Although currently the most widely used active substance in the treatment of FIP is the nucleoside analog GS-441524, in fact there are already several agents with antiviral activity that can be successfully used in the treatment of FIP. In this article, I would like to introduce you to currently used antivirals, or recommendations for their use.
Due to the absence of clinical studies other than GS-441524 and GC-376, unless otherwise stated, the recommended duration of treatment for FIP is still 12 weeks. This does not mean that the treatment cannot be shorter for a specific individual, but at the same time there are also cases where the treatment must be extended. It should also be noted that the treatment should always be terminated only after the assessment of the cat's clinical condition and the results of the blood test.
GS-441524
Currently the most widely used antiviral drug for the treatment of FIP. Nucleoside analog GS-441524 has been the subject of several clinical studies. The first to prove its effectiveness in the treatment of FIP was Dr. Niels Pedersen and his team. You can find his pioneering clinical study here.
The subject of this clinical study was injection form active substance, but it didn't take long, and tablet forms of the drug also appeared on the market. The originally determined dosage was gradually increased over time along with the decreasing price of the treatment, and nowadays it is good to stick to the values listed below. In addition, GS-441524 is a very safe antiviral, and because of minimizing the risk of relapse, it is better overdose, such as underdosing.
Unfortunately, the patent holder of GS-445424, Gilead, never licensed it to another company (with the exception of Bova), and is not even trying to commercialize this substance. For this reason, practically all medicines containing GS-441524 come from the black market.
In the case of a severe condition, it is possible and even advisable to use at least the first 3 days of the so-called booster dosage at the dosage level for neurological FIP, even if the cat does not have neurological FIP. There are even opinions that it is good to use neurological dosage for the first 14 days even in non-neurological forms of FIP (Dr. Addie).
| FIP type | GS-441524 - injection solutions |
|---|---|
| Wet FIP (abdominal effusion, without ocular and neurological symptoms) | 6 mg/kg once a day sc |
| Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms) | 8 mg/kg once daily SC |
| Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.) | 10 mg/kg once daily SC |
| Neurological FIP (neurological symptoms, eg anisocoria or mydriasis) | 12 mg/kg once daily SC |
| Relapse of FIP (usually associated with neurological manifestations) | 15 mg/kg once daily SC |
Arrival tablets got a little confused with the dosage during treatment, because some manufacturers started to list the so-called equivalent GS content so that the dosage used is "compatible" with injections, while other manufacturers state the real GS content. It is believed that the oral bioavailability of the drug is only about 50% compared to injections, so in practice it is necessary to count on twice the dosage of such tablets compared to injections, or simply use tablets with a known real GS content as tablets with a half-equivalent GS content. There is only one company licensed to use GS-441542 in tablet form in veterinary practice, and that is the British company Bova. Its GS 50 mg tablets are used for the legal treatment of FIP in Australia and the UK. Unfortunately, they are very expensive. It is necessary to take into account the price of 1 tablet approx. 1000 CZK. For this reason, similar to injectable solutions, tablets from the Chinese black market are mainly used for treatment.
Note that for neurological FIP, the recommendation is to split the dose twice a day. This is due to the presumed reduced absorption capacity of the drug in the digestive tract at an equivalent dosage higher than 10mg/kg.
| FIP type | GS441524 - tablets with the specified real GS content | GS441524 - tablets with the stated equivalent GS content |
|---|---|---|
| Wet FIP (abdominal effusion, without ocular and neurological symptoms) | 10-12 mg/kg once a day | 6 mg/kg once a day |
| Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms) | 12-16 mg/kg once a day | 8 mg/kg once a day |
| Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.) | 20 mg/kg once a day or 10 mg/kg twice a day | 10 mg/kg once a day or 5 mg/kg twice a day |
| Neurological FIP (neurological symptoms, eg anisocoria or mydriasis) | 12 mg/kg twice a day | 6 mg/kg twice a day |
| Relapse of FIP (usually associated with neurological manifestations) | 15 mg/kg twice a day | 7.5 mg/kg twice a day |
As already mentioned, GS-441524 is a safe antiviral, but on the other hand, neutropenia is very often observed after treatment, which can last for a very long time (up to several months). In the case of long-term and very significant neutropenia, the application of filgrastim - a factor that stimulates the formation of hematopoietic cells - can be considered.
GC376
Protease inhibitor GC376 is actually a first generation anti-FIP drug. Its effectiveness has been proven in the treatment of wet and dry FIP, but due to the significantly reduced ability to penetrate through the blood-ocular and blood-brain barrier, it is not suitable for the treatment of ocular or neurological forms of FIP. Given that very shortly after pilot study GC376 was lost to Dr. Niels Pedersen with the nucleoside analog GS-441524, the importance of the protease inhibitor GC376 has declined significantly. However, it turns out that it can be, and probably will be in the future, an important component of the combined treatment of FIP, for example together with GS-441524, where the effect of both active substances is mutually potentiated, and as a result is much more pronounced than with each active substance alone .
Currently, the company is trying to launch GC376 on the market Anivive.
| FIP type | GC376 - solution for injection |
|---|---|
| Wet FIP (abdominal effusion, without ocular and neurological symptoms) | 15 mg/kg 2x daily sc |
| Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms) | 15 mg/kg 2x daily sc |
| Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.) | it is not used |
| Neurological FIP (neurological symptoms, eg anisocoria or mydriasis) | it is not used |
| Relapse of FIP (usually associated with neurological manifestations) | it is not used |
GC376 is a safe antiviral, but its most significant side effect is a delay in the development of permanent teeth in young cats.
