LIVTENCITY (Maribavir)

What Is LIVTENCITY and What Is It Used For?

LIVTENCITY (maribavir) is an antiviral medication specifically designed to treat cytomegalovirus (CMV) infection in adults who have received an organ transplant or a haematopoietic stem cell (bone marrow) transplant. It is used when CMV infection has not responded to, or has recurred after, treatment with other antiviral agents.

LIVTENCITY contains the active substance maribavir, a benzimidazole riboside that represents a first-in-class antiviral targeting the CMV UL97 protein kinase. This unique mechanism of action distinguishes it from all previously available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, and cidofovir), which target the viral DNA polymerase. By inhibiting UL97, maribavir blocks several critical steps in the CMV replication cycle, including viral DNA replication, encapsidation of viral DNA into capsids, and the nuclear egress of viral capsids necessary for the production of mature infectious virus particles.

Cytomegalovirus (CMV) is a member of the herpesvirus family that infects a large proportion of the general population – studies estimate that 50–80% of adults worldwide carry the virus. In immunocompetent individuals, CMV typically causes no symptoms or only mild illness, and the virus remains dormant (latent) in the body indefinitely. However, in patients whose immune systems have been deliberately suppressed following organ or bone marrow transplantation – using immunosuppressive drugs to prevent graft rejection – CMV can reactivate and cause serious, potentially life-threatening disease.

CMV disease in transplant recipients can manifest as CMV syndrome (fever, malaise, bone marrow suppression) or as tissue-invasive disease affecting the gastrointestinal tract (colitis, oesophagitis), lungs (pneumonitis), liver (hepatitis), retina (retinitis), or central nervous system. Without adequate treatment, CMV disease is associated with increased morbidity, graft loss, and mortality. The standard first-line treatments for CMV infection in transplant patients – ganciclovir and valganciclovir – are effective for many patients but can fail due to viral resistance, intolerance (particularly bone marrow toxicity), or insufficient response. In these situations, LIVTENCITY provides a critically needed therapeutic option.

The approval of LIVTENCITY was supported by the pivotal SOLSTICE trial (Study 303), a phase 3, randomised, open-label, active-controlled study comparing maribavir 400 mg twice daily with investigator-assigned therapy (ganciclovir, valganciclovir, foscarnet, or cidofovir) in 352 transplant recipients with refractory CMV infection (with or without resistance). At week 8, 55.7% of patients receiving maribavir achieved confirmed CMV clearance compared with 23.9% of patients receiving conventional therapy – a statistically significant and clinically meaningful difference that led to regulatory approvals by the EMA and FDA.

What Should You Know Before Taking LIVTENCITY?

Before starting LIVTENCITY, inform your doctor about all medications you are taking, especially immunosuppressants and other antivirals. LIVTENCITY must not be used together with ganciclovir or valganciclovir. If you are taking cyclosporine, tacrolimus, sirolimus, or everolimus, more frequent blood monitoring will be required.

Contraindications

You should not take LIVTENCITY if any of the following apply:

• Allergy to maribavir or any other ingredient in the tablet (see the Contents section for a full list of ingredients)
• Concurrent use of ganciclovir – maribavir inhibits the UL97 kinase that is required to convert ganciclovir to its active form, potentially rendering it ineffective
• Concurrent use of valganciclovir – valganciclovir is converted to ganciclovir in the body and is subject to the same interaction mechanism

If you are currently taking ganciclovir or valganciclovir and your doctor has decided to switch you to LIVTENCITY, you must stop the previous medication before starting maribavir. Using these drugs together could lead to treatment failure and further development of antiviral resistance.

