Tramadol ER 300mg Capsules
WARNING: For all patients taking this drug:This is an opioid drug. Opioid drugs can put you at risk for drug use disorder. These can lead to overdose and death. You will be watched closely while taking this drug.Severe breathing problems may happen with this drug. The risk is highest when you first start taking this drug or any time your dose is raised. These breathing problems can be deadly. Call your doctor right away if you have slow, shallow, or trouble breathing.Even one dose of this drug may be deadly if it is taken by someone else or by accident, especially in children. If this drug is taken by someone else or by accident, get medical help right away.Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.Severe side effects have happened when opioid drugs were used with benzodiazepines, alcohol, marijuana, other forms of cannabis, or street drugs. This includes severe drowsiness, breathing problems, and death. Benzodiazepines include drugs like alprazolam, diazepam, and lorazepam. If you have questions, talk with the doctor.Many drugs interact with this drug and can raise the chance of side effects like deadly breathing problems. Talk with your doctor and pharmacist to make sure it is safe to use this drug with all of your drugs.Get medical help right away if you feel very sleepy, very dizzy, or if you pass out. Caregivers or others need to get medical help right away if the patient does not respond, does not answer or react like normal, or will not wake up.If you are pregnant or plan to get pregnant, talk with your doctor right away about the benefits and risks of using this drug during pregnancy. Using this drug for a long time during pregnancy may lead to withdrawal in the newborn baby. Withdrawal in the newborn can be life- threatening if not treated.Children:This drug is not approved for use in children. Severe and sometimes deadly breathing problems have happened with tramadol in children. Sometimes, this happened after surgery to remove tonsils or adenoids and in children who were rapid metabolizers of tramadol. Do not give to a child younger than 12 years of age. Do not give to a child younger than 18 years of age who is very overweight, has certain health problems like sleep apnea or other lung or breathing problems, or has had surgery to remove tonsils or adenoids. If your child has been given this drug, ask the doctor about the benefits and risks. @ COMMON USES: It is used to manage pain when daily pain treatment is needed for a long time. It is for use when non-opioid pain drugs do not treat your pain well enough or you cannot take them.
Drug Class
Opioid Analgesic
Pharmacologic Class
Centrally acting synthetic opioid analgesic; Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
Pregnancy Category
Not available (Risk Summary provided)
FDA Approved
Jan 1970
DEA Schedule
Schedule IV
Overview
What is this medicine?
Tramadol ER is a strong pain medicine that works in your brain to change how your body feels and responds to pain. It's an extended-release capsule, meaning it releases the medicine slowly over time to provide pain relief for a full day. It's used for ongoing, severe pain that needs around-the-clock treatment.
How to Use This Medicine
Taking Your Medication Correctly
To use this medication safely and effectively, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely.
Take this medication by mouth only. Do not inject or snort it, as this can cause severe side effects, including trouble breathing and death from overdose.
Swallow the medication whole. Do not chew, break, crush, or dissolve it before swallowing, as this can also cause severe side effects and death.
You can take this medication with or without food. However, some products must be taken consistently, either always with food or always without food. Be sure to understand how to take your specific product in relation to food. If you are unsure, consult your doctor or pharmacist.
Take this medication at the same time every day.
Do not use this medication for fast pain relief or on an as-needed basis.
* Do not use this medication for pain relief after surgery if you have not been taking similar medications.
If you have difficulty swallowing, discuss this with your doctor.
Storing and Disposing of Your Medication
Store this medication at room temperature in a dry place, away from the bathroom. Keep it in a safe location where children cannot see or reach it, and where others cannot access it. Consider using a locked box or area to secure the medication. Keep all medications away from pets.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about the best way to dispose of your medication, consult your pharmacist. You may also have access to drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and return to your regular schedule. Do not take two doses at the same time or take extra doses.
To use this medication safely and effectively, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely.
Take this medication by mouth only. Do not inject or snort it, as this can cause severe side effects, including trouble breathing and death from overdose.
Swallow the medication whole. Do not chew, break, crush, or dissolve it before swallowing, as this can also cause severe side effects and death.
You can take this medication with or without food. However, some products must be taken consistently, either always with food or always without food. Be sure to understand how to take your specific product in relation to food. If you are unsure, consult your doctor or pharmacist.
