Minimize the Risk of NSAIDs in Canine Patients

Minimize the Risk of NSAIDs in Canine Patients

By Dr Tarryn Dent (BSc Veterinary Biology, BVSc),
Marketing Manager, Zoetis

1. Get a Full Medical History

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most common classes of drugs used in our patients today and are frequently used in combination with other classes of analgesic drugs as part of a pain management program, or given concurrently with other drugs used to manage underlying conditions.2 Information on recent medications, previous drug adverse reactions, and any medical conditions should be evaluated prior to the dog beginning NSAID treatment.2

The use of NSAIDs with corticosteroids can significantly increase the risk of gastrointestinal adverse effects; similarly the concurrent use of different NSAIDs together may also increase the risk of gastrointestinal adverse events2, therefore NSAIDs should be avoided or used with extreme caution if the animal is currently on NSAIDs and/or corticosteroids.1 The history will also indicate if there was recent use of NSAIDs or corticosteroids and then adequate washout periods need to be considered (discussed later on).

NSAIDs are highly protein bound and most package inserts will indicate caution when using with other highly protein bound substances and that drug displacement from the proteins can occur. The clinical significance of these interactions is likely to be low, and the protein binding displacement interactions involving NSAIDs used for chronic management of osteoarthritis are unlikely to cause adverse effects in patients.2

COX-1 and COX-2 are involved in renal tubular function and renal blood flow regulation; therefore we cannot just assume that COX-1-sparing NSAIDs are safer for the kidneys.2 NSAIDs cause renal injury through inhibition of prostaglandins important in maintaining renal haemodynamics, although the exact mechanism is not yet understood.2 Important to note that healthy dogs administered approved doses of NSAIDs are at a low risk for developing renal adverse events.2

Ensure appropriate hydration and haemodynamic status when animals receiving NSAIDs undergo anaesthesia and/or surgical procedures or develop conditions which may result in dehydration or compromised haemodynamic status.2 The key aim of intervention is to maintain adequate renal perfusion.

What to be aware of is concurrent use of NSAIDs with other potentially nephrotoxic drugs (e.g. aminoglycosides) is not recommended as it increases the risk of renal injury.1 Practitioners should also observe additional precautions with renal function due to possible drug interactions with furosemide and use caution with angiotensin-converting enzyme inhibitors.1,2

2. Not all Patients are Candidates for NSAIDs

-Be discriminating in your patient selection and be cautious or avoid NSAIDs in patients with the following existing/anticipated conditions:

-Renal dysfunction: the effects of NSAIDs on the renal function of dogs with underlying renal disease have not yet been reported, therefore use cautiously in these patients.1,2

-Hepatic dysfunction:   there is very limited data of use of NSAIDs in animals with underlying hepatic disease, and no data indicating increased risk of NSAID hepatic toxicity in these animals

-If the NSAID dose needs to be reduced due to slower elimination of the drug, (cats or hepatic disease) the drug should be used with caution in these animals.1,2

-Cardiac dysfunction.1

-Low-flow states such as dehydration, hypovolemia, congestive heart failure, and hypotension. In such cases, IV fluid support and blood pressure monitoring should be available for anaesthetised animals.1

3. Give the Client Verbal and Written Instructions

Give the client verbal and written instructions to avoid contraindicated medications as mentioned above and to discontinue and alert the hospital at the first sign of an adverse event.1

Osteoarthritis is a life-long disease and the client buy in and understanding is the most important aspect to having a successful treatment program for the patient.

The client needs to understand the medication prescribed and extra time needs to be spent with these clients. This will ultimately lead to improved compliance and hopefully the owner will be able to pick up early signs of adverse events.

4. Recognise Early Signs of Adverse Effects (AEs) and Immediately Withdraw NSAID Treatment

It is critical that veterinarians provide the client information that describes the potential side effects. Signs of gastrointestinal toxicity usually emerge within the first 2 – 4 weeks; however they can occur at any point during administration.1

Recognition of early signs of adverse events, such as inappetence allows early intervention and a better prognosis.

5. Perform Laboratory Monitoring

Frequency of laboratory monitoring depends on the risk factors of the patient. Ideally laboratory monitoring should be done within the first month of initiating treatment and then every 6 months thereafter in low-risk patients.