Warnings and Precautions

Talk to your doctor or pharmacist before taking LIVTENCITY, especially if you are taking any of the following immunosuppressant medications commonly used in transplant recipients:

• Cyclosporine – LIVTENCITY may increase blood levels of cyclosporine, raising the risk of nephrotoxicity (kidney damage) and other toxic effects
• Tacrolimus – LIVTENCITY may increase tacrolimus blood levels, which can cause kidney toxicity, neurotoxicity, and metabolic disturbances
• Sirolimus – LIVTENCITY may raise sirolimus levels, increasing the risk of immunosuppressant-related adverse effects
• Everolimus – similar to sirolimus, LIVTENCITY may increase everolimus concentrations in the blood

If you are taking any of these immunosuppressants, your doctor will need to perform more frequent blood tests to monitor their levels. Elevated levels of these drugs can cause serious side effects including kidney damage, liver toxicity, and increased susceptibility to infections. Dose adjustments of your immunosuppressant may be required while you are taking LIVTENCITY and after you stop it.

Your doctor will also monitor your CMV viral load regularly during treatment to assess whether LIVTENCITY is effectively suppressing the virus. If CMV viraemia does not decrease or if it returns during treatment, your doctor may investigate for the emergence of maribavir-resistant CMV variants and consider alternative treatment strategies.

Use in Children and Adolescents

LIVTENCITY has not been studied in children and adolescents under 18 years of age. It should therefore not be used in this age group. Clinical trials specifically designed for paediatric transplant recipients with CMV infection may be ongoing; consult your doctor or specialist for the most current information regarding paediatric use.

Pregnancy and Breastfeeding

Pregnancy: LIVTENCITY is not recommended during pregnancy. The effects of maribavir on the developing foetus have not been studied in pregnant women. There is insufficient data to determine whether maribavir may cause harm to an unborn baby. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine. Your doctor will carefully weigh the potential benefits of treatment against the possible risks to the foetus.

Breastfeeding: It is not known whether maribavir passes into human breast milk. Because many drugs are excreted in breast milk and because of the potential for adverse effects in a nursing infant, breastfeeding is not recommended during treatment with LIVTENCITY. Discuss the benefits of breastfeeding against the benefits of continued antiviral treatment with your healthcare provider.

Driving and Operating Machinery

LIVTENCITY is considered to have no effect on your ability to drive or use machines. However, if you experience fatigue, dizziness, or other side effects that may impair your ability to perform these activities safely, you should refrain from driving or operating machinery until the effects have resolved.

Sodium Content

This medicine contains less than 1 mmol (23 mg) sodium per tablet, which means it is essentially “sodium-free”. This is relevant for patients on a sodium-restricted diet, such as those with heart failure or kidney disease.

How Does LIVTENCITY Interact with Other Drugs?

LIVTENCITY has significant interactions with several classes of medications, including immunosuppressants, antifungals, anticonvulsants, HIV antivirals, and certain common medications. Always inform your doctor about all medicines you are taking before starting LIVTENCITY.

Maribavir is metabolised primarily by CYP3A4 and CYP1A2, and it acts as an inhibitor of CYP3A4, CYP2D6, and the P-glycoprotein (P-gp) transporter. These properties mean that LIVTENCITY can affect the blood levels of many other medications, and that other drugs can affect the blood levels of LIVTENCITY itself. Your doctor or pharmacist must review all your current medications – including prescription drugs, over-the-counter medicines, and herbal supplements – before you start treatment.

Contraindicated Combinations

Major Interactions Requiring Monitoring

Minor Interactions

This is not a complete list of all possible drug interactions. Always ask your doctor, pharmacist, or nurse for a full review of your current medications before starting or stopping LIVTENCITY.

What Is the Correct Dosage of LIVTENCITY?

The recommended dose of LIVTENCITY is 400 mg (two 200 mg tablets) taken twice daily – once in the morning and once in the evening. The tablets can be taken with or without food, swallowed whole, or crushed and mixed with a soft food or liquid.

Always take this medicine exactly as your doctor, pharmacist, or nurse has instructed. If you are unsure about any aspect of your dosing, ask your healthcare provider for clarification. Do not change your dose or stop taking LIVTENCITY without first consulting your doctor, even if you are feeling better. Premature discontinuation could allow the CMV infection to return or worsen.

Adults

In clinical trials, patients were treated for a median duration of approximately 8 weeks, although some patients required longer courses of therapy. Your doctor will decide how long you should continue taking LIVTENCITY based on regular blood tests to measure your CMV viral load and your clinical condition.