Take this medication at the same time every day.
Do not use this medication for fast pain relief or on an as-needed basis.
* Do not use this medication for pain relief after surgery if you have not been taking similar medications.
If you have difficulty swallowing, discuss this with your doctor.
Storing and Disposing of Your Medication
Store this medication at room temperature in a dry place, away from the bathroom. Keep it in a safe location where children cannot see or reach it, and where others cannot access it. Consider using a locked box or area to secure the medication. Keep all medications away from pets.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about the best way to dispose of your medication, consult your pharmacist. You may also have access to drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and return to your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Do not drink alcohol while taking this medication, as it can cause dangerous side effects including severe drowsiness and breathing problems.
- Do not drive or operate heavy machinery until you know how this medication affects you, as it can cause dizziness and drowsiness.
- Store this medication securely away from children and pets, as accidental ingestion can be fatal.
- Do not crush, chew, or dissolve the extended-release capsules, as this can lead to rapid release and absorption of a potentially fatal dose.
- Discuss all other medications, supplements, and herbal products you are taking with your doctor to avoid dangerous drug interactions.
- Be aware of the signs of addiction, abuse, and misuse, and discuss any concerns with your healthcare provider.
Available Forms & Alternatives
Available Strengths:
- Tramadol 50mg Tablets
- Tramadol 50mg Tablets
- Tramadol Hcl ER 100mg (biphasic) Tb
- Tramadol ER 200mg Biphasic Tab
- Tramadol Hcl ER 300mg Tablets
- Tramadol ER 200mg Tablets
- Tramadol ER 100mg Tablets
- Tramadol ER 300mg Tablets
- Tramadol ER 100mg Tablets
- Tramadol ER 300mg Tablets
- Tramadol ER 200mg Tablets
- Tramadol ER 100mg Capsules
- Tramadol ER 200mg Capsules
- Tramadol ER 300mg Capsules
- Tramadol 100mg Tablets
- Tramadol 50mg Tablets
- Tramadol 100mg Tablets
- Tramadol 5mg/ml Solution
- Tramadol Hcl 25mg Tablets
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose for Tramadol ER is typically 100 mg once daily. The dose may be titrated in 100 mg increments every 5 days to achieve adequate analgesia with tolerable side effects. The maximum recommended dose is 300 mg once daily.
Dose Range:
100 - 300 mg
Condition-Specific Dosing:
chronic_pain:
For management of chronic pain requiring around-the-clock treatment for an extended period.
Pediatric Dosing
Neonatal:
Not established (Contraindicated in children younger than 12 years for pain, and younger than 18 years for post-tonsillectomy/adenoidectomy pain).
Infant:
Not established (Contraindicated in children younger than 12 years for pain, and younger than 18 years for post-tonsillectomy/adenoidectomy pain).
Child:
Not established (Contraindicated in children younger than 12 years for pain, and younger than 18 years for post-tonsillectomy/adenoidectomy pain).
Adolescent:
Not established for ER formulations. Contraindicated in adolescents younger than 18 years for post-tonsillectomy/adenoidectomy pain. Use with caution and consider risks vs. benefits for other pain in adolescents 12-18 years, especially those with risk factors for respiratory depression or ultra-rapid CYP2D6 metabolism.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment for mild impairment (CrCl 50-80 mL/min).
Moderate:
For CrCl <30 mL/min, Tramadol ER is not recommended. For immediate release, the dosing interval should be extended to 12 hours (max 200 mg/day).
Severe:
Tramadol ER is not recommended in patients with severe renal impairment (CrCl <30 mL/min).
Dialysis:
Tramadol is removed to a small extent by hemodialysis. Tramadol ER is not recommended in patients requiring dialysis.
Hepatic Impairment:
Mild:
No specific adjustment for mild impairment.
Moderate:
Tramadol ER is not recommended in patients with moderate to severe hepatic impairment (Child-Pugh Class B and C). For immediate release, the dosing interval should be extended to 12 hours (max 100 mg/day).
Severe:
Tramadol ER is not recommended in patients with severe hepatic impairment (Child-Pugh Class C).
