Odevixibat - An Overview

Overview

Intrahepatic cholestasis is a clinical condition affecting the liver. The drug works by stopping the function of certain bile acid transporters and reducing the reabsorption of bile acids from the intestine. It is available in oral pellets and capsules, which are to be administered as the physician advises. The instructions for administering pellets and capsules are different; hence, the instructions for administration are to be followed.

How Does the Drug Odevixibat Work?

The drug works by reducing the reuptake of the bile acids from the terminal ileum, which are the primary salt forms. This mechanism occurs by inhibiting the bile acid transporters.

Available Doses and Dosage Forms:

Oral Pellets:

• 200 Micrograms: White opaque body and ivory opaque cap imprinted with a A200 in black.

• 600 Micrograms: Ivory opaque body imprinted with A600 in black ink.

Capsules:

• 400 Micrograms: Capsule with white body and medium orange cap imprinted with A400 in black.

• 1200 Micrograms: A capsule with a medium orange cap and body imprinted with A1200.

Warnings:

The drug should never be consumed along with water. Hepatic impairment, vitamin K-deficient patients, liver function test abnormalities, and diarrhea should be considered before administering the drug Odevixibat. These conditions should be considered as the symptoms and situations can get worse with the continuation of the treatment with the drug.

For Patients:

Why Is Odevixibat Prescribed?

Odevixibat is prescribed for the treatment of intrahepatic cholestasis. The most common disorder of the liver that occurs during pregnancy. Intrahepatic cholestasis of pregnancy can occur due to many reasons. Reproductive hormones and health, environmental, and seasonal factors are also correlated with intrahepatic cholestasis causes; underlying liver disorders can also exaggerate the chances of increasing the cause of the development of intrahepatic cholestasis. Clinical symptoms examination and tests, including liver function tests and vitamin K levels, evaluate the condition. Immediate treatment is necessary to manage the condition, which aims not to compromise the patient's life. Drugs such as Ursodeoxycholic acid are the drug of choice, whereas Odevixibat is also used in the treatment.

How to Use Odevixibat?

The drug is to be administered at least four hours before or four hours after taking bile acid-binding resin in patients taking it. The medicine should not be crushed or should not be chewed.

Instructions for Administration:

Oral Pellets:

1. Things containing oral pallets are mixed with soft food. It should be noted that the medicine should not be mixed in liquids.

2. The shell containing the contents of the oral pellet is not to be swallowed whole as it is.

3. Take the drug Odevixibat along with a meal in the morning.

4. A small amount of soft food such as oatmeal, carrot or banana puree, rice pudding, chocolate pudding, or apple sauce up to 30 milliliters or two tablespoons is taken in a bowl. The food is kept at or below room temperature.

5. The medication's shell is open, and all the oral pallets are emptied into the bowl of soft food. The oral pellet shell must be tapped gently to ensure all contents are dispersed.

6. The fourth and fifth steps are repeated if more than one shell is required as a dose.

7. The food is mixed until the medication is well dispersed, and the entire dose is administered immediately.

8. After taking the dose, consume the water.

9. Storing the mixture is not recommended for future use.

Capsules:

1. Take the capsule with a meal in the morning.

2. The capsule should be followed on the whole with a glass of water.

3. If swallowing the whole capsule is difficult, the capsule can be opened, sprinkled, and mixed with soft food. Then, instructions for oral pellets are followed, and the medication is prepared and administered.

What Should Be Done if a Dose Is Missed?

The missed dose can be taken as soon as one remembers it and if it is time for the next dose. Remember that administration of double the dose than prescribed can lead to complications. Care should be taken each time while taking the drug.

How to Store the Drug Odevixibat?

The drug can be stored at 20–25°C (68–77°F) and also between 15–30°C (59–86°F).

Avoid Self-Medication:

The treatment prescribed for one individual cannot be the same for every individual suffering from this same disorder. The dosage is determined by the intensity of the condition and the individual's body condition, so it can differ. It is advised not to suggest or take this medication without a proper prescription from a healthcare provider.

Adverse Effects:

• Abdominal pain, vomiting, dehydration, and diarrhea were reported with the use of the drug. The patients are advised to contact a healthcare provider when they experience new or recurring symptoms.

• Changes or elevations in the liver function test are observed with the drug's intake. The patient is advised to get a liver function test done before starting treatment with Odevixibat. Any symptoms of liver problems, like vomiting, nausea, yellowish discoloration of the skin or whites of the eyes, loss of appetite, and abdominal pain, are noted.

• Serum levels of vitamins A, D, E, and K are to be monitored.

Instructions for Administration:

• The drug should not be mixed with liquids.

• Oral pellets should not be swallowed whole.

• Administration instructions given by the physician should be followed.

For Doctors

Indication:

The drug Odevixibat is is indicated for treating pruritis for three months in patients suffering from progressive familial intrahepatic cholestasis. It cannot be effective in type two patients suffering from progressive familial intrahepatic cholestasis with ABCB11 variance, which results in the complete absence of BSEP—3 bile salt export pump protein or its non-functional ability.

Dosing:

40 micrograms per kilogram is the recommended dosage, administered once daily in the morning along with meals. After three months, if there is no improvement in the patient's clinical condition, the dosage of Odevixibat will be increased. The dosage is then increased to 120 micrograms (mcg) per kilogram once daily, which should be at most six milligrams (maximum recommended daily dose). The dosage of the medication is dependent on the weight of the patient. Oral pallets are to be used by patients who weigh less than 19.5 kilograms. Patients weighing above 19.5 kilograms will use capsules of the same.

