Drug interactions with tramadol. Tramadol Drug Interactions: Essential Guide for Safe Usage
What are the potential drug interactions with tramadol. How can patients safely use tramadol with other medications. What precautions should be taken when combining tramadol with herbal supplements. How does tramadol interact with common prescription drugs.
Understanding Tramadol: A Synthetic Opioid for Pain Management
Tramadol is a synthetic opioid widely used in both human and veterinary medicine for pain management. In veterinary practice, it’s commonly prescribed for dogs, cats, and other small mammals, although its use is considered ‘off label’ or ‘extra label’. This means that while it’s not officially approved for veterinary use, veterinarians may prescribe it based on their professional judgment and experience.
Key Features of Tramadol
- Available in tablet, capsule, or compounded liquid form
- Can be given with or without food
- Takes effect within 1-2 hours for acute pain
- May take several weeks to show full effects for chronic pain
Why is tramadol considered a versatile pain medication? Its effectiveness in treating both acute and chronic pain, combined with its relatively lower risk of respiratory depression compared to other opioids, makes it a valuable option in pain management protocols.
Tramadol Administration: Best Practices and Precautions
Proper administration of tramadol is crucial for its effectiveness and safety. While it can be given with or without food, its bitter taste may necessitate administration with food or treats to ensure compliance, especially in pets.
Administration Guidelines
- Follow veterinarian’s instructions carefully
- Measure liquid forms accurately
- Never give tramadol with acetaminophen to cats
- If a dose is missed, give it when remembered or skip to the next scheduled dose
- Never double-dose or give extra doses
How should pet owners handle missed doses of tramadol? If a dose is missed, it’s best to give it as soon as remembered. However, if it’s close to the time for the next scheduled dose, skip the missed dose and continue with the regular dosing schedule. This approach helps maintain consistent pain relief without risking overdose.
Potential Side Effects of Tramadol in Animals
While tramadol is generally well-tolerated, it can cause side effects in some animals. The nature and severity of these side effects can vary between species and individual animals.
Common Side Effects in Dogs
- Sedation
- Tremors
- Dizziness
- Anxiety
- Decreased appetite
- Gastrointestinal issues (vomiting, diarrhea, constipation)
Common Side Effects in Cats
- Vomiting
- Constipation
- Sedation
- Dilated pupils
- Uneasiness
How can pet owners differentiate between normal side effects and signs of an overdose? While mild sedation or gastrointestinal upset may be expected, severe symptoms such as seizures, extreme incoordination, profound sleepiness, agitation, or rapid heartbeat could indicate an overdose and require immediate veterinary attention.
Drug Interactions: Tramadol’s Complex Interplay with Other Medications
Tramadol can interact with various medications, potentially altering its effectiveness or increasing the risk of side effects. Understanding these interactions is crucial for safe and effective pain management.
Medications Requiring Caution When Used with Tramadol
- Antidepressants (SSRIs, MAO inhibitors, tricyclic antidepressants)
- Azole antifungals
- Cimetidine
- Cyproheptadine
- Digoxin
- Ketamine
- Metoclopramide
- Ondansetron
- Other opioids
- Quinidine
- SAMe
- Sevoflurane
- Warfarin
- Yohimbine
Why is the interaction between tramadol and warfarin particularly noteworthy? Case reports have shown that tramadol can elevate the International Normalised Ratio (INR) in patients stabilized on warfarin, potentially increasing the risk of bleeding. This interaction typically occurs 3-4 days after starting tramadol and requires careful monitoring.
Tramadol and Herbal Supplements: Navigating Potential Interactions
While the focus is often on interactions between prescription medications, it’s equally important to consider potential interactions between tramadol and herbal supplements. Many pet owners use herbal remedies, and these can sometimes interact with conventional medications like tramadol.
Herbal Supplements to Watch
- St. John’s Wort: May decrease tramadol’s effectiveness
- Valerian Root: Can increase sedative effects
- Ginkgo Biloba: May increase bleeding risk when combined with tramadol and warfarin
- Kava: Potential for increased sedation and liver toxicity
How can pet owners safely use herbal supplements alongside tramadol? It’s crucial to inform your veterinarian about all supplements your pet is taking. They can advise on potential interactions and may recommend adjusting doses or discontinuing certain supplements during tramadol treatment.
Special Considerations: Tramadol Use in High-Risk Patients
While tramadol is generally considered safer than some other opioids, certain patient groups require special consideration and monitoring when using this medication.
