ublituximab

Ublituximab is a medication used in the treatment of relapsing multiple sclerosis (MS), an autoimmune disorder that affects the central nervous system. The body’s immune system mistakenly attacks and damages the protective sheath (myelin) around the nerve fibers, affecting communication between the nerve cells (neurons), and causing symptoms that include pain, fatigue, vision loss and neuromuscular problems.

Dysregulation of B-lymphocytes, immune cells that produce antibodies, is an important factor in the autoimmune activity in multiple sclerosis. Ublituximab reduces autoimmune activity by depleting the levels of B-lymphocytes. Ublituximab is an immunoglobulin G1 (IgG1) monoclonal antibody produced in the lab using DNA recombinant technology. Ublituximab specifically binds to CD20, a unique molecule (antigen) present on pre-B lymphocytes, immature and mature B lymphocytes, which leads to the breakdown and death of the B-cells.

Ublituximab is typically used in the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. Ublituximab is administered as an intravenous infusion slowly for over an hour or longer as required.

• Do not administer ublituximab to patients with:
  • History of life-threatening infusion reaction to ublituximab
  • Active hepatitis B virus infection
• Ublituximab can cause infusion reactions such as high temperature (pyrexia), nausea, headache, chills, throat irritation, redness of skin (erythema), influenza-like illness, rapid heart rate (tachycardia), and severe allergic reactions (anaphylaxis).
  • Monitor patients during infusion and at least for one hour after the first two infusions.
  • Administer appropriate pre-medications such as antihistamines, antipyretics and corticosteroids to reduce the risk of infusion reactions.
  • In the event of infusion reactions, interrupt the infusion, provide appropriate treatment and resume with reduced infusion rate. In case of life-threatening infusion reactions, discontinue ublituximab permanently and institute appropriate supportive treatment.
  • Advise patients to be alert for infusion reactions, which can occur up to 24 hours after infusion, and report immediately.
• Depletion of B-cells with ublituximab therapy can increase the risk for infections, including serious and fatal bacterial, fungal, new or reactivated viral infections including progressive multifocal leukoencephalopathy (PML) caused by JC virus, and hepatitis B virus (HBV) reactivation.
  • Screen patients for HBV and other infections, and do not initiate treatment in patients with active infections until the infection is resolved. In patients who are carriers of HBV or positive for HBV core antibody, consult a liver disease specialist before and during treatment.
  • PML is an opportunistic viral infection that affects the brain and typically occurs in immunocompromised patients. Monitor patients for neurological symptoms and if PML is diagnosed, discontinue ublituximab permanently.
• Administer all vaccinations according to immunization guidelines before starting ublituximab treatment.
  • Live and live-attenuated vaccines should be completed at least 4 weeks before treatment and inactivated vaccines, 2 weeks before treatment.
  • Safety of live and live-attenuated vaccines during or following ublituximab treatment has not been studied and is not recommended during treatment and until B-cell repletion back to baseline levels. Ublituximab may interfere with the effectiveness of inactivated vaccines.
  • Do not administer live or live-attenuated vaccines to infants exposed to ublituximab in the uterus, until B-cell count is confirmed to be normal. Inactivated vaccines may be administered as scheduled, however, vaccine immune response must be assessed to confirm effectiveness.
• Ublituximab can cause fetal harm. Screen women for pregnancy before each infusion and advise women of reproductive potential to use effective contraception during treatment and for 6 months after completion of treatment.
• Depletion of B-cells can lower the levels of all types of antibodies (immunoglobulins), increasing the risk for serious infections. Monitor immunoglobulin levels, especially in patients with opportunistic or recurrent infections, and consider discontinuing ublituximab in patients with infections or those who require treatment for low immunoglobulin levels.

Common side effects of ublituximab include:

• Infusion reactions including:
  • High temperature (pyrexia)
  • Chills
  • Headache
  • Influenza-like illness
• Decrease in neutrophil immune cells
• Decrease in immunoglobulins M, A and G (IgM, IgA and IgG)
• Upper respiratory tract infections
• Lower respiratory tract infections
• Herpes virus-associated infections
• Urinary tract infection
• Bacterial and viral infections
• Reactivation of hepatitis B virus infection
• Insomnia
• Pain in extremity
• Fatigue

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable solution

• 25 mg/mL (150 mg/6 mL single-dose vial)

Adult:

Multiple Sclerosis

• Indicated for treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
• First infusion: 150 mg intravenous (IV)
• Second infusion: 450 mg IV 2 weeks after first infusion
• Subsequent infusions: 450 mg IV 24 weeks after first infusion and then once every 24 weeks thereafter

Dosage Modifications

Infusion-related reactions

• Follow recommended infusion rates
• Note: Change in rate will increase total duration of infusion, but not the total dose
• Mild-to-moderate
  • Reduce infusion rate to half the rate at onset of reaction and maintain reduced rate for at least 30 minutes
  • If reduced rate tolerated, increase rate
• Severe
  • Immediately interrupt infusion and administer appropriate supportive treatment, as necessary
  • Restart infusion only after all symptoms have resolved
  • When restarting, begin at half of infusion rate at the time of onset of reaction; if tolerated, increase rate
• Life-threatening
  • Immediately stop infusion and permanently discontinue

Renal impairment

• Mild: No dosage adjustment necessary
• Moderate-to-severe: Pharmacokinetics are unknown

Hepatic impairment

• Mild: No dosage adjustment necessary
• Moderate-to-severe: Pharmacokinetics are unknown

Dosing Considerations

• Verify pregnancy status in females of reproductive potential before each infusion
• Before every infusion, assess if there is an active infection; if active infection is confirmed, delay infusion until infection resolves

Hepatitis B virus (HBV)

• Screen for HBV and quantitative serum immunoglobulin before initiating
• Confirmed active HBV (patients with positive hepatitis B surface antigen [HBsAg] and anti-HBV tests): Contraindicated
• Patients who are negative for HBsAg and positive for hepatitis B core antibody (HBcAb+) or who are carriers of HBV (HBsAg+): Consult liver disease experts before starting and during treatment

Serum immunoglobulins

• Before initiating, perform testing for quantitative serum immunoglobulins
• For low serum immunoglobulins, consult immunology experts before initiating

Vaccinations

• Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion
• Administer all immunizations according to immunization guidelines
  • Live or live-attenuated vaccines: At least 4 weeks before initiating, whenever possible
  • Non-live vaccines: At least 2 weeks before initiating

Monitoring for infusion-related reactions

• First 2 infusions: Closely monitor during and for at least 1 hour after completing infusions
• Subsequent infusions: Monitor at discretion of healthcare provider unless infusion reaction and/or hypersensitivity have been observed

Pediatric:

• Safety and efficacy not established

Overdose

• There is no information on ublituximab overdose. The drug is administered in hospital settings and overdose is unlikely.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of ublituximab include:
  • talimogene laherparepvec
• Serious interactions of ublituximab include:
  • axicabtagene ciloleucel
  • brexucabtagene autoleucel
  • ciltacabtagene autoleucel
  • deucravacitinib
  • epcoritamab
  • glofitamab
  • ibritumomab tiuxetan
  • idecabtagene vicleucel
  • lisocabtagene maraleucel
  • mosunetuzumab
  • obinutuzumab
  • ofatumumab
  • ofatumumab SC
  • rituximab
  • tisagenlecleucel
• Ublituximab has moderate interactions with al least 267 different drugs.
• Ublituximab has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no data on the safety of ublituximab use during pregnancy. Available data from case reports of pregnancies occurring during clinical trial with ublituximab are insufficient to identify drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Animal reproductive studies show ublituximab can cause fetal harm. Exposure of ublituximab to the fetus can cause immunosuppression in the newborn infant.
• Women of reproductive potential should use effective contraception during treatment with ublituximab and for 6 months after the last dose.
• There is no information on the presence of ublituximab in breastmilk, or its effects on milk production and on the breastfed infant. Decision to breastfeed should be based on the mother’s clinical need for ublituximab, benefits of breastfeeding to the infant, and potential risk to the infant from exposure to the drug or underlying maternal condition.

• Report immediately to your healthcare provider if you experience infusion reactions that may occur up to 24 hours after infusion. Symptoms include fever, chills, nausea, headache, throat irritation, skin redness, flu-like illness, rapid heartbeat, and severe allergic reactions (anaphylaxis).
• Report immediately if you have any symptoms of infection, including JC virus infection that can affect the brain with symptoms that include progressive weakness on one side of the body, clumsiness of limbs, vision problems, confusion, changes in thinking and memory, and personality changes.
• Do not take any live or live-attenuated vaccines during treatment and for several months after. Check with your physician before taking any scheduled vaccinations.