Tanya's Comprehensive Guide to Feline Chronic Kidney Disease

Tanya's Comprehensive Guide to Feline Chronic Kidney Disease

Appetite Loss, Nausea and Vomiting

Home > Key Issues > Appetite Loss, Nausea and Vomiting

Overview

  • Nausea, vomiting and loss of appetite are some of the most common problems in CKD cats.
  • There are a variety of possible causes, and there may be more than one reason for a cat to be exhibiting these symptoms.
  • Fortunately, in most cases there are treatments which can help make the cat feel much more comfortable, but in order to know which treatment would work best, you need to know the most likely cause in your cat’s case.
  • Toxins caused by the kidney disease are one of the most likely culprits in cats with creatinine over 3 mg/dl (USA) or 265 µmol/L (international).

Causes of Loss of Appetite, Nausea and Vomiting

Nausea, vomiting and loss of appetite are really common symptoms in CKD cats. Unfortunately, there are a large number of possible causes, so it can be confusing trying to decide what might be the cause in your cat’s case. To help you narrow it down, I would read below and also scan through the list of symptoms on the Index of Symptoms and Treatments page to see if any of them look familiar.

This page addresses appetite loss, nausea and vomiting caused by the toxins associated with CKD.  Generally speaking, affected cats will have a creatinine level over 3 mg/dl (US) or 265 µmol/L (international) (IRIS stages 3 or 4).

If your cat has relatively low kidney bloodwork values (creatinine of 2.5-3 mg/dl US, 200-300 µmol/L international) but nevertheless seems to vomit a lot, it might possibly be because of CKD-related toxins, but I would also ask your vet to rule out pancreatitis.

Uraemic Toxins and the Central Chemoreceptor Trigger Zone

In some cases, especially as the CKD progresses, the problem may be caused by toxins. As the kidneys gradually lose their ability to regulate and remove waste products effectively, these waste products build up in the blood. This is called uraemia and can make a cat feel very unwell.

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239 explain how uraemia can affect an area in the brain but outside the blood-brain barrier called the central chemoreceptor trigger zone. Many of the medications discussed below work on the central chemoreceptor trigger zone.

Although BUN is not itself a major toxin, there is a correlation between it and other toxins that are less easy to measure. Therefore, the higher your cat’s BUN or urea level, the higher the overall toxin load will be, and the more likely it is that s/he will feel sick and/or vomit. Feline CKD: current therapies – what is achievable? (2013) Korman R & White J Journal of Feline Medicine and Surgery 15(S1) pp29–44 says “Cats in CKD stages 3-4 often demonstrate gastrointestinal signs of uraemia (eg, inappetence, nausea, vomiting, stomatitis, gastrointestinal ulceration, diarrhoea, colitis) and addressing these may improve quality of life.”

Gastric Hyperacidity (Excess Stomach Acid)

Gastrin is a gastrointestinal hormone that stimulates the secretion of gastric acid, which helps the stomach digest food.

The kidneys are responsible for the excretion of gastrin, but in CKD this function may not work so well, resulting in the gastrin remaining in the stomach and potentially stimulating the production of too much gastric acid. Feline CKD: current therapies – what is achievable? (2013) Korman R & White J Journal of Feline Medicine and Surgery 15(S1) pp29–44 says “Gastrin is excreted by the kidneys and the concentration increases with CKD progression, increasing gastric acidity and the risk of ulceration.” This is known as gastric hyperacidity (excess stomach acid) and can make you feel very unwell. In severe cases stomach ulcers may develop, which may cause gastrointestinal bleeding.

It was widely accepted for many years that gastric hyperacidity is a concern for CKD cats, but more recently there has been some debate as to how big a role it plays in the symptoms commonly seen in CKD cats. Chronic use of maropitant for the management of vomiting and inappetence in cats with chronic kidney disease: a blinded placebo-controlled clinical trial (2014) Quimby JM, Brock WT, Moses K, Bolotin D, Patricelli K Journal of  Feline Medicine & Surgery 17(8) pp692-697says “Interestingly, the exact mechanism of why CKD cats suffer from decreased appetite and vomiting is not currently known. Gastrin hormone that is responsible for stomach acid production is elevated in CKD cats; however, increased stomach acidity and stomach ulceration have not been document [sic] in humans or cats with CKD.  It is suspected that CKD cats have an increase in toxins referred to as uremic toxins that trigger the vomiting center (chemoreceptor trigger zone of the area postrema) in their brains.”

Relationship among serum creatinine, serum gastrin, calcium-phosphorus product, and uremic gastropathy in cats with chronic kidney disease (2014) McLeland SM, Lunn KF, Duncan CG, Refsal KR & Quimby JM Journal of Veterinary Internal Medicine 28(3) pp827-37 compared CKD cats with healthy cats. They found that 84% of the CKD cats exhibited loss of appetite and 45% exhibited vomiting, but although the CKD cats did have higher levels of gastrin compared to the healthy cats, there did not appear to be any correlation with the severity of the CKD. The study states “Gastrointestinal signs in these animals may not necessarily be the result of gastric lesions such as gastric ulceration and inflammation, but perhaps the consequence of circulating uremic toxins interacting with the chemoreceptor trigger zone in the brain.” It should be noted that the cats in this study were dead (they were not killed because of the study), so the measurements taken were post-mortem and therefore did not examine whether treatments aimed at controlling gastrin levels had any effect.

Evaluation of gastric pH and serum gastrin concentrations in cats with chronic kidney disease (2017) Tolbert MK, Olin S, MacLane S, Gould E, Steiner JM, Vaden S & Price J Journal of Veterinary Internal Medicine 31(5) pp1414–1419 measured gastric pH in healthy cats and CKD cats over a maximum period of twelve hours, hypothesising that cats with excess stomach acid would have lower gastric pH. The study found that this was not the case and concludes “These findings suggest that cats with CKD may not have gastric hyperacidity compared to healthy cats and, therefore, may not need acid suppression. Thus, further studies to determine if there is a benefit to acid suppression in cats with CKD are warranted.”

Other Causes

Here are some other possible causes of nausea, vomiting and loss of appetite. If you already know that your cat has a particular problem, say, high phosphorus levels, you can click on the appropriate link where you will find more information on other symptoms associated with that condition, which may help you narrow down the cause:

Ask your vet to rule out any of these causes or to treat them if they are present. Treating any that are present should help improve or stop the vomiting and appetite loss and make your cat feel more comfortable. In some cases (e.g. controlling high phosphorus levels), it may also help slow the progression of the CKD.

Of course, it is possible for a CKD cat to have some of the above problems in addition to uraemia.

Symptoms

There is no test as such for toxins, but these are some of the symptoms you might see (though some of these may also be due to other causes, as mentioned under each category).

Loss of Appetite

Loss of appetite is very common in CKD cats and may well be caused by toxins. Human CKD patients have reported that their sense of smell and sometimes taste are impaired; this is thought to be caused by uraemic toxins, and probably occurs in cats too.

There are several other possible causes of lack of appetite, including dehydration, high phosphorus levels, anaemia, fluid retention or heart problems, crashing, metabolic acidosis, mouth ulcers, the use of antibiotics, constipation or hyperthyroidism medication. Dental problems may also cause appetite loss, as may pain.

Cats who do not eat are at risk of developing a potentially life-threatening condition known as hepatic lipidosis. The American Animal Hospital Association recommends that you should contact your vet if your cat has not eaten for one or two days.

Mar Vista Vet has some information about hepatic lipidosis, and mentions that a cat who has eaten only half to three quarters of his or her normal food intake for two weeks is also at risk.

Therefore, it is important to try to find the cause of the inappetence and treat it as quickly as possible. 

Managing the cat that won’t eat (2022) International Cat Care discusses inappetence and how to encourage your cat to eat.

Nausea

Nausea can be hard to detect, though it often presents as a lack of appetite. The cat may also lie scrunched up, looking uncomfortable. You may hear the stomach gurgling.  It is perfectly possible for a cat to have nausea but not to vomit.

High phosphorus levels, dehydration or anaemia may also cause nausea.

Vomiting

Many CKD cats vomit regularly without treatment. Chronic kidney disease (2007) Polzin D Delaware Valley Academy of Veterinary Medicine says “vomiting is reportedly found in one quarter to one third of cats with clinical signs of uremia.” Vomiting may be seen alone or in conjunction with the other symptoms in this section.

Sometimes there may be blood in the vomit — bright red blood is fresh blood, whilst older blood looks like ground coffee grains. This may be a sign of mouth ulcers or of gastrointestinal bleeding, but you should contact your vet immediately if you see this symptom — our George, a non-CKD cat, vomited old blood as the first symptom of severe liver disease.

Cats who vomit a lot are more likely to become dehydrated.

There is a difference between vomiting and regurgitation. Vomiting is usually accompanied by a lot of abdominal movement, whereas regurgitation happens suddenly and with less warning. Vomiting means the cat is emptying the stomach, whereas regurgitation is where food has not yet reached the stomach but is being ejected from the oesophagus more or less intact, often because of eating too fast or hairballs. Regurgitation is often sausage-shaped. Veterinary Partner explains the difference and has videos showing vomiting versus regurgitation.

Cats who vomit immediately after eating may have a gastric motility problem.

Occasionally vomiting is caused by constipation, particularly if your cat vomits before, during or immediately after using the litter tray. 

If you are giving your cat sub-Q fluids and s/he regularly vomits after fluids, this may because of the type of fluid used.

Diagnostic and therapeutic approach to chronic vomiting in cats (2014) Norsworthy G Veterinary Medicine is an algorithm to help narrow down the cause of vomiting in cats.

A practical approach to the common vomiting patient (2012) Burrows C Practica Veterinara III 7 pp14-20 discusses how to narrow down the cause of vomiting.

Why so many vomiting cats? Getting the diagnosis (2011) Little S Presentation to the 36th World Small Animal Veterinary Association World Congress has a flow chart for narrowing down the cause of the vomiting.

Vomiting cat cases: you can figure them out (2015) Zoran D NAVC/WVC Proceedings discusses how to narrow down the cause of vomiting and the possible treatments.

Diagnosis and management of acute and chronic vomiting in dogs and cats (2007) Tams TR Delaware Valley Academy of Veterinary Medicine discusses vomiting.

Vomiting in cats (2015) Primovic D Pet Place discusses vomiting.

Home care for the vomiting cat (2015) Primovic D Pet Place has tips on caring for a vomiting cat.

Vomiting White Foam

Vomiting does not just include food — the classic symptom in CKD cats is to vomit clear or white foam. This is often one of the first signs that people notice when their cat is developing CKD.

