EIDD-2801 (Molnupiravir)

Mechanism of action

EIDD-2801 is the isopropylester prodrug of N4-hydroxycytidine. With improved oral bioavailability in non human primates, it is hydrolyzed in vivo, and distributes into tissues where it becomes the active 5’-triphosphate form. The active drug incorporates into the genome of RNA viruses, leading to an accumulation of mutations known as viral error catastrophe. Recent studies have shown EIDD-2801 inhibits replication of human and bat coronaviruses, including SARS-CoV-2, in mice and human airway epithelial cells. A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.

Please note that the information mentioned below does not come from officially published results of clinical trials. This is information from one of the drug manufacturers.

EIDD-2801 testing in the treatment of FIP

At the end of 2020, testing of Molnupiravir for the treatment of FIP began.
A study entitled "Oral nutrition treatment effects on the survival time and quality of life for feline infectious peritonitis" included 286 cats diagnosed with FIP from around the world. Several animal clinics in the United States, the United Kingdom, Italy, Germany, France, Japan, Romania, Turkey, and China participated in this study. Due to ethical factors, no placebo control group was formed. The results of this study are: Of the 286 cases, no deaths occurred. 28/286 cases were cured after 4-6 weeks of treatment. 258/286 cases were cured after 8 weeks of treatment. 28/286 cases received this medicine at a dose of 30-40 mg / kg every 24 hours, of which 26 cases recovered after 4 weeks, including 2 cases with eye disease and 5 cases with neurological symptoms, while another 2 cases discontinued treatment after 6 weeks of treatment without relapse. At the time of publication of the results, all cats were still alive and without signs of disease 3-5 months after the end of treatment.

Dosage and duration of treatment

• Dry/Wet FIP: 25mg/kg q24h
• Ocular FIP: 37,5mg/kg q24h
• Neurological FIP: 50mg/kg q24h

Duration of treatment 5-10 weeks depending on the severity of the disease and the particular cat.

According to more recent pharmacokinetic data, administration of the drug twice daily is preferable.

As already mentioned, EIDD-2801 is the precursor of EIDD-1931. Thus, the relationship of EIDD-2801 to EIDD-1931 is equivalent to that of Remdesivir and GS-441524. Since the molecular weight of EIDD-2801 is 329.31 g-mol and EIDD-1931 is 259.22 g/mol, it can be assumed that the dosage ratio of EIDD-2801 and EIDD-1931 is governed by a ratio of 1.27. In other words, if we use EIDD-1931 in a dosage of 10mg/kg, we should use about 12.7mg/kg for EIDD-2801.
It should be noted at this point that EIDD-1931 is not commercially distributed and you will most likely encounter EIDD-2801. However, the existence of EIDD-1931 should be kept in mind in case you come across this medicine.

The pharmacokinetics of EIDD-2801 are different from those of GS441524 and therefore the drugs are administered twice daily. I recommend reading the articles below.

• Alternative treatments for cats with FIP and natural or acquired resistance to GS-441524
• The long history of Beta-d-N4-hydroxycytidine and its modern application to treatment of Covid-19 in people and FIP in cats.
• Dose calculator for Molnupiravir

It is important to note that while Covid-19 treatment in humans lasts 5 days, FIP treatment lasts much longer, and EIDD-2801 (Molnupiravir) may have mutagenic side effects that have not yet been studied to their consequences and may lead to cancer, for example. For this reason, it is recommended to treat FIP with the well-established GS441521 and to reach for Molnupiravir only in case of resistance to GS441524.

FIP Treatment in Czech/Slovak Republic

In 2021, one cat in the Czech Republic completed treatment with EIDD-2801 (end of treatment for wet FIP 24.7.2021 - currently healthy and after post-treatment). In the Slovak Republic, a cat with a third relapse of neurological FIP after treatment with GS441524 was treated. Treatment of this relapse was conducted using GS441524 and EIDD-2801 simultaneously. The cat is healthy, after posttreatment.

Molnupiravir availability in Czech/Slovak Republic

Unlike GC441524, Molnupiravir can also be obtained legally for the treatment of Covid-19 in addition to the black market.

7.12.2021 the Ministry of Health of the Czech Republic decided of conditional approval Molnupiravir under the tradename Lagevrio. Each pack contains 40 capsules containing 200 mg of Molnupiravir. The disadvantage of these capsules is the too high content of active substance and the very complicated division for use in cats. In any case, 1 pack should be enough for the whole treatment of ordinary wet / dry FIP for a cat weighing up to about 8 kg. Ocular and neurological FIP, similar to GS441524, require higher dosages. Due to the fact that Lagevrio contains Molnupiravir in powder form, it is not possible to divide the capsule at home and it is necessary to “encapsulate” it into smaller capsules, e.g. 20mg, ideal in a pharmacy. So out of 40 Lavegrio 200mg capsules, you should get 400 20mg capsules. It is a paid service. Without this, it is practically impossible to achieve a usable dosage for a cat.

According to the latest information (05.2022), it is really possible to order Lagevrio in a pharmacy with a valid (and veterinary) prescription for about 18-22 thousand CZK.

• Lagevrio package leaflet
• Summary of information about Lagevrio

Other manufacturers of Molnupiravir

Of course, Chinese drug manufacturers, who produced GC-376 or GS-441524, also responded immediately to information on the effectiveness of Molnupiravir in treating FIP. And so tablets (Hero Plus), Lucky, Kitty Care, etc. appeared on the market.