TANYA'S

COMPREHENSIVE GUIDE TO

FELINE CHRONIC KIDNEY DISEASE

 

 

TREATMENTS: ANTIBIOTICS AND PAINKILLERS

 

ON THIS PAGE:


Antibiotics:


Clavamox/Synulox


Baytril


Antirobe


Convenia


 

Painkillers


Opiates: Buprenorphine, Fentanyl, Tramadol


NSAIDs: Metacam, Onsior, Aspirin


Other Painkillers: Gabapentin, Paracetomol (Acetaminophen)


 

 

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Home > Treatments > Antibiotics and Painkillers

 


Overview                                                                                                                                                           


  • Neither antibiotics nor painkillers are a routine treatment for CKD cats.

  • Sometimes a cat will need antibiotics, to treat bacterial infections such as a urinary tract infection or a dental infection.

  • Similary, painkillers and/or anti-inflammatories may sometimes be required, perhaps following surgery or to help with arthritis.


Antibiotics                                                                                                            Back to Page Index


 

Antibiotics are not an integral part of treating CKD, so if your vet prescribes them, you should ask why. Some CKD cats may need them for other reasons, such as a urinary tract infection(UTIs), a kidney infection or dental problems, but they are not normally given routinely to a CKD cat. Commonly prescribed antibiotics for CKD cats include:

Most courses of antibiotics last for 10-14 days. However, if your cat has a kidney infection (pyelonephritis), a longer course is necessary, for 4-8 weeks. Some UTIs also need a longer course of around four weeks.

 

Although most antibiotics start to show an effect within 48 hours, once you begin a course of antibiotics, it is very important that you complete the course. If you do not do so, the bacteria may regroup and cause a stronger infection which has become resistant to that antibiotic. If your cat reacts badly to an antibiotic, contact your vet and discuss changing to another type.

 

When giving antibiotics, you may need to re-balance the bacteria in the gut with probiotics, especially if your cat develops diarrhoea. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis (2012) Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, Johnsen B & Shekelle PG Journal of the American Medical Association 307(8) pp1959-69 found that doing this may help with this type of diarrhoea, though further studies are needed to determine which probiotics work best for which antibiotic. A small amount of natural, unflavoured yoghurt may help, but since many cats are lactose intolerant, there is a risk that this might actually make the diarrhoea worse. You may therefore find it easier to buy a commercial product in capsule form instead. There are a number of different types available. East meets west: integrative veterinary medicine (2007) Silver RJ recommends using a product with 1-10 billion CFU units per day (scroll down to Probiotic Cultures near the bottom of the page). Consumer Lab has a report on what probiotics do and how to choose one. Here are some to consider:

  • Acidophilus is a good choice for rebalancing gut bacteria - Pet Education discusses this. Effects of lactobacillus acidophilus DSM13241 as a probiotic in healthy adult cats (2006) Marshall-Jones ZV, Baillon M-LA,Croft JM & Butterwick RF American Journal of Veterinary Research 67(6) pp1005-1012 concluded that "administration of this probiotic results in beneficial systemic and immunomodulatory effects in cats."

  • Culturelle contains lactobacillus. A typical feline dose is half a capsule in the morning and half a capsule in the evening while the cat is on antibiotics, but check with your vet.

  • Benebac is designed especially for pets, and is available from Revival Animal Health among others.

  • FortiFlora is a nutritional supplement for cats which contains a probiotic, though it also contains vitamins, amino acids and iron. I therefore think it is perhaps not the best choice of probiotic, but some cats love it, so it can be helpful if added in small quantities to make food or pills more tempting. It is available from Entirely Pets.

  • Although Azodyl is a form of probiotic, it is not given for the same reasons as probiotics generally (see Treatments), so should not be given at the same time as antibiotics; separate them by 6 hours.  

Clavamox/Synulox (Amoxicillin and Clavulanate)


Clavamox, known as Synulox or Noraclav in Europe, is a combination of two drugs, amoxicillin and clavulanate, which work together to treat or prevent bacterial infections in animals. Amoxicillin is an antibiotic in the penicillin family. Clavulanate is an inhibitor of an enzyme produced by bacteria, which could render the amoxicillin inactive if the clavulanate were not present. This means Clavamox may kill bacteria which amoxicillin alone could not kill. 

 

This antibiotic is often prescribed for urinary tract infections in CKD cats. It tends to be the antibiotic which most UK vets prescribe routinely for many infections. I happen to like Synulox, not least because it comes in flavoured pills in the UK which Harpsie would happily eat out of my hand. But unfortunately it can cause stomach upset, vomiting and loss of appetite in some cats. One of my other cats, Karma, just can't tolerate it for more than a few days. Apparently it is not uncommon for cats to be fine for a few days on this antibiotic but to then exhibit side effects towards the end of the course.  Giving food before you give the antibiotic may help, but if not, contact your vet to see if you should switch to a different antibiotic, but do not simply stop giving the Clavamox/Synulox because this may make the infection return. 

 

Mar Vista Vet has some information about Clavamox (be sure to click on the additional link about amoxicillin).

Pet Place also has some information about Clavamox (no need to register to read the article, just click on Close at the bottom of the irritating pop-up).

 

Baytril (Enrofloxacin)


Baytril is an extremely effective broad spectrum antibiotic (i.e. it works on a wide range of bacteria) which belongs to the fluoroquinolone family. It is particularly good for kidney infections, where it can reach bacteria deep in the kidneys which less powerful antibiotics cannot touch. It saved Harpsie's life on several occasions.

 

However, like any antibiotic, Baytril has possible side effects. The most worrying one with Baytril is that in certain rare cases it has caused retinal problems, including blindness, if given to cats in high doses. Blindness has reversed in some cases once the Baytril is stopped, but not in all.

 

Since the risk of retinal problems appears to be linked to dosage (the issue did not arise until the recommended dosage limits were dramatically increased), the official recommended dose in most countries is now 5 mg of Baytril per kg of bodyweight of the cat per day. For the overwhelming majority of cats, this is a safe dosage. Having said that, Dr I Jurk of Tufts University Cummings School of Veterinary Medicine (2003) mentions that although most cases of blindness have occurred in cats given larger doses of 10-20mg/kg, one cat had received a dose of only 4.6 mg/kg.

