(For veterinary information only)
WARNING
The size of the tablet/medication is NOT an indication of a proper dose. Never administer any drug without your veterinarian's input. Serious side effects or death can occur if you give medications to your pet without your veterinarian's advice.
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Brand Name: Varenzin™-Ca1 ("CA-1" indicates conditional FDA approval)
Strength: 25 mg/ml Oral Liquid
Molidustat is used to treat the non-responsive red blood cell shortage/anemia of chronic kidney disease. It acts by preventing removal of substances that stimulate bone marrow to make red blood cells and by improving the body's use of iron.
Presently, because Varenzin™-CA1 is conditionally approved, it can only be used in cats with anemia due to chronic kidney disease.
How This Medication Works
Every cell in the body needs oxygen for energy. Oxygen gets to tissues by hitching a ride in red blood cells (RBC). However, the number of RBCs in the blood needs to be just right. Too few (anemia) means tissues don’t get enough oxygen. Too many (polycythemia) can also be a problem because the blood may become so thick that it cannot flow properly. This can lead to blood clots, which can be fatal.
The body closely regulates how many RBCs it makes. Normally, when blood oxygen levels get too low (hypoxia), the kidney releases a protein called erythropoietin (EPO). This protein travels to the bone marrow and tells it to make red blood cells. With chronic kidney disease, the kidneys are unable to make enough EPO, bone marrow does not make enough RBCs, and the patient becomes anemic, which makes the patient even sicker.
However, the body has other mechanisms to increase RBC production in the bone marrow. When oxygen levels get too low, the body also turns on certain genes that help it to adapt to low oxygen. One of these genes makes a protein called "Hypoxia-Inducible Factor" (HIF). This protein can increase the formation of EPO by the kidneys even if the kidneys are diseased, and EPO formation can be found in other organs, such as the liver. HIF also helps the body move iron around more efficiently, so it can be used to increase RBC. When there are enough RBCs so that oxygen levels are back to normal in the tissues, the body destroys any remaining HIF. This way, the body makes sure that there are not too many RBCs in the blood.
Molidustat works by preventing the body from destroying HIF. This means that HIF will be present even if oxygen levels in the tissue are normal. The kidneys and other tissues respond to HIF by making more EPO, and the bone marrow increases RBC numbers, helping correct anemia and prevent hypoxia. HIF also ensures that iron is available for the bone marrow to make RBCs.
Currently, molidustat is only available under the brand name Varenzin™-Ca1 and is conditionally approved by the FDA in the United States for use in cats with chronic renal disease. "Conditionally approved" means that the drug is important for treating a serious or life-threatening disease, but proving that it is effective requires a difficult study. A drug that is conditionally approved will continue to be reviewed by the Food and Drug Administration for both safety and efficacy. As a conditionally approved drug, Varenzin™-Ca1 cannot be used in any species other than the cat, and in cats, it cannot be used for other causes of anemia.
How This Medication Is Used
If there are too many red blood cells, the blood becomes too thick and clots too easily. The goal is to have the right amount of red blood cells. Molidustat is meant to be used for a 28-day course, but the patient will require some red cell checks during that time. The medication is discontinued when the appropriate red cell amount is achieved but will probably need to be restarted later on when red cell numbers decline again.
Although this drug is used to tell the body to make more RBC in anemic patients, it is only useful in states of anemia that happen because the kidneys are too sick to make enough EPO. Otherwise, the body has plenty of EPO. Currently, molidustat is not used for any other cause of anemia.
Molidustat is administered once daily, in 28-day cycles, with one week of no treatment between cycles. Your cat's anemia must continue to be monitored throughout and even after treatment. The most common test is a packed cell volume (PCV) or hematocrit (HCT). This is to make sure the RBC count does not get too high or that it does not get so low that serious anemia develops again. Monitoring should begin at about 14 days of treatment. In studies in cats with anemia due to chronic kidney disease, weekly increases in the PCV or HCT of about two to four percent were detected as early as seven days into treatment.
Once the anemia is stabilized, monitoring of your pet’s RBC can be less frequent. Molidustat may be stopped if your pet’s anemia is stabilized, but monitoring should be continued even while not receiving molidustat to determine if and when molidustat therapy should begin again.
It is important to understand that molidustat does not treat renal disease and may not slow the progression of renal disease. It only treats one of the bad consequences of renal disease: anemia.
Side Effects
Because the body is being told to make more RBCs, one of the most serious side effects of molidustat may be too many RBCs (polycythemia). This may result in slowed blood flow and blood clots, which can be fatal.
Polycythemia may also contribute to hypertension (high blood pressure). Rarely, seizures may occur. The risk of these serious events is greater if molidustat is used in a cat that is not anemic.
Approximately 50% of cats using this medication will have an increase in vomiting, which is usually not severe. Of more concern is an increase in red blood cell numbers so great that the blood thickens and can clot abnormally. Monitoring the red blood cell count periodically will be important in preventing these situations.
To ensure that too many RBCs are not being made, your veterinarian should monitor RBCs in your pet approximately once per week by collecting blood for an HCT or PCV.
Interactions With Other Drugs
Drugs used to bind phosphate in the diet should not be administered at the same time as molidustat. Other drugs to avoid giving at the same time include antacids, iron supplements, or sucralfate. All of these can interfere with the body's absorption of molidustat. Stagger the administration of these other drugs.
Discuss with your veterinarian whether or not molidustat can be used at the same time as other drugs that stimulate or supplement EPO (such as recombinant erythropoietin). The use of these drugs with molidustat has not been studied in cats with chronic kidney disease.
Concerns And Cautions
- Molidustat should not be used in cats with a history of seizures.
- Molidustat should not be used in cats with abnormal blood clotting.
- Molidustat should not be used in cats under one year of age.
- It is important to monitor your cat’s RBCs weekly after the second week of treatment until the anemia has stabilized.
- If your cat has not started to respond to molidustat after three weeks, it is important to look for other causes of anemia, such as ongoing blood loss or iron deficiency.
- Your veterinarian may decide that more than one 28-day cycle is necessary for an adequate response. After each 28-day cycle, wait at least seven days before re-starting. Treatment may be intermittent for the rest of your cat's life, depending on your pet’s RBC as measured by an HCT or PCV.
- Iron supplementation is not necessary for molidustat to work unless your cat is iron deficient. Discuss this possibility with your veterinarian.
When Administering the Drug
- Molidustat can be given with or without food.
- If your cat vomits the dose within 15 minutes or only receives a partial dose, do not re-dose. Give the regular dose the next day.
- Wash hands after handling this medication.
- Shake well before each use.
- Rinse the syringe and allow it to dry (pull the plunger out) after each dose.
Warning: Please ask your veterinarian to demonstrate how to properly withdraw the drug from the vial. The printing on the exterior of the dosing syringe that accompanies the product may become unreadable if the medication comes in contact with the exterior of the syringe. This can make accurate dosing difficult. The risk can be reduced if the dosing syringe is firmly inserted into the medication bottle. Be sure to follow the dispensing directions closely.
Storage
Do not refrigerate. Store at room temperature away from light, and use the dosing syringe provided. A bottle should be stable for at least 28 days after it is opened.
Other Information:
Expect monitoring tests to be needed to determine patient response. This medication is given at finite intervals, not indefinitely. As previously stated, it should not be used in cats with a history of seizures.