Questions Asked by Attendees

At the end of the webinar I was asked a question about NSAIDs and administration with food. I made the point that it was important to follow the recommendations on feeding because it could significantly affect bioavailability. I mistakenly said that feeding did not significantly affect the bioavailability of mavacoxib (Trocoxil), in fact it is recommended to give Trocoxil with food otherwise bioavailability is significantly reduced. I apologise for this error in the talk.

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Q: Do you use cartrophen (pentosan phosphate) and how would you combine it with NSAID (egg given on alternative days)

Because of the clinical case load that I am involved with I do not have much direct experience with the use of pentosan polysulphate. A review of the safety of Cartrophen Vet in the dog was published in the JSAP in 2003 – and Cartrophen was reported to be very safe – with relatively few adverse effects associated with use (data based on reporting of adverse reactions via pharmacovigilance data). One concern with pentosan polysulphate is a decrease in blood clotting efficacy, which combined with NSAIDs (particularly aspirin and COX unselective drugs that may have a more pronounced effect on the blood clotting cascade), could precipitate bleeding, and the licensing regulations state that NSAIDs should not be given in combination with Cartrophen Vet. The effect of Cartrophen Vet on blood clotting is likely to be relatively short lived – but ideally I would avoid co-administration of NSAIDs during treatment – and start NSAIDs one week after the end of treatment. If the dog is very painful and you deem that the dog requires NSAIDs for analgesia choose a coxib, where the effects on blood clotting are likely to be minimal.

Q: I routinely give cats convenia but notice that nsaid concurrent administration is not recommended, as pain relief is quite often needed what would you recommend.

It is not recommended to give Convenia with NSAIDs because concurrent administration can result in higher than expected plasma concentrations of the NSAID due to a decrease in protein binding. This is more likely to be a clinically significant interaction in animals that have a low albumin concentration – where a further decline in protein binding of the NSAID might cause an adverse effect. Plasma albumin concentration also does not significantly affect binding of robenacoxib and free concentration of the drug – therefore although off license, if pain relief is needed in the home environment co-administration of an NSAID and Convenia is desirable. Avoid this combination in animals that are hypoproteinaemic.

Q: The NSAID that you give once a month – what are your thoughts?

I think that the concept of prolonged continuous dosing using a long acting agent is a good one because of the potential to reduce central sensitization and therefore dampen the cycle of pain. On the other hand I am cautious about the event of side effects developing and management in a long acting drug. Clinically mavacoxib appears to be safe and efficacious. It would not be my choice of drug if I thought that the animal was at an increased risk of side effects due to concurrent disease – and it also depend on whether the owner will remember to dose regularly when the interval is a month between treatments. However in general I like the principle of continued pain management – avoiding any dips and troughs in analgesia over time.

Q: What is your first line of therapy?

Currently there is no evidence to support superior analgesic efficacy of one NSAID over another, therefore in terms of provision of analgesia I am happy to use any of the licensed drugs. In terms of COX-2 selectivity I think it is advantageous to use a drug with some COX-2 selectivity or a drug that is a COXIB compared to a non-selective drug. My other considerations are tissue selectivity (advantageous), licensing restrictions, previous experiences of the dog with NSAIDs. I will choose one of carprofen, meloxicam or robenacoxib.

Q: Any suggestion that high doses of purified fish oil can have sufficient anti-inflam and analgesic effects in dogs?

There is moderate evidence that green lipped mussels provides a positive benefit in the management of dogs with osteoarthritis, although the quality of the studies was only moderate. Due to the limited number of high quality studies it is difficult to objectively evaluate the evidence provided by green lipped mussels. There are no studies to support the use of purified fish oil.

Q: What are your thoughts on giving an onsior injection and then sending home on previcox tablets?