Children

Elderly

Patients with Kidney or Liver Impairment

Missed Dose

If you miss a dose of LIVTENCITY, the action you should take depends on when you remember:

• If it is more than 3 hours before your next scheduled dose: take the missed dose as soon as you remember, then continue with your regular dosing schedule
• If it is less than 3 hours before your next scheduled dose: skip the missed dose entirely and take your next dose at the usual time
• Never take a double dose to make up for a missed dose, as this increases the risk of side effects

Overdose

If you take more LIVTENCITY than prescribed, contact your doctor immediately. There is no specific antidote for maribavir overdose. Treatment would be supportive and based on symptoms. In clinical studies, single doses of up to 1,600 mg have been administered without serious adverse effects, but higher doses may increase the risk and severity of side effects such as taste disturbance, nausea, and vomiting.

Stopping Treatment

Do not stop taking LIVTENCITY without talking to your doctor first, even if you feel well. Stopping treatment prematurely may allow the CMV infection to return or progress to more serious disease. If you take LIVTENCITY as recommended, you have the best chance of clearing the CMV infection. Your doctor will advise you when it is safe to stop based on sustained viral suppression confirmed by blood tests.

What Are the Side Effects of LIVTENCITY?

Like all medicines, LIVTENCITY can cause side effects, although not everyone experiences them. The most common side effects are taste disturbance (dysgeusia), nausea, diarrhoea, vomiting, and fatigue. These are generally mild to moderate and often improve as your body adjusts to the medication.

In the pivotal SOLSTICE clinical trial, the overall safety profile of maribavir was favourable compared to conventional anti-CMV therapies. Importantly, maribavir does not cause the significant bone marrow suppression (myelotoxicity) and kidney damage (nephrotoxicity) that are major dose-limiting toxicities of ganciclovir/valganciclovir and foscarnet, respectively. This makes it a valuable option for transplant recipients who are particularly vulnerable to these complications.

The taste disturbance associated with LIVTENCITY is the most distinctive side effect and is thought to be related to the drug’s mechanism of action. It can range from a metallic or bitter taste to a complete alteration of how foods taste. While often bothersome, it is generally reversible and typically resolves after the medication is discontinued. In some cases, the taste disturbance may contribute to nausea and appetite loss.

It is important to note that LIVTENCITY has a significantly lower rate of bone marrow suppression (neutropenia, thrombocytopenia) compared to ganciclovir and valganciclovir, and a significantly lower rate of kidney toxicity compared to foscarnet. In the SOLSTICE trial, treatment-emergent serious adverse events were less common in the maribavir group than in the conventional therapy group. This improved safety profile is a key advantage for transplant recipients who are already at risk from immunosuppressive therapy.

If you experience any side effects, including those not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. Reporting suspected side effects helps ensure ongoing monitoring of the medicine’s benefit-risk balance through your national pharmacovigilance authority.

How Should You Store LIVTENCITY?

Store LIVTENCITY at room temperature below 30°C (86°F), in its original container, out of the reach and sight of children. Do not use after the expiry date printed on the packaging.

Keep the tablets in the original high-density polyethylene (HDPE) bottle with the child-resistant cap securely closed to protect them from moisture. Do not transfer the tablets to a different container. Check the expiry date (marked “EXP” on the bottle and carton) before taking any tablets. The expiry date refers to the last day of the stated month.

Do not flush unused tablets down the toilet or discard them in household waste. Return any unused or expired medication to your pharmacy for safe disposal. Proper disposal of pharmaceuticals helps protect the environment from contamination.

Pack Sizes

LIVTENCITY 200 mg film-coated tablets are available in HDPE bottles containing 28, 56, or 112 (2 × 56) tablets. Not all pack sizes may be marketed in your country.

What Does LIVTENCITY Contain?

Each LIVTENCITY 200 mg tablet contains 200 mg of the active ingredient maribavir, along with inactive ingredients necessary for tablet manufacture. The tablets are blue, oval, convex, and debossed with “SHP” on one side and “620” on the other.

