, headache, somnolence, flushing, pruritus, vomiting, insomnia, and dry mouth.
Table 1: Incidence (%) of patients with adverse reaction rates ≥ 5% from two 12-week placebo-controlled studies in patients with moderate to moderately severe chronic pain by dose (N=1811).
MedDRA Preferred Term Tramadol Hydrochloride Extended-Release Tablets Placebo 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 (16) 81 (20) 90 (23) 57 (28) 28 (7) Nausea 61 (15) 90 (23) 102 (26) 53 (26) 32 (8) Constipation 49 (12) 68 (17) 85 (21) 60 (30) 17 (4) Headache 49 (12) 62 (16) 46 (12) 32 (16) 43 (11) Somnolence 33 (8) 45 (11) 29 (7) 41 (20) 7 (2) Flushing 31 (8) 40 (10) 35 (9) 32 (16) 18 (4) Pruritus 25 (6) 34 (9) 30 (8) 24 (12) 4 (1) Vomiting 20 (5) 29 (7) 34 (9) 19 (9) 11 ( 3) Insomnia 26 (7) 32 (8) 36 (9) 22 (11) 13 (3) Dry Mouth 20 (5) 29 (7) 39 (10) 18 (9) 6 (2) Diarrhea 15 (4) 27 (7) 37 (9) 10 (5) 17 (4) Asthenia 14 (4) 24 (6) 26 (7) 13 (6) 7 (2) Postural hypotension 7 (2) 17 (4) 8 (2) 11 (5) 9 (2) Sweating increased 6 (2) 8 (2) 15 (4) 13 (6) 1 (0) Anorexia 3 (1) 7 (2) 21 (5) 12 (6) 1 (0) Adverse reactions With Incidence Rates of 1.0% to <5.0% During Clinical Trials The following adverse reactions were reported from all the chronic pain studies (N=3108).
The lists below include adverse reactions not otherwise noted in Table 1.
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 Reactions With Incidence Rates of 0.5% to <1.0% and Serious Adverse Reactions Reported in at Least 2 patients During Clinical Trials 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 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of tramadol.
Because these 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.
Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Anaphylaxis : Anaphylaxis has been reported with ingredients contained in tramadol hydrochloride extended-release tablets.
Androgen deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time.
[see Clinical Pharmacology ( 12.2 )].
QT prolongation/torsade de pointes : Cases of QT prolongation and/or torsade de pointes have been reported with tramadol use.
Many of these cases were reported in patients taking another drug labeled for QT prolongation, in patients with a risk factor for QT prolongation (e.g., hypokalemia), or in overdose setting.
Metabolism and nutrition disorders: Hyponatremia : cases of severe hyponatremia and/or SIADH have been reported in patients taking tramadol, most often in females over the age of 65, and within the first week of therapy [see Warnings and Precautions ( 5.20 )].
Hypoglycemia : Cases of hypoglycemia have been reported in patients taking tramadol.
Most reports were in patients with predisposing risk factors, including diabetes or renal insufficiency, or in elderly patients [see Warnings and Precautions ( 5.21 )].
Hyperalgesia and Allodynia : cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration.
[see Warnings and Precautions ( 5.8 )]
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc.
at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 practice.
Tramadol hydrochloride extended-release tablet 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 reactions 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 1).
The most common adverse reactions from Table 1 occurring in ≥10% and ≥2 x placebo rate of the patients treated with tramadol hydrochloride extended-release tablets are dizziness (not vertigo), nausea, constipation, headache, somnolence, flushing, pruritus, vomiting, insomnia, and dry mouth.
Table 1: Incidence (%) of patients with adverse reaction rates ≥ 5% from two 12-week placebo-controlled studies in patients with moderate to moderately severe chronic pain by dose (N=1811).
MedDRA Preferred Term Tramadol Hydrochloride Extended-Release Tablets Placebo 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 (16) 81 (20) 90 (23) 57 (28) 28 (7) Nausea 61 (15) 90 (23) 102 (26) 53 (26) 32 (8) Constipation 49 (12) 68 (17) 85 (21) 60 (30) 17 (4) Headache 49 (12) 62 (16) 46 (12) 32 (16) 43 (11) Somnolence 33 (8) 45 (11) 29 (7) 41 (20) 7 (2) Flushing 31 (8) 40 (10) 35 (9) 32 (16) 18 (4) Pruritus 25 (6) 34 (9) 30 (8) 24 (12) 4 (1) Vomiting 20 (5) 29 (7) 34 (9) 19 (9) 11 ( 3) Insomnia 26 (7) 32 (8) 36 (9) 22 (11) 13 (3) Dry Mouth 20 (5) 29 (7) 39 (10) 18 (9) 6 (2) Diarrhea 15 (4) 27 (7) 37 (9) 10 (5) 17 (4) Asthenia 14 (4) 24 (6) 26 (7) 13 (6) 7 (2) Postural hypotension 7 (2) 17 (4) 8 (2) 11 (5) 9 (2) Sweating increased 6 (2) 8 (2) 15 (4) 13 (6) 1 (0) Anorexia 3 (1) 7 (2) 21 (5) 12 (6) 1 (0) Adverse reactions With Incidence Rates of 1.0% to <5.0% During Clinical Trials The following adverse reactions were reported from all the chronic pain studies (N=3108).
The lists below include adverse reactions not otherwise noted in Table 1.
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 Reactions With Incidence Rates of 0.5% to <1.0% and Serious Adverse Reactions Reported in at Least 2 patients During Clinical Trials 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 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of tramadol.
Because these 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.
Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Anaphylaxis : Anaphylaxis has been reported with ingredients contained in tramadol hydrochloride extended-release tablets.
Androgen deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time.
[see Clinical Pharmacology ( 12.2 )].
QT prolongation/torsade de pointes : Cases of QT prolongation and/or torsade de pointes have been reported with tramadol use.
Many of these cases were reported in patients taking another drug labeled for QT prolongation, in patients with a risk factor for QT prolongation (e.g., hypokalemia), or in overdose setting.
Metabolism and nutrition disorders: Hyponatremia : cases of severe hyponatremia and/or SIADH have been reported in patients taking tramadol, most often in females over the age of 65, and within the first week of therapy [see Warnings and Precautions ( 5.20 )].
Hypoglycemia : Cases of hypoglycemia have been reported in patients taking tramadol.
Most reports were in patients with predisposing risk factors, including diabetes or renal insufficiency, or in elderly patients [see Warnings and Precautions ( 5.21 )].
Hyperalgesia and Allodynia : cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration.
[see Warnings and Precautions ( 5.8 )]