Vomiting Water

Sometimes CKD cats drink a lot on water in one go, then vomit all or most of it up shortly afterwards. This may be a sign of excess stomach acid. It is possible that the cat has an urge to drink before vomiting so as to dilute the stomach acid.

Vomiting in the Morning

CKD cats often vomit in the morning. This tends to happen because if a cat goes a long time without eating (such as overnight, excess stomach acid has more time to attack the stomach lining and cause vomiting.

Lip Licking

This can be a sign of nausea and uraemia. It may also be a sign of dehydration or possibly pain. Less commonly, it can be a sign of anaemia. In rare cases it may be caused by longer term (over three months) use of metoclopramide (Reglan). 

Teeth Grinding

Cats who grind their teeth may have uraemia. Dental problems are another possible cause. It may also be a sign of dehydration. Very occasionally, this might be a sign of “rubber jaw”, caused by a condition related to CKD called secondary hyperparathyroidism.

Youtube has a video of a cat grinding his/her teeth.

Hoarseness

CKD cats may occasionally become rather hoarse because of acid reflux caused by excess stomach acid. 

In some cases hoarseness may be a sign of low potassium levels. Hoarseness is also sometimes seen in cats with hyperthyroidism. If accompanied by coughing, consider the possibilities of fluid retention or heart problems.

Drooling (Ptyalism)

Apart from uraemia, dental problems or mouth ulcers may also  cause drooling.

In some cases drooling may be a side effect of using maropitant (Cerenia).

2022 Consensus guidelines on management of the inappetent hospitalised cat (2022) Taylor S, Chan DL, Villaverde C, Ryan L, Peron F, Quimby J, O’Brien C & Chalhoub S Journal of Feline Medicine and Surgery 24(7) pp614-640 has a photo of a drooling cat on page 618.

Ptyalism/pseudoptyalism (2020) Allen J Clinician’s Brief discusses other possible causes of drooling.

The Pet Health Network has more information about drooling.

Pet MD also has some information.

Eating Grass

Cats commonly eat grass in order to help themselves vomit, particularly if they want to bring up a hair ball. CKD cats may eat grass for this reason, though they may also do it because they feel nauseous generally, and sometimes you feel a little better if you can actually vomit. It is normally fine to allow your CKD cat to eat grass, as long as it has not been treated with pesticides.

Yawning and Howling

These may sometimes be symptoms of uraemia. Howling may have other causes (see Index of Symptoms and Treatments). 

Hunched over Water Bowl

This can be a sign of nausea and uraemia. Occasionally it is a sign of dehydration. 

Playing with Water

Some cats like to play with their water bowls from an early age, but developing a bit of an obsession with water is a common new behaviour in CKD cats.  Some will play with their water bowl or paw at the water. You may see other new behaviours, such as drinking from showers or gutters, or hanging around sinks and begging for fresh running water from the tap. All these types of behaviour may indicate uraemia. Other possible causes include dehydration or diabetes.  

Sniffing, Licking or Looking at Food, then Walking Away

The cat may approach the food bowl and sniff or lick the food, then walk away. This is a pretty classic sign of uraemia in a CKD cat, but it may also indicate mouth ulcers.

Pawing at the Mouth

The most common reason for this is dental problems, but occasionally it is a sign of uraemia.

Increased Drinking (Polydipsia)

Increased drinking is common in CKD cats because they usually have problems maintaining hydration. However, it can also be a symptom of uraemia. The cat may drink more because, according to A glass of water immediately increases gastric pH in healthy subjects (2008) Karamanolis G, Theofanidou I, Yiasemidou M, Giannoulis E, TriantafyllouK & Ladas SD Digestive Diseases and Sciences 53(12) pp3128-3132, drinking water may briefly (only for a few minutes) reduce levels of stomach acid.

In some cases increased drinking may indicate diabetes.

Licking Gravy Only

The cat may lick the gravy only and leave any solid food behind. However, this may not indicate uraemia in all cats, only if it is a new behaviour — my cats do this all the time and they are healthy, they just prefer pâté-type foods. Another possible cause is dental problems.

Sitting Hunched Up

Since cats with uraemia have sore tummies, they may sit in a hunched up, uncomfortable position (“meatloafing”). In the worst case, this may indicate crashing, but only if you also see the symptoms described there.

Treatments

Although it is not possible to test for toxins, if your cat is showing any of the symptoms described above (e.g. vomiting white foam), I would definitely opt to treat. Many people find using the treatments outlined below as appropriate (with their vet’s approval, of course) helps their cats to feel noticeably better. Feline CKD: Current therapies – what is achievable? (2013) Korman R & White J Journal of Feline Medicine and Surgery 15(S1) pp29–44 says “Cats in CKD stages 3–4 often demonstrate gastrointestinal signs of uraemia (eg, inappetence, nausea, vomiting, stomatitis, gastrointestinal ulceration, diarrhoea, colitis) and addressing these may improve quality of life.”

IRIS treatment recommendations for CKD in cats (2023) International Renal Interest Society state “Treat vomiting/decreased appetite/nausea/weight and/or muscle loss with an antiemetic/appetite stimulant/antinausea agent (such as maropitant, ondansetron, oral or transdermal mirtazapine, or capromorelin).”

Although many CKD cats benefit from the treatments described below, the best treatment depends upon the cause of the problem. For example, many cats with anaemia lose their appetites, and the treatments on this page will not help with that, you need to treat the anaemia. You can check the Index of Symptoms and Treatments page for information on treatments for the other possible causes mentioned above.

People in the USA tend to be routinely offered treatments for reduced appetite, vomiting or nausea but this is not always the case in Europe. Although things are slowly improving, it is still quite possible that if you are in the UK in particular, you will be offered nothing. In this case, ask your vet to read the ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239, which state “Vomiting should be actively managed in cats with CKD and nausea should always be considered as a potential contributory cause in cats with inappetence.”

Managing inappetence and chronic kidney disease (2022) Larsen JA, Marks N, Bullen L & Wood MA Clinician’s Forum discusses various treatments for inappetence.

2022 Consensus guidelines on management of the inappetent hospitalised cat (2022) Taylor S, Chan DL, Villaverde C, Ryan L, Peron F, Quimby J, O’Brien C & Chalhoub S Journal of Feline Medicine and Surgery 24(7) pp614-640 also offer suggestions..

Simple Natural Treatments

I recommend trying these treatments first, because they need little effort, are inexpensive, are not invasive and can be tried immediately and without a vet visit (though please inform your vet if you wish to try slippery elm bark); yet for some cats they are extremely effective. In fact, for some cats, especially those in early stage CKD, these may be the only treatments they need, at least to start with.

If these treatments are going to help, you would normally see a difference (e.g. reduced vomiting) within a couple of days. If they are not sufficient, you can talk to your vet about moving on to using medications, as described further below.

Raising Your Cat’s Bowls

Normally a cat eats with the mouth lower than the stomach, but in CKD cats this can cause stomach acid to enter the oesophagus and trigger acid reflux. Keeping the cat’s food and water bowls higher than the stomach can help minimise this problem and may encourage your cat to eat and drink more.

Standing bowls on an upside-down flower pot can often create the correct height for your cat and provide a sturdy base: choose a flower pot of the appropriate height for your cat. Some pet stores also sell food dishes on legs, which are approximately 6 inches (15cm) high.

I’ve been using raised food bowls for years (well, my cats have). and my cats love them. In fact, they refuse to eat from anything else, and become really indignant if all the bowls are in the dishwasher at the same time. When I first started using them, I also noticed an increase in food intake compared to using other bowls. To the left you can see my silly kitten using his Classy Cat dish in his own inimitable way — he did eventually get the hang of it!

Necoichi raised bowls are also available from Amazon USA. These have good reviews, though some people think they are too small and/or too low.

Uah Pet sells a raised bowl that one member of Tanya’s Support Group recommends and that I think looks promising.

Amazon UK sells some raised bowls which at least one member of my support group has used, though I think these would be too deep for some cats, especially Persians.

The Art of Doing Stuff has ideas on making your own raised bowls, though I think the ones she uses are too deep for cats.

Feeding Before Bedtime

You may find that your cat tends to vomit more during the night or first thing in the morning. This may be because, if a cat goes a long time without eating, excess stomach acid has more time to attack the stomach lining.

Try to ensure that your cat eats before bedtime in order to prevent this — keeping food constantly in the stomach means the acids are more likely to attack the food rather than the stomach lining. It may also be worth setting up an automated feeder on a timer with food in it to keep your cat supplied with food throughout the night. There are links to such feeders here.

Slippery Elm Bark

A herbal remedy called slippery elm bark (SEB) is often very effective for cats with nausea, vomiting or appetite loss. It soothes the digestive tract, so it can also help with both constipation and diarrhoea.

The Holistic Treatments page has more detailed information on SEB. Please inform your vet if you wish to use slippery elm bark.

Nausea and Vomiting Medications

If the natural treatments above don’t work, you will probably have to consider trying additional treatments. Commonly used medications are:

  • maropitant (Cerenia): effective for vomiting but may also help to a degree with nausea. Also has some anti-inflammatory properties.

It is usually safe to use these treatments at the same time as slippery elm bark or famotidine, but check with your vet first.

Ondansetron and maropitant are usually very effective, particularly for cats whose CKD is more advanced. They may also be helpful for cats with additional issues, such as concurrent pancreatitis or IBD, or gastric motility problems. They work in different ways, so discuss with your vet whether one of them might be suitable for your cat.

I regularly hear from people whose vets are not familiar with the use of ondansetron or maropitant in CKD cats and therefore they are understandably reluctant to prescribe them. In such cases, I would refer your vet to the ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239, which say “Centrally acting antiemetics such as maropitant, mirtazapine, ondansetron and dolasetron should be considered for management.”

Managing pancreatitis and concurrent conditions (2009) Robertson J DX Consult 2(1) offers a brief overview of these treatments.

Ondansetron (Zofran)

Ondansetron is commonly used to control vomiting in cats with pancreatitis or cancer, but many people find it effective for CKD cats too.

Ondansetron was first approved for human use in 1990 for the treatment of vomiting caused by chemotherapy, so it has been around for a long time. I first heard of somebody using it for a CKD cat in 2002, but it was not used routinely in CKD cats until recently, mainly because it was extremely expensive. Since the generic version became available in the USA, however, it is becoming steadily more popular for use in CKD cats. Trade names include Zofran in the USA, Setronon in Europe and Emeset in the UK.

Ondansetron works by selectively inhibiting serotonin 5HT3 receptors (this is a different mechanism to that of metoclopramide, a medication that was previously used by some people, but which is no longer commonly prescribed) so it does not lower the seizure threshold as metoclopramide does.

