An update on treatment of FIP in the UK

In August 2021 remdesivir became legally available to UK vets for the treatment of FIP in cats. Since that time many cats and kittens have been treated and are still being treated successfully.

As with any novel formulation, with experience, adjustments are made in protocols and given the recent release (November 2021) of oral GS-441524 (50mg tablets) from a specials manufacturer in the UK (Figure 1), this article has been created to support practitioners in the use of remdesivir and GS-441524 in the management of FIP.

It is worth remembering that treatment may need to be tailored to the individual cat based on response, compliance and client finances. Specific protocols are listed to help vets make decisions with their clients, but will not be appropriate for all.

Treatment protocols (updated November 2021)

Drug dosages have increased from previous recommendations, based on the experience of our Australian colleagues who have treated more than 600 cats.

Although some cats responded to the previously recommended lower dosages, they found that recurrence at, or towards the end of, the 84-day (12-week) treatment period was possible, resulting in the need for extension of the treatment at a higher daily dosage. This was ultimately more expensive than if the treatment course had been started at a higher dosage.

When using remdesivir and/or GS-441524, treatment options now include a 12-week course of injectable remdesivir, transition from injectable remdesivir to oral GS-441524 or an entirely oral GS-441524 protocol. Suggested dosages, benefits and limitations of each protocol are provided further on.

Remdesivir cannot be given orally. Recommended drug dosages (Table 1) depend on clinical presentation – that is, whether an effusion is present and whether ocular and/or neurological involvement exists. This is due to variation in the tissue penetration of the drugs. Where doubt exists, use of the higher dosage is preferable.

Please note that these dosages of oral GS-441524 are higher than quoted in some publications – this is because these publications have used “black market” preparations of so-called GS-441524 in which the amount of active agent given to the cats was not confirmed.

The aforementioned provided dosages are based on experience using an oral preparation of known GS-441524 content.

Combined injectable and oral treatment protocols

The decision on when to move from injectable remdesivir to oral GS-441524 may depend on the cat’s tolerance of injections (or oral administration of tablets), formulation price differences (including cost of needles, syringes, sharps disposal, wastage), and owner preferences and finances. Experience suggests this transition can be made between 7 and 14 days of starting remdesivir IV or SC treatment.

The protocol chosen will depend on the severity of the FIP disease in the cat. Dosages are shown in Table 1.

Severe disease

Regarding severe disease (anorexic, dehydrated, cat usually will be hospitalised):

• Initial treatment with once-daily IV remdesivir (Table 1) for three to four days – that is, on days 1, 2, 3 and/or 4. This provides a loading dose of the drug. On each day, dilute the remdesivir dose required to a total volume of 10ml with saline and administer slowly over 20 to 30 minutes manually or with a syringe driver.
• Follow with once-daily SC remdesivir at the same dosage (Table 1) up to days 7 to 14.
• Change to once (or twice)-daily oral GS-441524 (Table 1) on days 8 to 15 and continue until at least day 84.

Less severe disease

Regarding less severe disease (normal hydration, eating):

• Initial treatment with once-daily SC remdesivir (Table 1) up to days 7 to 14.
• Change to once (or twice if very high neurological dosage needed)-daily oral GS-441524 (Table 1) on days 8 to 15 and continue until at least day 84.

Oral only treatment protocol

An oral GS-441524 treatment-only protocol is recommended if injectable not tolerated/possible financially:

• Once (or twice if very high neurological dosage needed) daily oral GS-441524 (Table 1) until at least day 84.

• Transient local discomfort/stinging on injection (see later on prevention).
• Development/worsening of a pleural effusion (not always proteinaceous) in the first 48 hours of treatment, sometimes requiring drainage.
• Cats may seem depressed or nauseated for a few hours after IV administration.
• Increases in alanine aminotransferase enzyme activity have been reported (unclear if due to underlying FIP disease or an adverse drug effect).
• Mild peripheral eosinophilia has been reported.

Options for cost-limited clients

Please note that, ideally, therapy should be given using the recommended formulations and dosages for as long as possible (up to 84 days) to increase likelihood of cure.