Pharmacology
Mechanism of Action
Tramadol is a centrally acting synthetic opioid analgesic. Its analgesic effect is due to a dual mechanism: 1) binding of the parent drug and its active metabolite (M1, O-desmethyltramadol) to ΞΌ-opioid receptors, and 2) weak inhibition of the reuptake of norepinephrine and serotonin. The M1 metabolite has a significantly higher affinity for ΞΌ-opioid receptors than the parent drug.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 75% (for immediate release, ER may vary slightly)
Tmax:
Approximately 12 hours (for ER formulations)
FoodEffect:
Administration with food does not significantly affect the rate or extent of absorption of Tramadol ER.
Distribution:
Vd:
Approximately 2.6 L/kg (parent drug)
ProteinBinding:
Approximately 20% (parent drug and M1 metabolite)
CnssPenetration:
Yes
Elimination:
HalfLife:
Approximately 6.3 hours (parent drug); Approximately 7.9 hours (M1 metabolite) for immediate release. For ER, effective half-life may be longer due to sustained release.
Clearance:
Approximately 0.8 L/h/kg (parent drug)
ExcretionRoute:
Renal (approximately 90% of dose, 60% as metabolites, 30% as unchanged drug)
Unchanged:
Approximately 30% (parent drug)
Pharmacodynamics
OnsetOfAction:
Approximately 1 hour (for immediate release); longer for ER formulations (sustained release)
PeakEffect:
Approximately 12 hours (for ER formulations)
DurationOfAction:
Approximately 24 hours (for ER formulations)
Safety & Warnings
BLACK BOX WARNING
Addiction, Abuse, and Misuse: Tramadol exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patientβs risk prior to prescribing Tramadol, and monitor all patients receiving Tramadol for the development of these behaviors and conditions.
Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with use of Tramadol. Monitor for respiratory depression, especially during initiation of Tramadol or following a dose increase.
Accidental Ingestion: Accidental ingestion of even one dose of Tramadol, especially by children, can result in a fatal overdose of tramadol.
Neonatal Opioid Withdrawal Syndrome: Prolonged use of Tramadol during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
CYP2D6 Ultra-Rapid Metabolism: Life-threatening respiratory depression and death have occurred in children who received tramadol. Some individuals are ultra-rapid metabolizers of tramadol due to a genetic polymorphism (CYP2D6). These individuals convert tramadol into its active metabolite, O-desmethyltramadol (M1), more rapidly and completely than other people. The M1 metabolite is a more potent ΞΌ-opioid agonist. Even at labeled doses, ultra-rapid metabolizers may have higher than anticipated M1 levels, leading to life-threatening respiratory depression or death. Because of the risk of life-threatening respiratory depression and death, tramadol is contraindicated in children younger than 12 years of age and in adolescents younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of tramadol in adolescents 12 to 18 years of age who have other risk factors for respiratory depression unless the benefits outweigh the risks. When prescribing tramadol, healthcare providers should choose the lowest effective dose for the shortest period of time and advise patients and caregivers about these risks.
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes: The concomitant use of Tramadol with all cytochrome P450 3A4 (CYP3A4) inhibitors or 2D6 (CYP2D6) inhibitors may result in an increase in tramadol plasma concentrations, which could increase or prolong adverse reactions, including serious respiratory depression. The concomitant use of Tramadol with CYP3A4 inducers or 2D6 inducers may result in a decrease in tramadol plasma concentrations, which could decrease efficacy. Avoid the use of CYP3A4 inhibitors, CYP2D6 inhibitors, CYP3A4 inducers, or CYP2D6 inducers in patients taking Tramadol. If concomitant use is necessary, monitor patients for respiratory depression and sedation.
Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with use of Tramadol. Monitor for respiratory depression, especially during initiation of Tramadol or following a dose increase.
Accidental Ingestion: Accidental ingestion of even one dose of Tramadol, especially by children, can result in a fatal overdose of tramadol.
