Varenzin™ frequently asked questions
Anaemia in cats with CKD
Anaemia is common in feline CKD. There are multiple factors contributing to CKD anaemia, but the main cause is the lack of erythropoietin (EPO), a renal hormone that controls the bone marrow’s production of red blood cells. Other contributing causes include fibrosis, oxidative stress, inflammatory cytokines, impaired iron mobilization, and blood loss.1
It is estimated that 15-30% of geriatric cats (>12 years ) will develop CKD, and 30-65% of these cats will develop anaemia2, as their renal disease progresses1. However, cats in IRIS stage 2 CKD can develop anaemia. Monitoring PCV regularly can detect a decreasing trend, allowing early detection and treatment of anaemia.
Anaemia affects the body negatively by causing weakness, lethargy, reduced quality of life and survival1,2. Severe anaemia may lead to cardiac issues. Lower tissue oxygenation associated with increases in cardiac workload may induce heart enlargement and congestive heart failure.
Cats with CKD have a poorer prognosis and reduced survival when anaemia is present2. Studies show that cats with CKD and hematocrit levels below 26% have significantly shorter survival times compared with those above 30%.3
Low blood red cell mass reduces oxygen delivery, increasing renal hypoxia and fibrosis. CKD cats with hematocrit values less than 26 % have significantly shorter survival times compared to those with hematocrits greater than 30%3, and a 1% increase in PCV has been associated with a 10% decrease in the risk of CKD progression4.
CKD is an inflammatory disease. The inflammatory cascade induces renal fibrosis and replacement of normal renal tissue. This includes replacement of REP cells, the specialized cells that are responsible for producing EPO, which has a proportional effect on red blood cell count decline. Monitoring PCV trends facilitates early detection of declining REP cells, before anaemia is advanced5. Regular PCV checks can guide early treatment.
Product information & indication
Varenzin™ contains molidustat, a member of a group of drugs called Hypoxia-Inducible Factor Prolyl Hydroxylase (HIF-PH) inhibitors. It stimulates a cat’s body to produce its own endogenous erythropoietin (EPO). Varenzin™ is the first and only approved treatment for CKD anaemia in cats.
GB: For the treatment of non-regenerative anaemia associated with chronic kidney
disease (CKD) in cats.
IE and NI: For the management of non-regenerative anaemia associated with chronic kidney disease (CKD) in cats, by increasing haematocrit/packed cell volume.Varenzin™ is an oral suspension in a 27ml bottle containing 25mg of sodium per ml.
Varenzin™ contains fish oil added to the primary carrier of sunflower oil. In an acceptability study, cats offered Varenzin™ showed high voluntary acceptance when offered in an empty food bowl (88% over 1 week)6.
Mechanism of action
HIF is a complex of proteins that switches on the activity of genes needed to make erythropoietin (EPO) and other factors that help cells adjust to low-oxygen conditions7. When oxygen levels drop, HIF becomes active (is said to be stabilized) and triggers EPO production, which in turn stimulates red blood cell production in the bone marrow.
HIF-PH is an oxygen-sensitive enzyme that degrades HIF (destabilizes HIF) when normal cellular oxygen levels exist, thus decreasing the production of erythropoietin (EPO). The opposite occurs in hypoxic conditions. In other words, normoxia switches HIF-PH on, while hypoxia switches HIF-PH off.7
Varenzin™ works by blocking the enzyme HIF-PH. By inhibiting HIF-PH, Varenzin™ allows HIF to stay active irrespective of cellular oxygen concentrations, which increases the body’s natural production of EPO and supports red blood cell formation in the bone marrow.8
In an efficacy field study, the treatment groups average weekly responses ranged from increases of +1.7% to +3.9%, when compared to baseline, starting as early as study day 7. Compared to the control group, the HCT and packed cell volume (PCV) were significantly greater on study day 21.9
As CKD advances, renal erythropoietin-producing cells in the kidney reduce in number and treatment response diminishes. Treating earlier takes advantage of the presence of more functional EPO producing cells in the kidney and may help limit further hypoxia and fibrosis2,5.
Safety and efficacy
Vomiting is the most common side effect reported. Vomiting is associated with the underlying CKD and was reported at similar rates in treated and control group, in the pivotal field study.
Varenzin is the first and only approved veterinary treatment for CKD anaemia. In the Varenzin™ pivotal field efficacy study involving 75 cats with CKD anaemia, 68% of the cats treated with Varenzin™ reached treatment success criteria compared to 17% in the control group, which compares favorably with studies on darbepoetin.10
Dosage and administration
The dosage of Varenzin™ is 5 mg/kg body weight administered orally once daily using the dosing syringe provided in the package. This equates to a low dosing volume of 0.2ml per kg.