Only take the following options listed below if absolutely necessary, as relapse may occur, which then requires longer treatment, increasing costs:

• Give oral GS-441524 treatment only for 84 days, as outlined previously.
• Give injectable remdesivir or oral GS-441524 for as many days as the owner can afford before switching to oral mefloquine 62.5mg two to three times weekly (for large cats give three times a week) or 20mg to 25mg orally once daily (if reformulation of tablets is possible – for example, Novalabs) for completion of an 84-day treatment protocol; mefloquine is cheaper than remdesivir and GS-441524, but more research is needed to judge its effectiveness in this situation.
• If an increase in remdesivir dosage is required (for example, due to neurological disease appearing during treatment) but cannot be afforded, mefloquine treatment can be added as adjunct treatment, as this is cheaper than remdesivir, although more research is needed to judge the effect of this combination.
• Feline interferon omega has also been used in the period following treatment with remdesivir/GS-441524 treatment, but further research is needed on this combination to judge if it is necessary.

Are oral treatments given with or without food?

Regarding whether oral treatments are given with or without food:

• GS-441524 is given on an empty stomach (wash down with a little water) – food can be given 30 minutes after treatment.
• Mefloquine is given with food, otherwise vomiting often results.

Do not forget to support clients giving oral medications, as this can also be challenging. Direct clients to the International Cat Care website for information.

International Cat Care has also produced two demonstration videos – one showing two people giving a tablet:

…the other showing the use of a pill popper:

• Ensure owners use a new needle each time to withdraw the drug from the bottle (this will reduce the risk of bacterial contamination of the bottle, as well as alcohol swabbing the reusable seal top of the bottle before entry of the needle).
• Ensure owners change the needle after withdrawing the drug from the bottle and before injection (puncturing the reusable seal will blunt the needle).
• Needle size preference varies; some prefer a 21G needle to make injecting quicker; others find a finer 23G needle is better tolerated, so it may be worth trying both if problems arise.
• Rotate the injection sites.
• Have remdesivir at room temperature before administration.
• Oral gabapentin (50mg to 100mg per cat) may be helpful and/or transmucosal or SC buprenorphine given at least 30 to 60 minutes before the remdesivir injection to induce mild sedation/analgesia.
• The area to be injected can also be clipped to help owners locate the appropriate site to inject and so that topical EMLA cream can be applied 40 minutes before injection, although surface desensitisation may not help as it is usually the remdesivir under the skin that causes discomfort.
• Ensure the full dose of injection is administered at each time point and encourage owners to report any mishaps as this may influence decisions if relapse occurs.
• Cats will need several weeks of treatment. Encourage owners to make the injection experience more positive by using treats around the time of injection, or stroking, brushing or playing with the cat if it is less food motivated. Suggest owners spend time each day with their cat positively engaged to avoid any damage to cat-owner relationships that can reduce compliance.

What should I expect during treatment?

During treatment:

• In the first two to five days you should see an improvement in demeanour, appetite, resolution of pyrexia and reduction in abdominal (Figure 2) or pleural fluid if an effusion is present (note that in some cases pleural fluid can transiently worsen in the first couple of days – if the cat is at home, advise owner to measure resting respiratory rate, plus respiratory effort) – effusion typically resolves by two weeks.
• If an effusion is still present at two weeks, consider increasing dosage to one that is greater than that being used – for example, increasing the dosage from that used for cats with effusions only.
• Serum albumin increases and globulin decreases (that is, they normalise) over one to three weeks, but note that globulins can initially increase when a large volume effusion is absorbed.
• Lymphopenia and anaemia may take longer to resolve, up to 10 weeks.
• Mild peripheral eosinophilia is a common finding and may be a favourable marker for disease resolution, as it is in COVID patients.
• Lymph node size reduces over a few weeks.
• If progress is not as expected, consider reviewing the diagnosis (see further on) and/or increasing dosage.

What do I need to monitor during treatment?

The following should be monitored during treatment:

• Ideally, serum biochemistry and haematology after two weeks, and then monthly.
• For cost-limited clients, monitor weight/demeanour/effusions (for example, by in-house scanning)/neurological signs/key biochemical abnormalities only (for example,measuring just globulin, bilirubin or spinning microhaematocrit tube for PCV/total protein/colour of plasma).
• Note alanine transaminase enzyme activity may increase – it is not clear if this is due to FIP pathology versus drug reaction, and it is not usually a reason to stop therapy. It is not known if the addition of hepatoprotective therapy (for example, S-adenosyl-L-methionine) is helpful in these cases.
• Point-of-care ultrasonography (POCUS) to monitor for effusion resolution and/or lymph node size.