Ondansetron (Zofran) for dogs and cats (2022) Dodman N Pet Place has some information about ondansetron.

Ondansetron Formulations

Ondansetron Pills

Ondansetron is available as 4mg or 8mg pills, and a commonly used dose is 1 mg each time it is given, so one pill contains four or eight doses. The pills are tiny, so can be hard to cut into quarters. A prescription is required.

Ondansetron Injectable

There is also an injectable form of ondansetron. The bottle may say it is for intravenous use, but many people give injectable ondansetron subcutaneously with no problems. In fact, Oral, subcutaneous and intravenous pharmacokinetics of ondansetron in healthy cats (2014) Quimby JM, Lake RC, Hansen RJ, Lunghofer PJ & Gustafson DL Journal of Veterinary Pharmacology and Therapeutics 37(4) pp348–353 found that subcutaneous administration was more effective than oral dosing.

Unfortunately injectable ondansetron stings a lot, but it may be with considering for a cat who is struggling to keep anything down, and it does work quickly — you should see results within a couple of hours. If you are giving sub-Qs, it can help if you give them before you give the ondansetron.

Ondansetron Transdermal

Colorado State University College of Veterinary Medicine looked at the use of transdermal ondansetron in cats. Assessment of absorption of transdermal ondansetron in normal research cats (2017) Zajic LB, Herndon AK, Sieberg LG, Caress AL, Morgan PK, Hansen RJ, Wittenburg LA, Gustafson DL & Quimby JM Journal of Feline Medicine and Surgery 19(12) pp1245-1248 found that “transdermal application of 4mg ondansetron does not result in clinically relevant serum concentrations of drug.”

Some members of Tanya’s CKD Support Group have nevertheless used transdermal ondansetron successfully, but I think I would try the other formulations first.

Ondansetron Dosage

Ondansetron Dosage Amount

Ondansetron (Zofran) for dogs and cats (2022) Dodman N Pet Place mentions that the usual dose for cats is 0.11mg per pound bodyweight, i.e. 1.1mg for a 10 lb (4.5kg) cat.

Plumb’s Veterinary Drug Handbook mentions an empiric dose of 0.5mg per kg bodyweight twice daily, so a 10 lb (4.5kg) cat would be given 2.25mg, so a higher dose.

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239 suggest 0.5-1.0 mg/per kg, given subcutaneously. This would mean a 10 lb (4.5kg) cat would receive 2.25-5.0 mg.

Many people start off giving 1 mg for each dose, and increase as necessary.

Ondansetron Dosage Frequency

It used to be the case that twice daily administration was recommended. This is what Plumb’s recommends.

Ondansetron (Zofran) for dogs and cats (2022) Dodman N Pet Place mentions that ondansetron can be given 2-3 times a day.

Twice a day may not be sufficient for many CKD cats. Oral, subcutaneous and intravenous pharmacokinetics of ondansetron in healthy cats (2014) Quimby JM, Lake RC, Hansen RJ, Lunghofer PJ & Gustafson DL Journal of Veterinary Pharmacology and Therapeutics 37(4)  pp348–353 states that “twice daily administration at 0.5 mg/kg is likely inadequate to maintain serum concentrations within the therapeutic range; higher or more frequent doses may be needed.” It further states that “the postulated therapeutic range — extrapolated from a previously published pharmacodynamic study — may not be accurate particularly if applied to repeated administration for chronic disease states.”

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239 recommend giving ondansetron subcutaneously every 6–8 hours, so three or four times a day.

The problem is that cats seem to vary widely in their ability to utilise ondansetron. Oral, subcutaneous and intravenous pharmacokinetics of ondansetron in healthy cats (2014) Quimby JM, Lake RC, Hansen RJ, Lunghofer PJ & Gustafson DL Journal of Veterinary Pharmacology and Therapeutics 37(4)  pp348–353 says that “Poor bioavailability should be taken into account when determining a route of administration for a patient as individual oral bioavailability ranged from 11 to 50% in the cats used in this study.” (The study used healthy cats). You may therefore need to experiment to find the optimum dose and frequency for your cat.

For acute vomiting, such as in a cat with pancreatitis, higher dosing may be necessary. For chronic nausea in CKD cats, however, many people find a dose of 1mg is fine, but needed at least twice daily, and if that doesn’t work, then three times daily. Some cats do need ondansetron four times a day.

I would start with a dose of 1 mg twice a day, and if you find this is not enough, speak to your vet about increasing the frequency initially, and if necessary, the dose.

Ondansetron Side Effects and Interactions

Possible side effects include constipation, low blood pressure and sleepiness. Humans have reported bad headaches. Drugs has more information about possible side effects.

It was previously reported that when given intravenously to humans in high doses, ondansetron may cause heart arrhythmias. In June 2012 The US Food & Drug Administration reported that “a 32 mg single intravenous dose of ondansetron (Zofran, ondansetron hydrochloride, and generics) may affect the electrical activity of the heart (QT interval prolongation), which could pre-dispose patients to develop an abnormal and potentially fatal heart rhythm known as Torsades de Pointes.” Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis (2014) Freedman SB, Uleryk E, Rumantir M & Finkelstein Y Annals of Emergency Medicine 64(1) pp19-25 looked into this and concluded “No reports describing an arrhythmia associated with single oral ondansetron dose administration were identified.” For those apparently affected by intravenous ondansetron “A significant medical history (67%) or concomitant use of a QT-prolonging medication (67%) was identified in 83% of reports. Approximately one third occurred in patients receiving chemotherapeutic agents, many of which are known to prolong the QT interval. An additional third involved administration to prevent postoperative vomiting.” This is probably not a concern for most CKD cats, but discuss with your vet if you are worried.

Drugs mentions that using ondansetron at the same time as famotidine may increase the risk of heart arrhythmias, though it is rare.

There is some debate as to whether ondansetron causes serotonin syndrome. The US Food and Drug Administration states that it may, though it says that “The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center.” It also says that serotonin syndrome is more common when given at the same time as medications such as mirtazapine (used in CKD cats as an appetite stimulant). Drugs also mentions that using ondansetron and mirtazapine together may increase the risk. However, Can 5-HT3 antagonists really contribute to serotonin toxicity? A call for clarity and pharmacological law and order (2014) Rojas-Fernandez CH Drugs — Real World Outcomes 1(1) pp 3–5 disputes that ondansetron causes serotonin syndrome. Discuss with your vet whether to give both medications, and if you do so, give them at least two hours apart.

Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT3  spinal receptot 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 may reduce the painkilling effects of tramadol by up to 50% in humans. It is not known if the same applies to cats.

Ondansetron Sources

Ondansetron Pills

USA

You can be charged as much as US$6 for a single pill, so you need to shop around because it is possible to buy the generic pills for a lot less. You may be able to obtain them even more cheaply with a pet medication card (see Obtaining Supplies Cheaply).

Good RX allows you to search for discounted medications in your area in the USA. Often offers very good prices.

Honeybee Health 30 tablets (8mg) for $6, but does not ship to all states.

Costco 30 tablets (4mg) from US$26.66, depending upon the manufacturer and your location (I searched for NYC).

Health Warehouse 9 tablets (4mg) for US$10, but the first order can take up to two weeks.

Thriving Pets One tablet (4mg) costs US$1. Get a 5% discount on orders over US$100 with the code tanya.

UK

Many UK chemists can supply ondansetron with a prescription from your vet. It is usually cheaper to buy more pills at one time.

Hyperdrug sells 4mg ondansetron tablets for £0.31 per tablet.

Ondansetron Injectable

USA

Entirely Pets sells a 40mg/20ml vial (forty doses for many cats) for US$6.99 per vial.

Allivet sells a 40mg/20ml vial (forty doses for many cats) for US$8.99 per vial.

Thriving Pets sell ten 2 ml vials in a 2mg/ml strength for US$43.95. Get a 5% discount on orders over US$100 with the code tanya.

Chewy sells 20ml of a 2 mg/ml strength injectable for US$8.99.

Walgreens sells ondansetron injectable in a 20ml vial in a 2mg/ml strength for around US$8. You may be able to use the Goodrx card.

Dolasetron (Anzemet)

I occasionally hear from people who are using another drug in the family as ondansetron, dolasetron (Anzemet). The main advantage of dolasetron is that it only needs to be given once a day, but for some reason it is not used often in CKD cats and seems to be more commonly used for cats with pancreatitis.

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 mention a dose of 1.0 mg/kg once a day given subcutaneously, so a 10 lb (4.5kg) cat would receive 4.5mg each day subcutaneously.

However, Preliminary pharmacokinetics of intravenous and subcutaneous dolasetron and pharmacodynamics of subcutaneous dolasetron in healthy cats (2018) Herndon AK, Quimby JM, Sieberg LG, Davis L, Caress AL, Ligas S, Hansen RJ, Wittenburg LA & Gustafson DL Journal of Feline Medicine and Surgery 20(8) pp721-727 found that a dose of 0.8 mg/kg given intravenously or subcutaneously did not last for 24 hours in the body and did not appear to prevent vomiting in healthy cats. A higher dose of 1mg/kg also did not prevent vomiting. The study concludes that further research is necessary to determine the efficacy and optimal dose for cats.

Plumb’s Veterinary Drug Handbook mentions that dolasetron should not be given to patients with certain types of heart problem, and should be used with caution in cats with low potassium levels.

Pharmacologic control of vomiting (2009) Tams TR CVC in Kansas City Proceedings has some information about dolasetron.

Maropitant (Cerenia)

Maropitant (Cerenia) is a treatment for vomiting that works by inhibiting neurokinin (NK) inhibitors. In other words, it works by blocking the stimulation of the part of the brain that instigates vomiting. Maropitant: novel antiemetic (2015) Trepanier LA Clinician’s Brief Feb 2015 pp75-77 explains more about how it works.

Maropitant use in cats (2020) Quimby JA Today’s Veterinary Practice May/Jun 2020 states “Maropitant may be particularly useful in cats with chronic kidney disease because the drug targets receptors in the CRTZ and vomiting center in the brain, where uremic toxins are sensed, and also targets receptors in the gastrointestinal tract.”

The injectable form is approved for the treatment of vomiting and nausea in cats (and dogs) in Europe and the USA. In Europe, injectable maropitant is also approved for travel sickness in cats. Treatment for visceral pain with the new NNK-1 receptor antagonist maropitant in cats (2011) Boscan P, Monnet E, Twedt D & Nyiom S, found that maropitant may also be an effective painkiller, so it may be a good choice for a vomiting cat with pancreatitis.