Neonatal Opioid Withdrawal Syndrome: Prolonged use of Tramadol during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
CYP2D6 Ultra-Rapid Metabolism: Life-threatening respiratory depression and death have occurred in children who received tramadol. Some individuals are ultra-rapid metabolizers of tramadol due to a genetic polymorphism (CYP2D6). These individuals convert tramadol into its active metabolite, O-desmethyltramadol (M1), more rapidly and completely than other people. The M1 metabolite is a more potent ΞΌ-opioid agonist. Even at labeled doses, ultra-rapid metabolizers may have higher than anticipated M1 levels, leading to life-threatening respiratory depression or death. Because of the risk of life-threatening respiratory depression and death, tramadol is contraindicated in children younger than 12 years of age and in adolescents younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of tramadol in adolescents 12 to 18 years of age who have other risk factors for respiratory depression unless the benefits outweigh the risks. When prescribing tramadol, healthcare providers should choose the lowest effective dose for the shortest period of time and advise patients and caregivers about these risks.
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes: The concomitant use of Tramadol with all cytochrome P450 3A4 (CYP3A4) inhibitors or 2D6 (CYP2D6) inhibitors may result in an increase in tramadol plasma concentrations, which could increase or prolong adverse reactions, including serious respiratory depression. The concomitant use of Tramadol with CYP3A4 inducers or 2D6 inducers may result in a decrease in tramadol plasma concentrations, which could decrease efficacy. Avoid the use of CYP3A4 inhibitors, CYP2D6 inhibitors, CYP3A4 inducers, or CYP2D6 inducers in patients taking Tramadol. If concomitant use is necessary, monitor patients for respiratory depression and sedation.
Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Rarely, allergic reactions can be fatal.
Signs of depression or mood changes, including:
+ Suicidal thoughts or feelings
+ Emotional ups and downs or abnormal thinking
+ Anxiety or lack of interest in life
Signs of low sodium levels, such as:
+ Headache
+ Trouble focusing or memory problems
+ Feeling confused or weak
+ Seizures or changes in balance
Severe dizziness or fainting
Feeling confused or disoriented
Seizures
Chest pain or pressure, or a rapid heartbeat
Difficulty urinating or frequent urination
Breathing difficulties, including:
+ Slow or shallow breathing
+ Noisy breathing
+ Sleep apnea (breathing problems during sleep)
Changes in vision
Severe constipation or stomach pain, which may indicate a bowel problem
Serotonin syndrome, a potentially life-threatening condition, may occur, especially when taking certain other medications. Seek immediate medical attention if you experience:
+ Agitation or changes in balance
+ Confusion or hallucinations
+ Fever or abnormal heartbeat
+ Flushing or muscle twitching or stiffness
+ Seizures or shivering and shaking
+ Severe diarrhea, nausea, or vomiting
+ Severe headache
Stevens-Johnson syndrome or toxic epidermal necrolysis, a severe skin reaction, may occur. Seek immediate medical attention if you notice:
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Red or irritated eyes
+ Sores in your mouth, throat, nose, or eyes
Other Possible Side Effects
Most people experience few or no side effects. However, some individuals may encounter mild or moderate side effects. If you experience any of the following, contact your doctor or seek medical attention if they bother you or persist:
Feeling dizzy, drowsy, tired, or weak
Constipation, diarrhea, nausea, or vomiting
Dry mouth
Headache
Itching
Sleep disturbances
* Flushing or excessive sweating
Reporting Side Effects
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Rarely, allergic reactions can be fatal.