 

A kg is 2.2 lbs, so, for example, the maximum daily dose for a 10 lb cat is 22.5mg per day, calculated as follows:

  • 10lb cat = a 4.5kg cat x 5mg per kg = 22.5mg per day.

The recommended maximum course of treatment is 30 days (although Harpsie was on a longer course a couple of times for his kidney infections with no problems). Baytril is given once daily; giving it more frequently actually reduces its effectiveness. Bayer, the manufacturer, recommends giving it on an empty stomach, ideally an hour before food, preferably wet food.

 

Most people give Baytril in pill form, but it doesn't taste very nice, so it is also available as a chewable tablet called Taste Tabs. There is an injectable form of Baytril but it is only approved for dogs. Some people have used it for cats, although there is a small risk of an abscess at the injection site.

 

Baytril must not be given orally within two hours of products containing calcium or aluminium (such as phosphorus binders) or iron (such as Pet Tinic), because they may inhibit absorption of the Baytril. Sucralfate must also be give separately from Baytril for the same reason. Drugs has some information about this.

 

Baytril may lower the seizure threshold, so may not be the best choice in cats with a tendency to have seizures. Although Harpsie had epilepsy, fortunately for us he never had any problems with Baytril.

 

Mar Vista Vet has a good overview of Baytril.

 

Pet Place has some information about Baytril (no need to register, just click Close at the bottom of the annoying pop up).

 

Bayer, the manufacturer of Baytril, has some information on the risks of blindness in cats.

 

Dosage and duration of treatment is a report from Bayer, the manufacturer of Baytril, on the recommended dosage and length of treatment. It mentions that Baytril appears to be most effective when it is given once daily.

 

US Food and Drug Administration has a copy of a letter sent by Bayer to American vets outlining the risks of blindness at high doses and recommending a maximum dose of 5mg per kg bodyweight per day.

 

Tufts University Cummings School of Veterinary Medicine (2003) has a summary of the situation regarding Baytril and blindness in cats by Dr Isabel Jurk, head of ophthalmology.

 

Enrofloxacin-associated retinal degeneration in cats (2001) Gelatt KN, van der Woerdt A, Ketring KL, Andrew SE, Brooks DE, Biros DJ, Denis HM, Cutler TJ Veterinary Ophthalmology 4(2) pp99-106 reports on the risks of blindness and recommends adhering closely to the guidelines regarding the maximum recommended dose.

 

Antirobe (clindamycin)


Antirobe (clindamycin) belongs to the lincosamide family of antibiotics. It is approved for use in dogs but is used off-label for cats. Antirobe is often prescribed for dental problems because it is particularly good at killing anaerobic bacteria which are commonly found in the mouth.

 

Like most antibiotics, Antirobe may cause an upset stomach. It should be used with caution in CKD cats - the normal dosage may need to be adjusted. The manufacturers recommend that kidney and liver bloodwork should be checked if Antirobe is given for longer than 30 days.

 

Mar Vista Vet has some information about clindamycin.

Pet Place also discusses clindamycin.

 

Convenia (cefovecin)


Convenia is an injectible antibiotic in the cephalosporin class which was approved in Europe in 2006 and in the USA in 2008. It is approved in the USA for the treatment of skin infections in dogs and cats and urinary tract infections in dogs. In Europe it is approved for these conditions but also for the treatment of urinary tract infections in cats.

 

Convenia is only available as an injection. It lasts 14 days, so is very convenient, particularly for cats who hate to be pilled. Efficacy and safety of cefovecin for the treatment of urinary tract infections in cats (2008) Passmore CA, Sherington J, Stegemann MR Journal of Small Animal Practice 49(6) pp295-301 found that an injection of Convenia was as effective as a 14 day course of cephalexin.

 

Most people I have heard from who have used Convenia were pleased with it. My Ollie was given this for a urinary tract infection but his UTI symptoms began to return about 10 days after the shot, so we switched to Synulox, which seemed to work better for him.

 

However, like any antibiotic, Convenia has potential downsides. Possible side effects commonly seen with antibiotics include lethargy, vomiting and diarrhoea. There may also be skin irritation at the injection site. Drugs reports on possible side effects, some of which are quite severe, such as rare reports of haemolytic anaemia or pulmonary oedema.

 

If your cat does have a bad reaction, the fact that Convenia is so long lasting becomes a disadvantage, because your cat's body remains exposed to the drug. Convenia can remain in the body for up to 65 days. The European Medicines Agency recommends that Convenia should be reserved for use in animals whose conditions have not responded to or are not expected to respond to other antibiotics. Pet Place mentions that "Maximum treatment should not exceed 2 injections." Other resources state that it may be used up to three times.

 

Convenia has not been tested in cats with severe kidney problems, but Drugs reports that some cats in a safety study had mild elevations in BUN and creatinine levels after using Convenia.

 

Famotidine (Pepcid AC) can interfere with antibiotics in the cephalosporin family such as Convenia, so you should separate the two treatments.

 

Pfizer product overview sheet an overview of the US version of Convenia.

 

Pfizer prescribing information for the USA.

 

National Office of Animal Health in the UK provides contra-indications and warnings re the use of Convenia.

Drugs reports on the safety testing of Convenia in cats and dogs.

 

Painkillers and Anti-Inflammatories                                                               Back to Page Index


 

Firstly, I must emphasise that CKD is not usually a painful disease, so does not normally require painkillers. However, a CKD cat may occasionally require a painkiller, e.g. if the cat has arthritis or pancreatitis, or has dental work or some other type of surgery done, or develops a saddle thrombus. Therefore it can be helpful to know about the various painkillers that may be used in cats. This section covers the following:

It is easier to stop pain developing rather than trying to control it once it has begun, so if for example your cat is about to have a dental, be sure to discuss pain control with your vet in advance.

 

It can be rather difficult to find a suitable painkiller, because many painkillers which work well for dogs and humans are not appropriate for cats. The Winn Feline Foundation is sponsoring a study into pain in cats, Development of outcome assessment instruments for chronic pain in cats, at the University of Pennsylvania, which it is hoped will help develop suitable painkillers in the future.

 

The Veterinary Anesthesia and Analgesia Support Group has a helpful overview of the various painkillers available.

 

The Veterinary Anesthesia and Analgesia Support Group has a slightly older overview of the various painkillers available.