Maropitant only needs to be given once a day and does appear to be very effective for some cats, usually (though not always) taking effect within an hour. Chronic use of maropitant for the management of vomiting and inappetence in cats with chronic kidney disease: a blinded placebo-controlled clinical trial (2015) Quimby JM, Brock WT, Moses K, Bolotin D, Patricelli K Journal of  Feline Medicine and Surgery 17(8) pp692-697 found that there was a significant reduction in vomiting in CKD cats given maropitant; however, it did not seem to improve appetite.

Maropitant use in cats (2020) Quimby JM Today’s Veterinary Practice May/Jun 20 has an overview of maropitant use in cats

Some people find maropitant works better for their cats than ondansetron, so if you are not finding ondansetron as effective as you hoped, even though you are dosing optimally, you may wish to talk to your vet about trying maropitant instead.

Maropitant Formulations

Maropitant is available in either injectable or pill form. Both are intended to prevent vomiting, but the injectable form is also designed to treat acute vomiting.

Only the injectable form is approved for use in cats, but the pill form is used off label.

Maropitant Tablets

Maropitant comes in 16mg-sized tablets so you will have to break them into suitable sizes for your cat. Make sure you are not given larger size tablets intended for humans.

The oral form seems to taste horrible.

Maropitant Injectable

Unfortunately there is no generic injectable form of maropitant, and injectable Cerenia is expensive. A typical dose would be 4mg daily (0.4 ml), so a 20 ml vial of a 10mg/ml concentration provides 50 doses. You may be able to get maropitant more cheaply from a compounding pharmacy.

Injectable maropitant stings very badly, though keeping it in the fridge may help with this. Prevomax is an injectable form of maropitant that was introduced in the UK and Europe in early 2018. It contains a preservative that is supposed to reduce the pain of injection. The same applies to Vetemex, which was released in the UK market in 2020.

Once opened, the vial should be stored in the fridge. Drugs states that it will keep for 90 days in the fridge, but that the stopper should not be punctured more than 25 times, so whether you can really get 50 doses from your vial is debatable.

Maropitant Transdermal

Evaluation of the efficacy of transdermal administration of maropitant in managing vomiting in cats (2022) Boukaache Y, Ferret ML, Khoukh VDK, Enache A, Iwaszkiw D, Bertin S & Bruno F Open Veterinary Journal 12(5) pp618-621 found that transdermal maropitant appeared to help with vomiting in 75% (six) of the cats in the study. However, these cats did not appear to have CKD (though several of them had pancreatitis) and were experiencing acute vomiting rather than the more chronic form associated with CKD.

Wedgewood Pharmacy in the USA offers two types of transdermal maropitant. (It also sells tablets scored into four to make them easier to split). They will accept orders from vets in all US states apart from North Carolina.

Your local compounding pharmacy may also be able to help.

Maropitant Dosages

Maropitant Oral

Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats (2008) Hickman MA, Cox SR, Mahabir S, Miskell C, Lin J, Bunger A, McCall RB Journal of Veterinary Pharmacology and Therapeutics 31(3) pp220-9 states “The results indicate that maropitant is an effective, well tolerated and safe anti-emetic in cats at a dose of 1.0 mg/kg.”

The manufacturer recommends this dose, as do Plumb’s Veterinary Drug Handbook and Pet Place.

A 10 lb cat (4.5 kg) cat would therefore receive 4.5 mg a day, or a quarter of a 16mg tablet.

However, some cats need up to double this dose, i.e. 2mg per kg (2.2lbs) a day, or 9 mg a day (half a 16mg tablet a day) for a 10lb (4.5kg) cat.

Many vets seem concerned that 2mg/kg might be too high a dose, but it is recommended by ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239, which state “2 mg/kg q24h [once a day].” I have heard from a few people who think this dose may have caused some lethargy in their cats but I have not heard of any other issues.

Oral maropitant is famous for tasting horrible, even if you try to use a flavoured variety. Many people place the medication in a gelatine capsule in order to hide the taste. Unfortunately the pills should not be given in Pill Pockets or mixed with food as this may stop them being properly absorbed in the cat’s body, but some people do give them this way and still find them effective.

The European Medicines Agency states that halved tablets should be stored in the foil they came in and that the shelf life of halved tablets is only two days. One person spoke to the manufacturer and was told they will keep longer than that, others have been told by the manufacturer that the two day rule does apply. I have not heard from anybody who throws away the last half or quarter of their tablets, but if you think your cat’s response to maropitant seems to be inconsistent (e.g. your cat vomits every fourth day), this might explain why.

Maropitant Injectable

The European Medicines Agency states that the injectable form is given:

  • “once daily under the skin (1ml per 10 kg bodyweight) for up to five days”
  • the injectable form comes in a 10mg/ml strength, so 1ml contains 10mg
  • Therefore a 10 lb (4.5kg) cat would receive 4.5mg a day, or 0.45 ml.

Plumb’s Veterinary Drug Handbook states that

  • 0.5 to 1 mg per kg bodyweight can be given for up to five days.
  • Therefore a 10 lb (4.5kg) cat would receive 2.25-5.00 mg a day, or 0.225-0.5ml a day.

As with the oral medication, some cats do fine on the lower dose, whilst others require the higher dose. I have heard from a few people who think the higher dose may have caused some lethargy in their cats but I have not heard of any other issues.

Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats (2008) Hickman MA, Cox SR, Mahabir S, Miskell C, Lin J, Bunger A, McCall RB Journal of Veterinary Pharmacology and Therapeutics 31(3) pp220-9 states “Safety of maropitant was determined following 15 days of subcutaneous (SC) administration at 0.5-5 mg/kg. Maropitant was well tolerated in cats at doses that exceeded the efficacious anti-emetic dose range of the drug by at least a factor of 10.”

The injectable form seems to sting some cats (unless you are using Prevomax or Vetemex), though keeping it in the fridge before use, and injecting it into the fluids lump after giving sub-Qs may make it sting less.

Maropitant Dosing Frequency

One of the main problems with maropitant is the issue of whether you should have regular breaks when giving it.

The manufacturer used to recommend that maropitant should only be given short term to dogs, for a maximum of five days at a time. Off label use of drugs in veterinary medicine (2013) Coates J PetMD explains that using maropitant for longer can reduce dopamine levels in the central nervous system and lead to tremors.

In 2015, the manufacturer announced that the FDA had approved a change in the labelling of maropitant in tablet form to allow for it to be given once daily to dogs over the age of seven months until the vomiting is resolved. The recommendation for dogs aged between two and seven months remained at a maximum of five days at a time.

In the manufacturer’s study into the use of injectable maropitant in cats, the maropitant was only given for five days. As far as I am aware, the manufacturer has not assessed maropitant when given daily to cats for longer periods, whether injectable or in tablet form. Therefore most people giving maropitant to their cats used to err on the side of caution and would give maropitant for up to five days, take a break, then use it again. Plumb’s Veterinary Drug Handbook mentions that the medication should be stopped for at least 48 hours in these circumstances.

Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats (2008) Hickman MA, Cox SR, Mahabir S, Miskell C, Lin J, Bunger A, McCall RB Journal of Veterinary Pharmacology and Therapeutics 31(3) pp220-9 gave maropitant for fifteen days without a break in cats with no apparent problems, though one cat did have minor tremors while asleep. I know that after learning about this study, some people have given their cats maropitant for longer than five days and not seen any adverse effects.

Chronic use of maropitant for the management of vomiting and inappetence in cats with chronic kidney disease: a blinded placebo-controlled clinical trial (2015) Quimby JM, Brock WT, Moses K, Bolotin D, Patricelli K Journal of  Feline Medicine and Surgery 17(8) pp692-7 gave 4 mg of maropitant orally to cats once every day for 14 days without a break. Colorado State University College of Veterinary Medicine, which led this study, has stated that it is prepared to give its patients maropitant on a daily basis without a break.

Veterinary Partner used to say “Originally, a five days on/one day off schedule was recommended for long-term use but, now that maropitant has been out for many years, long-term use has come to be more common without skipping days.” As at 2024, Veterinary Partner merely says “Maropitant is used once a day to control nausea.”

Some members of Tanya’s CKD Support Group do give maropitant without a break. Others use it but do take a break and use ondansetron on break days.

Be guided by your vet on the best approach for your cat, and monitor your cat closely for tremors or shaking.

Maropitant Side Effects and Interactions

Possible side effects include vomiting, lethargy, diarrhoea, anorexia, twitching and drooling. Maropitant should not be used if there is any gastrointestinal obstruction, and should be used with caution if liver or heart problems are present (it may increase the QT interval and the risk of arrhythmias). Drugs has more information.

The European Medicines Agency says “Since maropitant could affect heart activity, Cerenia should be used with caution in animals with certain heart conditions.” I do not know which heart conditions this is referring to, but check with your vet if your cat has any kind of heart condition. 

The European Medicines Agency also says (clause 4.8 on page 9) that “Cerenia should not be used concomitantly with Ca-channel antagonists as maropitant has affinity to Ca-channels.” In principle this means that maropitant should not be used with calcium channel blockers such as amlodipine (Norvasc or Istin, commonly used to treat high blood pressure in CKD cats).  ‘Concomitantly’ has a rather vague medical meaning in that it means during the same time period, but in this context I don’t know exactly what time period the EMA is referring to, i.e. do they mean at the same time or on the same day? Both of these medications tend to be given once daily, so they have a relatively long effect. I suspect that giving them both on the same day but 12 hours apart (i.e. one in the morning and one in the evening) would probably be acceptable, and indeed one member of Tanya’s CKD Support Group reported in 2020 that her cat vomited if she gave maropitant and amlodipine close together, but there was no vomiting if they were given 12 hours apart. Discuss the best approach for your cat with your vet.

The European Medicines Agency also warns that medical attention should be sought if maropitant gets in your eyes.

Cerenia information sheet (tablets) states that maropitant may interact with phenobarbital, used to control epilepsy, and NSAIDs.

Cerenia information sheet (injectable) also mentions this.

Maropitant Sources

If you are in the USA, you could consider signing up for the Zoetis Pet Care Rewards Scheme. This gives you credits that you can spend at many vets.

Maropitant Tablets

Maropitant comes in 16mg-sized tablets so most people use these and break them into suitable sizes for their cat. Make sure you are not given larger size tablets intended for humans.

USA

Valley Vet sells four 16mg tablets for US$23.15 with free shipping for orders over US$60 (shipping costs US$7 otherwise). I have used Valley Vet myself in the past for other products with no problems.

Allivet sells four 16mg tablets for US$23.15.

Chewy sells four 16mg tablets for US$23.15. I’m beginning to see a pattern here…

Costco apparently sells maropitant cheaply (in March 2021 one member of Tanya’s CKD Support Group was able to buy four 16mg tablets for US$12.99, though I’m sure the price will have gone up since then) but it usually has to be ordered, which can take a few days.