I don’t recommend this strategy because Previcox is not licensed to follow a NSAID injection and Onsior injection is not currently licensed to be followed by previcox. There is anecdotal evidence to suggest that we shouldn’t mix different NSAIDs without an adequate wash-out period, although probably a shorter wash out period or minimal period is needed after a single injection of a NSAID.

Q: At what stage do you start using tramadol as adjunctive therapy?

In most animals (unless I believed there was a significant neuropathic component to the pain) I would introduce tramadol as my 1st adjunctive analgesic agent to NSAID therapy. I would start thinking about other drugs if the dog was still significantly painful after 2-3 weeks of NSAID therapy. At the same time as starting NSAIDs I would have discussed strategies like weight management, physiotherapy, and nutraceuticals with the owner – and suggested that the dog start with a glucosamine supplement at an appropriate dose. However these strategies can take 6-8 weeks to start to be effective. I would attempt to tailor off the tramadol after the dog had been on glucosamine therapy for about 8 weeks –to see if NSAIDs and the adjunctive measures were adequate without tramadol. If the dog developed clinically significant side effects with the NSAID I would stop the NSAID and start the tramadol immediately. Depending on your NSAID it may be worth trying a different NSAID that is more COX-2 selective or tissue selective after stopping NSAID therapy for 7-10 days, tramadol can be used to provide analgesia in the intervening period.

Q: What would you consider to be the best time to inject a NSAID for elective surgery?

In a dog that is healthy, and hypotension is not expected during surgery / anaesthesia I would give the NSAID before the start of surgery – for robenacoxib about 30 minutes before, for carprofen and meloxicam 30 mins or greater before the start of surgery –if practical – e.g. after induction of anaesthesia. If I am in any doubt about the animal’s CVS stability, renal function, blood clotting etc. or if I think I may need to give steroids during surgery – e.g. airway surgery with a risk of oedema I would delay until the animal was completely recovered from anaesthesia, normotensive and able to maintain normal fluid balance.

Q: so in a geriatric cat with painful OA and severe renal compromise, what drug do you choose to switch to long-term?

This is a difficult question – as I would be worried about renal function with NSAIDs if the animal had severe renal disease  – I would probably try amantadine first off – it’s an NMDA receptor antagonist (similar to ketamine) and has been shown to provide adjunctive analgesia in combination with NSAIDs – no studies have looked at the drug alone. There are also no studies in cats – although people are using it in cats. In the very short term the cat may require transient hospitalization for buprenorphine therapy for a few days to see if the amantadine is having any effect. I would avoid tramadol as cats find it so bitter and aversive. Gabapentin would be another drug that I would consider second line for the long term – or try switching to gabapentin if amantadine is ineffective. I would also start supplementing with glucosamine.

Q: so if you are doing a full dental clearance on an elderly cat with moderate elevations in urea/creatinine compromise, do you give a full dose nsaid dose pre op or not? I have concerns but also don’t want the animal to be painful

I would not give a NSAID pre-operatively to this patient because of the risk of hypotension during a potentially protracted anaesthesia for a full dental clearance. I would provide peri-operative analgesia with opioids – e.g. buprenorphine 20 µg/kg for 24 – 36 hours and also carry out appropriate local nerve blocks before the start of the dental using bupivicaine (maxillary and mandibular nerve block), local infiltration around any teeth that are to be removed – care with total dose of bupivicaine to avoid overdose (max dose 2mg/kg in total). Once the cat is fully recovered from anaesthesia, normotensive and maintaining fluid balance you could think about giving NSAIDs at this time point. A full dental clearance will be painful – so it’s a balance against sufficient analgesia to maintain drinking and eating to avoid hypotension and the risks of NSAIDs if the cat becomes hypotensive worsening renal function. NSAIDs are not necessarily contraindicated but the owner should be fully informed of the risks and when not to give a dose. I would be sure that the cat was eating well voluntarily before I gave the first NSAID dose.

Q: How much time should you give for a ‘wash out’ period when switching b/n NSAIDs?