Active Ingredient

The active substance is maribavir. Each film-coated tablet contains 200 mg of maribavir. Maribavir is a benzimidazole riboside with the molecular formula C₁₅H₁₉Cl₂N₃O₃ and a molecular weight of 376.24 g/mol.

Inactive Ingredients (Excipients)

The other ingredients are:

• Tablet core: Microcrystalline cellulose (E460(i)), sodium starch glycolate, and magnesium stearate (E470b)
• Film coating: Polyvinyl alcohol (E1203), macrogol/polyethylene glycol (E1521), titanium dioxide (E171), talc (E553b), and brilliant blue FCF aluminium lake (E133)

These are standard pharmaceutical excipients used to ensure proper tablet formation, disintegration, and absorption. The blue colour of the tablets comes from the brilliant blue FCF aluminium lake dye in the film coating.

Sodium Content

This medicine contains less than 1 mmol (23 mg) sodium per tablet, which means it is essentially “sodium-free”. This is relevant for patients following a sodium-restricted diet.

Tablet Appearance

LIVTENCITY 200 mg tablets are blue, oval (elliptical), biconvex film-coated tablets debossed with “SHP” on one side and “620” on the other side. They are packaged in high-density polyethylene (HDPE) bottles with child-resistant closures.

How Does LIVTENCITY Work in the Body?

LIVTENCITY works by inhibiting the CMV UL97 protein kinase, a viral enzyme essential for multiple stages of the CMV replication cycle. This unique mechanism is distinct from all other available anti-CMV drugs and allows maribavir to be effective against CMV strains resistant to conventional therapies.

Cytomegalovirus encodes its own protein kinase, called pUL97, which plays a critical role in multiple steps of the viral life cycle. The UL97 kinase phosphorylates several viral and cellular substrates that are necessary for efficient viral DNA replication, for packaging (encapsidation) of the viral genome into newly formed capsids, and for the egress (exit) of mature capsids from the nucleus into the cytoplasm. Without functional UL97, the virus cannot complete its replication cycle and cannot produce new infectious particles.

Maribavir binds competitively to the ATP-binding site of the UL97 kinase, blocking its ability to phosphorylate its substrates. This results in a multi-pronged inhibition of CMV replication: viral DNA synthesis is impaired, newly replicated DNA cannot be properly packaged, and viral capsids become trapped within the nucleus. The net effect is a dramatic reduction in the production of mature, infectious CMV virions.

This mechanism is fundamentally different from that of existing anti-CMV drugs. Ganciclovir and valganciclovir work by inhibiting the viral DNA polymerase (pUL54) after being phosphorylated by UL97, while foscarnet directly inhibits the DNA polymerase, and cidofovir is a nucleotide analogue that also targets DNA polymerase. Because maribavir targets a different viral enzyme (UL97 kinase rather than UL54 polymerase), it can retain activity against CMV strains that have developed resistance mutations in the UL54 gene. This is a key advantage in the treatment of refractory CMV infection.

Pharmacokinetic Profile

After oral administration, maribavir is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations (C_max) are typically reached within 1 to 3 hours after dosing. The oral bioavailability is approximately 35–40%. Food does not significantly affect the overall exposure (AUC) to maribavir, so the tablets can be taken with or without food.

Maribavir is approximately 98% bound to plasma proteins. It is extensively metabolised in the liver, primarily by CYP3A4 and CYP1A2, to inactive metabolites. The terminal elimination half-life at steady state is approximately 4.3 hours, which is the basis for twice-daily dosing. Approximately 61% of an administered dose is excreted in the urine (primarily as metabolites) and 18% in the faeces. Less than 2% of the parent compound is excreted unchanged in the urine, indicating extensive hepatic metabolism.

Resistance

As with all antiviral agents, resistance to maribavir can develop during treatment. Resistance is most commonly associated with mutations in the UL97 gene (the drug’s target). The most frequently observed resistance mutations include T409M and H411Y. Compensatory mutations in the UL27 gene have also been reported. Your doctor will monitor your CMV viral load regularly, and if the virus is not responding adequately to treatment, resistance testing may be performed to guide further management.

Frequently Asked Questions About LIVTENCITY