Feline Infectious Peritonitis (FIP)

There are now legally available antiviral treatments in many countries, and they have been studied in peer- reviewed publications from Taylor, S. et al, 2023, Coggins, S. et al, 2023, Green,J. et al 2023. Antivirals remdesivir (injection SC or IV) and GS-441524 (tablets or suspension) have been shown to be effective in 85%+ cases. Email fip@bova.co.uk for information on ordering medication in your region.

The first successful treatment studies used injectable GS-441524, but most evidence in recent years has been based on oral GS-441524, which has shown great success

Oral formulations can be cheaper but importantly, injectable medications are associated with more adverse effects (especially pain on injection). The prodrug to GS-441524, remdesivir, is available as an injectable agent; it was commonly used a few years ago as it was the only antiviral available in some countries but its cost and pain on subcutaneous injection mean that oral GS-441524 is more commonly used, whenever available. It is best to keep injectable remdesivir only for initial intravenous use in cats that are too weak to swallow oral medication.

Tablet and liquid formulations of GS-441524 are variably available. The liquid formulations are favoured by some:

• Easier to administer to some cats (i.e., often voluntarily accepted in small amount of a high value treat)
• Easier to dose accurately (potential for cost saving in the long-term)

Unpublished studies suggest that some cats absorb GS-441524 better when administered as a liquid suspension (c.f. as a tablet); worth considering if response to treatment is less than expected

Yes, they can transition, however, it would be prudent to start the course again so that the correct drug concentration is given for the full treatment period.

GS-441524 can be given in a small amount of food, ideally after a period of fasting (which can also increase appetite and acceptance of medication) and at least an hour before a main meal to help the absorption of the drugs. The tablets (crushed) or suspension can be put into liquid treats for example or other tasty food. Avoid putting it into a main meal. Support owners to give tablets directly into a cat’s mouth if needed (demonstrate and direct owners to https://icatcare.org/advice/how-to-give-your-cat-a-tablet.) Suggest owners make giving medication a positive experience by following with a treat (without medication), a brush or playing with a toy (depending on the cat’s preference).

Most published evidence is with 12 weeks/84-days of GS-441524

• Response rates with 12 weeks/84-days of recommended dosages are > 85/90%

Evidence is emerging for successful outcomes with shorter courses e.g., 6 week/42-days of oral GS-441524

Note that successful 6 week/42-day courses are primarily described in cats with predominantly effusive disease that respond very quickly to treatment – so consider using shorter (< 12 weeks/84-day) courses in cats with effusions which respond rapidly to treatment (i.e., normalised clinical signs and blood test results by 28-days of treatment)

Rapid resolution of clinical signs, within 28-days

Normal biochemistry – useful to look for an albumin:globulin ratio (A:G) of > 0.6

Two normal serum alpha-1-acid glycoprotein (AGP) measurements 2 weeks apart before stopping treatment are encouraging; serum amyloid A (SAA) measurements can be used if AGP is not available, but may not be as reliable, giving falsely elevated results

The medication is well tolerated. Changes in blood results include mild ALT elevations, eosinophilia, and lymphocytosis which do not require specific treatment. Urolithiasis has been reported with black-market medications. Remdesivir injection may cause pain SC and should be diluted and given slowly IV with hypotension and reduced demeanour possible.

The risk of relapse is around 10% and relapse generally occurs shortly after the treatment course is completed but can occur during treatment. Note that relapse can result in different clinical signs from the original presentation. Late relapse (or reinfection) is possible but current research suggests this is a rare occurrence. Relapses can be successfully treated.

Fever, lethargy, altered demeanour, anorexia, and effusions → improve by 2-5 days

Effusions → usually resolve by 14 days

• During initial treatment, effusions may worsen before improving
• Monitor for dyspnoea & be prepared to drain if it occurs

Serum globulin may increase initially due to effusion reabsorption; A:G ratio normalises over several weeks (look for A:G ratio > 0.6)

Bilirubin should be reducing within 7 days if elevated and normalize by 21 days

AGP may increase in some cases in the first week; however, it should be decreasing in all cases by week 2. With successful treatment, it is usually normal by 28 days

Mild hyperglobulinaemia & mild abdominal lymphadenomegaly can persist at the end of treatment – this doesn’t seem to be associated with FIP relapse

No, evidence shows that over 85% of cats respond to once-daily treatment. However, therapeutic drug monitoring (TDM) (unpublished studies) suggests a benefit of twice-daily treatment. For cats challenging to medicate, focusing on consistent once-daily treatment is reasonable, with monitoring of response.