 

Signs of Pain in Cats


Unfortunately cats instinctively try to hide the fact that they are in pain, and some of the signs of pain in cats are different to what you might expect, e.g. purring, restlessness. Other possible signs include growling, avoiding interactions, sleeping a lot or sitting in a hunched position. The following links may help you determine if pain is a concern for your cat:

 

The Cat Hospital of Chicago explains more about signs of pain in cats and pain management.

 

American Animal Hospital Association gives a short list of possible signs of pain in cats (Table 3).

 

Pet Place has an overview of pain in cats (no need to register to read the article, just click on Close at the bottom of the annoying pop-up).

 

Opiates


Opiates are narcotics, which means they belong to the same drug family as morphine. These drugs are  derived from the poppy and are the most powerful painkillers.  

The Veterinary Anesthesia and Analgesia Support Group has an overview of opiates.

 

Buprenorphine (Buprenex, Vetergesic)


Buprenorphine is a narcotic which is thirty times more potent than morphine. Trade names include Buprenex (USA) and Vetergesic (UK).

 

Buprenorphine should not be given orally because it is ineffective when given in such a way. It can be given as an injection, but in cats it is commonly given in intrabuccal form, i.e. it is squirted into the mouth towards the cheek. It is flavourless so most cats tolerate this well. When given into the cheek, buprenorphine is absorbed through the mucus membrane and usually takes effect quickly, within 30 minutes, with its effects lasting for eight hours (although Colorado State University College of Veterinary Medicine is currently researching a sustained release version of buprenorphine which lasts up to three days). The usual dose is 0.01-0.03 mg/kg if given into the mouth, so a 10lb cat (4.55kg) would receive 0.046- 0.136 mg up to three times a day. Since these are tricky amounts to calculate, many vets provide small syringes containing the correct dose and you just gently squeeze the contents into your cat's mouth towards the cheek.

 

Most people I've heard from find buprenorphine extremely effective with few side effects. The most common side effect is sedation and it may also slow breathing. You may see dilated pupils. It makes some cats purr more and become very affectionate, whilst other cats become restless.

 

Buprenorphine is cleared by the liver so it tends to be a good choice for CKD cats who need ongoing pain control. However, cats with CKD may eliminate it more slowly, so discuss with your vet whether to lower the dose. Be careful if you are using it with cyproheptadine (an appetite stimulant) because using both together may result in an increased sedative effect.

 

Unfortunately buprenorphine can be expensive. Although the 5ml vials tend to be cheaper, it is better to buy the 1ml vials because there is a preservative added to the 5 ml vials which gives the medication an unpleasant taste.

 

Viovet in the UK sells buprenorphine for £14.12 for five 1ml vials.

 

Diamondback Drugs in the USA apparently sell a two month supply of buprenorphine for under US$30.

 

Mar Vista Vet has an overview of buprenorphine.

 

Systemic update of buprenorphine by cats after oral mucosal administration (2003) Robertson SA, Taylor PM & Sear JW Veterinary Record 152(22) pp675-8 found that administering buprenorphine via the oral mucosal route was as effective as injecting it, and the majority of owners preferred this method of administration.

 

The National Office of Animal Health in the UK provides an overview of buprenorphine, including information on side effects and interactions with other medications.

 

Pet Place also has some information about buprenorphine (no need to register to read the article, just click on Close at the bottom of the pop-up).

 

Fentanyl (Duragesic)


Fentanyl is also a narcotic belonging to the same drug family as morphine. Therefore it is a very effective painkiller. It is usually given in the form of a patch (like a plaster) on the skin which slowly releases the medication for 4-5 days. Side effects are uncommon and usually minor e.g. allergy to the patch adhesive. The most common serious side effect (although it is still relatively rare) is an adverse effect on breathing, which may manifest itself as lethargy. Fortunately removing the patch should quickly resolve any problems.

 

Fentanyl should not be used in cats taking Anipryl for cognitive dysfunction. Heat can increase the amount of Fentanyl released, which could be very dangerous, so access to heat (e.g. heated cat beds) should be removed for any cat with a Fentanyl patch. Care should be taken to ensure that the cat cannot remove the patch or lick it.

 

My Indie (non-CKD) had extensive dental extractions, and was given a Fentanyl patch to help her oral pain. The patch was applied to a small area of shaved skin on one of her back legs, and lasted for several days. It worked very well for her, she was a little subdued but that was the only side effect (which might actually have been due to the after effects of the surgery). However, up to a third of cats absorb less of the medication than is needed for effective pain control, so be aware of the signs of pain in cats so you can ensure it is working properly for your cat.

 

Mar Vista Vet has some information about Fentanyl.

 

Tramadol


Strictly speaking Tramadol is not an opiate but it has some effect on opioid receptors, so I am including it in this category.

 

Tramadol is a safe treatment when used at appropriate dosage levels and side effects are rare, but include sedation and constipation. It has been known to cause hallucinations and seizures in humans so should be used with caution in cats with a history of seizures. Unfortunately Tramadol tastes very bitter to cats.

 

Tramadol is available as a generic which means it is inexpensive. It is commonly sold as a 50mg tablet, and is dosed at 1 to 2 mg/kg 2-3 times a day, so a 10 lb (4.55kg) cat would receive 4.5 - 9mg 2-3 times a day. In practice many people simply start with a quarter of a 50mg tablet (12.5mg) twice a day. It is metabolised largely by the liver but around 30% is excreted by the kidneys so your vet may wish to reduce the dose for a CKD cat.

 

Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT3 spinal receptor involvement in acute pain in humans (2002) Arcioni R, della Rocca M, Romano S, Romano R, Pietropaoli P & Gasparetto A Anesthesia and Analgesia 94(6) pp1553-7 reports that ondansetron (commonly used for nausea in CKD cats) may reduce the painkilling effects of tramadol by up to 50% in humans.

Mar Vista Vet has some information about Tramadol. It mentions that using Tramadol at the same time as an appetite stimulant called mirtazapine increases the risk of serotonin syndrome.

 

Wedgewood Pharmacy gives an overview of Tramadol.