UK

Vet UK sells 16mg tablets for £2.45 each.

VioVet sells four 16mg tablets for £10.18.

Canada

Pets Drug Mart sells 16 mg size tablets for CAN$3.51 each.

Maropitant Injectable

USA

Thriving Pets sell a 20ml vial of 10 mg/ml strength for US$329.95. This provides around 50 doses (depending upon the size of the cat), so each dose would cost US$6.60. A prescription is required. You may get 5% off with the code tanya.

UK

Prevomax and Vetemex are both available in a 20ml vial of 10 mg/ml size.

Canada

Pets Drug Mart sells a 20ml vial of 10 mg/ml for CAN$199.95 This provides around 50 doses (depending upon the size of the cat), so each dose would cost around CAN$4.

Gastroprotectants (Acid Blockers)

There are two main classes of gastroprotectant used in CKD cats:

Until relatively recently, it was routinely recommended that CKD cats should be given gastroprotectants, and usually as the first step in a treatment plan for vomiting and nausea. 11 guidelines for conservatively treating chronic kidney disease (2007) Polzin D, Veterinary Medicine Dec 2007 say “H2 blockers are most commonly used, and few adverse effects have been attributed to their use. Antiemetics are typically added when anorexia, nausea, or vomiting persist despite the use of an H2 blocker.”

However, recently there has been some debate as to whether CKD cats actually suffer from gastric hyperacidity (excess stomach acid) that needs controlling (see above). ACVIM consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats (2018) Marks SL, Kook PH, Papich MG, Tolbert MK & Willard MD Journal of Veterinary Internal Medicine 32(6) pp1823-1840 states “This report challenges the dogma and clinical practice of administering GI protectants for the routine management of gastritis, pancreatitis, hepatic disease, and renal disease in dogs and cats lacking additional risk factors for ulceration or concerns for GI bleeding.” The paper adds “There is no evidence to support the prophylactic use of gastroprotectants in dogs and cats with International Renal Interest Society (IRIS) stages1-3 renal disease. Additional studies are warranted to determine the benefits of acid suppression in animals with IRIS stage 4 renal disease.”

Perhaps because of this debate, these medications have fallen rather out of favour, with most people favouring ondansetron or maropitant. However, whilst ondansetron or maropitant are certainly useful, some people still use gastroprotectants because they find them effective plus they are cheap and easily available over the counter in most countries (though please do not use any of these treatments without your vet’s approval)

Histamine H2 Antagonists

Histamine H2 antagonists block the production of stomach acid rather than neutralise it. Famotidine (Pepcid AC), ranitidine (Zantac 75) and cimetidine (Tagamet) all belong to this category of medications.

Because histamine H2 antagonists are long-acting, they have long been considered a good choice for treating stomach acid problems. Current concepts for the management of chronic renal failure in the dog and cat — early diagnosis and supportive care (2005) Sanderson S Presentation to the 30th World Congress of the World Small Animal Veterinary Association states that it is generally recommended to use such treatments in CKD cats once creatinine is over 3 mg/dl (USA) or 265 mmol/L (international).

That is quite an old paper and recently there has been a lot of debate in scientific circles as to how effective the histamine H2 antagonists are in CKD cats. This is largely because of a study, Evaluation of gastric pH and serum gastrin concentrations in cats with chronic kidney disease (2017) Tolbert MK, Olin S, MacLane S, Gould E, Steiner JM, Vaden S & Price J Journal of Veterinary Internal Medicine 31(5) pp1414–1419, which measured gastric pH in healthy cats and CKD cats over a maximum period of twelve hours, hypothesising that cats with excess stomach acid would have lower gastric pH. The study found that this was not the case and concludes “These findings suggest that cats with CKD may not have gastric hyperacidity compared to healthy cats and, therefore, may not need acid suppression..”

Because of this study, I hear from people whose vets are now reluctant to prescribe histamine H2 antagonists, even if they have used them before. I think this response is premature, and may be caused by some statements made in the study, e.g. it states “Chronic administration of acid suppressants has been associated with calcium and PTH derangements, osteoporosis, and pathologic fractures in at risk human populations.”

That statement refers to humans, not to cats. In addition, this study looked at only ten CKD cats, 50% of whom were in IRIS Stage 2, so below the level where these medications are normally used. Even the study itself does not advise against giving them, saying “additional studies are warranted both to evaluate gastric pH in cats with later stages of CKD as well as to determine if there is an actual benefit of acid suppression in cats with CKD.”

ACVIM consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats (2018) Marks SL, Kook PH, Papich MG, Tolbert MK & Willard MD Journal of Veterinary Internal Medicine 32(6) pp1823-1840 states “Critical assessment of acid suppressants in experimental models and dogs and cats with spontaneous disease is sparse, and most of the studies evaluating the efficacy of acid suppressants were performed in healthy animals.” Or, as in the 2014 McLeland study cited above, deceased. The consensus statement concludes “Renal disease: No evidence for acid suppressant therapy in animals with IRIS 1-3 CKD. More data is needed for animals in IRIS stage 4.”

Evaluation of gastroprotectant administration in hospitalized cats in a tertiary referral hospital (2023) Ullal TV, Marks SL, Evenhuis JV, Figueroa ME, Pomerantz LK & Forsythe LR Journal of Feline Medicine and Surgery 25(10) states that 60% of the cats treated with gastroprotectants had no valid medical reason for receiving them.

Famotidine (Pepcid AC)

Famotidine (Pepcid AC) has long been a popular treatment in the USA for feline CKD cats, though less so in recent times as the medications discussed above become more popular. It seems to be an effective treatment, though there are very few studies into the use of famotidine in cats, particularly CKD cats, and recent studies are questioning its effectiveness. One such study, Evaluation of the effect of orally administered acid suppressants on intragastric pH in cats (2015) Parkinson S, Tolbert K, Messenger K, Odunayo A, Brand M, Davidson G, Peters E, Reed A & Papich MG Journal of Veterinary Internal Medicine 29(1) pp104-112, states “These results suggest that both omeprazole formulations provide superior acid suppression in cats compared to famotidine or placebo” but this small study was conducted in healthy cats. Many people do tell me that famotidine does seem to help their cat feel better.

As a side effect, famotidine may reduce parathyroid hormone levels in CKD patients. Famotidine reduces serum parathyroid hormone levels in uremic patients (1991) Arik N, Arinsoy T, Sayín M, Taşdemir I, Yasavul U, Turgan C, Caglar S Nephron 59(2) p333 explains more about this. I would not use famotidine to treat elevated PTH levels only.

During the Covid-19 pandemic, it was discovered that elderly human patients with Covid-19 appeared to have a better chance of survival if they were taking famotidine, with the result that many pharmacies sold out.

Pet Place has more information about famotidine.

Famotidine Formulations

Famotidine is available as a generic or, in the USA, under the brand name Pepcid AC. Famotidine may be sold under a different name in your country (e.g. Amfamox, Famox or Pepcidine in New Zealand and Australia). General Medical shows which trade names famotidine is known by in various countries.

Famotidine is available in the USA as a tablet, oral suspension or as an injectable.

Famotidine Tablets

USA

Pepcid AC (Original Strength) in the USA contains 10mg of famotidine. If you opt for the brand name, there are quite a few Pepcid products available so make sure you buy the correct one. You need Pepcid AC 10mg but not the chewable type, and not Pepcid Complete, both of which have some ingredients which make them unsuitable for CKD cats. 

There is also a new version called Pepcid Maximum Strength, which is the same as Pepcid AC except that it contains twice as much famotidine, so be very sure you have the correct strength (10mg tablets).

Using generic famotidine is acceptable, but make sure it is the correct strength and that it does not contain any additional ingredients.

Walmart sells 90 10mg tablets under its own Equate brand for US$8.36

UK

Pepcid AC has been discontinued in the UK and replaced by PepcidTwo. PepcidTwo contains magnesium and calcium in addition to famotidine, so it is not suitable for CKD cats.

Famotidine does exist in generic form and is available from chemists, but only in 20mg size, which could be difficult to cut into cat-sized doses; plus it requires a prescription from your vet.

If you really want to use famotidine, it is sometimes available from Amazon UK in the 10mg strength at prices ranging from £5-65 (search for Pepcid AC or famotidine), though I couldn’t find any when I last looked.

Summit Veterinary Pharmaceuticals sells famotidine in compounded cat-sized tablet form in a 5mg size (so you only need to cut the pills in half) but your vet has to order it for you. 

PCCA sells famotidine to vets in compounded cat-sized form, though they do actually offer 2.5mg capsules. They also sell 100ml of famotidine 2.5mg per ml, with a 90 day expiry from manufacture.

Bova UK A veterinary specials manufacturer that sells chicken flavour 5mg tablets. These can only be ordered by your vet.

Famotidine Oral Suspension

Famotidine is also available as an oral suspension (liquid) in the USA. It is widely available from compounding pharmacies, and usually costs around US$20 for a month’s supply.

Famotidine Injectable

Some people prefer to use injectable famotidine because famotidine tastes very bitter in pill or oral suspension form. You can use the injectable either by injecting it directly into your cat, or if your cat is on sub-Qs, by adding it to the injection port of your IV line.

There are two types of famotidine injectable. There is a 10mg/ml strength without preservative, which is available in 2ml vials. Because it contains no preservatives. This has a short shelf life (it is intended for single use in humans). There is also  a 10mg/ml strength available in a 20ml size vial. This contains a preservative and can be re-used, though it needs to be shipped chilled and should be kept in the fridge after you receive it. It is safe to take it out of the fridge about 30 minutes before using it so it can warm up a little before use.

Injectable famotidine is often out of stock so you may have to search for it.

Thriving Pets sell the 10mg/ml injectable form of famotidine in a 20ml size for US$43.95 in the USA. If you want to give the usual famotidine dose of 2.5mg, you would give 0.25ml, thus the 20ml size contains 80 doses altogether. Get a 5% discount with code tanya.

Famotidine Dosage

Famotidine is excreted by the kidneys, and cats with CKD cannot process it as efficiently as healthy cats, so it may accumulate in the cat’s body and cause problems. Drug dose adjustments for disease (2010) Trepanier LA CVC in Washington Proceedings discusses the need to adjust dosing levels for some medications when diseases including CKD are present.

Below are suggestions for famotidine dosages for CKD cats, but be guided by your vet. You should only use famotidine with your vet’s approval. Do not start with the maximum dose, it could be risky.

