Update on treating FIP using antiviral drugs

In the UK, antivirals with high efficacy in the treatment of FIP have been legally available since 2021 (initially remdesivir and subsequently, its active form GS-441524). In that time, we have gained experience in managing the disease and monitoring treatment, and seen excellent outcomes.

Legally available sources of antivirals effective for FIP now exist in many other countries, although in some parts of the world, sadly, no quality-assured, legally available supply remains.

This article summarises the current advice on treatment of FIP to aid practitioners managing these cases and is based on current available information; however, the information will likely change as more experience and publications become available. It includes information on the recently available additional antiviral EIDD-1931 (the active form of molnupiravir). Treatment needs to be tailored to the individual cat based on response, compliance and client finances.

For more information on making an FIP diagnosis, view “Further Reading” at the end of this article.

Treatment protocols (updated May 2024)

Legally available antivirals in the UK and other countries via import now include remdesivir (injectable), GS-441524 (oral suspension and oral tablets) and EIDD-1931 (oral tablets). The following advice is based on published and unpublished data, and experience.

Treatment of individual cases remains the responsibility of the attending veterinary surgeon. The following dosages are based on experience using reputable preparations of known antiviral content. Extrapolation is not applicable to other oral preparations where the active component and/or its content are not known or provided by the manufacturer.

Use of oral GS-441524 for the whole treatment course, including at the start

Oral GS-441524 (available as a suspension 50mg/ml and tablets of 25mg or 50mg) can be used from the start of FIP treatment for the entire treatment course (for example, 12 weeks/84 days; see section on duration of treatment courses).

It is important to support owners in medicating their cats, which can be challenging. Oral GS-441524 suspension or tablets can be given with a small treat (tablets can be crushed for this) or directly into the cat’s mouth.

Further study is needed to review the effect of food on absorption, but it is recommended to give in a small treat or on an empty stomach, leaving a gap of an hour or more before feeding a larger meal.

Fasting cats overnight can increase their hunger to facilitate medicating in the morning, and similarly for an evening dose. However, starving kittens is never recommended, as they cannot cope with this. Any withholding of food needs to be tailored to the age of the cat.

Injectable remdesivir is reserved for cats that cannot be medicated orally

Injectable remdesivir (10mg/ml) is effective in the treatment of FIP, but is associated with some side effects (see section on side effects) – particularly pain on SC injection, which is seen in 50% of cats.

Previous FIP treatment protocols suggested this be used at the start of treatment before transitioning to oral GS-441254. However, we now know that FIP cats can be treated successfully with oral GS-441524 from their first day of treatment. This avoids pain on injections and reduces the costs of the treatment (dose for weight of cat for GS-441524 is cheaper than remdesivir).

Use of injectable remdesivir should be reserved for the following situations:

• severe neurological signs and inability to swallow or tolerate oral medication
• extremely dehydrated/sick cats
• cats that cannot be orally medicated for other reasons

In some circumstances, if a cat is hospitalised and has a poor appetite that is affecting the ability to medicate it, 48 hours of remdesivir (given intravenously, not subcutaneously) can result in significant clinical improvements, which might facilitate subsequent oral medication with GS-441524. The remainder of the treatment course can then be given as oral GS-441524.

The transition between remdesivir and oral GS-441524 can be immediate; that is, from one treatment to the next.

Duration of antiviral treatment

Recommendations have usually been to treat for 84 days/12 weeks minimum, and most of the authors’ experience is with 12-week courses. However, we know that cats have been successfully treated with shorter courses of oral GS-441524 (at 15mg/kg by mouth once a day) for 42 days/6 weeks (personal communication; Hartmann, Hofmann-Lehmann and Gunn-Moore).

Publications are in preparation for these shorter courses, but the knowledge of these studies, and the reduced costs associated with 6 weeks compared to 12 weeks of treatment, means we should also consider them if appropriate for the patient. Further study is needed to learn about the experience and reported outcomes for different durations of treatment.

If treated cats respond rapidly, with resolution of clinical signs (including effusions) and normalisation of biochemistry abnormalities (and, if available, normalised serum alpha-1 acid glycoprotein [AGP] levels at four and six weeks), the attending clinicians could consider stopping and monitoring the cat carefully for possible relapse.

This would include (if available) checking AGP and/or biochemistry four weeks after stopping treatment, increasing confidence of remission if results remain normal. AGP is not available in many countries, and it might be that serum amyloid A can be used similarly, but further studies are needed. Communication with owners should discuss that, currently, most published response rates and outcomes are for cats treated for 12 weeks.

Dosage recommendations

With experience and as yet unpublished data on therapeutic drug monitoring (TDM), dosage recommendations have increased from previous FIP treatment protocols. However, one must remember that published evidence shows more than 85% of cats respond to the previously recommended drug dosages, which is still a great response.

