Xromi

Sickle Cell Anemia

Xromi is specifically indicated for use in pediatric patients, aged 2 years and older, who have sickle cell anemia. It is prescribed for patients who experience recurrent moderate to severe painful crises associated with the condition.

The primary goals of treatment with Xromi include:

• Reducing the frequency of painful episodes, often referred to as sickle cell crises.
• Decreasing the need for blood transfusions.

Because Xromi is an oral solution, it provides an alternative for children or patients who have difficulty swallowing capsules. While the active ingredient, hydroxyurea, is also used to treat certain types of cancer and other blood disorders, Xromi is specifically labeled for the management of sickle cell anemia in the pediatric population.

Mechanism of Action

Xromi contains hydroxyurea, a medication that helps manage sickle cell anemia by changing the composition of red blood cells. In people with this condition, red blood cells can become hard, sticky, and shaped like a sickle or crescent moon. These abnormal cells often get stuck in small blood vessels, blocking blood flow and causing intense pain or organ damage.

The primary way Xromi works is by:

• Increasing fetal hemoglobin: It encourages the body to produce more fetal hemoglobin (HbF). This type of hemoglobin is usually present in high amounts at birth but decreases as a person grows.
• Preventing sickling: Higher levels of fetal hemoglobin help prevent red blood cells from deforming into a sickle shape. This keeps the cells rounder and more flexible.
• Improving blood flow: Because the cells stay flexible, they can move more easily through the blood vessels, which reduces the frequency of painful episodes and the need for blood transfusions.

While the exact biological process of how hydroxyurea increases fetal hemoglobin is not fully understood, it is also known to interfere with DNA synthesis by inhibiting an enzyme called ribonucleotide reductase. This action may also contribute to how the medication affects the production and behavior of blood cells.

Common Side Effects

Many people using Xromi experience mild to moderate side effects. These may include:

• Nausea and vomiting
• Diarrhea or constipation
• Loss of appetite
• Mouth sores or redness
• Skin changes, such as darkening, thinning, or rashes
• Temporary hair loss
• Weight gain

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Contact a healthcare provider if you experience:

• Low blood cell counts: This can lead to frequent infections, fever, chills, unusual bruising, or bleeding.
• Skin ulcers: Painful sores or ulcers, particularly on the legs or feet.
• Lung problems: New or worsening cough, fever, or shortness of breath.
• Liver issues: Yellowing of the eyes or skin, dark urine, or pain in the upper right stomach area.
• Secondary cancers: Long-term use of hydroxyurea may increase the risk of developing other cancers, such as skin cancer or leukemia.

Boxed Warnings

Severe Bone Marrow Suppression: Xromi can cause a significant decrease in blood cell counts, including white blood cells, platelets, and red blood cells. This can increase the risk of serious infections or bleeding. Treatment is usually not started if blood counts are too low and may be interrupted if they drop significantly during therapy. Frequent blood tests are required to monitor these levels.

Risk of Cancer: Hydroxyurea is known to be carcinogenic. Long-term use has been linked to secondary cancers, such as leukemia and skin cancer. Protection from sun exposure and regular skin examinations are recommended to reduce the risk of skin malignancies.

Other Precautions

Embryo-Fetal Toxicity

Xromi can cause harm to an unborn baby. Females of reproductive potential should use effective contraception during treatment and for at least six months after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment and for at least one year after the last dose. This medication may also affect fertility in both men and women.

Vaccinations

Live vaccines should be avoided while taking Xromi. Because the medication suppresses the immune system, the body may not respond correctly to the vaccine, or the vaccine could cause a serious infection.

Skin and Vascular Issues

Some patients may develop skin ulcers or vascular toxicities, particularly those with certain blood disorders. These issues can be severe and may require the medication to be discontinued. Patients should report any new sores or changes in skin color to a healthcare provider immediately.

Drug Interactions

Using Xromi with certain antiviral medications used for HIV, such as didanosine or stavudine, can increase the risk of severe side effects. These include fatal liver damage, pancreatitis, and severe nerve pain in the hands and feet.

Pregnancy

Xromi can cause fetal harm if taken during pregnancy. It is important to discuss pregnancy status and family planning with a healthcare provider before starting this medication. If pregnancy occurs during treatment, a clinician should be notified immediately.

Effective contraception is recommended for patients of reproductive potential:

• Females: Use effective birth control during treatment and for at least 6 months after the final dose.
• Males: Use effective birth control during treatment and for at least 1 year after the final dose. This medication may also impact male fertility.

Breastfeeding

Hydroxyurea is known to pass into breast milk. Due to the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended while taking Xromi. Patients should consult their healthcare provider to discuss the risks and determine the best feeding plan for their infant.

Available Forms

Xromi is available in the following form:

• Oral Solution: A liquid medication that is swallowed.

This medication is a liquid version of hydroxyurea. It is designed to be measured and taken by mouth using an oral dosing syringe.

FDA Approval Status

Xromi (hydroxyurea) received FDA approval on September 27, 2021. It is approved for use in pediatric patients aged 2 years and older who have sickle cell anemia with recurrent moderate to severe painful crises. The primary goal of treatment is to reduce the frequency of these crises and the necessity for blood transfusions.

Boxed Warning

The FDA-approved labeling for Xromi includes a boxed warning regarding serious safety risks:

• Severe Myelosuppression: Treatment with hydroxyurea can lead to dangerously low levels of white blood cells, red blood cells, and platelets. Healthcare providers must monitor blood counts weekly during the initial phase of treatment and periodically thereafter. Dosage adjustments or temporary discontinuation may be necessary if blood counts fall below specific levels.
• Malignancies: Hydroxyurea is a known human carcinogen. Long-term use has been associated with the development of secondary cancers, including leukemia and skin cancer. Patients are encouraged to use sun protection and undergo regular skin examinations.

Usage and Monitoring

Because of the risks associated with this medication, it is typically prescribed by specialists experienced in managing sickle cell disease. Regular laboratory monitoring is a standard regulatory requirement for patients taking this drug to ensure safety and to adjust the dose based on the patient's weight and blood response.

Stopping Xromi

There is currently no evidence to suggest that Xromi causes physical dependence or a specific withdrawal syndrome when the medication is discontinued. Unlike certain other medications, such as opioids or sedatives, hydroxyurea does not typically require a tapering schedule to prevent physical illness upon stopping.

Risks of Discontinuation

While withdrawal symptoms are not expected, stopping Xromi can have significant effects on the condition being treated. You should not stop taking this medication without consulting your healthcare provider. Potential risks of stopping treatment include:

• Recurrence of Symptoms: For patients with sickle cell anemia, stopping the medication may lead to an increase in the frequency and severity of painful crises.
• Increased Transfusions: Discontinuing treatment may result in a higher need for blood transfusions.
• Blood Count Changes: Xromi works by affecting the production of blood cells. When the drug is stopped, blood cell counts will eventually return to their baseline levels, which may affect the management of the underlying disease.

Your doctor will likely monitor your blood counts and overall health if you need to stop treatment to ensure your condition remains stable.