High-Risk Patient Groups
- Animals with seizure disorders
- Pets with liver or kidney disease
- Geriatric animals
- Debilitated patients
- Pregnant or lactating animals
Why do these groups require extra caution with tramadol use? These patients may have altered drug metabolism or increased sensitivity to side effects. For example, animals with liver disease may metabolize tramadol more slowly, potentially leading to drug accumulation and increased risk of side effects.
Proper Storage and Handling of Tramadol
Proper storage of tramadol is essential to maintain its effectiveness and prevent accidental ingestion by pets or children. Different formulations may have specific storage requirements.
Storage Guidelines
- Store tablets and capsules at room temperature (25°C/77°F)
- Protect from moisture and light
- Avoid extreme heat and cold
- Refrigerate liquid preparations unless otherwise specified
- Keep out of reach of children and pets
How does proper storage impact tramadol’s effectiveness? Proper storage ensures that the medication remains stable and potent until its expiration date. Exposure to heat, light, or moisture can degrade the drug, potentially reducing its effectiveness or altering its properties.
Emergency Situations: Recognizing and Responding to Tramadol Overdose
While tramadol is generally safe when used as directed, accidental overdose can occur. Recognizing the signs of overdose and knowing how to respond can be life-saving.
Signs of Tramadol Overdose
- Seizures
- Severe incoordination
- Extreme sleepiness
- Agitation
- Rapid heartbeat
What should pet owners do in case of suspected tramadol overdose? If an overdose is suspected, it’s crucial to contact a veterinarian or emergency animal hospital immediately. Do not wait for symptoms to worsen, as prompt treatment can prevent serious complications.
Emergency Response Steps
- Contact your veterinarian or an emergency animal hospital
- Provide information about the amount ingested and when
- Follow the veterinarian’s instructions carefully
- Be prepared to bring your pet in for immediate treatment if advised
Tramadol, while an effective pain management tool, requires careful consideration of potential drug interactions, proper administration, and vigilant monitoring for side effects. By understanding these aspects, veterinarians and pet owners can ensure the safe and effective use of tramadol in animal patients.
As research in veterinary pharmacology continues to evolve, our understanding of tramadol’s interactions and optimal use in different species and conditions may expand. Always consult with a veterinarian for the most up-to-date information and personalized advice for your pet’s specific needs.
Remember, the key to successful pain management with tramadol lies in open communication between pet owners and veterinarians, careful adherence to prescribed dosages and administration guidelines, and prompt reporting of any concerning symptoms or side effects. With these practices in place, tramadol can be a valuable tool in improving the quality of life for pets suffering from acute or chronic pain.
Tramadol | VCA Animal Hospital
What is tramadol?
Tramadol (brand names: Ultram®, ConZip®, Durela®, Ralivia®, Rybix®, Ryzolt®, Tridural®, Zytram®) is a synthetic opioid used to treat pain in dogs, cats, and other small mammals.
Its use in small animals to treat pain is ‘off label’ or ‘extra label’. Many drugs are commonly prescribed for off label use in veterinary medicine. In these instances, follow your veterinarian’s directions and cautions very carefully as their direction may be significantly different from those on the label.
How is tramadol given?
Tramadol is given by mouth in the form of a tablet, capsule, or a compounded liquid. It may be given with or without food, but due to its bitter taste, giving it with food may be required. If vomiting occurs when given on an empty stomach, give future doses with food or a treat. Liquid forms of this medication should be measured carefully.
Never give tramadol with acetaminophen (Ultracet®) to cats, as acetaminophen is extremely toxic to cats.
This medication will usually take effect quickly, in about 1 to 2 hours, and improvement in clinical signs should follow. However, in pets with chronic pain, this medication can take up to a few weeks before full effects are noted.
What if I miss giving my pet the medication?
If you miss a dose, give it when you remember, but if it is close to the time for the next dose, skip the dose you missed and give it at the next scheduled time, and return to the regular dosing schedule. Never give your pet two doses at once or give extra doses.
Are there any potential side effects?
Side effects could include sedation, tremors, dizziness, anxiety, decreased appetite, vomiting, diarrhea, or constipation in dogs. In cats, possible side effects include vomiting, constipation, sedation, dilated pupils, or uneasy feeling.
Adverse effects may include seizures, incoordination, extreme sleepiness, agitation, or fast heartbeat, and these may be signs of an overdose. Contact your veterinarian if you note these signs.
This short-acting medication should stop working within 24 hours, although effects can be longer in pets with liver or kidney disease.
Are there any risk factors for this medication?