 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)


Non-steroidal anti-inflammatory drugs help reduce inflammation and also offer some degree of pain control. NSAIDs work by blocking prostaglandin production. They do this by binding with enzymes called cyclo-oxygenase (COX). There are two forms of COX, COX-1 and COX-2. COX-1 is protective, particularly in the kidneys and the digestive tract, whereas COX-2 produces pain and inflammation. The goal is therefore to reduce levels of COX-2 while not affecting COX-1, although even reducing levels of COX-2 only does not entirely remove the risk of side effects.

 

Meloxicam (Metacam) is a COX-2 preferential NSAID, i.e. it works effectively on COX-2 to reduce pain and inflammation but also reduces levels of COX-1 to some degree. Robenacoxib (Onsior) is a COX-2 selective NSAID, i.e. it works effectively on COX-2 to reduce pain and inflammation but does not affect levels of COX-1.

 

NSAIDs are commonly used in human and canine medicine. They can be very helpful for conditions such as arthritis. Unfortunately cats tend to metabolise them poorly, plus there is only limited research into their longer term use in cats, so many vets are reluctant to use these drugs in cats. The Veterinary Anesthesia and Analgesia Support Group says that "Extreme caution should be exercised when employing NSAIDís in cats."

 

The most common side effects of NSAIDs seen in cats are kidney problems and gastro-intestinal problems. Since CKD cats already have kidney problems and often also have gastro-intestinal problems such as stomach acid, NSAIDs are therefore not the best choice for CKD cats. However, sometimes you may have to use them e.g. if your cat has severe arthritis, because ongoing pain is not acceptable.

 

NSAIDS should not be used at the same time as corticosteroids. Close monitoring is required if they are used in cats taking ACE inhibitors (e.g. Fortekor) or diuretics because using these treatments together increases the risk of kidney problems.

 

Non-steroidal anti-inflammatory drug (NSAID) toxicity in dogs and cats: pathophysiology, diagnosis and monitoring (2006) Totten J, Brown HM, LeRoy BE explains more about the risks of using NSAIDs and what warning signs to watch for.

 

What every practitioner should know about NSAIDs in cats (2007) Hardie EM discusses various NSAIDs and the importance of dosage.

 

The Veterinary Anesthesia and Analgesia Support Group has an overview of the use of NSAIDs.

 

ISFM and AAFP consensus guidelines: long-term use of NSAIDs in cats (2010) Journal of Feline Medicine and Surgery 12, pp521-538 is a paper by the International Society of Feline Medicine and the American Association of Feline Practitioners. On page 530 there is a box discussing the use of NSAIDs in cats with renal disease. Boehringer-Ingelheim, the manufacturer of Metacam, gave a grant to help facilitate the development of these guidelines.

 

Effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal function (2007) Brown SA State of the Art in Renal Disease in Dogs and Cats Proceedings, Vetoquinol Academia reports (page 31) on the use of NSAIDs in CKD. Dr Brown states "It has long been known that NSAIDs have a good margin of renal safety for short- term use in healthy animals. Unfortunately, we often use them in aged animals with a variety of clinical or subclinical conditions or in animals undergoing anesthesia and surgery. The study of the effects of NSAIDs on the kidney shows that the COX-2 selective drugs are not necessarily safer for the kidneys. In well hydrated otherwise healthy cats with IRIS stages I and II Chronic Kidney Disease (CKD), NSAIDs seem to be generally well tolerated.

 

How to use NSAIDs in animals with chronic kidney disease (2012) Brown SA Presentation to the Florida Veterinary Medical Association 83rd Annual Conference is a very technical guide.

 

Robenacoxib (Onsior)


Robenacoxib is a non-steroidal anti-inflammatory drug (NSAID). It has been approved for use in cats in the UK since 2009 for the treatment of acute pain and inflammation associated with musculoskeletal disorders (e.g. arthritis) for up to six days. It was approved for use in cats in the USA in April 2011. The US approval is to control post-operative pain and inflammation, for which it can be used once daily for up to three days.

 

Since robenacoxib is 30% excreted by the kidneys, it should be used with caution in cats with CKD, who should be monitored closely. Do not use robenacoxib at the same time as steroids. Close monitoring is required if it is used in cats taking ACE inhibitors (e.g. Fortekor) or diuretics because using these treatments together increases the risk of kidney problems.

 

Onsior Cat Package Leaflet is the leaflet that comes with the UK form of Onsior.

 

The National Office of Animal Health in the UK provides an overview of Onsior.

 

Aspirin


Aspirin is another NSAID. Aspirin can be toxic to cats, who can only metabolise it very slowly, so it is not usually used as a painkiller in cats, although it is occasionally used to treat heart problems when the benefits outweigh the risks. In such cases it is usually only given in very low doses once every three days.

 

Aspirin may cause metabolic acidosis.

 

Mar Vista Vet has information on aspirin.

 

Carprofen (Rimadyl)


Carprofen is an NSAID used to treat arthritis in dogs. The manufacturers advise against using it in cats, so I would not use it.

 

Toxicology brief: managing acute carprofen toxicosis in dogs and cats (2009) Mensching D Veterinary Medicine reports on the risks of using carprofen and possible signs of toxicity.

 


Meloxicam (Metacam or Meloxidyl)


 

Meloxicam is also a non-steroidal anti-inflammatory drug (NSAID) available in both injectible and liquid (oral) form. Although it is approved in the UK for the ongoing treatment of arthritis in cats (and I myself used it successfully for my PKD but not CKD cat), there are concerns that it may cause kidney disease, particularly when used at higher doses, as sometimes happens in the USA where cat-sized doses are not available.  

Meloxicam Overview


Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) available in both injectible and liquid (oral) form. Under the name of Metacam it is approved for use in dogs in both forms, but since cats tend to metabolise NSAIDs very poorly, in the USA Metacam is only approved for use in cats in its injectible form. This is because it is intended to be a one-off treatment as a painkilling injection following surgery. However, the injectible form has only been tested on cats given one particular type of anaesthesia.

 

The situation was similar in Europe, where only the injectible version of Metacam was approved for one-off use in cats following surgery. This changed in June 2007 when the oral form of Metacam was licensed for cats for longer term pain management e.g. for use in cats with arthritis. This feline oral version of Metacam is a 0.5mg/ml oral suspension compared to the canine version which is a 1.5mg/ml suspension. Another oral version of meloxicam for cats in the same strength (0.5mg/ml) was introduced in the UK in 2011 under the name of Meloxidyl.