Based on TDM studies, we also now know that individual cats vary in their absorption of oral GS-441524, with those absorbing poorly likely requiring higher dosages to achieve clinical and biochemical remission. It is important that dosage of oral GS-441524 is adjusted according to clinical response, given these variations in absorption and limited availability of TDM to guide treatment. 

Based on our collective experience, our current dosage recommendations are the following:

• The daily dosage of oral GS-441524 can be given once daily (every 24 hours) or divided twice daily (every 12 hours). Some cats might benefit from twice-daily treatment to optimise serum levels of GS-441524.

• For cats challenging to medicate, and responding well, once-daily treatment is acceptable.

• Higher dosages might overcome issues with poor absorption in some cats and have a better chance of crossing the blood-brain barrier and the blood-eye barrier.

• Dosage should be adjusted according to response (and TDM if measured and available).

Failing to increase dose as the kitten grows appears to be a common cause for poor response to treatment and treatment failure.

TDM of oral GS-441524 during treatment

TDM is available currently at The University of Edinburgh. Cats are sampled after three to five doses of starting the oral GS-441524. Ideally, 1.5ml serum and 0.5ml ethylenediamine tetra-acetic acid should be taken at peak (2 to 3 hours post-dose) or trough (9 to 12 hours post-dose) times after GS-441524 is given. This can be combined with AGP measurement. Email Rachael Hammond via rachael.hammond@ed.ac.uk for information on submission. Results can allow adjustment of GS-441524 dosage or frequency of administration.

What to expect in cats during treatment of FIP

In the first two to five days, you should see an improvement in demeanour, appetite, resolution of pyrexia and reduction in abdominal or pleural fluid (if present).

More clinical signs attributable to FIP might be seen during the initial few days of treatment; that is, before the medication has had time to take effect. This can include development or recurrence of pleural fluid, which might require drainage (if the cat is at home, advise the owner to measure resting respiratory rate and respiratory effort). Neurological signs or uveitis may also develop (for example, owners might notice a change in iris colour). If neurological or ocular changes are noted, the drug dosage should be reviewed in case an increase is indicated.

Effusions usually resolve by two weeks. If an effusion is still present at two weeks, consider increasing the dosage (by 5mg/kg/day to 10mg/kg/day, and consider splitting into twice-daily doses if treated orally once daily).

Serum albumin increases and globulin decreases (that is, they normalise) might take several weeks, but note that globulins can initially increase when a large volume effusion is absorbed. In some cases, globulins might remain mildly increased, even at the end of a successful treatment course, and this mild hyperglobulinaemia has not been associated with relapse in our experience, if all other parameters have normalised.

Lymphopenia and anaemia might take longer to resolve – up to 10 weeks. A lymphocytosis (and eosinophilia) can also occur during successful treatment.

Enlarged lymph nodes typically reduce in size over a few weeks of treatment, but in some cases they do not return to normal size nor normal ultrasonographic echogenicity – even by the end of treatment. However, this does not seem to signify FIP relapse if all other parameters have returned to normal; treatment can be stopped as planned and the patient monitored.

If progress is not as expected, consider reviewing the diagnosis and/or increasing dosage. Occasionally, other antivirals can be considered.

Some cats fail to respond to antiviral treatment, often deteriorating in the first two weeks; some cats might be too sick for the antivirals to work (although consider IV remdesivir in sick cats that cannot be medicated otherwise). Relapse is uncommon (less than 10%), but tends to occur in the first few weeks after stopping treatment.

Using therapeutic drug monitoring to inform dosing, and/or higher dosages, might result in higher response rates. Survival times are long (although we are all still learning about this), with late relapses (or reinfections) rarely reported.

Since the drugs have only been available since late 2021, we do not yet know if cats that appear to be cured stay that way life long, but result so far are very encouraging.

Note on using antiviral treatment trials as an aid to diagnosis

In some situations, it is not possible to achieve a definitive diagnosis of FIP due to cost constraints, availability of testing or instability of the patient precluding invasive testing.

Antiviral treatment trials can be considered using an appropriate dosage and objective measures to identify improvement; for example, serial neurological or ocular examinations. Improvements in demeanour and return of normothermia are expected within 48 hours, and add confidence to the presumed diagnosis of FIP.

Note that effusions can take longer to resolve (see section on what to expect in cats during treatment), and improvements in haematology and biochemistry abnormalities can also take weeks. Failure to improve on an adequate dosage of antivirals should prompt investigation for an alternative diagnosis. Most cats are notably better by 2 to 5 days, while a small number of cats can take up to 10 days; however, some positive signs have usually been seen before then.