Starting dose:2.5 mg once every other day i.e. quarter of a 10mg tablet once every two days e.g. Mon/Wed/Fri.
Intermediate dose (if starting dose does not seem to be helping):2.5mg once a dayi.e. quarter of a 10mg tablet once a day
Maximum dose:2.5mg twice a day i.e. quarter of a 10mg tablet twice a day, 5mg a day in total

Some people find that after a while, famotidine seems to be less effective. The frequency of oral famotidine administration influences its effect on gastric pH in cats over time (2019) Golly E, Odunayo A, Daves M, Vose J, Price J, Hecht S, Steiner JM, Hillsman S & Tolbert MK Journal of Veterinary Internal Medicine 33(2) pp544-550 concluded that famotidine does become less effective over time when given twice daily but that this can be avoided if instead it is given every other day.

If you are only giving famotidine once a day or every other day, I would recommend doing so at bedtime because this seems to help cats who vomit at night or first thing in the morning. Famotidine tastes quite bitter and can make cats foam at the mouth, so you may find it easier to give it in a gelatin capsule (gelcap) or to use the injectable form (see above). It usually takes effect pretty quickly, within a couple of days for most cats.

Once you start giving famotidine, it is usually better to continue giving it regularly even if your cat appears better, so excess stomach acid cannot start building up again.

Famotidine Side Effects and Interactions

The most common side effects in humans are constipation or diarrhoea.

Although famotidine can be purchased over the counter, please do NOT give it without first discussing it with your vet, particularly if your cat has advanced CKD, because it is excreted by the kidneys so it may not be appropriate.

Some cats, particularly those with high bloodwork (creatinine over 5 mg/dl (USA) or 450 µmol/L (international)), do not seem to do well on famotidine, perhaps because their kidneys cannot excrete it efficiently as described above. These cats may in fact exhibit increased vomiting and appetite loss when given it — this happened to our Thomas. Drugs mentions how an overdose may cause vomiting. If your cat’s vomiting and appetite loss do not improve after two days of using famotidine, ask your vet about switching to another treatment.

Medicine Net mentions that famotidine may cause anaemia in humans. This does not appear to be a problem in cats given oral famotidine, but there are rare reports of intravenous famotidine causing haemolytic anaemia in cats. Risk of hemolytic anemia with intravenous administration of famotidine to hospitalized cats (2008) de Brito Galvao JF & Trepanier LA Journal of Veterinary Internal Medicine 22(2) pp325-9 found that “the IV route appeared safe when famotidine was administered over 5 minutes.”

Chronic kidney disease (CKD) in dogs and cats — staging and management strategies (2015) Chew D Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference states that “Calcium carbonate binds phosphorous [sic] best in an acidic environment (pH approx. 5) and binding capacity is reduced in the neutral pH range. Many CKD patients receive inhibitors of gastric acid secretion potentially reducing calcium carbonates ability to bind phosphorous.” I did use calcium-based binders and famotidine with Ollie with no problems, but if you are using calcium-based phosphorus binders such as Ipakitine or Pronefra, I would discuss the situation with your vet.

Famotidine can interfere with antibiotics in the cephalosporin family such as cefovecin (Convenia), so you should separate the two treatments by two hours. I am sometimes asked why I mention this when Convenia is an injectable medication. H2-antagonist cephalosporin interactions (2003) Ali A Thesis states “These interaction studies with H2-receptor antagonists in gastric as well as blood pH revealed that simultaneous use of these drugs depressed the availability of the antibiotic as well as cimetidine, ranitidine and famotidine.” Plumb’s Veterinary Drug Handbook does not mention cefovecin (Convenia) specifically, but does mention that taking other members of the cephalosporin family with food may offset the reduced absorption of the antibiotic.

Drugs mentions that using famotidine at the same time as ondansetron may increase the risk of heart arrhythmias, though it is rare.

Famotidine may reduce the absorption of vitamin B12 from food. Proton pump inhibitor and histamine H2 receptor antagonist use and vitamin B12 deficiency (2013) Lam JR, Schneider JL, Zhao W & Corley DA Journal of the American Medical Association 310(22) pp2435-2442 found that in humans “gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency.” Therefore if you are using famotidine, it might be worth supplementing vitamin B12.

I used to recommend giving famotidine at least two hours apart from sucralfate (Carafate or Antepsin) or metoclopramide (Reglan), because, according to Plumb’s Veterinary Drug Handbook, these other medications could bind with the famotidine and thereby reduce its effectiveness. However, the most recent edition of Plumb’s does not mention this requirement, so it appears that you do not need to separate famotidine from these other medications after all.

RX Med states that “concomitant use of aluminum hydroxide/magnesium hydroxide at commonly used doses, does not influence the pharmacodynamics or bioavailability of Pepcid AC.” Plumb’s does still recommend separating famotidine from phosphorus binders and ACE inhibitors. I would try to err on the side of caution and still separate famotidine from phosphorus binders and ACE inhibitors if you can, but if this is difficult for you, e.g. because of work commitments, just do the best you can.

Proton Pump Inhibitors (PPIs)

Proton pump inhibitors (PPIs) are also used to control stomach acid, but do not work in the same way as histamine H2 antagonists. Histamine H2 antagonists work by blocking acid after it has been produced, whereas PPIs work by inhibiting the release of acid into the stomach in the first place. They are therefore often used for the treatment of stomach ulcers, but are also sometimes used in CKD cats.

Omeprazole (Prilosec, Losec)

Omeprazole is the most commonly used PPI in CKD cats.

Antisecretor activity of omeprazole in the conscious gastric fistula cat: comparison with famotidine (1989) Coruzzi G & Bertaccini G Pharmacological Research 21(5) pp499-506 found that omeprazole was “approximately fivefold less potent than famotidine” and most effective when the stomach was at the peak of acid production.

However, Evaluation of the effect of orally administered acid suppressants on intragastric pH in cats (2015) Parkinson S, Tolbert K, Messenger K, Odunayo A, Brand M, Davidson G, Peters E, Reed A & Papich MG Journal of Veterinary Internal Medicine 29(1) pp104-12 found that omeprazole (in both tablet form, and a reformulated paste form normally used for horses) appeared to be more effective than famotidine. It also found that omeprazole is “generally well tolerated” in cats.

The failure of oral stomach acid suppressants in cats (2020) is a final report from the EveryCat Foundation on the Parkinson study, which compared newer PPIs (esomeprazole, lansoprazole, and dexlansoprazole). It mentions that only esomeprazole appeared to suppress acid in cats, and it took four days to have any effect.

The effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on on intragastric pH in cats (2015) Šutalo S, Ruetten M, Hartnack S, Reusch CE & Kook PH Journal of Veterinary Internal Medicine 29(3) pp840-6 concluded that “twice-daily PO [orally] administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once-daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats.”

ACVIM consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats (2018) Marks SL, Kook PH, Papich MG, Tolbert MK & Willard MD Journal of Veterinary Internal Medicine 32(6) pp1823-1840 state “Despite the long list of potential adverse effects associated with PPI treatment, the quality of evidence underlying these associations is consistently low.”  The paper also refers to “recent studies that have documented adverse effects of long-term supplementation of PPIs in humans and animals.”

Veterinary Partner has some information about omeprazole.

PetCoach also has some information.

Omeprazole Formulations

Omeprazole is available over the counter in many countries in both tablet (omeprazole) and slow release capsule (omeprazole magnesium) form. Discuss which formulation to use with your vet.

Omeprazole Tablets

The tablets usually come in a 20.6mg strength. They are enteric-coated, so are not supposed to be broken up. Plumb’s Veterinary Drug Handbook (7th Edition) says “Omeprazole capsules or tablets should not be crushed or chewed.” However, Evaluation of the effect of orally administered acid suppressants on intragastric pH in cats (2015) Parkinson S, Tolbert K, Messenger K, Odunayo A, Brand M, Davidson G, Peters E, Reed A & Papich MG Journal of Veterinary Internal Medicine 29(1) pp104-12 found that if you split the tablets into cat-sized doses, “enteric-coated omeprazole tables are effective for acid suppression in spite of the disruption of the enteric coating.” Some members of Tanya’s Support Group do use the tablets for their cats (split into cat-sized doses) and find them effective.

Drugs has a list of US brands showing whether they are tablets or capsules.

Walgreens sells 42 tablets in the 20.6mg strength for US$23.99. Sometimes it offers buy one, get one half price deals.

Pets Drug Mart in Canada sells 10mg capsules for CAN$1.08 each.

Omeprazole Capsules

The capsules usually come in a 20.6mg strength and contain omeprazole magnesium. The magnesium helps to make the product delayed release, so the omeprazole reaches the stomach intact, where it is needed.

Magnesium is not ideal for CKD cats, but some of the magnesium will be part of the capsule, which you discard. However, the tiny beads within the capsule are also coated because they need to reach the stomach intact.

In theory the capsules should not be used for cats, because slow release medicines are not supposed to be opened, but an entire capsule is too big for a cat. Quite a few members of Tanya’s CKD Support Group have opened and used capsules successfully for their cats. Plumb’s Veterinary Drug Handbook (7th Edition) says “Omeprazole capsules or tablets should not be crushed or chewed. If reducing the dose of the commercially available capsules, the capsule contents should be re-inserted into a gelatin capsule so they cannot be chewed.” However, many people do simply mix the capsule contents with their cat’s food, see below.

If your vet agrees to you using capsules, you will see that each capsule contain beads (microspheres). You should open one of the capsules and count the microspheres. The number varies depending upon the manufacturer. Once you know how many beads your chosen product contains, you can calculate your cat’s dose. For example, if your 20mg capsule contains 100 beads, and you want to give your cat 2.5mg, you would give your cat 12-13 beads once a day.

Unfortunately many omeprazole capsules have too many beads to count, especially in the USA. CVS sells its own version of omeprazole capsules, but members of my support group find they usually contain tiny beads which seem to carry a lot of static and are therefore very difficult to count. One group member did count them though, and found there were close to 3000 beads in one capsule! Walgreens used to sell reasonable capsules but recently they seem to be a tablet within a capsule. Kroger apparently sells a generic form of omeprazole with not too many beads, though not everybody has had success in finding them. Altosec generic capsules apparently only contain about twenty beads.

Drugs has a list of US brands showing whether they are tablets or capsules.

Vet Rx Direct sells omeprazole capsules for US$0.43 each (10g) and US$0.53 (20mg). A member of Tanya’s Support Group tells me these contain countable beads. A prescription is required.

Omeprazole Compounded

Some people prefer to have omeprazole compounded into capsules or a liquid for their cats. Plumb’s Veterinary Drug Handbook (2011) states “Use caution when using compounded omeprazole products; bioequivalence has been an issue with some compounded preparations.”