Remdesivir
This is another drug from Gilead. In fact, it is the so-called prodrug of the above GS-441524. After the application of remdesivir, intracellular metabolism to GS-441524 occurs in the organism. Remdesivir was marketed by Gilead under the trade name Veklury and has played a significant role in the treatment of Covid-19 in humans. However, its use in veterinary practice is very questionable and impractical. Firstly, it lacks approval for veterinary use and secondly, it is very expensive. Application is also a weak point of the drug, as it is intended for intravenous administration. The concentration of Veklura after reconstitution is only 5mg/ml.
The company Bova managed to obtain a license for the use of remdesivir for veterinary use and produces a product with a concentration of 10 mg/ml, which can be used in the form of subcutaneous injections. Unfortunately, the price is very high, so it is not used much in common practice.
Remdesivir has approximately 2x the molecular weight of GS-441524, so the dosage of remdesivir must be approximately 2x higher than that of GS-441524.
| FIP type | Remdesivir - solution for injection |
|---|---|
| Wet FIP (abdominal effusion, without ocular and neurological symptoms) | 10-12 mg/kg once a day iv/sc |
| Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms) | 10-12 mg/kg once a day iv/sc |
| Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.) | 15 mg/kg once daily iv/sc |
| Neurological FIP (neurological symptoms, eg anisocoria or mydriasis) | 20 mg/kg once a day iv/sc |
| Relapse of FIP (usually associated with neurological manifestations) | 25 mg/kg once a day iv/sc |
Molnupiravir
Antiviral with a long history primarily intended for the treatment of Covid-19 in humans. Molnupiravir (EIDD-2801) is incorporated into the genome of RNA viruses and causes random mutations resulting in the so-called virus bug disaster. The drug exists in the form tablets or capsules. Most legally manufactured drugs (e.g. Lagevrio) contain capsules containing 200 mg of the active substance, and re-encapsulation of the drug is necessary for use in the treatment of FIP. Of course, Chinese manufacturers also produce tablets intended for direct use in animals. Although molnupiravir is not strictly the drug of first choice in the treatment of FIP, it shows great potential in the treatment of FIP relapses, resistance to GS-441524, or can be an important part of FIP combination therapy.
| FIP type | Molnupiravir |
|---|---|
| Wet FIP (abdominal effusion, without ocular and neurological symptoms) | 8 mg/kg twice a day |
| Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms) | 8-10 mg/kg twice a day |
| Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.) | 10-12 mg/kg twice a day |
| Neurological FIP (neurological symptoms, eg anisocoria or mydriasis) | 12 mg/kg twice a day |
| Relapse of FIP (usually associated with neurological manifestations) | 15 mg/kg twice a day |
With molnupiravir, as with GS-441524, neutropenia can often be observed after the end of treatment, especially at high dosages.
Mefloquine
Mefloquine is an interesting substance that has its primary application in the treatment of malaria in humans. It is not effective as a monotherapy in the treatment of FIP, but it is shown that it can play an important role in the adjunctive treatment of FIP, for example with GS-441524. It mainly makes it possible to reduce the price of FIP treatment or reduce the risk of relapse. The normal length of treatment using GS-441524 is about 12 weeks, but in principle it is possible to shorten this treatment to about 8 weeks and use mefloquine for the next 4 weeks. In Europe, mefloquine is available under the trade name Lariam. One tablet contains up to 250 mg of active substance. In practice, the drug is administered at a dose of 12.5 mg/kg twice a week, or 62.5 mg twice a week for one cat. This corresponds to 1/4 tablet of Lariam twice a week (for example, Monday and Thursday). Lariam must be given with food, otherwise there is a higher probability of the cat vomiting.
I strongly reiterate the fact that mefloquine is not intended for the treatment of FIP as a monotherapy, and should always follow as a supplement after the treatment of FIP with one of the above-mentioned antivirals, or in combination with them.
| FIP type | Mefloquine (Lariam) |
|---|---|
| Wet FIP (abdominal effusion, without ocular and neurological symptoms) | 62.5 mg per cat twice a week |
| Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms) | 62.5 mg per cat twice a week |
| Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.) | 62.5 mg per cat twice a week |
| Neurological FIP (neurological symptoms, eg anisocoria or mydriasis) | 62.5 mg per cat twice a week |
| Relapse of FIP (usually associated with neurological manifestations) | 62.5 mg per cat twice a week |
Other antivirals
It turns out that there is actually up to several dozen of potentially suitable antivirals applicable to the treatment of FIP. Unfortunately, no clinical studies have yet been conducted for many of them, which are important not only for the verification of effectiveness, but mainly for the determination of cytotoxicity. The goal, of course, is to cure the animal without causing poisoning or other health problems that would lead to the cat's death.
Combined therapies
The currently used FIP treatment usually takes the form of monotherapy, that is, the drug contains only one active substance. Unfortunately, this approach has the disadvantage that it is only a matter of time before resistance to the used antiviral begins to manifest itself. The way out of this situation is combined therapy, when 2 or more antivirals are used simultaneously for the treatment of FIP. It is not an entirely simple issue, as in some combinations the therapeutic effect is significantly strengthened, but there are also combinations where, on the contrary, the therapeutic effect is weakened. Currently, the most likely drug combinations are the pairs GS-441524 and Molnupiravir, or GS-441524 and GC376. Regarding the second named combination, it has already taken place in China study, the result of which is really encouraging. In addition to curing all cats, the treatment time was reduced from 12 weeks to 4 weeks. It turns out that a dosage of GS-441524 5mg/kg/24h and GC-376 20mg/kg/12h could be used to achieve a therapeutic effect. However, this combination therapy still needs further independent verification of efficacy.
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