Signs of depression or mood changes, including:
+ Suicidal thoughts or feelings
+ Emotional ups and downs or abnormal thinking
+ Anxiety or lack of interest in life
Signs of low sodium levels, such as:
+ Headache
+ Trouble focusing or memory problems
+ Feeling confused or weak
+ Seizures or changes in balance
Severe dizziness or fainting
Feeling confused or disoriented
Seizures
Chest pain or pressure, or a rapid heartbeat
Difficulty urinating or frequent urination
Breathing difficulties, including:
+ Slow or shallow breathing
+ Noisy breathing
+ Sleep apnea (breathing problems during sleep)
Changes in vision
Severe constipation or stomach pain, which may indicate a bowel problem
Serotonin syndrome, a potentially life-threatening condition, may occur, especially when taking certain other medications. Seek immediate medical attention if you experience:
+ Agitation or changes in balance
+ Confusion or hallucinations
+ Fever or abnormal heartbeat
+ Flushing or muscle twitching or stiffness
+ Seizures or shivering and shaking
+ Severe diarrhea, nausea, or vomiting
+ Severe headache
Stevens-Johnson syndrome or toxic epidermal necrolysis, a severe skin reaction, may occur. Seek immediate medical attention if you notice:
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Red or irritated eyes
+ Sores in your mouth, throat, nose, or eyes
Other Possible Side Effects
Most people experience few or no side effects. However, some individuals may encounter mild or moderate side effects. If you experience any of the following, contact your doctor or seek medical attention if they bother you or persist:
Feeling dizzy, drowsy, tired, or weak
Constipation, diarrhea, nausea, or vomiting
Dry mouth
Headache
Itching
Sleep disturbances
* Flushing or excessive sweating
Reporting Side Effects
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Difficulty breathing or shallow breathing
- Extreme drowsiness or difficulty waking up
- Bluish lips or fingernails
- Severe dizziness or lightheadedness
- Confusion or hallucinations
- Seizures
- Agitation, rapid heart rate, sweating, muscle stiffness (signs of serotonin syndrome)
- Severe constipation
- Swelling of the face, lips, tongue, or throat (allergic reaction)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction and its symptoms.
Respiratory issues, including asthma, breathing difficulties, or sleep apnea, as well as high blood carbon dioxide levels.
Gastrointestinal problems, such as stomach or bowel blockage or narrowing.
Kidney or liver disease, which may affect how your body processes the medication.
A history of suicidal thoughts or previous substance abuse or dependence, including alcohol or other drugs.
If your doctor has informed you that you are a rapid metabolizer of certain medications.
Recent consumption of large amounts of alcohol or use of drugs that may impair your actions, such as phenobarbital or pain medications like oxycodone.
Current or recent use of specific medications, including:
+ Carbamazepine
+ Another medication containing the same active ingredient as this drug
+ Buprenorphine, butorphanol, linezolid, methylene blue, nalbuphine, or pentazocine
+ Certain antidepressants or Parkinson's disease medications taken within the last 14 days, such as isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline, as they may cause a dangerous increase in blood pressure
* If you are breast-feeding, as this medication is not recommended during breast-feeding.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist to ensure safe treatment. Do not start, stop, or change the dosage of any medication without consulting your doctor first.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction and its symptoms.
Respiratory issues, including asthma, breathing difficulties, or sleep apnea, as well as high blood carbon dioxide levels.
Gastrointestinal problems, such as stomach or bowel blockage or narrowing.
Kidney or liver disease, which may affect how your body processes the medication.
A history of suicidal thoughts or previous substance abuse or dependence, including alcohol or other drugs.
If your doctor has informed you that you are a rapid metabolizer of certain medications.
Recent consumption of large amounts of alcohol or use of drugs that may impair your actions, such as phenobarbital or pain medications like oxycodone.
Current or recent use of specific medications, including:
+ Carbamazepine
+ Another medication containing the same active ingredient as this drug
+ Buprenorphine, butorphanol, linezolid, methylene blue, nalbuphine, or pentazocine
+ Certain antidepressants or Parkinson's disease medications taken within the last 14 days, such as isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline, as they may cause a dangerous increase in blood pressure
* If you are breast-feeding, as this medication is not recommended during breast-feeding.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist to ensure safe treatment. Do not start, stop, or change the dosage of any medication without consulting your doctor first.
Precautions & Cautions
Important Warnings and Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Caution with Daily Activities
Until you know how this medication affects you, avoid driving and other activities that require you to be alert. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying down position. Be cautious when climbing stairs.
Dosage and Administration
Do not exceed the dosage prescribed by your doctor. Taking more than the recommended amount can increase the risk of severe side effects.
Interactions with Other Medications
Do not take this medication with other strong pain medications or use a pain patch without consulting your doctor first. If your pain worsens, you become more sensitive to pain, or experience new pain after taking this medication, contact your doctor immediately. Do not take more than the prescribed amount.
Seizure Risk
This medication may increase the risk of seizures, particularly in individuals with certain health conditions, those taking specific medications, or those who consume excessive alcohol. Discuss your risk of seizures with your doctor.
Tolerance and Dependence
Long-term or high-dose use of this medication can lead to tolerance, where the medication may not work as effectively, and you may require higher doses to achieve the same effect. If you experience a decrease in the medication's effectiveness, contact your doctor. Do not take more than the prescribed amount.