Nevertheless, some members of Tanya’s Support Group do use compounded omeprazole without problems.

Omeprazole Dosage

Omeprazole Dosage: Amount

Pet Place states that “The typical dose administered to animals is 0.25 to 0.5 mg per pound (0.5 to 1.0 mg/kg), every 24 hours or once daily.” Based on the per pound dosage, a 10 lb (4.5kg) cat would receive 2.5 to 5 mg once a day (which is actually a little more than 0.5 to 1.0 mg/kg).

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239 recommend “0.5–1 mg/kg q12–24h PO,” which would mean a 10 lb (4.5kg) cat would receive 2.5 to 5 mg once or twice a day.

The effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on on intragastric pH in cats (2015) Šutalo S, Ruetten M, Hartnack S, Reusch CE & Kook PH Journal of Veterinary Internal Medicine 29(3) pp840-6 used a dosage of 1.1-1.3 mg/kg, in which case a 10 lb (4.5kg) cat would receive 5 to 5.85 mg.

Many people on Tanya’s CKD Support Group start with a dose of 1 mg/kg, so a 10lb (4.5kg) cat would receive 4.5 mg.

Omeprazole is excreted via the liver and kidneys, so speak to your vet about a suitable dose for your cat, especially if your cat has more advanced kidney disease.

Omeprazole Dosage: Frequency

Previously (and as per the Pet Place link above), omeprazole was dosed once daily. However, The effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on intragastric pH in cats (2015) Šutalo S, Ruetten M, Hartnack S, Reusch CE & Kook PH Journal of Veterinary Internal Medicine 29(3) pp840-6, assessed the effectiveness of once daily versus twice daily dosing and concluded that “twice-daily PO [orally] administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once-daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats.”

This study looked at the use of omeprazole in a small group of healthy cats. Whether the same approach is appropriate for CKD cats is debatable, bearing in mind that omeprazole is excreted via the liver and kidneys, and there are other possible side effects and risks (see below).

Nevertheless, ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239 recommend “0.5–1 mg/kg q12–24h PO,” which would mean a 10 lb (4.5kg) cat would receive 2.5 to 5 mg once or twice a day.

Some members of Tanya’s CKD Support Group do give omeprazole twice a day rather than once (with their vet’s approval). Many of those I hear from think this helps their cats, but as ever, be guided by your vet regarding the best approach for your cat.

Omeprazole Dosage: Length of Treatment

The main disadvantage with omeprazole is that in humans, it is used for 14 days only and then not used again for four months.

Plumb’s Veterinary Drug Handbook mentions that it is thought to be safe to use omeprazole in dogs for at least four weeks.

A prospective, placebo-controlled pilot evaluation of the effect of omeprazole on serum calcium, magnesium, cobalamin, gastrin concentrations and bone in cats (2016) Gould E, Clements C, Reed A, Giori L, Steiner JM, Lidbury JA, Suchodolski JS, Brand M, Moyers T, Emery L & Tolbert MK Journal of Veterinary Internal Medicine 30(3) pp779-86 found that giving omeprazole to six healthy cats for eight weeks did not seem to have an adverse effect on the examined perameters, however, this was a very small study into healthy cats.

ACVIM consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats (2018) Marks SL, Kook PH, Papich MG, Tolbert MK & Willard MD Journal of Veterinary Internal Medicine 32(6) pp1823-1840 state “Our consensus opinion is that PPIs should be tapered in dogs and cats after prolonged use of >3-4 weeks.”

Still, I do know of some people who have used omeprazole on an ongoing basis with no apparent problems. Be guided by your vet as to the best course of action for your cat.

Omeprazole: Speed of Response

Some cats respond to omeprazole within a day, but it can take up to a week to take effect. During this period, or if omeprazole alone does not seem to be sufficient to help your cat, your vet may ask you to start or continue using other treatments.

It is acceptable to use omeprazole at the same time as famotidine or ranitidine, as long as your vet approves. Can famotidine and omeprazole be combined on a once-daily basis? (2007) Fändriks L, Lönroth H, Pettersson A & Vakil N Scandinavian Journal of Gastroenterology 42(6) pp689-94 found that doing so was safe in healthy humans, and some members of my support group do the same for their cats.

Cats vary a lot in how effective omeprazole is for them. The effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on on intragastric pH in cats (2015) Šutalo S, Ruetten M, Hartnack S, Reusch CE & Kook PH Journal of Veterinary Internal Medicine 29(3) pp840-6 states “We saw considerable individual variation in response to treatment with omeprazole…For example, 1 cat consistently had close to 100% acid suppression, whereas another had extremely poor acid suppression.”

Omeprazole: How to Give

Unlike acid blockers such as famotidine (Pepcid), omeprazole is tasteless. Therefore many people just mix the correct number of beads from the capsule formulation (see above) with their cat’s food.

Omeprazole Risks

It has been known for some time that the use of PPIs such as omeprazole has been associated with a higher risk of acute kidney injury. In 2016  a human study, Proton pump inhibitor use and the risk of chronic kidney disease (2016) Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J & Grams ME Journal of the American Medical Association Internal Medicine 176(2) pp238-246 reviewed the use of PPIs in humans and found that “Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.” The authors further state “Use of PPIs may lead to chronic kidney disease through recurrent acute kidney injury or hypomagnesemia.” The risk was higher when the PPIs were taken twice a day rather than once a day.

Proton pump inhibitors associated acute kidney injury and chronic kidney disease: data mining of US FDA adverse event reporting system (2021) Wu B, Li D, Xu T, Luo M, He Z & Li Y Scientific Reports 11 looked at records of adverse effects in humans taking PPIs and found that the median time taken for AKI to occur was 23 days, and 177 days for CKD. The study concludes “A high proportion of renal injury occurred after the first year of PPI treatment and the median time was longer for CKD than AKI.”

Analysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis (2019) Makunts T, Cohen IV, Awdishu L & Abagyan R Nature Scientific Reports 9(2282) checked over 10 million FDA Adverse Event Reporting System records and concluded that PPIs increased the risk of CKD and acute kidney injury in humans. It states “Although H2RAs have not been shown to be as effective as PPIs, they might be considered as alternatives for patients who are at high risk of developing renal and electrolyte imbalances.”

Omeprazole use and risk of chronic kidney disease evolution (2020) Guedes JVM, Aquino JA, Castro TLB, Augustode Morais F, Baldoni AO, Belo VS & Otoni A Plos One 15(3) compared human CKD patients using omeprazole with patients not using omeprazole. The study concludes “there was a higher percentage of CKD progression in users (70.6%) compared to non-users (10.5%).”

However, a study in cats, Retrospective analysis of the effect of acid-suppressant therapy on clinicopathologic parameters of cats with chronic kidney disease (2018) Gould E, Klos J, Price J, Harris T, Vaden S & Tolbert MK Journal of Feline Medicine and Surgery 20(6) pp520-527, looked at the effects of acid suppressant therapy (acid blockers, proton pump inhibitors and both combined) in CKD cats. It concludes “Results of this retrospective study suggest that cats with CKD receiving PPI therapy may develop alterations in blood sodium concentrations but do not experience more rapid progression of CKD.”

An unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor ADMA (2013) Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, Leiper J & Cooke JP Circulation 128(8) pp845-53 found that proton pump inhibitors may increase the risk of major adverse cardiovascular events. However, a later study, Proton pump inhibitors and vascular function: a prospective cross-over pilot study (2015) Vascular Medicine 20(4) pp309-316 found that “PPI use [Prevacid] did not significantly influence vascular endothelial function. Larger, long-term and blinded trials are needed to mechanistically explain the correlation between PPI use and adverse clinical outcomes, which has recently been reported in retrospective cohort studies.”

ACVIM consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats (2018) Marks SL, Kook PH, Papich MG, Tolbert MK & Willard MD Journal of Veterinary Internal Medicine 32(6) pp1823-1840 states “Despite the long list of potential adverse effects associated with PPI treatment, the quality of evidence underlying these associations is consistently low.”

Omeprazole Side Effects and Interactions

According to Plumb’s Veterinary Handbook, possible side effects include nausea, vomiting and diarrhoea. Urinary tract infections, proteinuria or central nervous system disturbances may also be seen. Omeprazole may also cause a low white blood cell count (neutrophils), though this is rare.

The US Food & Drug Administration (2011) states that the long term use (usually for more than a year) of medications such as omeprazole may lead to decreased magnesium levels in the body that cannot necessarily be corrected with magnesium supplements

One known problem with proton pump inhibitors is that they may inhibit the absorption of nutrients from food, particularly Vitamin B12 and calcium. It is recommended that omeprazole should only be used in humans for eight weeks. Proton pump inhibitor and histamine H2 receptor antagonist use and vitamin B12 deficiency (2013) Lam JR, Schneider JL, Zhao W & Corley DA Journal of the American Medical Association 310(22) pp2435-2442 found that in humans “gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency.” Adverse effects of long-term proton pump inhibitor therapy (2011) Sheen E & Triadafilopoulos G Digestive Diseases & Sciences 56(4) pp931-50 mentions that long term use in humans is becoming increasingly common and reviews the possible adverse effects of long term use. The study concluded that the benefits of longer term treatment outweigh the risks for most patients, but that elderly or chronically ill patients “theoretically could be at increased risk from long-term therapy.” Therefore if you use omeprazole for any length of time, ask your vet if you should start or increase a vitamin B12 supplement.

Retrospective analysis of the effect of acid-suppressant therapy on clinicopathologic parameters of cats with chronic kidney disease (2018) Gould E, Klos J, Price J, Harris T, Vaden S & Tolbert MK Journal of Feline Medicine and Surgery 20(6) pp520-527 looked at the effects of acid suppressant therapy (acid blockers, proton pump inhibitors and both combined) in CKD cats. It concludes “A significant increase in blood sodium concentration (change of 3.12 mmol/l) was found independent of stage in cats receiving PPI therapy.” However, the use of acid blockers did not seem to have any adverse effect on the progression of the CKD.

If omeprazole is stopped, there may be a rebound effect, i.e. there may be an increase in stomach acid production that is higher than that before the treatment was begun. This can last a couple of weeks. Gastric acid rebound after a proton pump inhibitor. Narrative review of literature (2018) Rochoy M, Dubois S, Glantenet R, Gautier S & Lambert  M Therapie 73(3) pp237-246 looked into this and concludes “Daily PPI exposure for more than 4 weeks is likely to trigger a rebound of acid hypersecretion about 15 days after discontinuation, and lasting from a few days to several weeks depending on the duration of the exposure.”