This is a difficult question – a longer wash-out is likely to be needed if the dog has reduced liver function because drug accumulation is more likely (generally). Currently there are no evidence based recommendations –most people recommend between 5-7 days. Tramadol can be used to provide analgesia in the intervening time period.

Q: is it best to keep on low dose nsaids daily, or is it ideal to use and when required?

It depends on the animal and severity of pain – but if the owner reports that the dogs shows altered demeanor / mobility / agility or other changes in behaviour that could be indicative of pain (e.g. restlessness) on a daily basis I would dose the dog daily – even if this was at a lower than the licensed dose (e.g. ¾ or ½ dose). There is good evidence to support central sensitization in dogs with OA (extrapolating data from other species) – and effective continuous pain management is likely to help obtund central sensitization and therefore “break the cycle” of pain. This is more likely to be achieved with daily dosing compared to intermittent dosing. If, on the other hand, the dog is generally comfortable / pain free apart from after long walks / heavy exercise I would suggest that the owners controls the exercise better so that the amount is reduced and regular – and think about non pharmacological options first.

Q: is it advisable to start a patient on nsaids as soon as signs of poor mobility, and reduced activity levels are observed/ perceived by the owner?

Decision making about when to start an animal on NSAID therapy is difficult – the risk of side effects must be balanced against the detrimental effects of chronic pain and quality of life. I would probably recommend a short course of NSAID therapy in an animal with this stage of disease – and at the same time start with glucosamine therapy, think about exercise management – i.e. regular exercise of similar activity levels and if appropriate weight management. Diet changes e.g. to Hills J/D are also worthwhile considering. Once these non-pharmacological measures have been established (4-6 weeks later) I would try stopping the NSAIDs to see if the dog deteriorates in demeanor or mobility. If not then you can stop NSAID therapy until it is required later as the disease progresses.

Q: I understand from a medical friend that cortisone/nsaid combinations are not a problem.  Is this so, and is so, why the difference?

In any species there is a risk that the combination of a corticosteroid and a NSAID will cause an increased likelihood of side effects, particularly gastric side effects. I do not have information about the relative safety of this combination in man compared to animals. GI side effects and ulceration are a huge problem in people taking NSAIDs – and the combination with steroids will increase the risk of side effects further. Maybe people are able to report warning signs of an adverse effect earlier –i.e. Nausea and sickness – therefore the combination can be stopped before overt side effects resulting from gastrointestinal ulceration develop. I would not recommend steroids and NSAIDs together in dogs – there is evidence to show that this combination is associated with adverse gastrointestinal events in dogs.

Q: how long do you recommend to leave from one NSAID and another when you swap type in chronic therapy?

This is a difficult question to give a definitive answer to because we don’t have an evidence base to support this sort of decision making. Generally I recommend leaving 5-7 days (with the exception of mavacoxib – 2-4 weeks). Tramadol can be used to provide analgesia in the intervening period.

Q: Could you comment on the drug PLT, as it sometimes seem to give pain relief when Nsaids and steroids alone do not

PLT does appear to be very effective in some dogs, but the drug combination is also associated with a significant risk of side effects, therefore it is certainly not my first line drug. With end stage disease where other drugs prove ineffective it may be worth evaluating the drug in some animals. The risk of GI ulceration must be carefully considered.

Q: my own dog is currently on rimadyl, gabapentin and tramadol, plus j-d and seraquin and has weekly hydro. He has 3 legs. 1 hind limb has had tplo, his only forelimb has OCD and he has had sx for medial coronoid dx. I am considering qol. He is only 4 yrs. old. Can i add in amantadine with all of the above!!?

Yes you can add amantadine into the above cocktail and there is definitely logic in doing this if your dog is still painful – at a dose of 5mg/kg once daily. It may be that it is very difficult to find an effective drug cocktail for an animal that is so “orthopaedically challenged”, particularly because of the required weight bearing on the forelimb.

