Source: Health Products and Food Branch (CA) Revision Year: 2020
ZYTRAM XL (tramadol hydrochloride controlled release tablets) is indicated for the management of moderate to moderately severe pain in adults who require continuous treatment for several days or more.
The safety and efficacy of ZYTRAM XL has not been studied in the pediatric population. Therefore, use of ZYTRAM XL tablets is not recommended in patients under 18 years of age.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease or other drug therapy.
Healthy elderly subjects aged 65 to 75 years administered tramadol have plasma concentrations and elimination half-lives comparable to those observed in healthy subjects less than 65 years of age. ZYTRAM XL should be administered with greater caution in patients older than 75 years, due to the greater potential for adverse events in this population (see WARNINGS AND PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
All doses of opioids carry an inherent risk of fatal or non-fatal adverse events. This risk is increased with higher doses. For the management of chronic non-cancer, nonpalliative pain, it is recommended that a maximum daily dosage of 400 mg (66.7 morphine milligram equivalent) of ZYTRAM XL not be exceeded. Each patient should be assessed for their risk prior to prescribing ZYTRAM XL, as the likelihood of experiencing serious adverse events can depend upon the type of opioid, duration of treatment, level of pain as well as the patient’s own level of tolerance. In addition, the level of pain should be assessed routinely to confirm the most appropriate dose and the need for further use of ZYTRAM XL (see DOSAGE AND ADMINISTRATION, Adjustment or Reduction of Dosage).
ZYTRAM XL should only be used in patients for whom alternative treatment options are ineffective or not tolerated (e.g., non-opioid analgesics), or would be otherwise inadequate to provide sufficient management of pain (e.g., immediate-release opioids).
ZYTRAM XL tablets must be swallowed whole and should not be cut, broken, chewed, dissolved or crushed, since this can lead to the rapid release and absorption of a potentially fatal dose of tramadol (see WARNINGS AND PRECAUTIONS).
ZYTRAM XL (tramadol HCl controlled release tablets) should be used with caution within 12 hours pre-operatively and within the first 12-24 hours post-operatively (see WARNINGS AND PRECAUTIONS, Peri-operative Considerations).
ZYTRAM XL is not recommended for minor pain, or acute short-term pain that may be treated adequately through lesser means where benefit does not outweigh the possible opioid-related side effects.
Due to possible differences in pharmacokinetic properties, ZYTRAM XL tablets are not interchangeable with other tramadol-containing products.
The maximum recommended daily dose of ZYTRAM XL should not be exceeded.
ZYTRAM XL is not indicated for rectal administration.
ZYTRAM XL is designed to allow for once daily dosing, i.e., dosing at 24-hourly intervals. Treatment with ZYTRAM XL should generally be initiated at 150 mg.
The 75 mg and 100 mg tablets allow for smaller dose increases and can be used for initiation, titration or adjustments of dosage.
The usual initial dose is one 150 mg tablet daily. If adequate pain relief is not achieved, the dosage should be gradually titrated upwards. The maximum recommended daily dose is 400 mg.
The safety and efficacy of ZYTRAM XL has not been studied in the pediatric population. Therefore, use of ZYTRAM XL tablets is not recommended in patients under 18 years of age.
Respiratory depression has occurred in the elderly following administration of large initial doses of opioids to patients who were not opioid-tolerant or when opioids were co-administered with other agents that can depress respiration. A dose adjustment is not usually necessary in patients up to 75 years without clinically manifest hepatic or renal insufficiency. In elderly patients over 75 years elimination may be prolonged. It is recommended that a reduced daily dose should be considered as an alternative to a prolongation in dosage interval. ZYTRAM XL should be initiated at a low dose and slowly titrated to effect (see WARNINGS AND PRECAUTIONS and ACTION AND CLINICAL PHARMACOLOGY).
The usual initial dose of ZYTRAM XL for patients who have not previously received opioid analgesics is 150 mg every 24 hours.
Patients currently receiving other oral immediate-release tramadol preparations may be transferred to ZYTRAM XL tablets at the same or lowest nearest total daily tramadol dosage.
The elimination half-life of tramadol and its active metabolite may be prolonged in patients with renal and/or hepatic insufficiency. A starting dose of 150 mg daily is recommended. Upward dosage titration should be done with careful monitoring.
Tramadol is contraindicated in patients with severe renal impairment and/or severe hepatic impairment (creatinine clearance less than 30 mL/min and/or Child-Pugh Class C, see CONTRAINDICATIONS).