 

In the USA, meloxicam also appears to be being used more and more frequently off-label for cats in its liquid (oral) form on an ongoing basis, but because there is no feline version available, vets are using the canine version, theoretically at reduced doses. However, since meloxicam is often dosed in drops rather than precise measurements, this may lead to overdosing.

 

Unfortunately meloxicam may be nephrotoxic, i.e. toxic to the kidneys. In fact, it may in some cases cause permanent damage to the kidneys (papillary necrosis), with the result that a number of cats seem to have developed acute kidney injury or chronic kidney disease after taking meloxicam.

 

This is not inevitable. One study, Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03mg/kg for treatment of osteoarthritic pain in cats (2008) Gunew MN, Menrath VH, Marshall RD Journal of Feline Medicine & Surgery 10(3) pp235-41 monitored forty cats who were given meloxicam for arthritis for almost six months, three of whom had pre-existing renal disease. The study found that "no deleterious effect on renal function was detected in cats studied."

 

Retrospective case-control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease (2011) Gowan RA, Lingard AE, Johnston L,  Stansen W, Brown SA, Malik R Journal of Feline Medicine & Surgery 13(10) pp752-761 retrospectively examined the records of a veterinary practice over a five year period and concluded that "long-term therapy with meloxicam at a median dose of 0.02 mg/kg/day can be administered safely to aged cats with CKD, provided they are clinically stable. The results further suggest that meloxicam may actually slow the progression of renal disease in cats with both DJD and CKD by direct or indirect  mechanisms." The study goes on to speculate that meloxicam might slow the progression of CKD by reducing proteinuria (recent studies indicate that medications in the same family as meloxicam can reduce proteinuria in humans and rats).

 

A retrospective analysis of the effects of meloxicam on the longevity of aged cats with and without overt chronic kidney disease (2012) Gowan RA, Baral RM, Lingard AE, Catt MJ, Stansen W, Johnston L & Malik R Journal of Feline Medicine and Surgery 14(12) pp876-81 looked into the use of meloxicam in cats with CKD. This study examined the records of 82 cats over the age of seven who had been given meloxicam for six months or longer. 47 of the cats were known to have CKD, the other 35 showed no obvious signs of CKD. The study states "Long-term treatment with oral meloxicam did not appear to reduce the lifespan of cats with pre-existent stable CKD, even for cats in IRIS stages II and III."

 

Nevertheless, in October 2010 the US Food & Drug Administration announced that a "black box warning" would be added to meloxicam products, which states: "Warning. Repeated use of meloxicam in cats has been associated with acute renal failure and death. Do not administer additional injectable or oral meloxicam to cats. See contraindications, warnings and precautions for detailed information."

 

Meloxicam Dosing


It appears that the dosing used is critical. In the USA, since the feline form of meloxicam is not available, vets have to use the three times as strong canine form, and it may be that they are not adjusting the dose appropriately for cats, especially if they give it in drops (Metacam comes with a dropper dispenser) directly into the cat's mouth rather than measuring it out in mg first. The Dear Doctor letter states: "Metacam Oral Suspension is not licensed in the U.S. for use in cats. Unfortunately adverse events in cats do occur. These have been reported at a consistent level over the past 5 years and the majority following the inappropriate off-label administration of the more concentrated 1.5 mg/mL formulation in cats."

 

It also appears to be riskier if a cat is given injectible meloxicam followed by the oral form. Freedom of Information Summary (2004) from the US Food and Drug Administration concludes: "Meloxicam, when initially dosed as a subcutaneous injection followed by oral dosing for nine days at > 0.3 mg/kg was associated with severe adverse effects, including death."

 

The National Office of Animal Health explains more about the recommended dose for cats in the UK. The usual dose of the 0.5 mg/ml  strength of oral meloxicam is as follows (a kg is 2.2 lbs):

  • 0.1mg/kg for the first dose;

  • 0.05mg/kg for subsequent doses given once a day;

  • the oral form should not be given after using the injectible form.

The Veterinary Anesthesia and Analgesia Support Group mentions some even more cautious dosing protocols for long term use, as follows:

Lascelles Protocol (VAA 2007)

  • 0.1 mg/kg for 1 to 3 days;

  • thereafter 0.025 mg/kg every 48 to 72 hours. For accurate dosing use TB or insulin syringe minus needle. 

Robertson VCNA Protocol (SAP 2008)

  • 0.05 mg/kg on the first day
  • 0.025 mg/kg every 24 hours or less (titrate to lowest effective dose. 

Gunew et al Protocol (FMS 2008)

  • 0.01-0.03 mg/kg once daily.
  • this is the protocol used in the above study.

We did use meloxicam for Harpsie when his arthritis flared up acutely in 2004 following a fall off a sofa while we were out and he was in dreadful pain which other pain medications did not seem to help (he was literally screaming). It worked very well and caused no long term problems for him, but since Harpsie had PKD, we only used it at a very low dose, and much less frequently than normally recommended, and it still controlled the pain effectively. We checked his kidney values a month later (they were fine).  

 

Although meloxicam is very effective at controlling pain, I would not recommend its use in a cat who already has CKD. Nor does the UK National Office of Animal Health, which states "Do not use in animals suffering from gastro-intestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function and haemorrhagic disorders". However, in Effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal function (2007) Brown SA State of the Art in Renal Disease in Dogs and Cats Proceedings, Vetoquinol Academia, Dr Brown states on page 31 "In well hydrated otherwise healthy cats with IRIS stages I and II Chronic Kidney Disease (CKD), NSAIDs seem to be generally well tolerated." He recommends close monitoring, avoiding dehydration or low blood pressure, and not using for more than ten days.

 

If you choose to use meloxicam in a cat without CKD, I would use a lower dose than is usually recommended.

 

If you do use meloxicam and your cat develops kidney disease, please see below for information on how best to treat it, and how to report it to the authorities.

 

Meloxicam may interact with ACE inhibitors such as benazepril (Fortekor or Lotensin) or enalapril (Enacard) so do not give both medications to your cat  without checking with your vet first. 

 

Development of an injection site sarcoma shortly after meloxicam in an unvaccinated cat (2011) Munday JS, Banyay K, Aberdein D, French AF Journal of Feline Medicine & Surgery 13(12) pp988-91 reports on a cat who developed sarcoma (a form of cancer) where meloxicam was injected. This is extremely rare.