Q: What analgesic would you choose after GI surgery?

Generally I would recommend avoiding NSAIDs after GI therapy although there are little data to support decision making during this period. Presumably gut damage resulting from surgery will be at increased risk of ulceration or decreased healing in a NSAID environment although the clinical significance of this is likely to depend on the invasiveness of the gut surgery and the health of the gut. Opioids are excellent analgesics for acute pain after GI surgery – side effects seen in man with opioid therapy e.g. constipation, gut stasis, do not seem to be clinically problematic in dogs – and pain itself can reduce gut motility. Therefore while hospitalized I would give systemic opioids combined with oral tramadol – and send the dog home on oral tramadol.

Q: what would be the wash out period for Trocoxil?

The published data indicate that in healthy dogs the half-life of mavacoxib varies between 2-4 weeks. Therefore ideally I would allow a period of 4 weeks between stopping mavacoxib and starting another NSAID. Tramadol is an alternative drug that can be used to provide analgesia in the intervening period.

Q: would you give nsaids in a suspicious cat suffering from an intoxication, without any blood test performed??

No, I would avoid NSAIDs and manage any acute pain with opioids until I had identified the underlying cause of disease or had at least identified which organ systems are likely to be affected and how severe effects are likely to be. Always consider that multiple systemic abnormalities can lead to reduced CVS function and hypotension. Even with a blood test showing normal renal function I would avoid NSAIDs until I had stabilized the animal and had a good idea how the disease was likely to progress.

Q: As a first line Nsaid would you go for the preferential or selective cox 2 inhibitor for chronic use?

I don’t think that there is currently enough evidence to definitively support the selection of a COXIB over a selective drug in terms of drug efficacy and drug side effects. For some reason (? Underlying genetics) some dogs respond better to some NSAIDs compared to others – although this cannot be predicted. If a dog was mildly intolerant of one NSAID it is worth switching to a more selective (COXIB) or tissue selective NSAID to see if side effects are less on the more selective drugs.

Q: Can you use nsaid’s on one day and steroids on other day? Is it risky for SE? What is your opinion about this regime?

I think using alternate day dosing of steroids and NSAIDs is very likely to increase the risk of gastrointestinal side effects – as the NSAID drugs will likely not be cleared from the system before dosing of the steroid. Even if side effects do not appear very accurately I think in the medium to long term the risk is unacceptably high.

Q: When NSAIDs start to be less efficacious in progressive OA would you increase dose of NSAID or give an adjunctive therapy (e.g. tramadol)

If you are not already giving the licensed daily dose of the NSAID then I would increase the dose of the NSAID to the licensed daily dose – as long as side effects were not a problem. I would give this a few days to see if it’s effective before introducing tramadol –

Q: Sorry – how long does it take for nsaids to start taking effect orally?

Peak plasma concentrations are reached relatively rapidly after oral administration of most NSAIDs – approximately 1 hour. It is important to follow recommendations about giving with food or not, as feeding will alter the bioavailability of some orally administered NSAIDs

Q: hi. Thanks.  Have you much information on the use of ketamine as a central desensitiser for pain?

“Ketamine is an NMDA receptor antagonist. The NMDA receptor contributes to the up regulation of the pain pathway and activation of this receptor is a critical component of central sensitization. There is limited clinical evidence to support the role of ketamine as an analgesic for acute pain in dogs and cats although it is being increasingly used for this purpose. Most dose recommendations for use of ketamine are based on one paper and a subsequent experimental paper suggests that this dose (10µg/kg/min) may not be great enough. I do use ketamine but never as a first line drug – always in combination with opioids – usually by CRI.

Q: Acupuncture should be included in non-pharmacological therapies – would you agree?

I personally do not have much experience of using acupuncture as part of a holistic approach to pain management for osteoarthritis but many owners and practitioners of acupuncture report success in their patients. I think it is definitely worth considering as part of a holistic protocol.

