What are the potential drug interactions with tramadol. How can patients safely use tramadol with other medicines and supplements. What precautions should be taken when combining tramadol with other medications. What are the risks of mixing tramadol with certain drugs.

Understanding Tramadol: A Synthetic Opioid for Pain Management

Tramadol is a synthetic opioid widely used to treat pain in both humans and animals. In veterinary medicine, 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 specifically approved for veterinary use, veterinarians may prescribe it based on their professional judgment and experience.

Tramadol is available in various forms, including tablets, capsules, and liquid preparations. It’s typically administered orally and can be given with or without food. However, due to its bitter taste, some pets may require it to be given with food to ensure they take the medication.

How Quickly Does Tramadol Take Effect?

Tramadol usually begins to work within 1 to 2 hours of administration. However, for pets with chronic pain conditions, it may take up to a few weeks before the full effects are noticeable. This gradual onset of action is important to keep in mind when evaluating the medication’s effectiveness.

Potential Side Effects and Risks of Tramadol in Pets

While tramadol is generally considered safe when used as directed, it can cause side effects in some animals. These effects can vary between species and individual pets.

• In dogs: sedation, tremors, dizziness, anxiety, decreased appetite, vomiting, diarrhea, or constipation
• In cats: vomiting, constipation, sedation, dilated pupils, or uneasiness

More severe adverse effects, which may indicate an overdose, include seizures, incoordination, extreme sleepiness, agitation, or rapid heartbeat. If you observe any of these signs in your pet, it’s crucial to contact your veterinarian immediately.

Are There Any Contraindications for Tramadol Use in Pets?

Tramadol should not be used in pets that are hypersensitive to opioids. Caution is advised when using tramadol in animals with certain pre-existing conditions or states:

• Seizure disorders
• Liver or kidney disease
• Geriatric or debilitated pets
• Pregnant or lactating animals

Additionally, tramadol should not be used in conjunction with medications that decrease brain or lung function, as this combination can potentially lead to dangerous side effects.

Critical Drug Interactions with Tramadol

When prescribing or taking tramadol, it’s essential to be aware of potential drug interactions. Certain medications can interact with tramadol, altering its effectiveness or increasing the risk of side effects.

Which Medications Require Caution When Used with Tramadol?

The following medications should be used with caution when given alongside tramadol:

• Antidepressants (including SSRIs and tricyclic antidepressants)
• Azole antifungals
• Cimetidine
• Cyproheptadine
• Digoxin
• Ketamine
• MAO inhibitors
• Metoclopramide
• Ondansetron
• Other opioids
• Quinidine
• SAMe
• Sevoflurane
• Warfarin
• Yohimbine

It’s crucial to inform your healthcare provider or veterinarian about all medications, including vitamins, supplements, or herbal therapies, that you or your pet are taking to avoid potential interactions.

Tramadol and Warfarin: A Noteworthy Interaction

One particularly significant interaction that has been observed is between tramadol and warfarin, an anticoagulant medication commonly used to prevent blood clots. Evidence from both local and international case reports suggests that this interaction can lead to an elevated International Normalised Ratio (INR) in some individuals, potentially resulting in bruising or hemorrhage.

How Does the Tramadol-Warfarin Interaction Manifest?

The interaction between tramadol and warfarin typically occurs 3-4 days after tramadol is introduced in patients who are already stabilized on warfarin therapy. While the exact mechanism of this interaction hasn’t been fully determined, it’s crucial for healthcare providers and patients to be aware of this potential risk.

Patients taking warfarin who are prescribed tramadol should be closely monitored, particularly in the first week after starting tramadol. Regular INR checks may be necessary to ensure the anticoagulant effect remains within the desired therapeutic range.

Safe Use and Storage of Tramadol

Proper use and storage of tramadol are crucial for both its effectiveness and safety. Whether you’re taking tramadol yourself or administering it to a pet, following the prescribed dosage and storage instructions is essential.

What Should I Do If I Miss a Dose of Tramadol?

If you miss a dose of tramadol, take it as soon as you remember. However, if it’s close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Never take or give two doses at once to make up for a missed dose, as this can increase the risk of side effects or overdose.