For at-risk patients monitoring can be done more frequently, such as every 2-4 months depending on the risk-factor assessment.1

Other literature advises to do an initial baseline hepatic and renal panels by clinical chemistries before initiating chronic NSAID therapy, then testing again in the first two weeks and thereafter periodically. This allows the clinician to assess trends and absolute values and to investigate any increases in hepatic enzymes that may occur. 2

6. Utilise a Balanced, Integrated Analgesic

Approach as Part of NSAID-Sparing Strategies

A pre-examination questionnaire for the owner, of behavioral changes or abnormalities would be the first step in recognising and assessing pain, however thereafter there should be measures put in place for not only veterinary assessment at regular intervals, but rather to also have primarily pet owner observation and input.1 This will allow the veterinarian to monitor how the patient is doing and if the pain is under control.

NSAIDs form the cornerstone of oral osteoarthritis therapy and controls the chronic inflammation and pain. If the chronic pain is not controlled it will lead to peripheral and central sensitisation and lead to progression of the disease.2

Current evidence shows that using NSAIDs at the labeled dose for long term treatment is beneficial and does not increase the NSAID-induced adverse events as the duration of treatment continues.1,2

If a patient responds well to a NSAID during chronic pain management but then experiences an increase in pain due to progression of the underlying disease, then rather than switching NSAIDs it may be more appropriate to add another analgesic from a different class of drugs.2

A holistic approach to osteoarthritis pain management is encouraged, paying attention to weight control, hydrotherapy, physiotherapy, and potentially acupuncture can all assist with pain management.2

Once again discussing the treatment plan, goals and expectation to the owner is vital to the success of treatment.

7. Consider Washout Periods

In the event that a patient after initiating therapy has an adverse reaction or an inadequate response to a NSAID, switching to a different NSAID may be indicated.2 Most experts recommend a washout period between switching oral NSAIDs for chronic pain management to avoid the potential for adverse effects, however clinically relevant washout periods remain controversial and largely undefined.1,2

Conservative washout periods for NSAIDs, apart from aspirin and mavacoxib, have been 5 – 7 days, assuming the switch is not due to adverse effects.2

Aspirin should not be administered because there are safer alternatives, however if a course of treatment with aspirin has been started in a dog, the recommended washout period before starting an approved veterinary NSAID is up to 10 days.1

When switching from a corticosteroid to a NSAID, if it is a short-acting corticosteroid 7 days washout period applies, however if longer acting corticosteroids, a longer washout period should be considered.1

If the reason for switching is due to adverse effects from a NSAID, additional precautions should be considered before starting another NSAID. If the adverse event is gastrointestinal, ideally you should wait until all clinical signs have resolved before beginning the new treatment. The addition of prostraglandin E analogues (misoprostil) and gastroprotectants can also be considered.2

8. Use Gastroprotectants

Use gastroprotectants to either treat suspected gastropathy or prevent its occurrence, especially if no washout period is implemented. Proton pump inhibitors, H2 antagonists, misoprostol, and sucralfate can be helpful.1  The afferent renal artery and the gastric mucousal arteries use PG E to vasodilate in conditions of hypovolaemia to ensure bloodflow.  NSAIDs block the ability of the body to compensate in this manner and causes local ischaemia. This is where misoprostol has a role to play.

9. Dose Optimization

Work out dosage on lean body weight. Some clinicians recommend titrating to the lowest effective dose, however there is no definitive evidence that the dose reduction of NSAID lowers the risk of adverse events.1 In the case of Trocoxil®, the dosage of 2 mg/kg body weight is already the lowest effective dose, therefore decreasing the dose is not advised.

References:

1. Epstein M., et al. 2015 AAHA/AAFP Pain Management Guidelines for     Dogs and Cats. J Am Anim Hosp Assoc. 2015; 51 : 67 – 84.

2. KuKanich B., Bidgood T., Knesl O. Clinical pharmacology of

    nonsteroidal anti-inflammatory drugs in dogs. Veterinary Anaesthesia     

    and Analgesia. 2012; 39: 69 – 90.

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