Q: should you dose NSAIDs for lean ideal body weight?

Ideally all drugs should be dosed to lean bodyweight – and very potent drugs (such as dexmedetomidine) are dosed on body surface area in order to dose appropriately based on metabolic body size. With NSAIDs there is often quite a large dose range recommended by manufacturers – hence dogs within a wide bodyweight range are recommended to receive the same dose. Accurate dosing (where possible) is advantageous – hence with an obese dog receiving meloxicam I would try to estimate lean body weight and dose on this weight.

Q: have you any comments on tens machines for dogs

Unfortunately I have not had any experience of using a tens machine in dogs.

Q: What will be your drug of choice for an individual animal who is in pain but unable to tolerate NSAID’s at all? Thank you

A: It would depend on the type of pain I thought that the dog was experiencing. With neuropathic pain I would be considering gabapentin – but this can take a couple of weeks to be effective. With acute pain I would start with opioids – in hospitalized patients. For a more inflammatory type pain I would probably start with tramadol / amantadine. If the dog is unable to tolerate NSAIDs I wouldn’t try paracetamol instead.

Q: Have you any experience of using codeine for pain in older dogs when nsaids have lots of side effects or as adjunctive meds?

I don’t have any personal experience of using oral codeine but pharmacokinetic studies indicate that the oral bioavailability of codeine is very low – approximately 4% indicating very high first pass metabolism. Therefore it will not be effective in dogs given orally.

Q: what is the half-life of paracetamol in dogs? I thought it is fairly short? And therefore not that useful for constant pain

The plasma half-life of paracetamol is quite short in dogs, but with anti-inflammatory drugs plasma concentration does not relate very well to effect site concentration. No studies that have simultaneously studied the pharmacokinetics and pharmacodynamics (analgesic effects) of paracetamol have been carried out; therefore it is difficult to comment on the analgesic efficacy at the present time.

Q: your views on reducing the daily metacam dose to a maintenance dose?

I think that you’re asking about a dose reduction strategy here. Dose reduction is recommended by many people because of the underlying rationale that if you can minimise the dose of an NSAID the incidence of side effects is likely to be less. There is no evidence to support the statement that lower than the licensed dose of NSAID will have benefits in terms of side effects – although it recognised that side effects are significantly more likely in dogs given a higher than recommended dose. On the other hand if the dose is “too low” or too infrequent – e.g. every other day dosing for example, there is a risk that break through pain may occur – which is uncomfortable for the dog and will also drive central sensitization and heightened pain sensation. I think whether to “dose titrate” depends on the dog and the owner and their ability to assess pain in their animal. Some owners are very tuned in with their dog’s pain – and for these owners dose reduction can be quite effective – good pain management is maintained and dose reduction may have some advantages in terms of side effects. If the owners is not able to assess the animal’s pain very well then I would recommend sticking to the licensed daily dose.

Q: Hello, if a dog is otherwise healthy, and tolerating long-term NSAIDs well for osteoarthritis treatment – would you advocate staying on the recommended dose of NSAID’s (i.e., dosing to lean body weight with metacam or sticking with 2mg/kg/day rimadyl), or do you advocate titrating down to ‘lowest effective dose?’

I think that the ability to dose accurately is an advantage of meloxicam – where you can exactly tailor the dose administered to the bodyweight of the animal – although the other oral NSAIDS where a dose range is given have been shown to be efficacious and safe in research studies.  It appears to be difficult to “spot” dogs that will develop side effects with NSAIDs because these can occur when the NSAID is given at the licensed dose. See the answer to the question above regarding dose reduction as the same principles apply here.

THE CONTENT OF THE WEBINAR AND THE ANSWERS TO THE QUESTIONS THAT FOLLOWED ARE THE VIEWS OF THE SPEAKER AND DO NOT REFLECT THE VIEWS OF VETOQUINOL.