Low Blood Sugar
This medication can cause low blood sugar, which may require hospitalization. If you experience symptoms such as dizziness, headache, fatigue, shaking, rapid heartbeat, confusion, hunger, or sweating, contact your doctor immediately.
Dependence and Withdrawal
Long-term or regular use of opioid medications like this one can lead to dependence. Suddenly stopping or reducing the dose can increase the risk of withdrawal or other severe problems. Consult your doctor before changing your dosage. Follow your doctor's instructions, and report any increased pain, mood changes, suicidal thoughts, or other adverse effects.
Alcohol Interactions
Do not consume alcohol or products containing alcohol while taking this medication, as it can lead to unsafe and potentially fatal effects.
Hormonal Effects
Long-term use of opioid medications can cause a decrease in sex hormone levels. If you experience a decreased interest in sex, fertility problems, irregular menstrual periods, or ejaculation problems, contact your doctor.
Adrenal Gland Problems
Taking an opioid medication like this one can lead to a rare but severe adrenal gland disorder. If you experience extreme fatigue, weakness, fainting, severe dizziness, nausea, vomiting, or decreased appetite, contact your doctor immediately.
Special Considerations for Older Adults
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Caution with Daily Activities
Until you know how this medication affects you, avoid driving and other activities that require you to be alert. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying down position. Be cautious when climbing stairs.
Dosage and Administration
Do not exceed the dosage prescribed by your doctor. Taking more than the recommended amount can increase the risk of severe side effects.
Interactions with Other Medications
Do not take this medication with other strong pain medications or use a pain patch without consulting your doctor first. If your pain worsens, you become more sensitive to pain, or experience new pain after taking this medication, contact your doctor immediately. Do not take more than the prescribed amount.
Seizure Risk
This medication may increase the risk of seizures, particularly in individuals with certain health conditions, those taking specific medications, or those who consume excessive alcohol. Discuss your risk of seizures with your doctor.
Tolerance and Dependence
Long-term or high-dose use of this medication can lead to tolerance, where the medication may not work as effectively, and you may require higher doses to achieve the same effect. If you experience a decrease in the medication's effectiveness, contact your doctor. Do not take more than the prescribed amount.
Low Blood Sugar
This medication can cause low blood sugar, which may require hospitalization. If you experience symptoms such as dizziness, headache, fatigue, shaking, rapid heartbeat, confusion, hunger, or sweating, contact your doctor immediately.
Dependence and Withdrawal
Long-term or regular use of opioid medications like this one can lead to dependence. Suddenly stopping or reducing the dose can increase the risk of withdrawal or other severe problems. Consult your doctor before changing your dosage. Follow your doctor's instructions, and report any increased pain, mood changes, suicidal thoughts, or other adverse effects.
Alcohol Interactions
Do not consume alcohol or products containing alcohol while taking this medication, as it can lead to unsafe and potentially fatal effects.
Hormonal Effects
Long-term use of opioid medications can cause a decrease in sex hormone levels. If you experience a decreased interest in sex, fertility problems, irregular menstrual periods, or ejaculation problems, contact your doctor.
Adrenal Gland Problems
Taking an opioid medication like this one can lead to a rare but severe adrenal gland disorder. If you experience extreme fatigue, weakness, fainting, severe dizziness, nausea, vomiting, or decreased appetite, contact your doctor immediately.
Special Considerations for Older Adults
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
Overdose Information
Overdose Symptoms:
- Slowed or stopped breathing
- Extreme drowsiness or unresponsiveness
- Pinpoint pupils
- Cold, clammy skin
- Limp muscles
- Loss of consciousness
- Seizures
- Cardiac arrest
What to Do:
Seek immediate emergency medical attention. Call 911 or your local emergency number. If available, administer naloxone if the patient is unresponsive and has signs of respiratory depression. Call 1-800-222-1222 (Poison Control) for further guidance.