 

Meloxicam Links


Effects of meloxicam on plasma iohexol clearance as a marker of glomerular filtration rate in conscious healthy cats (2009) Goodman LA, Brown SA, Torres BT, Reynolds LR & Budsberg SC American Journal of Veterinary Research 70(7) pp826-30 checked the glomerular filtration rate (a measure of kidney function) in six healthy cats before and after short-term administration of meloxicam and did not find any deterioration.

 

Metacam Package Insert for Cats (NADA141-219) relates to the injectible form of Metacam in the USA. It now carries a "black box warning" as required by the FDA which states: "Warning.  Repeated use of meloxicam in cats has been associated with acute renal failure and death.  Do not administer additional injectable or oral meloxicam to cats.  See contraindications, warnings and precautions for detailed information."

 

The Metacam Professional Insert (NASA 141-213) for the oral suspension version of Metacam,  approved by the US Food and Drug Administration, states (page 2): "renal failure has been reported as an outcome of repeated oral dosing of cats".

 

Freedom of Information Summary (2004) from the US Food and Drug Administration mentions on page 23 that, following the use of Metacam for post-operative pain, 8.3% of the cats in the study had elevated BUN levels, and 12.5% had anaemia. In comparison, there were no cases of elevated BUN levels in cats in the study given another post-operative painkiller, although 6.1% of them did have anaemia (one possible cause of anaemia is inflammation, which may partly explain this finding). The paper concludes: "Meloxicam, when initially dosed as a subcutaneous injection followed by oral dosing for nine days at > 0.3 mg/kg was associated with severe adverse effects, including death."

 

The American Association of Feline Practitioners gives some guidance to American vets considering using Metacam.

 

The US Food and Drug Administration reprimanded the manufacturers of Metacam in 2004 for misleading claims for the product and omission of important safety information.

 

The European Medicines Agency states (P36) "do not use in animals suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function." It also says (P103) that the use of Metacam should be avoided in dehydrated animals "as there is a potential risk of renal toxicity", and warns that the oral form of Metacam should not be used following use of the injectible form.

 

Pet Place states "Meloxicam can adversely affect kidney function by causing sudden severe injury to the kidneys (papillary necrosis)."

 

Mar Vista Vet also has some information about meloxicam and recommends avoiding its use in cats with kidney, liver or heart disease, as well as in cats who are dehydrated or who have stomach ulcers.

 

Provet has some warnings about the use of meloxicam.

 

Metacam UK is the manufacturer's British website about the use of meloxicam in dogs. It mentions the recent approval of the drug for ongoing use in cats, but has very little information about this.

 

Metacam USA is the manufacturer's American website about the use of Metacam in dogs.

 

Dealing with Adverse Reactions to Meloxicam


If you believe your cat has developed kidney disease as a result of using meloxicam in the form of Metacam, you should report this to the manufacturers. The number to call in the USA is 1-866-METACAM (638-2226). You will probably find yourself speaking to a Dr Carey or a Dr Grubb, who should work with your vet to devise a treatment plan. If you are in Canada, the contact number is 1-800-325-9167 but the manufacturer will only speak to vets.

 

Most cats who suffer kidney disease as a result of using Metacam are suffering from acute kidney injury (AKI) and their bloodwork may be extremely high, with creatinine often in the high teens. Do not give up hope! Acute kidney injury is difficult to treat, but not impossible: an aggressive treatment plan should see those numbers dramatically reduce in most cases, and in some cases a complete recovery from a case of acute kidney injury is possible. In fact, one person was told by the manufacturer that 77% of cats affected by Metacam make a full recovery with prompt and proper treatment, so don't opt for euthanasia immediately. However, I understand that the manufacturer considers a creatinine in the 3s to indicate that the cat is stabilised, and whilst this is certainly not a critical level nor grounds for euthanasia, it does indicate some residual kidney damage. 

 

A treatment programme which includes 4-5 days of IV fluid therapy (hospitalisation), followed by 4-6 weeks of sub-Q fluids at home, is often recommended by the manufacturers, but talk to them and see what they suggest for your cat. I would also suggest that you ask the manufacturers to pay your veterinary costs - I know they have done this for some people, although they have not necessarily paid the full costs. It would appear that they may pay more if your vet calls.

 

If you are in the USA, you should also make a report to the Food & Drug Administration. Apparently the manufacturers are not obliged to report any cases of kidney problems to the FDA because renal failure is already listed in the package insert as a possible side effect (see the second link above),but I believe it is very important for the FDA to be fully aware of the scale of the problem. FDA Consumer Complaints Co-ordinator has details of the relevant contacts for each state.

 

If you are in Canada, you should report it to the Veterinary Drugs Directorate.

 

If you are in the UK, you should report it to the Veterinary Medicines Directorate.

 

Other Painkillers


Gabapentin


Gabapentin is an anti-convulsant (used to prevent seizures) but may help with pain, particularly arthitic or neuropathic pain. It may cause sedation. It may be risky to give anti-seizure medication to a cat who has never had a seizure.

 

Gabapentin is excreted via the kidneys so the dose should be reduced for CKD patients, who need close monitoring while on the drug. Gabapentin should not be stopped suddenly but gradually tapered down.

 

Mar Vista Vet has some information about Gabapentin.

 

Paracetamol/Acetaminophen


Paracetamol (UK) or acetaminophen or Tylenol (USA) is toxic to cats, with a very narrow safety margin, so even a tiny dose can be extremely dangerous. Please never give your cat paracetamol/acetaminophen.

 

Tylenol (acetaminophen) toxicosis in cats (1998) is an article by the Indiana Animal Disease Diagnostic Laboratory.

The 10 most common toxicoses in cats (2006) Merola V & E Dunayer Veterinary Medicine June 2006 pp339-342 lists acetaminophen at number 8.

 

 

 

Back to Page Index

This page last updated: 05 December 2013

Links on this page last checked: 27 April 2012

 

The group is hosted on yahoo!groups, part of yahoo. It has its own address separate from Tanya's website. You can either click here or copy and paste this link into your browser:

 

http://pets.groups.yahoo.com/group/tanyas-ckd-support/

 

If you are already familiar with yahoo!groups, just click on the link and apply to join (and don't forget to complete the short questionnaire you'll be sent), but if you'd like to know more about how the group works, read on.