How Should Tramadol Be Stored?

Tramadol tablets or capsules should be stored at room temperature, around 25°C (77°F), away from moisture and light. While brief temperature excursions between 15°C to 30°C (59°F to 86°F) are generally acceptable, extreme heat or cold should be avoided.

Liquid preparations of tramadol often require refrigeration. Always check the product label for specific storage instructions, as these can vary between different formulations.

Monitoring and Emergency Situations with Tramadol

While there’s no specific monitoring required for tramadol use, it’s important to be vigilant for any signs of adverse effects or changes in condition. Your healthcare provider or veterinarian may conduct periodic check-ups to ensure the medication is working effectively and not causing any problems.

What Should I Do in Case of a Suspected Tramadol Overdose?

If you suspect an overdose or observe severe adverse reactions to tramadol, it’s crucial to seek immediate medical attention. Signs of a potential overdose or severe reaction may include:

• Seizures
• Incoordination
• Extreme sleepiness
• Agitation
• Rapid heartbeat

In such cases, contact your healthcare provider or veterinarian immediately. If they’re unavailable, follow their instructions for contacting an emergency facility.

Tramadol in Veterinary Medicine: Special Considerations

While tramadol is widely used in human medicine, its application in veterinary practice comes with some unique considerations. As mentioned earlier, its use in animals is often ‘off label’, meaning veterinarians must rely on their expertise and available research to determine appropriate dosages and usage.

Can Tramadol Be Used in All Pet Species?

While tramadol is commonly used in dogs and cats, its effectiveness and safety profile can vary between species. For instance, recent studies have questioned its efficacy in managing pain in cats. Always consult with a veterinarian before using tramadol or any other medication in pets, as they can provide species-specific advice and dosing instructions.

It’s also crucial to note that some formulations of tramadol for human use may contain other ingredients that are toxic to pets. For example, tramadol combined with acetaminophen (Ultracet®) should never be given to cats, as acetaminophen is extremely toxic to felines.

The Future of Tramadol Use and Research

As with many medications, our understanding of tramadol continues to evolve. Ongoing research aims to better understand its mechanisms of action, potential interactions, and optimal use in both human and veterinary medicine.

What Are the Current Areas of Research Regarding Tramadol?

Current areas of research involving tramadol include:

• Investigating its efficacy in various pain conditions
• Exploring potential new formulations or delivery methods
• Studying its long-term effects and safety profile
• Examining its use in different animal species
• Investigating potential new drug interactions

As new research emerges, guidelines for tramadol use may be updated. It’s important for healthcare providers, veterinarians, and patients to stay informed about the latest recommendations and findings related to tramadol use.

In conclusion, while tramadol can be an effective tool for pain management in both humans and animals, its use requires careful consideration of potential interactions, side effects, and individual patient factors. By staying informed and working closely with healthcare providers or veterinarians, patients and pet owners can help ensure the safe and effective use of this medication.

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

1. Scher ML, Huntington NH, Vitillo JA. Potential interaction
   between tramadol and warfarin. Ann Pharmacotherapy 1997;31:646-647.
2. Sabbe JR, Sims PJ, Sims MH. Tramadol-warfarin interaction.
   Pharmacotherapy 1998;18(4):871-873.
3. Adverse Drug Reactions Advisory Committee (ADRAC), Australia.
   Tramadol-warfarin interaction. ADRAC Bulletin 2004;23(4).
4. Boeijinga JK, van Meegan E, van den Ende R. Lack of interaction
   between tramadol and coumarins. J Clin Pharmacol 1998;38:966-970.
5. CSL (New Zealand) Limited. Tramal (tramadol) data sheet
   October 2005.
   www.medsafe.govt.nz/profs/Datasheet/t/TramalcapSRtabinjoraldrops.pdf
6. Pharmaco (NZ) Limited. Zytram BD (tramadol) data sheet
   20 February 2006. www.medsafe. govt.nz/profs/Datasheet/z/ZytramBDtab.pdf
7. 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. Long-term use of opioid analgesics or barbiturates stimulates the development of cross-tolerance.
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. Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website