Drug Interactions
Contraindicated Interactions
- Monoamine Oxidase Inhibitors (MAOIs) or within 14 days of MAOI use (risk of serotonin syndrome, seizures)
- Alcohol (risk of profound sedation, respiratory depression, coma, death with ER formulations)
- Other opioid analgesics (risk of additive CNS depression, respiratory depression)
- Benzodiazepines and other CNS depressants (risk of profound sedation, respiratory depression, coma, death)
Major Interactions
- Serotonergic drugs (SSRIs, SNRIs, TCAs, triptans, mirtazapine, St. John's Wort, linezolid, methylene blue) - increased risk of serotonin syndrome and seizures
- CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) - decreased formation of M1, potentially reducing efficacy
- CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, ritonavir) - increased tramadol exposure, increased risk of adverse effects
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) - decreased tramadol exposure, potentially reducing efficacy
- Carbamazepine (significant reduction in tramadol plasma levels, increased risk of seizures)
- Warfarin (increased INR, bleeding risk)
Moderate Interactions
- Digoxin (rare reports of digoxin toxicity)
- Coumarin derivatives (monitor INR)
Minor Interactions
- Not specifically categorized as minor for tramadol due to its complex pharmacology and potential for serious interactions.
Monitoring
Baseline Monitoring
Pain assessment (intensity, character, location)
Rationale: To establish baseline pain level and guide initial dosing.
Timing: Prior to initiation of therapy
Respiratory rate and depth
Rationale: To assess baseline respiratory function, especially important due to risk of respiratory depression.
Timing: Prior to initiation of therapy
Mental status (level of consciousness, cognitive function)
Rationale: To assess baseline neurological status and identify risk for sedation.
Timing: Prior to initiation of therapy
Renal and hepatic function tests (CrCl, LFTs)
Rationale: To identify impairment that may require dose adjustment or contraindicate use.
Timing: Prior to initiation of therapy
History of substance abuse or mental health disorders
Rationale: To assess risk for addiction, abuse, and misuse.
Timing: Prior to initiation of therapy
Routine Monitoring
Pain assessment
Frequency: Regularly, at each visit or as clinically indicated
Target: Achieve acceptable pain control with minimal side effects
Action Threshold: Inadequate pain control or intolerable side effects warrant dose adjustment or alternative therapy.
Signs of respiratory depression (decreased respiratory rate, shallow breathing, cyanosis)
Frequency: Regularly, especially during initiation and dose titration
Target: Respiratory rate >12 breaths/min, normal depth
Action Threshold: Respiratory rate <10 breaths/min, shallow breathing, or signs of hypoxia require immediate intervention (e.g., naloxone, respiratory support).
Level of sedation/consciousness
Frequency: Regularly, especially during initiation and dose titration
Target: Alert and oriented, able to perform activities of daily living
Action Threshold: Excessive sedation (e.g., somnolence, difficulty arousing) requires dose reduction or discontinuation.
Bowel function (constipation)
Frequency: Regularly
Target: Regular bowel movements
Action Threshold: Severe constipation requires intervention (e.g., laxatives, stool softeners).
Signs of serotonin syndrome (agitation, hallucinations, tachycardia, fever, hyperreflexia, incoordination, nausea, vomiting, diarrhea)
Frequency: Monitor closely, especially with concomitant serotonergic drugs
Target: Absence of symptoms
Action Threshold: Presence of symptoms requires immediate discontinuation of tramadol and supportive care.
Signs of opioid use disorder (e.g., craving, compulsive use, loss of control, continued use despite harm)
Frequency: Ongoing assessment
Target: Absence of signs
Action Threshold: Presence of signs requires referral for addiction treatment.
Symptom Monitoring
- Respiratory depression
- Excessive sedation
- Dizziness
- Nausea
- Vomiting
- Constipation
- Pruritus
- Seizures
- Serotonin syndrome (agitation, confusion, rapid heart rate, dilated pupils, muscle rigidity, sweating, diarrhea, headache, shivering)
- Adrenal insufficiency (fatigue, weakness, dizziness, nausea, vomiting, anorexia)
- Androgen deficiency (decreased libido, impotence, amenorrhea, infertility)
Special Patient Groups
Pregnancy
Prolonged use of tramadol during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS), which may be life-threatening if not recognized and treated. NOWS can occur hours to days after birth. Advise pregnant patients of the risk of NOWS and ensure appropriate treatment will be available. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Limited data, but potential for congenital malformations with opioid exposure. Risk of NOWS if prolonged use continues into later trimesters.