 

I own and run the group, but I am ably assisted by two moderators, Anne V and Anne A. They help with membership queries, approve messages, and do lots of boring admin stuff behind the scenes to help the group run smoothly for the members.

 

The group has various sections, including a photos section and a realtime chat function but for most people the most important part of the group is its message section. Basically, a member who wants support, vet recommendations, or to hear how others are coping with a particular problem, sends a message to the rest of the group. Other members then respond if they can. All messages sent to the group are stored in a message archive which members can search if they wish.

 

The group is private, i.e. messages sent to it are only visible to members, so people are not posting to the internet at large. The names of group members are also private, so nobody will know you are a member unless you choose to send messages to the group.

 


Joining the Group                                                                                                                        Back to Page Index


 

There are two ways to join the group, via the group's website or via e-mail:

 

How to Join the Group via E-mail


Just send an e-mail to

tanyas-ckd-support-subscribe@yahoogroups.com

You should then receive an e-mail in response asking you to confirm that you definitely want to join the group. Just click Reply and send.

 

If you join the group via e-mail, you will be able to send and receive e-mails to the group, but you will not be able to access the group website and read the message archives or look at the photos. If you wish to do that, you will need to set up a yahoo! ID by visiting the group website.

 

How to Join the Group via the Web


You can visit the group's homepage and follow the instructions. If you do this, yahoo!groups will help you set up your yahoo! ID, which gives you access to the group message archive etc. A yahoo! ID is not the same thing as an e-mail address.

 

Here are the steps to follow. Don't worry, this all sounds far worse than it is! You should find that in practice it all works more smoothly than it sounds when you're trying to explain it in writing:

 

Existing yahoo! ID

  1. Go to the group website: http://pets.groups.yahoo.com/group/tanyas-ckd-support/

  2. Click on the Join this Group button and you'll be taken to a Sign In to Yahoo! page.

  3. Sign in and link Tanya's Support Group to your existing account.

  4. Choose the e-mail address you wish to use for the group (see below).

  5. There is a little box for you to tell me why you would like to join the group. You don't need to be inventive or fancy, it's not a competition, it's just an extra check by yahoo!groups to keep spammers out.

  6. Choose your message delivery options (see below).

  7. Scroll down and click on the blue Join button at the bottom right of the page.

New yahoo! ID

  1. Go to the group website: http://pets.groups.yahoo.com/group/tanyas-ckd-support/

  2. Click on the Join this Group button and you'll be taken to a Sign In to Yahoo! page.

  3. Scroll down a little and click on the Create New Account button.

  4. On the next page you can create your new account. Some people are somewhat inventive in their responses, but in such cases it is important to remember what responses have been given in case the information is needed later to access the account. I can't see any of this stuff, it's entirely private between you and yahoo!groups, so I cannot help in case of later queries. 

  5. Once the account is successfully set up, you'll be taken to a Congratulations! page.

  6. Before you click on the Continue button on the Congratulations! page, untick the box that makes yahoo! your homepage (unless that is what you want).

  7. Also click on the Edit Marketing Preferences link below the Continue button. This takes you to another page where they helpfully opt you in to everything, so go through and set it as you wish.

  8. Then on the same separate page click on Account Info at the top of the page. You will be asked for your password again and taken to the Account Info page. Click on Profile and opt out of the various choices as you wish. The key thing is, you do have choices here, you can make things as public or private as you wish.

  9. Now click on the Continue button on the original page. You will be taken back to the group page to choose your membership settings.

  10. Choose the e-mail address you wish to use for the group (see below).

  11. There is a little box for you to tell me why you would like to join the group. You don't need to be inventive or fancy, it's not a competition, it's just an extra check by yahoo!groups to keep spammers out.

  12. Choose your message delivery options (see below).

  13. Scroll down and click on the blue Join button at the bottom right of the page.


Membership Settings                                                                                          Back to Page Index


 

There are various choices you need to make regarding your membership of the group. The most important are which e-mail address to use, and which way you read messages sent to the group by group members.

 

Membership Settings: Your E-mail Address


You need to decide which e-mail address you wish to use for the group. If you have created a yahoo! ID, yahoo!groups will normally have also set up a free yahoo! e-mail account for you based on your new yahoo ID. You can use this e-mail address to access the group if you wish, but it's not essential, you can use any e-mail address you wish. Since yahoo! is now scanning messages for advertising purposes (similar to gmail), I would recommend not using yahoo! e-mail if possible (though it would probably be better than using your work address for private stuff).

 

If you do not want to use your free yahoo! e-mail address, click on Add e-mail address to add a different one. Be aware, if you don't add a new address here, yahoo! will use the yahoo! e-mail address as a default address. So if you don't receive the membership questionnaire, it may well be because it's gone to your new yahoo! e-mail address.

 

If you ever wish to change the e-mail address you are using for the group, you can do that here:

http://pets.groups.yahoo.com/group/tanyas-ckd-support/join

 

Membership Settings: Message Delivery


This sets up how you will access messages that are sent to the group.

 

This is a pretty active group. If you're looking after your CKD cat, you want support but you probably don't want a full inbox all the time. To help you manage this issue, you have three options for messages, and you can switch between them all as you wish:

  1. Individual E-mails

  2. Daily Digest

  3. Web Only (No e-mail)

Individual E-mails


This is the default setting. If you apply to join the group via e-mail, you will end up with this setting. If you apply to join the group via the group's webpage, if you don't choose one of the other settings, this is the one you will end up with.

 

This setting means that as soon as somebody sends a message to the group, it is sent directly to your inbox. It's a good choice if you might want to know immediately if somebody has responded to you, or if you would like to store some of the group messages for your reference. It's also good for being able to quickly delete messages which don't interest you.

 

The downside is that this is a busy group, averaging 50-100 group messages each day, so your inbox can quickly get full. One solution is to create a folder to use for group messages. All messages sent to the group have a tag in the subject line [tanya-crf] so you can filter all messages from the group to a new folder using this tag if you wish.

 

With both individual e-mail and message digest options, you can also choose the format of messages sent to you (Display Format), either Fully Featured (html, pretty colours etc.) or Traditional (plain text).

