Xevudy: Uses, Dosage & Side Effects

What Is Xevudy and What Is It Used For?

Xevudy contains the active substance sotrovimab, a recombinant human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody. It was engineered to recognize and bind to a highly conserved epitope on the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, the virus responsible for COVID-19. The spike protein is the part of the virus that attaches to human cells through the angiotensin-converting enzyme 2 (ACE2) receptor. By blocking this interaction, sotrovimab prevents the virus from entering host cells, which in turn stops viral replication and limits the progression of the infection.

Sotrovimab was derived from S309, a natural antibody originally isolated from a patient who had recovered from SARS-CoV-1 (the virus that caused the 2003 SARS outbreak). Because S309 recognizes a conserved epitope on the spike protein shared between SARS-CoV-1 and SARS-CoV-2, it was engineered for therapeutic use against COVID-19 with the expectation that it would retain neutralizing activity against a broad range of SARS-CoV-2 variants. The antibody was further modified with an LS mutation (M428L/N434S) in the Fc region, which extends the half-life of sotrovimab to approximately 49 days and enhances its distribution to the respiratory mucosa, the primary site of SARS-CoV-2 infection.

Xevudy is indicated for the treatment of COVID-19 in adults and adolescents (aged 12 years and older and weighing at least 40 kg) who do not require supplemental oxygen and who are considered at increased risk of progressing to severe COVID-19. Risk factors for severe disease include, but are not limited to:

• Advanced age: People aged 60 years and older, particularly those 65 and above, are at significantly higher risk of hospitalization and death from COVID-19.
• Obesity: A body mass index (BMI) of 30 or above is an independent risk factor for severe COVID-19.
• Chronic cardiovascular disease: Including coronary artery disease, heart failure, and hypertension.
• Chronic respiratory disease: Including chronic obstructive pulmonary disease (COPD), moderate-to-severe asthma, and interstitial lung disease.
• Diabetes mellitus: Both type 1 and type 2 diabetes increase the risk of severe illness.
• Chronic kidney disease: Including patients on dialysis.
• Immunocompromising conditions: Such as organ transplant recipients, patients on immunosuppressive therapy, or those with primary immunodeficiency.
• Sickle cell disease: Associated with increased vulnerability to infections including COVID-19.

The clinical evidence supporting the efficacy of Xevudy comes primarily from the COMET-ICE trial (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early), a randomized, double-blind, placebo-controlled phase III study. In this trial, sotrovimab demonstrated a statistically significant 79% reduction in the risk of hospitalization or death due to any cause through day 29 compared with placebo in non-hospitalized patients with mild-to-moderate COVID-19 and at least one risk factor for disease progression. The primary endpoint was met with strong statistical significance, and the results formed the basis for conditional marketing authorization by the European Medicines Agency (EMA) and Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA).

What Should You Know Before Receiving Xevudy?

Before you are given Xevudy, your healthcare provider needs a complete picture of your medical history, current medications, and any known allergies. While Xevudy has been shown to be generally well tolerated, certain precautions apply. This section covers the key considerations that both patients and clinicians should be aware of before administration.

Contraindications

Xevudy must not be given to patients who have a known hypersensitivity to sotrovimab or to any of the excipients listed in the product information. If you have previously experienced a severe allergic reaction to a monoclonal antibody product, it is essential to inform your healthcare provider, as the risk of a similar reaction may be elevated. Before each infusion, your medical team will ask about your allergy history and will have appropriate emergency equipment and medications available in case a reaction occurs.

Warnings and Precautions

Xevudy can cause hypersensitivity reactions, including anaphylaxis, which in rare cases may be life-threatening. Allergic reactions have been reported in up to 1 in 10 patients, and while most are mild to moderate, severe reactions (anaphylaxis) can occur in up to 1 in 1,000 patients. Signs of a serious allergic reaction may include widespread rash or hives, swelling of the face, lips, or throat, wheezing or difficulty breathing, a sudden drop in blood pressure, and a feeling of faintness or collapse. If any of these occur during or after the infusion, medical care should be sought immediately.

Infusion-related reactions are also common (up to 1 in 10 patients) and can develop during or shortly after the infusion, although reactions have been reported up to 24 hours or later after treatment. Symptoms may include flushing, chills, fever, difficulty breathing, rapid heartbeat, and low blood pressure. For this reason, patients are monitored during the infusion and for at least 1 hour afterward. If a mild or moderate infusion-related reaction occurs, the infusion rate may be slowed or temporarily stopped. If a severe reaction occurs, the infusion must be discontinued and appropriate medical treatment administered immediately.

Children and Adolescents

Xevudy is not authorized for use in children under 12 years of age or in adolescents who weigh less than 40 kg. There are insufficient data on the safety and efficacy of sotrovimab in these populations. In adolescents aged 12 years and older who weigh at least 40 kg, the recommended dose is the same as for adults (500 mg single intravenous infusion).