Monitoring during treatment

Clinical response is most important to monitor; a failure to improve might necessitate an increase in dosage. Monitoring should be adequate to assess response, but, particularly when the cat is doing well, repetition of costly tests that are unlikely to alter treatment (for example, limiting testing to previously abnormal parameters and basic screen) and multiple, potentially stressful clinic visits should be limited.

Owners should be encouraged to weigh their cat at home (for example, using inexpensive baby scales) and keep a diary of appetite and demeanour, respiratory rate and other parameters as indicated.

The following recommendations will change depending on the cat’s response to treatment:

• After 48 hours, an improvement in demeanour and normothermia is expected. A verbal report of progress and ease of medicating the cat should be obtained around this time.

• After two weeks, weight, demeanour and effusions (in-house scanning, abdominal girth measurement) should be reviewed. Additionally, serum biochemistry and haematology can be assessed, adapting to cost constraints as needed (for example, consider whether measurement of total protein, PCV and plasma colour assessment, using a spun microhaematocrit tube, could be used as a cost-effective and rapid initial screen to indicate whether additional testing is indicated). Normalisation of serum AGP (if available and elevated before treatment) might be useful to predict remission.

• After six weeks, the cat should be re-examined and the previously outlined assessments repeated.

• After 12 weeks, the cat should be examined before stopping treatment, and all assessments should ideally be normal. Mild persistent hyperglobulinaemia and mild abdominal lymphadenomegaly are sometimes reported, and not associated with relapse. If all other parameters are normal (including AGP if available) then treatment can still be stopped.

Monitoring after treatment

Once treatment is completed (usually 12 weeks’ duration, but evidence emerging of success with 6 weeks of treatment in selected cases; see previous section), cats should be monitored for relapse by their owners, including loss of appetite, weight changes or other clinical signs.

The clinical signs of relapse might differ from those at initial diagnosis (for example, neurological signs in cats that previously had effusions). Ideally, the cat is examined approximately four weeks after stopping treatment. Monitoring AGP, if available, might provide reassurance if it remains normal. Any clinical signs should be promptly investigated. 

Side effects of remdesivir and GS-441524

Side effects for these drugs can include the following:

• Remdesivir can cause pain on SC injection in 50% of cats, so pre-treatment with analgesics (such as gabapentin, pregabalin and buprenorphine) is recommended.

• Cats might seem depressed or nauseated for a few hours after IV remdesivir administration.

• Remdesivir and GS-441524 might result in mild increases in alanine transaminase (ALT) enzyme activity that do not require specific treatment (seen in approximately 30% of cats). Although some vets prescribe hepatoprotectants such as S-adenosylmethionine (SAME) supplements, the need for these has not been confirmed, and so their use should be balanced with funds and ease of administering oral medication.

• Mild eosinophilia and lymphocytosis are also reported, and do not require treatment.

• Uroliths of GS-441524 have been rarely described, although not with the legally available GS-441524 or remdesivir preparations, so it might be that they occur when illegal or unlicensed preparations containing higher (often unknown) levels of antivirals are used. It might be prudent when using high dosages of antivirals to increase water intake and investigate any urinary signs that develop. Urine can be assessed for crystals that could represent GS-441524.

Supportive care for FIP cats

Cats with FIP might benefit from various types of supportive care. No specific supplements have been studied alongside antivirals, and multiple oral medications might not be optimal due to compliance (as well as additional costs). However, sick and dehydrated cats might require IV fluid therapy.

The following interventions can be considered depending on the case:

• Affected cats might be painful (for example, from pleural and peritoneal inflammation, distension from masses, uveitis and neurological lesions). Treatment with opioids, such as buprenorphine, might be of benefit and other drugs such as NSAIDs (if hydration status and renal parameters are normal, and the cat is eating) as part of multimodal analgesia.

• Repeat drainage of pleural effusions might be required during the initial treatment period if associated with dyspnoea.

• Abdominal effusions are not normally drained, unless they are causing respiratory compromise due to pressure.

• Cats with FIP have often lost weight and body condition, so nutrition is a priority. Appetite stimulants such as mirtazapine (and/or capromorelin oral solution) might be useful, and some sick cats benefit from feeding tube placement short term, and this can also facilitate medicating. Since nasal tubes are poorly tolerated by cats and might cause depression, cats with profound anorexia that cannot be alleviated by the drugs described might benefit from an oesophagostomy tube being placed.

• Drugs such as maropitant might benefit cats feeling nauseous and encourage eating.

• Occasionally, FIP can cause severe (sometimes haemolytic) anaemia, and blood transfusion can be considered alongside antivirals.

• Hepatoprotectants (for example, SAME) with or without silybin are not usually required, even in cats with ALT enzyme activity increases.

