Data from FDA - Curated by EPG Health - Last updated 22 December 2016

Indication(s)

INDICATIONS & USAGE SECTION Tramadol hydrochloride extended-release tablets are indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time.

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Advisory information

contraindications
CONTRAINDICATIONS SECTION Tramadol hydrochloride extended-release tablets should not be administered to patients who have previously demonstrated hypersensitivity to tramadol, any other component of this product or opioids. Tramadol hydrochloride extended-release tablets are contraindicated in any situation where opioids are contraindicated, including acute intoxication with any of the following: alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs. Tramadol hydrochloride extended-release tablets may worsen central nervous system and respiratory depression in these patients.
Special warnings and precautions
PRECAUTIONS SECTION Acute Abdominal Condition The administration of tramadol hydrochloride extended-release tablets may complicate the clinical assessment of patients with acute abdominal conditions. Use in Renal and Hepatic Disease Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. Tramadol hydrochloride extended-release tablets have not been studied in patients with severe renal impairment (CLcr < 30 mL/min). The limited availability of dose strengths and once daily dosing of tramadol hydrochloride extended-release tablets do not permit the dosing flexibility required for safe use in patients with severe renal impairment. Therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe renal impairment (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION). Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver. The pharmacokinetics of tramadol hydrochloride extended-release tablets has not been studied in patients with severe hepatic impairment. The limited availability of dose strengths and once daily dosing of tramadol hydrochloride extended-release tablets do not permit the dosing flexibility required for safe use in patients with severe hepatic impairment. Therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe hepatic impairment (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).
Adverse reactions
ADVERSE REACTIONS SECTION Tramadol hydrochloride extended-release tablets were 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 generally7 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). 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 (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) 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) 35 (8.8) 32 (15.8) 18 (4.4) Pruritus 25 (6.2) 34 (8.5) 30 (7.5) 24 (11.9) 4 (1) Vomiting 20 (5) 29 (7.3) 34 (8.5) 19 (9.4) 11 (2.7) Insomnia 26 (6.5) 32 (8) 36 (9) 22 (10.9) 13 (3.2) Dry Mouth 20 (5) 29 (7.3) 39 (9.8) 18 (8.9) 6 (1.5) Diarrhea 15 (3.7) 27 (6.8) 37 (8.5) 10 (5) 17 (4.2) Asthenia 14 (3.5) 24 (6) 26 (6.5) 13 (6.4) 7 (1.7) Postural hypotension 7 (1.7) 17 (4.3) 8 (2) 11 (5.4) 9 (2.2) Sweating increased 6 (1.5) 8 (2) 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% to <5% 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% 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

Usage information

Dosing and administration
DOSAGE & ADMINISTRATION SECTION Tramadol hydrochloride extended-release tablets should not be used in patients with: creatinine clearance less than 30 mL/min, severe hepatic impairment (Child-Pugh Class C) (See PRECAUTIONS, Use in Renal and Hepatic Disease). Tramadol hydrochloride extended-release tablets must be swallowed whole and must not be chewed, crushed, or split (see WARNINGS, Misuse, Abuse and Diversion of Opioids and DRUG ABUSE AND ADDICTION). Adults (18 years of age and over) Patients Not Currently on Tramadol Immediate-Release Products For patients not currently treated with tramadol immediate-release (IR) products, tramadol hydrochloride extended-release tablets should be initiated at a dose of 100 mg once daily and titrated up as necessary by 100 mg increments every five days to relief of pain and depending upon tolerability. Tramadol hydrochloride extended-release tablets should not be administered at a dose exceeding 300 mg per day. Patients Currently on Tramadol Immediate-Release Products For patients maintained on tramadol IR products, calculate the 24-hour tramadol immediate-release (IR) dose and initiate a total daily dose of tramadol hydrochloride extended-release tablets rounded down to the next lowest 100 mg increment. The dose may subsequently be individualized according to patient need. Due to limitations in flexibility of dose selection with tramadol hydrochloride extended-release tablets, some patients maintained on tramadol IR products may not be able to convert to tramadol hydrochloride extended-release tablets. Tramadol hydrochloride extended-release tablets should not be administered at a dose exceeding 300 mg per day. The concomitant use of tramadol hydrochloride extended-release tablets with other tramadol products is not recommended (see WARNINGS). Individualization of Dose Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Start at the lowest possible dose and titrate upward as tolerated to achieve an adequate effect. Clinical studies of tramadol hydrochloride extended-release tablets have not demonstrated a clinical benefit at a total daily dose exceeding 300 mg. In general, dosing of an elderly patient (over 65 years of age) should be initiated cautiously, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. Tramadol hydrochloride extended-release tablets should be administered with even greater caution in patients over 75 years, due to the greater frequency of adverse events seen in this population.

More information

Category Value
Authorisation number ANDA201384
Orphan designation No
Product NDC 61919-892
Date Last Revised 06-06-2016
Type HUMAN PRESCRIPTION DRUG
RXCUI 833709
Marketing authorisation holder DirectRX