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before receiving Xevudy. There are limited clinical data on the use of sotrovimab during pregnancy. As a human IgG1 monoclonal antibody, sotrovimab has the potential to cross the placental barrier, particularly during the second and third trimesters of pregnancy. Your doctor will carefully evaluate the potential benefit of treating your COVID-19 infection against any theoretical risks to you and your unborn child.

It is not known whether sotrovimab is excreted into human breast milk. Human IgG antibodies are known to be present in breast milk, so there is a possibility that sotrovimab could be transferred to a breastfed infant. If you are breastfeeding, you should discuss the risks and benefits with your doctor before receiving treatment. A decision should be made on a case-by-case basis considering the clinical benefit of treatment and the importance of breastfeeding to the infant.

Driving and Using Machines

Xevudy is not expected to affect your ability to drive or operate machinery. However, if you experience any side effects such as dizziness, weakness, or fatigue following the infusion, you should avoid driving or operating machinery until you feel well enough to do so safely.

How Does Xevudy Interact with Other Drugs?

Sotrovimab is a monoclonal antibody (a large protein molecule) that is eliminated from the body through intracellular catabolism (breakdown by cells) rather than through the liver’s cytochrome P450 (CYP) enzyme system. Because it does not interact with CYP enzymes, sotrovimab is not expected to cause the types of drug–drug interactions commonly seen with small molecule drugs that are metabolized by the liver. This is an important distinguishing feature of monoclonal antibody therapeutics compared with many conventional medications.

No formal drug interaction studies have been performed with Xevudy. However, based on its pharmacological properties and mechanism of elimination, clinically significant pharmacokinetic interactions with other medicinal products are not anticipated. Sotrovimab is unlikely to affect the plasma levels of co-administered drugs, and other drugs are unlikely to affect the levels or activity of sotrovimab.

Considerations with Other COVID-19 Treatments

There are limited data on the concomitant use of Xevudy with other anti-SARS-CoV-2 monoclonal antibodies or antiviral agents. If a patient is receiving or has recently received other COVID-19 treatments, the potential for overlapping therapeutic effects or unintended interactions should be considered on a case-by-case basis. In clinical practice, sotrovimab has been used alongside supportive care and standard-of-care treatments for COVID-19 without notable interaction concerns.

Vaccines

Xevudy is not a substitute for vaccination against COVID-19. The administration of sotrovimab may theoretically interfere with the immune response to COVID-19 vaccines if given close together. Current guidance from the WHO and other health authorities recommends a waiting period (typically 90 days) between receiving monoclonal antibody treatment and receiving a COVID-19 vaccine. Patients should consult their healthcare provider for specific guidance regarding vaccination timing.

Always tell your doctor or pharmacist about all the medicines you are taking, including prescription drugs, over-the-counter medications, vitamins, and herbal supplements. While drug interactions with Xevudy are not expected based on its mechanism of action and metabolism, a complete medication history helps your healthcare team provide the safest and most effective care.

What Is the Correct Dosage of Xevudy?

Xevudy is designed to be given as a one-time treatment. Unlike many other medications that require ongoing daily dosing, sotrovimab is administered as a single intravenous infusion. The drug must be prepared and administered by qualified healthcare professionals in a clinical setting equipped to manage potential infusion reactions and anaphylaxis.

Adults

The 500 mg dose of sotrovimab is supplied as a single-use vial containing 500 mg of the active substance in 8 mL of concentrate. Before administration, the concentrate must be diluted in a 50 mL or 100 mL infusion bag containing either 0.9% sodium chloride solution or 5% dextrose solution. Detailed preparation and administration instructions are provided in the product information for healthcare professionals.

Adolescents (12 Years and Older)

The dosing for adolescents aged 12 years and older who weigh at least 40 kg is identical to the adult dose. Clinical data suggest that the pharmacokinetic profile of sotrovimab in this age group is comparable to that in adults, supporting the use of the same fixed dose without the need for weight-based adjustment.

Children Under 12 Years

Xevudy is not authorized for use in children under 12 years of age or in adolescents weighing less than 40 kg. There are insufficient safety and efficacy data in these populations to support a dosing recommendation.

Elderly Patients

No dose adjustment is required for elderly patients. In the COMET-ICE trial, a substantial proportion of enrolled patients were aged 55 years and older, and no significant differences in safety or efficacy were observed between older and younger age groups. The pharmacokinetics of monoclonal antibodies are generally not significantly altered by age, supporting the use of the standard 500 mg dose in elderly patients.

Renal and Hepatic Impairment

No dose adjustment is required in patients with renal impairment or hepatic impairment. Sotrovimab is a monoclonal antibody that is catabolized intracellularly and is not eliminated through renal or hepatic metabolic pathways. Therefore, impaired kidney or liver function is not expected to meaningfully affect the pharmacokinetics of sotrovimab.