Mirtazapine: Caution

Mirtazapine (trade name is Remeron in the USA and Zispin in the UK) is an anti-depressant but it can also cause an increase in appetite, and it may also have anti-emetic (anti-vomiting) properties according to Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: a masked placebo-controlled crossover clinical trial (2013) Quimby JM & Lunn KF Veterinary Journal 197(3) pp651-655, which found that “the oral administration of 1.88 mg [⅛ of a 15mg tablet] of mirtazapine every other day for 3 weeks to cats with CKD resulted in significantly increased appetite. Additionally, significant weight gain, increased activity and decreased vomiting were demonstrated.”

Although mirtazapine can be a very effective appetite stimulant, I am concerned that cats may be offered mirtazapine and nothing else discussed on this page. I am always nervous about the use of appetite stimulants because whilst some cats may eat because of such medications, they could be doing so despite still feeling horrible. I think it is extremely important to ensure that the cat is not only eating, but is also as comfortable as possible.

I would certainly not rule out using mirtazapine, which can be very helpful for CKD cats and which is discussed in detail here, but please do also talk to your vet about whether any of the other treatments discussed on this page should also be used.

Not Recommended

Ranitidine (Zantac 75)

Ranitidine is a histamine H2 antagonist (trade name is Zantac 75) that works in a similar way to famotidine. Pet Place has more information about it.

Ranitidine was previously quite popular, with some people preferring to use ranitidine, especially if their cat had experienced increased vomiting with famotidine, as happens with a small number of cats (usually those with creatinine over 5 mg/dl USA or 450 µmol/L international).

Ranitidine and Cancer-Causing Ingredient

Ranitidine used to be available in tablet, injectable and oral suspension form, and was widely available throughout the world. Unfortunately in September 2019 Zantac was recalled worldwide because it may contain a carcinogenic (cancer-causing) ingredient called N-nitrosodimethylamin (NDMA). The US Food & Drug Administration explains more about this.

The recall initially applied only to Zantac, not to generic versions of ranitidine. However, on 1 April 2020 the US Food & Drug Administration requested the removal of all ranitidine products from the market with immediate effect. This means ranitidine will not be available in any form in the USA, and many other countries are taking the same approach. The FDA further advises that you should not use any ranitidine which you currently have in your possession.

The US Food and Drug Adminstration has some FAQs about the removal, and states that it also applies to compounded and injectable ranitidine.

Europe and the UK suspended all licences for ranitidine in November 2020.

Canada takes a different approach to ranitidine. Health Canada says “Based primarily on animal studies, NDMA is classified as a probable human carcinogen. We are all exposed to low levels of NDMA through a variety of foods (such as smoked and cured meats, dairy products and vegetables), drinking water and air pollution. NDMA is not expected to cause harm when ingested at low levels. For example, a person taking a drug that contains NDMA at or below the acceptable level every day for 70 years is not expected to have an increased risk of cancer.”

Health Canada also states “Health Canada permitted companies wishing to resume sales to do so provided they test every batch of ranitidine product before releasing it and regularly throughout its shelf life, to demonstrate that products do not contain higher than accepted levels of NDMA.”

The Pharmaceutical Journal reported in 2021 that some manufacturers are working on producing versions of ranitidine without the cancer-causing ingredient, and though this is apparently difficult to achieve, one manufacturer was given a revised certificate by the European Directorate for the Quality of Medicines and Healthcare in July 2021.

Pharmacoepidemiological research on N-nitrosodimethylamine-contaminated ranitidine use and long-term cancer risk; a population-based longitudinal cohort study (2022) Wang C-H, Chen I-I, Chen C-H & Tsung Tseng Y-T International Journal of Environmental Reseach and Public Health 19(19) p12469 found that ranitidine did appear to increase the risk of cancer in Taiwanese patients using increasingly larger ranitidine doses, but says further research is necessary.

As far as I know, there is no research into this issue in cats, and even in humans the risk is small. Nevertheless, I have decided to remove ranitidine from this page because it is now virtually impossible to obtain ranitidine except in Canada, plus there are safer options out there.

Cimetidine (Tagamet)

There is a small chance you will be offered cimetidine, which, like famotidine and ranitidine, is a histamine H2 antagonist. Cimetidine has many more drug interactions than either famotidine or ranitidine, including with amlodipine (a calcium channel blocker used to treat heart disease or high blood pressure), and diazepam (Valium), which is sometimes used as an appetite stimulant. It also has the most marked rebound effect (a temporary increase in stomach acid) if it is stopped. I would therefore suggest using famotidine. 

Pet Place has some information about cimetidine.

If you do use cimetidine, the Merck Veterinary Manual recommends separating it from phosphorus binders and from sucralfate (Carafate or Antepsin).

Chronic kidney disease (CKD) in dogs and cats — staging and management strategies (2015) Chew D Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference states that “Calcium carbonate binds phosphorous [sic] best in an acidic environment (pH approx. 5) and binding capacity is reduced in the neutral pH range. Many CKD patients receive inhibitors of gastric acid secretion potentially reducing calcium carbonates ability to bind phosphorous.” I did use calcium-based binders and famotidine with Ollie with no problems, but if you are using cimetidine in addition to calcium-based phosphorus binders such as Ipakitine or Pronefra, I would discuss the situation with your vet.

Cimetidine can interfere with antibiotics in the cephalosporin family such as cefovecin (Convenia), so you should separate the two treatments by two hours. H2-antagonist cephalosporin interactions (2003) Ali A Thesis states “These interaction studies with H2-receptor antagonists in gastric as well as blood pH revealed that simultaneous use of these drugs depressed the availability of the antibiotic as well as cimetidine, ranitidine and famotidine.”

Cimetidine may reduce the absorption of vitamin B12 from food. Proton pump inhibitor and histamine H2 receptor antagonist use and vitamin B12 deficiency (2013) Lam JR, Schneider JL, Zhao W & Corley DA Journal of the American Medical Association 310(22) pp2435-2442 found that in humans “gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency.” Therefore if you are using cimetidine, it might be worth supplementing vitamin B12.

The effects of cimetidine on renal function in patients with renal failure (1980) Larsson R, Bodemar G, Kagedal B, Walan A Acta medica Scandinavica 208 (1-2) pp27-31 explains that cimetidine may cause an increase in creatinine levels. If your cat’s creatinine levels rise while using cimetidine, you may find they improve once you stop the medication.

Top ten potential drug interactions on dogs and cats (2008) Trepanier LA Presentation to the World Small Animal Veterinary Association World Congress recommends using famotidine rather than cimetidine, as do I.

Metoclopramide (Reglan or Emeprid)

Metoclopramide is a prescription medication that works by regulating stomach contractions. This means it can help with nausea caused by a lack of motility in the stomach. Pet Place has some information about gastric motility problems in cats.

Since metoclopramide can cross the blood/brain barrier, it also acts on the brain to control feelings of nausea. However, it appears that it is not actually particularly effective in cats. Current approaches to vomiting in cats and puppies (2013) Gaschen FP, Lee JA, Parnell N, Richter K, Tams TR, Twedt D & Gloyd K Pfizer Roundtable Discussion states “I don’t use metoclopramide in cats anymore. I am not completely convinced it is that effective as an antiemetic in cats. Evidence suggests that cats don’t have dopamine receptors in the chemoreceptor trigger zone, which is metoclopramide’s site of action.”

In 2009, the US Food and Drug Administration issued a warning regarding the chronic use of metoclopramide because this had been linked to a condition called tardive dyskinesia, i.e. involuntary and repetitive movements of the body, which may continue even after the treatment is stopped. One such movement mentioned by the FDA is lipsmacking (although it should be noted that lipsmacking in CKD cats is normally caused by gastric hyperacidity or nausea, anaemia or dehydration). The FDA therefore recommends that products containing metoclopramide should not be used for longer than three months.

In July 2013 the European Medicines Agency went further and announced that metoclopramide should only be used short term (up to five days) and that it should only be used in adults “for the prevention and treatment of nausea and vomiting such as that associated with chemotherapy, radiotherapy, surgery and in the management of migraine.” In addition, it recommended that dosages should be lowered.

Obviously these warnings apply to humans, but since there are now other treatments available, as outlined above, that are far more effective and carry fewer risks, I would not recommend using metoclopramide. If for some reason you do decide to use it, be sure to discuss these warnings with  your vet before using metoclopramide.

Veterinary Partner has more information on metoclopramide.

Metoclopramide Dosages

Metoclopramide comes in 10 and 5mg tablets or a liquid. Injectable metoclopramide is also available as 5mg/ml in 2 ml or 10 ml vials. It must be given 20-30 minutes before eating.

A typical dose would be 0.1 to 0.2 mg per pound (0.2 to 0.5 mg per kg) every six to eight hours, so a 10lb (4.5kg) cat would get 1 mg to 2 mg at a time. Plumb’s Veterinary Drug Handbook mentions that dosages may need to be reduced in animals with kidney disease, so be guided by your vet.

Metoclopramide Side Effects and Interactions

Please see the important warning above.

Metoclopramide may have various side effects, including constipation, hyperactivity and agitation or drowsiness.

Metoclopramide also lowers the seizure threshold, so should not be given to cats prone to seizures.

Drugs mentions that it may increase the risk of bronchospasm in asthmatics, and intravenous metoclopramide may worsen hypertension (high blood pressure).

I used to recommend giving metoclopramide at least two hours apart from famotidine (Pepcid AC) or ranitidine (Zantac 75) because, according to Plumb’s Veterinary Drug Handbook, the metoclopramide could bind with these other medications and reduce their effectiveness. However, the most recent edition of Plumb’s does not mention this interaction, so it appears that you do not need to separate metoclopramide from these other medications after all.

Using metoclopramide as well as mirtazapine (an appetite stimulant) increases the risk of serotonin syndrome. You can read more about this and what to watch for here.

Drs Foster and Smith have some information about possible side effects. They also mention that metoclopramide is similar to PABA, the sunscreen component, so people who are allergic to PABA should not touch metoclopramide.

Pepto-Bismol

Please do not use Pepto-Bismol. It contains a type of salicylate, similar to what is found in aspirin, and cats are not able to metabolise this easily, so it may be fatal even in small doses.

Pet Place warns against using Pepto-Bismol in cats.

Antacids

Some vets recommend the use of antacids, such as Tums or Mylanta. Some products in this family do actually work well in CKD cats as phosphorus binders, but they are not usually strong enough to help control gastric hyperacidity.

Also, many of these products contain magnesium but the use of products containing magnesium is not usually recommended for CKD cats, who tend to have high levels of magnesium generally. 

This page last updated: 04 July 2025

Links on this page last checked: 04 July 2025