Tramadol should not be used it pets that are hypersensitive to opioids. It should be used with caution in patients with seizure disorders, liver or kidney disease, or in geriatric, debilitated, pregnant, or lactating pets. Do not use tramadol in conjunction with medications that decrease brain or lung function.
Are there any drug interactions I should be aware of?
The following medications should be used with caution when given with tramadol: antidepressants, azole antifungals, cimetidine, cyproheptadine, digoxin, ketamine, MAO inhibitors, metoclopramide, ondansetron, opioids, quinidine, SAMe, sevoflurane, SSRI and tricyclic antidepressants, warfarin, and yohimbine.
Be sure to tell your veterinarian about any medications (including vitamins, supplements, or herbal therapies) that your pet is taking.
Is there any monitoring that needs to be done with this medication?
There is no specific monitoring that needs to be done while your pet is taking this medication. Your veterinarian may monitor your pet to be sure that the medication is working. Monitor at home for adverse effects.
How do I store tramadol?
Tramadol tablets or capsules should be stored at room temperature around 25°C (77°F), away from moisture and light. Excursions in temperatures between 15°C to 30°C (59°F to 86°F) are permitted, but extreme heat and cold should be avoided.
Tramadol liquid preparations will likely need to be refrigerated, but always follow the storage recommendations on the product label.
What should I do in case of emergency?
If you suspect an overdose or an adverse reaction to the medication, call your veterinary office immediately. Signs of an adverse reaction or overdose of tramadol include seizures, incoordination, extreme sleepiness, agitation, or fast heartbeat. If your veterinarian is not available, follow their directions in contacting an emergency facility.
Evidence For Tramadol-Warfarin Interaction
Published: October 2006
This article is more than five years old. Some content may no
longer be current.
Prescriber Update 27(2): 23-24.
October 2006
Ruth Savage, Medical Assessor, CARM, New Zealand Pharmacovigilance
Centre, Dunedin
Local and international case reports provide evidence of an interaction
between oral tramadol and warfarin in some individuals, leading to an elevated
International Normalised Ratio (INR) and in some instances bruising or haemorrhage.
The mechanism has not been determined. The interaction usually occurs
3-4 days after tramadol is commenced in patients stabilised on warfarin.
The decrease in INR after tramadol is withdrawn may take several days.
Where it is necessary to prescribe tramadol with warfarin there should be
close monitoring of the INR, especially during the first week of treatment
with tramadol.
CARM reports show marked increases in INR
Up to 31 July 2006, the Centre for Adverse Reactions Monitoring (CARM)
had received a total of 116 reports of suspected adverse reactions to tramadol.
Three of these reports were of increased International Normalised Ratio
(INR), ranging from 7.0 to 12.3 occurring when oral tramadol was given to
patients taking warfarin. Two patients were symptomatic: one with
petechiae and one with melaena. Onset time after tramadol was commenced
was one, two and seven days. A fourth patient taking warfarin was
found to have bruising and a haematoma eight days after commencing tramadol.
The extent to which tramadol contributed to the elevated INR in the four
patients is not entirely clear as one patient may have taken an incorrect
dose of warfarin and the other three were also prescribed antibiotics.
However, tramadol seemed the most likely cause in two of these cases.
Published case reports provide further evidence
Firmer evidence of an interaction with oral tramadol can be found in
two published case reports.1,2
A 76-year-old man had been on a stable dose of warfarin for six months when
he developed purpura and was found to have an INR of 7.3. He had been
taking tramadol 50mg three times daily for one month. There had been
no other changes to his prescribed medication, and he had not taken any
over-the-counter medicines.1 A 61-year-old
woman on a stable regime of medicines including warfarin had recently finished
taking tramadol 50mg six hourly for two weeks. She presented with
extensive bruising of the right upper arm, and was found to have an INR
of 10.6. Warfarin was withheld for three days until her INR reduced
sufficiently for the warfarin to be reinstated, although initially a lower
dose was required.2
Similar reports in Australia
Case reports published in 2004 by the Australian Adverse Drug Reactions
Advisory Committee (ADRAC) detail 11 reports of elevated INR or haemorrhage
when tramadol was taken with warfarin. 3
The median onset time after addition of tramadol to stabilised warfarin
therapy was four (range 3-7) days, with the exception of one outlier at
six weeks. Five reports described recovery within 1-4 days of tramadol
being discontinued, with or without reduction in the dose of warfarin.
Two patients, aged 76 and 88 years, died of haemorrhagic stroke.