If a non-opioid analgesic is being provided, it may be continued. If the non-opioid is discontinued, consideration should be given to increasing the opioid dose to compensate for the non-opioid analgesic. ZYTRAM XL can be safely used concomitantly with usual doses of other non-opioid analgesics.
Dose titration is the key to success with opioid analgesic therapy. Proper optimization of doses scaled to the relief of the individual’s pain should aim at regular administration of the lowest dose of controlled release tramadol (ZYTRAM XL) which will achieve the overall treatment goal of satisfactory pain relief with acceptable side effects.
Dosage adjustments should be based on the patient’s clinical response. In patients receiving ZYTRAM XL it is recommended that doses be slowly titrated, with dosage adjustments generally separated by 7 days, to a dose which provides satisfactory pain relief for a full 24 hours, with acceptable side effects.
Physical dependence with or without psychological dependence tends to occur with chronic administration of opioids, including ZYTRAM XL. Withdrawal (abstinence) symptoms may occur following abrupt discontinuation of therapy. These symptoms may include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.
Following successful relief of moderate to severe pain, periodic attempts to reduce the opioid dose should be made. Smaller doses or complete discontinuation may become feasible due to a change in the patient’s condition or mental state. Patients on prolonged therapy should be withdrawn gradually from the drug if it is no longer required for pain control. In patients who are appropriately treated with opioid analgesics and who undergo gradual withdrawal for the drug, these symptoms are usually mild (see WARNINGS AND PRECAUTIONS). Tapering should be carried out under medical supervision.
Patients should be informed that reducing and/or discontinuing opioids decreases their tolerance to these drugs. If treatment needs to be re-initiated, the patient must start at the lowest dose and titrate up to avoid overdose.
Opioid analgesics may only be partially effective in relieving dysesthetic pain, post-herpetic neuralgia, stabbing pains, activity-related pain and some forms of headache. That is not to say that patients with advanced cancer suffering from some of these forms of pain should not be given an adequate trial of opioid analgesics, but it may be necessary to refer such patients at an early time to other forms of pain therapy.
If rescue medications are warranted for episodes of pain in the course of appropriate adjustments of ZYTRAM XL dose, medications such as acetaminophen, ibuprofen or tramadol IR may be given. Fentanyl products should not be used as rescue medication in patients taking ZYTRAM XL. If immediate release tramadol is used as rescue medication, the total daily dose of tramadol should not exceed 400 mg. Selection of rescue medication should be based on individual patient conditions. For patients whose dose has been titrated to the recommended maintenance dose, without attainment of adequate analgesia, the total daily dose may be increased, unless precluded by side effects.
ZYTRAM XL may be taken with or without food, with a glass of water. The empty matrix tablet remnants may be visible in the stool, or via colostomy.
If a patient forgets to take one or more doses, they should take their next dose at the normal time and in the normal amount.
For management of a suspected drug overdose, contact your regional poison control centre immediately.
Deaths due to overdose have been reported with abuse and misuse of tramadol, by ingesting, inhaling, or injecting the crushed tablets. Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids.
Acute overdosage with tramadol can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, miosis, bradycardia, toxic leukoencephalopathy, delayed post-hypoxic leukoencephalopathy, hypotension, vomiting, circulatory collapse, seizures, and death. In addition, cases of QT prolongation have been reported during overdose.
Primary attention should be given to the establishment of adequate respiratory exchange through the provision of a patent airway and controlled or assisted ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Naloxone will not antagonize tramadol’s inhibitory effects on serotonin reuptake and norepinephrine reuptake. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.
While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with naloxone administration. Seizures may be controlled with diazepam.
Tramadol is minimally eliminated from the serum by hemodialysis or hemofiltration. Therefore treatment of acute tramadol intoxication with hemodialysis or hemofiltration alone is not appropriate.
Evacuation of gastric contents may be useful to remove any unabsorbed drug.
Store ZYTRAM XL tablets at room temperature (15°C – 30°C). Protect from light, moisture and high humidity.
ZYTRAM XL should never be disposed of in household trash.
Disposal via a pharmacy take back program is recommended. Unused or expired ZYTRAM XL should be properly disposed of as soon as it is no longer needed to prevent accidental exposure to others, including children or pets. ZYTRAM XL should not be shared with others and steps should be taken to protect it from theft or misuse. The patient should speak to their pharmacist about temporary storage options, if required, until the medication can be returned to the pharmacy for safe disposal.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