 

Message Digest


This means that you receive e-mails from the group, but yahoo!groups waits until there are about 25 messages available and sends them to you all in one go. With this option, you would therefore only receive 2-4 e-mails a day from the group, but it means you have to wait for responses (though you can still check on the group website for messages) and it can be more difficult to find what you are looking for within each digest.

 

With both individual e-mail and message digest options, you can also choose the format of messages sent to you (Display Format), either Fully Featured (html, pretty colours etc.) or Traditional (plain text).

 

Web Only (No Mail)


This means that you receive no messages at all from the group. This is a wise choice if you are using a work e-mail address, or if you cannot cope with the group's message volume. With this system you simply go to the group's website and read the messages that interest you there. Even if this is not your usual choice, it can be helpful to use this option if you are going on holiday.

 

So make your choices, then click the Join button at the bottom right of the page.

 


Important: Membership Questionnaire                                                           Back to Page Index


OK, so you've successfully applied to join the group. However, there is one more thing you need to do in order to join. I want to protect the group members from spammers, so whichever way you apply to join the group, you will receive a short questionnaire asking:

  1. Your first name

  2. The country where you live

  3. Your CKD cat's name and age

You need to respond to this before your membership will be approved.

 

Please don't worry about saying "the right thing." This is not a test to see if you are "good enough" for the group, everybody is welcome here, whoever they are or wherever they come from, as long as they want to help their cat. This questionnaire is basically just to reassure us that you are a real person applying to join rather than somebody trying to sell stuff and spam the group, but it also enables us to tailor our responses to your group messages e.g. if we moderators know where you live, we will not suggest treatments not available there.

 

Please note, only the two Annes and I can see your responses to these questions. The group will not know anything about you unless you choose to introduce yourself.

 

Once you respond to the questionnaire, your membership application should be approved very quickly (most people are approved within two hours or less).

 

Occasionally the questionnaire goes missing. You think we haven't sent it, and we think you haven't responded! If we haven't heard from you five days after you apply to join, we will send you a reminder. Unfortunately, we can only use the address you've used to sign up for the group, so if you've accidentally used your new yahoo e-mail address without realising it (see above), you won't see either the questionnaire or our reminder. If you don't hear from us, please simply write to us at tanyas-ckd-support-owner@yahoogroups.com and let us know. Please respond to the three questions in your response and we will either approve you (if your membership is pending) or send you a personal invitation to join the group (if your membership application has disappeared into a black hole).

 


Messages                                                                                                                                          Back to Page Index


 

Message Options: Sending Messages


You don't have to post, you can just lurk if you prefer.

 

If you wish to change the name that appears on messages you send to the group, Yahoo! explains how you can do that.

 

Starting a Thread


  1. You can simply send an e-mail to ask your question by sending it to tanyas-ckd-support@yahoogroups.com.

  2. You can go to the group website, click on Post Message in the sidebar on the left, and then write your message there.

Replying to an Existing Message


Messages sent in response to another message on the group also go directly to the group, not to the individual to whom you are replying. Therefore if you wish to respond to a message somebody else has sent, you can simply click reply on your e-mail programme. If you reply via the group website, you can click on the message in the group archives, then click reply which is top left above the message.

 

If you're changing the subject, or replying to a Digest (which have the subject line of Digest No. xxx), please change the subject line appropriately to something more meaningful. And please remove everything except that to which you are replying.

 

If you wish to reply privately to somebody, you will need to press reply, then delete the group e-mail address and paste their personal e-mail address into the To: line if you are using e-mail. If you are replying via the group website, you will see a little envelope over on the right under the person's name. If you click on that, your message will go to that person.

 

Message Content


You are welcome to discuss anything relating to care of your CKD cat. We do have a few guidelines we ask people to follow though:

  1. Please do not refer to vets or vet clinics by name for legal reasons. Just say "my vet" or "Dr J".

  2. Please do not ask for money or other donations.

  3. Since this is a very busy group, we ask that condolences are sent privately to the bereaved group member. Certain other messages should also be sent privately e.g. short "me too" messages, off topic posts etc.

  4. Please trim your posts.

Moderation of Messages


When you first join the group, your messages will be moderated for a short while. This means that they will not reach the group immediately, but will first be read and approved by one of the moderators. We do this to ensure that:

  1. you are not a spammer;

  2. you are keeping to other group guidelines (e.g. not naming your vet publicly);

  3. you are trimming your messages appropriately.

If you comply with the group guidelines sent to you when you join the group, you will be taken off moderation quickly. The main reason people stay on moderation is because they do not trim their posts. So please read up on this in the group guidelines. If you get stuck, just ask for help.

 


Leaving the Group                                                                                                Back to Page Index


 

Some people decide to leave the group. Their cat may have died, or they may find the message volume is too much, or they simply decide it's not the place for them. Leaving is fine, but if you're thinking of leaving simply because you cannot cope with message volume, please consider changing your message options first, such as by going no mail. This means your inbox will not be full, but you can still reach out for support quickly when you need it.

 

If you are leaving because your cat has died, please consider joining our sister group, Tanya's Feline Loss Support:

http://pets.groups.yahoo.com/group/tanyas-feline-loss/

 


Conclusion                                                                                                            Back to Page Index


I do hope you've decided to join Tanya's CKD Support Group! It can give you support, it can give you hope. It can make you smile too - where else would people share your thrill at hearing that your constipated cat has pooped? (Believe me, when you've been dealing with CKD for a while, things like this are real triumphs which can absolutely make your day).

 

I personally read every message sent to the group. I don't respond to every post (my priority is running this website) but I do keep an eye on things and post occasionally if I can add to what has already been said.

 


Group Quick Links                                                                                               Back to Page Index


Some of these only work if you are already a member of the group.

 

Weblinks


Group homepage:                                                 http://pets.groups.yahoo.com/group/tanyas-ckd-support/

Managing your membership options:                  http://pets.groups.yahoo.com/group/tanyas-ckd-support/join

Messages archive                                                 http://pets.groups.yahoo.com/group/tanyas-ckd-support/messages

 

E-mail Addresses


Sending a message to the group via e-mail:        tanyas-ckd-support@yahoogroups.com

Group owner e-mail address:                                 tanyas-ckd-support-owner@yahoogroups.com

Joining the group via e-mail:                                   tanyas-ckd-support-subscribe@yahoogroups.com

Leaving the group via e-mail:                                  tanyas-ckd-support-unsubscribe@yahoogroups.com