The interaction may occur in a sub-group of patients
In a pharmacodynamic study4 of the effect
of oral tramadol on INR in 19 patients stabilised on phenprocoumon (a coumarin
anticoagulant), two patients had clinically significant increases in INR
to 6.0 and 7.3, respectively, while taking tramadol. However, the
mean difference in INR for all participants did not reach statistical significance.
The mechanism of the interaction is unclear, but these results suggest that
the interaction may be associated with a variation in metabolism and that
only a sub-group of patients will be affected. This possibility is
supported by the small number of case reports in the Australian database
compared with total prescriptions for oral tramadol.3
Increased INR monitoring necessary when tramadol prescribed
with warfarin
Although the mechanism has not been elucidated, there is evidence for
an interaction between oral tramadol and warfarin in some, but probably
not all, individuals. The CARM case reports, where antibiotics were
also implicated, are a reminder that more than one interaction may be occurring.
The interaction between tramadol and warfarin is documented in the product
information for tramadol.5-7
It is unclear whether the interaction occurs with injectable tramadol.3
Close monitoring of the INR should be undertaken when it is necessary
to prescribe tramadol for patients taking warfarin, especially during the
first week of treatment with tramadol.
Competing interests (author): none declared.
References
- Scher ML, Huntington NH, Vitillo JA. Potential interaction
between tramadol and warfarin. Ann Pharmacotherapy 1997;31:646-647. - Sabbe JR, Sims PJ, Sims MH. Tramadol-warfarin interaction.
Pharmacotherapy 1998;18(4):871-873. - Adverse Drug Reactions Advisory Committee (ADRAC), Australia.
Tramadol-warfarin interaction. ADRAC Bulletin 2004;23(4). - Boeijinga JK, van Meegan E, van den Ende R. Lack of interaction
between tramadol and coumarins. J Clin Pharmacol 1998;38:966-970. - CSL (New Zealand) Limited. Tramal (tramadol) data sheet
October 2005.
www.medsafe.govt.nz/profs/Datasheet/t/TramalcapSRtabinjoraldrops.pdf - Pharmaco (NZ) Limited. Zytram BD (tramadol) data sheet
20 February 2006. www.medsafe.govt.nz/profs/Datasheet/z/ZytramBDtab.pdf
- AFT Pharmaceuticals Ltd. Tramadol data sheet 8 December
2005. www.medsafe.govt.nz/profs/Datasheet/t/TramadolHydrochloridecap.pdf
Tramadol drug interactions with other drugs (compatibility) | Vidal.ru
Effects when used simultaneously with drugs | |
Naltrexone madol there is a significant decrease (up to a complete blockade) of the effects of the latter. | |
Fluvoxamine | Increased risk of seizures and serotonin syndrome. |
Carbamazepine | Decreased plasma concentration of tramadol and its analgesic effect. |
Antipsychotics | Increased risk of seizures. |
Phenobarbital (barbiturates) | With the systematic use of barbiturates, especially phenobarbital, there is a possibility of a decrease in the analgesic effect of opioid analgesics.![]() |
Paroxetine | Cases of serotonin syndrome and seizures have been described. |
Fluoxetine | Serotonin syndrome has been reported. Additive risk of seizures. |
Citalopram and enantiomers | Increased risk of seizures. This combination should be avoided. |
Lithium salt | Tramadol inhibits the reuptake of norepinephrine and serotonin and increases the release of serotonin. With the simultaneous use of tramadol and lithium preparations, there is a possibility of synergism of this effect. Patients require constant monitoring and, if necessary, correction of the dosing regimen of both drugs. |
Flupentixol | Additive risk of convulsions and increased CNS depressant effect. This combination should be avoided. |
Naloxone | Naloxone activates respiration, eliminating analgesia after the use of opioid analgesics (including fentanyl).![]() |
Serotonin reuptake inhibitors | Increased risk of seizures. |
Anti-seizure drugs | Increased risk of seizures. |
Warfarin | Increased anticoagulant effect of warfarin. |
Olanzapine | Increased risk of increased inhibitory effect on the central nervous system, as well as seizures. |
Pimozide | Additive CNS depressant effect and risk of seizures when tramadol is administered to patients receiving pimozide. This combination should be avoided. |
Sulpiride | Increased risk of seizures. This combination should be avoided, especially in patients susceptible to seizures. |
MAO inhibitors | Possible serotonin syndrome. |
Serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, other drugs that lower the seizure threshold | Increased risk of seizures.![]() |