Some clinicians adjust the oral GS-441524 dosage dependent on signs seen with FIP:

• No ocular or neurological signs ± effusion 15 mg/kg q24h (or 7.5 mg/kg q12h)
• Ocular signs ± effusion 15-20 mg/kg q24h (or 7.5-10 mg/kg q12h)
• Neurological signs ± effusion 10 mg/kg q12h
• Some cats absorb GS-441524 better with q12h dosing c.f. q24h dosing, hence the option to split the dose and give q12h; worth considering if response to treatment is less than expected

Other clinicians use a standard oral GS-441524 dosage regardless of the signs seen with FIP:

Any FIP presentation 15 mg/kg PO q24h. This dosage is largely based on the treatment of FIP with effusions, usually without neurological or ocular signs, although cats with such signs have also responded. Additionally, the published study reporting results with 15 mg/kg PO q24h GS-441524 treatment hospitalise the cats for the first week of treatment, allowing prompt antiviral medication with intensive supportive care, and this may influence the success rate.

For example:

• Effusion still present > 14 days
• Persistent pyrexia
• Development of neurological signs or uveitis
• Persistently increased AGP (or SAA)

Note that the following alone do not indicate treatment failure:

• Globulins increase during early treatment due to reabsorption of effusions
• Mild lymphadenopathy (on abdominal ultrasonography) and mild serum hyperglobulinaemia may persist

Troubleshooting if response is not as expected:

• Ensure given dose reflects:
  • Any weight gain experienced during improvement – the GS-441524 dosage needs to be maintained despite weight gain, meaning doses will need to increase
  • The manifestation of FIP (i.e., following the development of neurological signs or uveitis, higher dosages may be needed)
• Consider:
  • Increasing dosage by 5 mg/kg/day
  • Splitting dosing q12h (if giving q24h)
  • Switch to oral liquid suspension (if on tablets) in case this is better absorbed

Reconsider the diagnosis of FIP – how sure were you of the diagnosis
before starting treatment? Consider differential diagnoses for FIP
– shown in ABCD toolsuccess rate.

This varies according to type of FIP with ocular and neurological cases requiring higher dosages than cats with the non-effusive or effusive form. However, response is individual and should be adjusted according to clinical and biochemical improvement. Access the document for dosage information and remember to adjust the dosage as the cat gains weight and kittens grow (encourage owners to monitor weight at home).

Ideally yes, but if the cat needs corticosteroids give them! A recent abstract study presented at ECVIM 2024 found that prednisolone (0.5–2 mg/kg/day) did not impede short-term recovery, nor survival, in cats with FIP receiving GS-441524 treatment

Examples of FIP-related conditions / clinical signs that may need corticosteroids are:

• Uveitis (topical corticosteroids are usually adequate)
• Immune-mediated haemolytic anaemia (IMHA; usually characterised by a worsening, often non-regenerative, anaemia despite antiviral treatment, with a positive in-saline agglutination test or Coombs’ test) after ruling out other 2° causes of IMHA such as haemoplasmas and retroviruses
• Severe neurological signs such as those associated with raised intracranial pressure

The cat may also have concurrent disease that is not FIP-related but for which corticosteroids are needed e.g., inflammatory bowel disease/chronic enteropathy, lymphoma, asthma (inhaled corticosteroids are preferred, ideally fluticasone)

There is no evidence to support the use of immunostimulants alongside direct-acting antivirals in the treatment of FIP. Remember, >85/90% cats respond to antivirals like GS-441524 without immunostimulants being given

A multimodal approach to FIP treatment does sound sensible and immunostimulants have been used in human medicine alongside antivirals in the management of systemic viral diseases (e.g., infectious hepatitis)

Before effective direct-acting antivirals were available, immunostimulants had been used alone for treatment of FIP, with some – albeit very limited – efficacy

Controlled studies are needed as it may be that immunostimulants could be useful in a proportion of cases, likely as adjunctive treatment If recommending immunostimulants, as an adjunctive agent, consider the evidence-base, the cost they add to protocols, and the potential increase in caregiver burden

Mefloquine is a cheap, readily available drug used to treat malaria in people

It also has antiviral properties; but its antiviral effects are far, far less than GS-441524

It is given orally with food to reduce the risk of vomiting – severe nausea is common, even if given with food, and may require maropitant and/or ondansetron as per anecdotal evidence

Dosages used in cats have varied in different studies:

• 62.5 mg 2-3x/week
• 10-12.5 mg/kg 2x/week
• 4 mg/kg PO q24h

Occasionally, mefloquine has been used if a caregiver cannot afford more effective antivirals or if antivirals have to be given for a shorter period of time than is ideal due to cost or compliance – in which case mefloquine has been given for a period of time after stopping antivirals However, no controlled studies exist to show its use as a single or adjunct treatment

No specific supplements nor special diets are needed during FIP treatment; however, cats with FIP are often in reduced body condition at diagnosis. Hence, an energy dense, easily digestible diet appropriate for their life stage is indicated

For cats with poor appetite, antiemetics (e.g., maropitant) and appetite stimulants (e.g., mirtazapine) may improve voluntary food intake

Anorexic cats may benefit from an oesophageal feeding tube (medications can also be given via the tube)

Some cats are very unwell at diagnosis and will need to be hospitalised for fluid therapy and other intensive care

Hypoglycaemia and hypotension may need to be addressed with dextrose infusions and vasopressors, respectively