If I am seeing a positive response to treatment, when do I stop treatment?

Regarding when to stop treatment if you are seeing a positive response to treatment:

• Not before 84 days (12 weeks).
• Confirm resolution of previous abnormalities (clinically, POCUS, serum biochemistry and haematology).
• Only stop treatment once cat has been normal (clinically, and on serum biochemistry and haematology) for at least two weeks (ideally four weeks).

If I am seeing no response or only a partial response to treatment, what do I do?

If you are seeing no response or only a partial response to treatment:

• Ensure that you are still confident that the cat has FIP – review diagnosis, look for additional pathology, consider repeat sampling (for example, external laboratory analysis of any fluid; cytology or biopsy of lymph nodes).
• If biochemical abnormalities (hyperglobulinaemia and the albumin to globulin ratio in particular) remain present after 6 to 8 weeks then increase dose as for relapse (see later) by 3mg/kg to 5mg/kg per day and continue the course, not stopping until parameters normalise for at least 2 weeks as stated above for “when do I stop treatment?” – this may well include extending the course over 12 weeks.

What do I monitor after treatment?

Regarding what to monitor after treatment:

• Advise the owner to monitor the cat closely for any clinical relapse – this monitoring should continue for 12 weeks after completion of treatment.
• Ideally, repeat serum biochemistry and haematology two weeks and one month after stopping treatment (to detect any changes that could suggest early relapse).
• Note that relapse can occur with clinical signs, but without any significant biochemical/haematological abnormalities.

Relapse

In the event of relapse – for example, recurrence of effusion, pyrexia, development of ocular or neurological signs, or return of hyperglobulinaemia:

• Ensure that you are still confident that the cat has FIP – review diagnosis, look for additional pathology, consider repeat sampling (for example, external laboratory analysis of any fluid; cytology or biopsy of lymph nodes).
• If relapse occurs during treatment, increase dosage of remdesivir or GS-441524 and monitor as aforementoned, ensuring treatment is not stopped before the cat has been normal 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 (see earlier).
• If relapse occurs after completion of treatment, restart treatment with remdesivir or GS-441524 at a higher dosage (typically 3mg/kg to 5mg/kg higher per day than dosage used previously) and treat for another 12 weeks. The increased dosage used depends on the dosage the cat is on at the time of the relapse and the nature (for example, severity and/or development of neurological signs) of the relapse, but can be up to that recommended for neurological FIP (20mg/kg – see Table 1). It is possible some cats will respond to a shorter course, but ideally treatment for relapse after completion of a course of treatment is continued for the full 12 weeks to limit repeat relapse.
• If it is not possible to increase the dose of remdesivir or GS-441524 (for example, the highest neurological dosage of 20mg/kg is already in use) consider use of mefloquine as adjunct treatment (see earlier) while continuing remdesivir or GS-441524 treatment at the same dosage.

Adjunctive treatments

• If the cat is on prednisolone treatment, this should be weaned off then stopped while giving remdesivir or GS-441524, unless it is required for short-term management of specific immune-mediated disease arising as a result of FIP – for example, haemolytic anaemia.
• Supportive therapies such as antiemetics, appetite stimulants, fluid therapy and analgesics can be given with remdesivir or GS-442415 as required.

Potential future updates

We are constantly learning about treatment with these drugs and advice may change in time. Other agents – for example, protease inhibitors (such as GC374) and other nucleoside analogues (such as molpurinavir) have also been trialled in cats, but are not commercially available at this time. How these agents and other immunomodulatory agents (such as polyprenyl immunostimulant) will fit into a future protocols is unknown at this time.

• Drugs mentioned in this article are used under the cascade.

Acknowledgement

Thank you to Richard Malik and Sally Coggins for their advice in producing this article.

FIP advice line

The authors have come together to run the FIP advice email address answering queries on the new treatments on a voluntary basis, and disseminating information to vets and vet nurses in the UK. So far they have answered more than 150 emails on the advice line.