Dosing Considerations:

Before starting the treatment, the pattern of variability in levels of liver function tests is established so that liver injury can be identified. Liver functioning tests are performed and monitored. If new liver test abnormalities are detected due to the administration of the drug, the drug is to be stopped, and the symptoms are monitored and treated. Once the liver test amenities are stabilized, the drug can be restarted at the lowest dose and increased depending on the drug tolerance shown by the patient. If liver test abnormalities keep recurring, the drug is to be permanently stopped. Upon experiencing hepatic decompensation events like ascites, variceal hemorrhage, and hepatic encephalopathy, the drug Odevixibat is to be permanently discontinued.

Pharmacology:

Mechanism of Action:

Odevixibatis is an inhibitor of IBAT, the ileal bile acid transporter. By inhibiting ileal bile acid transporters (IBAT), it reduces the accumulation of bile acids in the liver. Reabsorption of bile acids is decreased from the terminal ileum. The reuptake of bile salts is decreased along with a decrease in the levels of serum bile acids.

Pharmacodynamics:

Serum bile acid levels are reduced when Odecixibat is administered. Within four to eight weeks of treatment with the drug, the concentrations are reduced. Although the concentrations of serum bile acid alter very frequently over time, they are maintained throughout the treatment with the drug Odevixibat over four months.

Pharmacokinetics

The concentration of the drug Odevixibat ranges from 0.06 to 0.72 nanogram per milliliter in pediatric patients. 0.06 to 0.72 nanogram per milliliter are the measurable concentrations of the drug. Plasma concentrations of the drug are almost below the values obtained following single or frequent administration.

Absorption

Following the oral administration of the drug, minimal absorption occurs. Maximum absorption reaches between one and five hours when seven milligrams of Odevixibat is administered to healthy adults.

Effect of Food:

The effect of the Odevixibat is decreased when a high-fat meal and a single dose of the drug are consumed in three to four and half hours.

Distribution:

The plasma protein binding of the drug is greater than 99 percent.

Elimination:

82.9 percent of the drug is eliminated through feces, which denotes that the drug remained unchanged at 97 percent.

Nonclinical Toxicity:

Carcinogenesis:

The drug did not seem to be paving the way for cancer when treated on animals at oral doses of up to 100 milligrams per kg per day. A maximum dose of approximately 450 times more than the recommended dose was administered in animals to obtain the carcinogenesis result.

Mutagenesis:

The drug was negative in several tests to determine the mutagenesis status.

Impairment of Fertility:

No adverse effects on the reproductive function in males and females were reported when the dosage increased to 1000 milligrams per kilogram per day administered in rats.

Warnings and Precautions:

• Liver Test Abnormalities: Liver test baseline values are obtained and monitored during treatment. The dose can be reduced when abnormalities in these levels occur, or the treatment can be interrupted depending on the clinical condition. Even upon interrupting the treatment, the occurrence of persistent liver test abnormalities leads to a complete discontinuation of the treatment.

• Diarrhea: Dehydration is treated. Treatment should be interrupted or discontinued if the patient suffers from persistent diarrhea.

• Fat-Soluble Vitamin Deficiency: Baseline levels of fat-soluble vitamins (FSV) are obtained and monitored during the treatment. If a deficiency of fat-soluble vitamins is observed, a supplement is administered. Despite FSV supplementation, if the deficiency persists or worsens, treatment with Odevixibatis is discontinued.

Contraindications:

Odevixibat is contraindicated in patients who develop hypersensitivity to the drug or any of its components.

Drug Interactions:

• Biologic Binding Resins: They are to be administered at least four hours before or after the administration of the drug Odevixibat. The efficacy of Odevixibat can decrease as the bile acid binding resins bind with the drug in the gut.

• Effect of Other Drugs on Odevixibat: Itraconazole has no clinically significant effect when administered with a single drug dose.

• Effect of the Drug Odevixibat on Other Drugs: The use of Midazolam along with 7.2 milligrams of Odevixibat decreased Midazolam's effect by 29 percent in 24 hours, which cannot be clinically correlated.

Other Specifications:

Pregnancy:

Major birth defects, adverse development of organs, or miscarriages have not been reported when the drug Odevixibat is administered in pregnant women. Based on certain reports, the drug Odevixibat can causes malformations of the heart when the fetus is exposed to it during pregnancy. Malformations of larger blood vessels and vascular structures, along with the abnormal formation of the heart, is observed when the drug is orally administered to animals during organogenesis (animal studies). Usually, the risk of major birth defects and abnormal formations along with miscarriages was reported to increase from two to four percent.

Lactation:

By oral administration, the drug undergoes low absorption, and the infant is not exposed to the drug upon breastfeeding. Effects on milk production or effects on an infant who is breastfed have not been reported yet. Fat-soluble vitamin absorption can be reduced during the administration of Odevixibat. Monitoring these levels can help manage strategies to increase fat-soluble vitamin (FSV) levels. The health benefits along with the development and benefits of breastfeeding are considered along with the mother's clinical condition for the treatment with the drug Odevixibat and any adverse effects that can occur on breastfed children due to the underlying maternal condition.

Pediatric Use:

Effective national safety of the drug Odevixibat has been observed in patients aged three months to 17 years in the treatment of pruritis. The use of the drug in this age is proven beneficial and supported through various evidences. Liver abnormalities and symptoms of the gastrointestinal system, such as vomiting and diarrhea along with abdominal pain, are commonly occurring adverse reactions.

Geriatric Use:

The administration of Odevixibat and its effectiveness in treating elderly patients has not yet been established. Hepatic impairment safety and FICCI of the drug in patience with hepatic impairment has not yet been established.