• Generally, corticosteroids are contraindicated in the treatment of FIP with antivirals to avoid adverse effects and immunosuppression. If an anti-inflammatory agent is required in cats undergoing FIP treatment, consider using an NSAID (if hydration status and renal parameters are normal, and the cat is eating). However, cats with uveitis might need topical corticosteroids, and cats with severe neurological signs occasionally require short-term systemic corticosteroids (one to five days) to reduce inflammation. Rarely, cats with FIP develop immune-mediated haemolytic anaemia, and these often require systemic corticosteroid treatment for more than a few days to help resolve the anaemia alongside the antiviral treatment.

In the event of a poor response during treatment or relapse

If, for example, recurrence or lack of resolution of effusion, pyrexia, development of new ocular or neurological signs, or persistent clinical pathology abnormalities occur, consider the following:

• Ensure you are still confident that the cat has FIP. Review diagnosis, look for additional pathology, consider repeat sampling (for example, external laboratory analysis and culture of any fluid and cytology or biopsy of lymph nodes with or without feline coronavirus antigen or ribonucleic acid detection, but bear in mind that finding the virus is more difficult when on treatment) and AGP.

• If relapse occurs during treatment, increase dosage of GS-441524 (or remdesivir) by 5mg/kg/day to 10mg/kg/day and consider splitting into twice-daily doses if treated orally once daily) and monitor as outlined, ensuring treatment is not stopped before the cat has been normal clinically and on clinical pathology for at least two weeks. The increased dosage used will depend on the dosage the cat is on at the time of the relapse, the nature of the relapse and finances, but can be up to that recommended for neurological FIP (Table 1) or even higher (please seek guidance when considering this).

• If relapse occurs after completion of treatment, restart GS-441524 (or remdesivir) course at a higher dosage (by 5mg/kg/day to 10mg/kg/day and consider splitting into twice-daily doses if treated orally once daily previously). The optimum duration for repeat treatment is not known, but 12-week repeat treatment has been used successfully. The increased dosage used will depend on the dosage the cat was previously treated with and the nature of the relapse, but can be up to that recommended for neurological FIP (Table 1).

• Consider TDM, if available, to check serum GS-441524 levels to inform dosing.

• If the cat is already receiving a high dosage of GS-441524 and/or TDM serum levels are adequate, consider switching to EIDD-1931 and seeking guidance (FIP advice email or specialists), as adjunct treatments such as mefloquine, feline interferon or polyprenyl immunostimulant might be options.

EIDD-1931

EIDD-1931 (the active form of molnupiravir) is another antiviral effective for the treatment of FIP in cats; although, our knowledge on its usage is much less than for GS-441524. The recommended dosage is 15mg/kg every 12 hours, and it is available in 60mg tablets for oral use.

Potential adverse effects include cytopenia – especially neutropenia; rarely pancytopenia – reduced appetite/nausea, increased ALT enzyme activity and potentially, renal compromise. Use of EIDD-1931 should, therefore, be reserved for the following scenarios:

• Cats failing to respond to treatment with GS-441524 or remdesivir despite adequate dosage (ideally assessed with TDM if possible and available).

• Cats relapsing after treatment with GS-441524 or remdesivir at adequate dosages.

No contraindication to routine worming or flea treatment for cats on GS-441524 or remdesivir exists. No information is available on response to vaccination of cats receiving treatment for FIP. Prospective studies are needed, but analysis of treated cases suggests that cats can be safely vaccinated after or during successful treatment without causing relapse of FIP.

Vaccination should be given as recommended for the cat depending on its environment and risk (see WSAVA or European Advisory Board on Cat Diseases vaccination guidelines). If urgent vaccination is needed during treatment due to risk of infectious disease then they should only be given if the cat is clinically well.

If veterinary visits and procedures are necessary, clinic stays should be minimised, and Cat Friendly Clinic protocols and handling implemented to reduce stress to the cat.

Treatment with feline interferon, polyprenyl immunostimulant or mefloquine

Combinations of feline interferon omega, polyprenyl immunostimulant and mefloquine have been used in the period following the end of treatment with GS-441524 (or remdesivir) in some cats; however, no evidence currently exists to suggest they are needed, as high response rates of more than 85% have been seen without these adjunct treatments.

Mefloquine has also been used to treat cats with FIP when cost constraints absolutely prohibit the use of a full course of, or increased dosage of, more effective antivirals such as GS-441524. Studies are needed to evaluate its effectiveness, but it should only be used when no absolutely no alternatives are available, as GS-441524 is known to be very effective.

• Some drugs in this article are used under the veterinary medicine cascade.

• The authors wish to thank Richard Malik, Alex Kennedy, and Sally Coggins for their advice and assistance in producing this article.