Cats with severe neurological signs and seizures may need antiepileptic treatment; corticosteroids may be needed if increased intracranial pressure is suspected

Many cats with FIP will be in painbecause of inflammation (e.g., uveitis, peritonitis, pleuritis, hepatic or renal capsule distension) &/or increased intracranial pressure. Analgesia should be provided

Antiemetics, such as maropitant, may help support adequate food intake

Cats with uveitis will, initially at least, need topical corticosteroids, with intraocular pressure measured in case of glaucoma development

Although relatively uncommon, we are recognising cases of associative (secondary) immune-mediated haemolytic anaemia (IMHA) with FIP (both with and without effusions). Anaemia is usually moderate, and non-regenerative in type despite the haemolytic cause. To diagnose IMHA with FIP, cats should have a positive in-saline agglutination test or Coombs’ test, and other causes of associative IMHA, particularly haemoplasmosis by PCR, and retroviruses, should ideally be ruled out. IMHA tends to be recognised by cats developing a worsening anaemia, sometimes after starting antiviral therapy. Some also have a thrombocytopenia.

Most cats with IMHA associated with FIP need corticosteroid treatment despite the FIP disease responding well to antivirals. Start with a low prednisolone dosage of 1 mg/kg/day PO (can increase to 2 mg/kg/day if inadequate response upon rechecking haematology after 1-2 weeks).  If a good response to treatment occurs (resolution of anaemia, often within a month), the prednisolone can be tapered by 50% every 2-4 weeks. If possible, try to stop the prednisolone by the time antivirals are finished. Most cats (around 75%) respond well to treatment but relapses can occur, despite successful treatment of the FIP, necessitating longer term corticosteroids. 

Some vets also use clopidogrel to prevent clots because both FIP and IMHA can cause hypercoagulable states, but studies have not been performed to confirm that this is needed as adjunct treatment.

Yes

Evidence is emerging that cats can still have favourable response to treatment, and addressing comorbidities is likely to be an important factor in the success of treatment. But be aware of longer-term prognosis of cats with concurrent FeLV infection

Abstract ISCAID 2024: FeLV-positive cats responded to antivirals similarly to FeLV-negative cats in initial 6-month period but after this period there was progressive mortality in the FeLV-positive cats, but no further mortality in FeLV-negative cats i.e. they saw the ‘expected’ progressive mortality with FeLV infection

Abstract ECVIM 2024: No difference between cats with and without coinfections (e.g. feline herpesvirus, retroviruses) in the success of antiviral treatment for FIP

Yes

Ideally, wait ≥ 4-weeks after completing antiviral treatment (to check for relapse once medication has been discontinued, although uncommon)

If delaying neutering is not an option, neutering while on treatment is possible once they are clinically normal:

Ensure neutering is performed in a cat friendly clinic and manner – think about reducing stress when travelling to clinic, use of anxiolytics, analgesics (including local analgesia blocks) and minimise hospitalisation time

e.g., because the stress of not neutering (e.g., behavioural consequences of oestrus) or risk of pregnancy is greater than the potential stress of neutering

e.g., in a rehoming situation

Timing – ideally neuter 2-4 weeks before due to complete the antiviral treatment (so that the antiviral is still being given as the cat recovers from the neutering and any stress involved with this)

Yes, if the cat is clinically normal & vaccination is indicated i.e., there is a risk of infection from the infectious agents that vaccines protect against

Ideally, wait ≥ 1 month after completing antiviral treatment (to check for relapse once medication discontinued, although uncommon)

If delay is not an option, vaccination while on treatment is possible; however, we have no data on vaccine efficacy when given during antiviral treatment (theoretically possible that some antivirals may affect replication of live vaccines e.g., FCV) although failure of vaccines given in this period has not been reported to our knowledge either

Important to assess the risk profile of the cat (vaccination history; indoor/outdoor; in-contacts) to decide on which vaccines are indicated. The WSAVA, AAFP, and ABCD provide guidelines to guide you in the risk assessment for vaccination need. Measurement of feline panleukopenia/parvovirus antibody titres is an option to decide if a vaccine containing this agent is needed

As always, minimise stress by using Cat Friendly Clinic techniques

Yes

Many cats have been treated without problems, prescribe in accordance with their risk profile for infection with parasites

The role of the caregiver is very important

Keep stress to a minimum

Weigh the cat regularly and accurately at home

• 1-2 x/week – with guidance on thresholds that would indicate when dose adjustments are needed
• Use paediatric/baby scales for accuracy (particularly important in growing kittens) – caregiver can purchase a set for regular use at home

Offer a balanced diet suitable for their life stage

Look out for other signs developing e.g., ocular signs, such as change in the colour of the iris

On discharge/dispensing of medication, discuss the owner’s ability to administer medication, the cat’s appetite, activity, clinical signs, and the importance of weighing regularly

Regular contact with the primary care clinic via verbal updates:

• After 48h of treatment (within normal working hours) – then as dictated by response

Contact clinic immediately if unable to administer medication, inappetent, or if any new clinical signs appear