The 27 mL bottle is designed to provide approximately one month (30 days) treatment for a cat weighing 4.5 kg.
Elanco has not conducted any studies where Varenzin™ was administered mixed with food. Per the SPC, the product should be administered with the syringe directly into the cat’s mouth.
For treating cats with bodyweight greater than 6.0 kg, calculate the dose using 0.2 ml/kg bodyweight and round up to the nearest 0.1 ml.
The safety of Varenzin™ was established in field studies for up to 6 months when administered alone or in combination with other medications needed to alleviate clinical signs of CKD. There was no evidence of adverse effects attributed to Varenzin when given alone or in combination with other medications.
Based on information in humans, consider staggered administration of Varenzin™ and phosphate binders or iron supplements (at least 1 hour apart), to prevent potentially decreased absorption of molidustat.
Treatment and monitoring
Varenzin can be started when a cat's PCV drops below the reference range of 28%10.
Treated cats should initially have their hematocrit (HCT) or packed cell volume (PCV) levels monitored weekly beginning about the 14th day of the 28-day treatment cycle. Discontinue Varenzin™ if the HCT or PCV exceeds the upper limit of the reference range. According to IRIS anaemia treatment guidelines, if the PCV exceeds 40%, the drug should be temporarily discontinued. 2
After treatment cessation, the hematocrit (HCT) or packed cell volume (PCV) should be periodically checked. When the HCT or PCV levels are below the lower limit of the reference range a new treatment cycle may be started. According to IRIS anemia treatment guidelines, treatment can be restarted when PCV falls below 30%, the goal being to maintain a PCV of between 30%-40%.2
It can be continued as long as the hematocrit (HCT) or packed cell volume (PCV) does not exceed the upper limit of the reference range. IRIS guidelines recommend maintaining a PCV of between 30% - 40%.2
Treated cats should initially have their haematocrit (HCT) or packed cell volume (PCV) levels monitored weekly beginning about the 14th day of the 28-day treatment cycle to ensure HCT or PCV does not exceed the upper limit of the reference range.
Discontinue treatment if the HCT or PCV exceeds the upper limit of the reference range. After treatment cessation the haematocrit level should be periodically checked. When the HCT or PCV level declines below the lower limit of the reference range, a new treatment cycle should be started.
If a cat does not respond to treatment after 3 weeks, it is recommended to re-examine the animal for any other underlying condition that may contribute to anaemia, such as iron deficiency, inflammatory diseases or blood loss. It is advised to treat the underlying condition before restarting treatment.
Storage
Varenzin™ should not be stored above 30⁰C as packaged for sale is 3 years.
Shelf life of the veterinary medicinal product as packaged for sale: 3 years
Shelf life after first opening the immediate packaging: 28 days
Keep the bottle in the outer carton.
Do not store above 30°C.
- Chalhoub, S. Langston, C., et al. 2011. Anemia of renal disease: What is it, what to do and what’s new. J Feline Med Surg. 13:629-640.
- https://www.iris-kidney.com/treatment-of-anemia-in-cats-with-ckd
- Merten 2011
- Chakrabarti S, Syme HM, Elliott J. Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med. 2012 Mar-Apr;26(2):275-81.
- Elliott J. Therapeutics of managing reduced red cell mass associated with chronic kidney disease - Is there a case for earlier intervention? J Vet Pharmacol Ther. 2023 May;46(3):145-157.
- Elanco Study ID 204976
- Moslehi J et al. J Clin Invest 2019;130:4-6
- Haase VH. Hypoxia-inducible factor-prolyl hydroxylase inhibitors in the treatment of anemia of chronic kidney disease. Kidney Int Suppl (2011). 2021 Apr;11(1):8-25.
- Charles S et al. J Vet Int Med 2024;38:197-204
- Schmidt F et al. J Vet Int Med 2026;40
Varenzin™ Oral Suspension for Cats contains molidustat sodium. Legal category POM-V in UK.
Further information can be found in the Summary of Product Characteristics. Use medicines responsibly (UK): NOAH. Advice should be sought from the prescriber prior to use. Prescription decisions are for the person issuing the prescription alone.
Varenzin™, Elanco™ and the diagonal bar logo are trademarks of Elanco or its affiliates.
For product related technical queries, contact the Elanco Vets team:
Telephone: 01256 353131, selecting option 1 for technical services
Email: ElancoVets@elanco.com*
*please note this inbox will be checked during the next business day. If you require an urgent response to a product-use query, suspected adverse event or quality complaint regarding an Elanco product, please call 01256 353131 choosing option 1 for technical services. Outside of office hours, your call will be forwarded to our medical answer service and an Elanco representative will call you back. Thank you for your understanding.