Preparation and Administration

Xevudy must be prepared and administered by qualified healthcare professionals using aseptic technique. The key steps include:

1. Remove the vial from refrigerated storage (2°C to 8°C) and allow it to equilibrate to room temperature, protected from light, for approximately 15 minutes.
2. Visually inspect the vial to ensure it is free of particulate matter and that the vial is undamaged. The solution should be clear, colorless to yellow or brown.
3. Gently swirl the vial several times before use. Do not shake or vigorously agitate.
4. Withdraw 8 mL from the vial and inject into a 50 mL or 100 mL infusion bag containing 0.9% sodium chloride or 5% dextrose. Remove and discard 8 mL from the infusion bag before adding the drug to maintain volume.
5. Gently rock the infusion bag 3 to 5 times. Do not invert or shake.
6. Administer as an intravenous infusion over 15 minutes (50 mL bag) or 30 minutes (100 mL bag) at room temperature. Use a 0.2 micron in-line filter.

What Are the Side Effects of Xevudy?

Like all medicines, Xevudy can cause side effects, although not everybody gets them. The side effect profile of sotrovimab is generally consistent with that expected of monoclonal antibody therapeutics administered by intravenous infusion. Most adverse events are related to the immune system’s response to the infused antibody (hypersensitivity reactions) or to the infusion process itself (infusion-related reactions). In clinical trials and post-authorization surveillance, the following side effects have been reported:

Infusion-related reactions typically develop within minutes to hours of the infusion but can occasionally occur up to 24 hours or later after treatment. If you experience any of the symptoms described above – particularly difficulty breathing, swelling of the face or throat, widespread rash, rapid heartbeat, dizziness, or a feeling of faintness – you should seek medical attention immediately. Your healthcare team is trained to recognize and manage these reactions and will monitor you closely during and after the infusion.

The overall incidence of adverse events in the COMET-ICE trial was comparable between the sotrovimab group and the placebo group, suggesting that sotrovimab is well tolerated when used as directed. Most reported side effects were mild to moderate in severity and resolved without long-term consequences.

If you experience any side effects, including those not listed here, tell your doctor, pharmacist, or nurse. You can also report suspected side effects to your national pharmacovigilance authority (e.g., the EMA in Europe, the FDA MedWatch program in the United States, or the MHRA Yellow Card Scheme in the United Kingdom) to help monitor the ongoing benefit-risk profile of Xevudy.

How Should Xevudy Be Stored?

Xevudy is a biological product that requires proper storage conditions to maintain its stability and effectiveness. As a patient, you will not typically need to handle or store Xevudy yourself, as it is prepared and administered by healthcare professionals in a clinical setting. However, the following storage information is provided for completeness:

• Unopened vials: Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Do not freeze: Freezing may damage the antibody and render it ineffective.
• Light protection: Keep the vial in the original packaging to protect from light.
• After dilution: The diluted solution is intended for immediate use. If immediate administration is not possible, the diluted solution may be stored at room temperature (up to 25°C) for up to 6 hours, or in a refrigerator (2°C to 8°C) for up to 24 hours, from the time of dilution through the end of administration.
• Expiry date: Do not use this medicine after the expiry date stated on the label and carton after “EXP.” The expiry date refers to the last day of the stated month.

Keep this medicine out of the sight and reach of children. Do not dispose of any medicines via wastewater or household waste. Your healthcare team will ensure proper disposal of unused medicine in accordance with local regulations to protect the environment.

What Does Xevudy Contain?

Active Substance

The active substance is sotrovimab. Each single-use vial contains 500 mg of sotrovimab in 8 mL of concentrate for solution for infusion, corresponding to a concentration of 62.5 mg/mL. Sotrovimab is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells and is a fully human IgG1κ monoclonal antibody directed against the SARS-CoV-2 spike protein.

Inactive Ingredients (Excipients)

• Histidine
• Histidine monohydrochloride
• Sucrose
• Polysorbate 80 (E 433) – see section on warnings regarding polysorbate content
• Methionine
• Water for injections

Appearance

Xevudy is a clear, colorless to yellow or brown liquid supplied in a single-use glass vial with a rubber stopper and an aluminium flip-off seal. Each carton contains one vial. The solution should be inspected visually before administration; if particulate matter or visible damage is observed, the vial should be discarded and a new one used.

Manufacturer and Marketing Authorization

The marketing authorization holder for Xevudy is GlaxoSmithKline Trading Services Limited, based in Dublin, Ireland. The medicine is manufactured by GlaxoSmithKline Manufacturing S.p.A. at their facility in San Polo di Torrile, Parma, Italy. Sotrovimab was co-developed by GlaxoSmithKline (GSK) and Vir Biotechnology, Inc., combining GSK’s expertise in infectious disease drug development with Vir’s platform for engineering monoclonal antibodies against viral targets.