Second Trimester:
Risk of NOWS if prolonged use continues into later trimesters.
Third Trimester:
High risk of neonatal opioid withdrawal syndrome (NOWS) with prolonged use. Risk of respiratory depression in the neonate if used close to delivery.
Lactation
Tramadol and its active metabolite (M1) are present in breast milk. There are reports of serious adverse reactions in breastfed infants, including excess sedation and respiratory depression. The decision to discontinue breastfeeding or discontinue the drug should take into account the importance of the drug to the mother and the risk to the infant. Monitoring of breastfed infants for signs of sedation and respiratory depression is recommended.
Infant Risk:
L3 (Moderately Safe) to L4 (Potentially Hazardous) - Risk of sedation, respiratory depression, and withdrawal symptoms in the infant. Avoid if possible, or use lowest effective dose for shortest duration and monitor infant closely.
Pediatric Use
Tramadol ER is contraindicated in children younger than 12 years of age. It is also contraindicated in adolescents younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid use in adolescents 12 to 18 years of age who have other risk factors for respiratory depression (e.g., obesity, sleep apnea, severe pulmonary disease) unless the benefits outweigh the risks. Due to the risk of life-threatening respiratory depression, tramadol is generally not recommended for pediatric patients.
Geriatric Use
Elderly patients (65 years and older) may be more sensitive to the adverse effects of tramadol, particularly respiratory depression and sedation. Start with lower doses and titrate slowly. Monitor closely for adverse effects. Renal and hepatic function should be assessed, as impairment is more common in this population.
Clinical Information
Clinical Pearls
- Tramadol ER is for chronic, around-the-clock pain, not for as-needed or acute pain.
- Due to its dual mechanism of action (opioid and SNRI), tramadol carries risks of both opioid-related adverse effects (respiratory depression, addiction) and serotonergic effects (serotonin syndrome).
- Never crush, chew, or dissolve extended-release tramadol capsules, as this can lead to rapid release of a potentially fatal dose.
- Patients should be educated on the signs of respiratory depression and serotonin syndrome, and when to seek emergency medical attention.
- Careful patient selection and risk assessment for addiction, abuse, and misuse are crucial before initiating tramadol.
- Concomitant use with benzodiazepines, other CNS depressants, or alcohol is contraindicated or requires extreme caution due to additive respiratory depression and sedation.
- Monitor for signs of opioid-induced androgen deficiency with long-term use.
Alternative Therapies
- Other extended-release opioid analgesics (e.g., morphine ER, oxycodone ER, hydromorphone ER, tapentadol ER)
- Non-opioid analgesics for chronic pain (e.g., NSAIDs, acetaminophen, duloxetine, gabapentin, pregabalin)
- Interventional pain management techniques (e.g., nerve blocks, spinal cord stimulation)
- Physical therapy, occupational therapy, psychological therapies (e.g., CBT)
Cost & Coverage
Average Cost:
Varies widely, typically $50 - $300+ per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 for generic, Tier 3 or higher for brand-name ER formulations
General Drug Facts
If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others, and do not take medication prescribed to someone else.
This medication is accompanied by a Medication Guide, which provides crucial information for patients. It is important to read this guide carefully and review it again each time your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider.
In the event of an overdose, a medication called naloxone can be administered to help treat the condition. Discuss obtaining and using naloxone with your doctor or pharmacist. If an overdose is suspected, seek immediate medical attention, even if naloxone has been administered. Be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.
In case of a suspected overdose, contact your local poison control center or seek emergency medical care immediately. When seeking help, be prepared to provide information about the substance involved, the quantity taken, and the time of the incident.
This medication is accompanied by a Medication Guide, which provides crucial information for patients. It is important to read this guide carefully and review it again each time your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider.
In the event of an overdose, a medication called naloxone can be administered to help treat the condition. Discuss obtaining and using naloxone with your doctor or pharmacist. If an overdose is suspected, seek immediate medical attention, even if naloxone has been administered. Be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.
In case of a suspected overdose, contact your local poison control center or seek emergency medical care immediately. When seeking help, be prepared to provide information about the substance involved, the quantity taken, and the time of the incident.