Livtencity (maribavir)

No dosing information is available for this tab.

Maribavir is administered orally as tablets without regard to meals. If necessary, tablets may be dispersed or crushed and then swallowed or administered via a nasogastric (NG) or orogastric (OG) tube.

In order to administer dispersed or crushed tablets by mouth, place the appropriate number of tablets for the prescribed dose into a suitable container. If desired, the tablets may be crushed. Add the appropriate volume of drinking water to make a suspension (see Table 1).

Table 1. Number of Tablets and Volume of Drinking Water Needed to Make a Suspension for Administration of Dispersed or Crushed Maribavir Tablets by Mouth.

Recommended Dosage (mg) Number of 200 mg Tablets Volume of Drinking Water (mL) 400 Two 30 800 Four 60 1200 Six 90

Swirl the container gently to keep the particles from settling, and administer the suspension, which has a bitter taste, before it settles. Rinse the container with 15 mL of drinking water, administer the rinse water, and repeat as necessary until no particles are left in the container.

For administration through a NG or OG tube (French size 10 or larger): initially, remove the cap (if applicable) and plunger out of a 50 or 60 mL catheter tip compatible syringe or equivalent. Add 2 tablets into the syringe body and place the plunger back in the syringe; only 2 tablets can be administered via NG or OG tube at a time. Draw 30 mL of drinking water into the syringe and hold the syringe with the tip pointing upward. Pull the plunger further to a higher volume position to allow for some air space in the syringe. Place the cap back on the syringe (if applicable). Shake the syringe well for about 30 to 45 seconds or until the tablets are completely dispersed. Once the tablets are completely dispersed in the syringe, remove the cap from the syringe again (if applicable) and attach the syringe to the NG or OG tube and administer the dispersion before it settles. Draw 15 mL of water using the same syringe and flush through the same NG or OG tube. Repeat the prior step until no particles are left in the syringe by visual inspection. For doses of 800 mg (four 200 mg tablets) and 1,200 mg (six 200 mg tablets), repeat process until prescribed dose is reached. The same syringe, NG, or OG tube can be used.

Store maribavir tablets at 20-25degreesC (excursions permitted between 15-30degreesC). The maribavir suspension may be prepared ahead of time and stored at room temperature for up to 8 hours.

No dosing information is available for this tab.

Maribavir is metabolized primarily by cytochrome P-450 (CYP) isoenzyme 3A4, and to lesser extent, by CYP isoenzyme 1A2. In vitro, maribavir is not a substrate of CYP isoenzymes 2B6, 2C8, 2C9, 2C19, 3A5; uridine diphosphate-glucuronosyltransferase (UGT) 1A4, 1A6, 1A10, 2B15; organic anion transporting polypeptide (OATP) 1B1, 1B3; or bile salt export pump (BSEP).

In vitro studies indicate that maribavir is an inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Weak Cyp3a4 Inhibitors/Ubrogepant (> 50 Mg)

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of ubrogepant.(1)

CLINICAL EFFECTS: Concurrent use of ubrogepant with weak CYP3A4 inhibitors may result in an increase in exposure of ubrogepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when used concomitantly with weak CYP3A4 inhibitors. Initial dose of ubrogepant should not exceed 50 mg when used concomitantly with weak inhibitors of CYP3A4. A second dose may be given within 24 hours but should not exceed 50 mg when used concurrently with weak CYP3A4 inhibitors.(1) For patients on avapritinib: this interaction applies only to gastrointestinal stromal tumor (GIST) patients on avapritinib 200 mg or 300 mg.(2)

DISCUSSION: Coadministration of ubrogepant with verapamil, a moderate CYP3A4 inhibitor, resulted in a 3.5-fold and 2.8-fold increase in area-under-curve (AUC) and concentration maximum (Cmax), respectively. No dedicated drug interaction study was conducted to assess concomitant use with weak CYP3A4 inhibitors. The conservative prediction of the maximal potential increase in ubrogepant exposure with weak CYP3A4 inhibitors is not expected to be more than 2-fold.(1) Weak inhibitors of CYP3A4 include: amiodarone, amlodipine, anamorelin, asciminib, avapritinib, azithromycin, Baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, camizestrant, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, delavirdine, deutivacaftor, dihydroberberine, diosmin, elinzanetant, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, maribavir, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, pirtobrutinib, propiverine, propofol, ranitidine, ranolazine, resveratrol, roxithromycin, rucaparib, simeprevir, sitaxsentan, skullcap, teriflunomide, ticagrelor, tolvaptan, trofinetide, vepdegestrant, viloxazine, vonoprazan, and ziftomenib. (3,4)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Maribavir/Ganciclovir; Valganciclovir

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Maribavir may inhibit pUL97 protein kinase which catalyzes the phosphorylation step required for activation of ganciclovir or valganciclovir.(1)

CLINICAL EFFECTS: Concurrent administration of maribavir with ganciclovir or valganciclovir may antagonize the antiviral activity of ganciclovir or valganciclovir, resulting in decreased clinical efficacy and/or virological failure of ganciclovir and valganciclovir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of maribavir states that the concurrent use of maribavir with ganciclovir or valganciclovir is not recommended.(1)

DISCUSSION: Ganciclovir and valganciclovir require activation via phosphorylation to the active form by human CMV pUL97 protein kinase.(2,3) The antiviral activity of maribavir is mediated by competitive inhibition of the protein kinase activity of pUL97 and may antagonize the antiviral activity of ganciclovir or valganciclovir.(1) In the setting of combination therapy, in vitro data suggests antagonistic activity when maribavir is coadministered with ganciclovir or valganciclovir.(4-7)

Maribavir/Selected Anticonvulsants

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Selected anticonvulsants that are strong inducers of CYP3A4 may accelerate the metabolism of maribavir.(1)

CLINICAL EFFECTS: The concurrent administration of selected anticonvulsants may result in decreased levels and effectiveness of maribavir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of maribavir states that concurrent use with selected anticonvulsants requires a dose adjustment of maribavir. If maribavir is coadministered with carbamazepine, increase the maribavir dose to 800 mg twice daily. If maribavir is coadministered with fosphenytoin, phenobarbital, phenytoin, or primidone, increase the maribavir dose to 1200 mg twice daily.(1) If concurrent use is necessary, closely monitor for treatment response.(1)

DISCUSSION: In vitro data shows that maribavir is metabolized by CYP3A4. A study in 200 subjects with concurrent maribavir 800 mg twice daily or 400 mg twice daily and carbamazepine 600 mg daily resulted in an increase in maribavir area-under-curve (AUC) and maximum concentration (Cmax) by 40% and 53%, respectively.(1) A study in 200 subjects with concurrent maribavir 1200 mg twice daily or 400 mg twice daily and phenobarbital 100 mg daily resulted in an increase in maribavir AUC and Cmax by 80% and 117%, respectively.(1) A study in 200 subjects with concurrent maribavir 1200 mg twice daily or 400 mg twice daily and phenytoin 300 mg daily resulted in an increase in maribavir AUC and Cmax by 70% and 205%, respectively.(1) Selected anticonvulsants linked include: barbiturates, carbamazepine, fosphenytoin, phenobarbital, phenytoin, and primidone.(2-3)

Maribavir/Selected Strong Cyp3a4 Inducers

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Strong inducers of CYP3A4 may accelerate the metabolism of maribavir.(1)

CLINICAL EFFECTS: The concurrent administration of a strong CYP3A4 inducer may result in decreased levels and effectiveness of maribavir.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The manufacturer of maribavir states that concurrent use with strong CYP3A4 inducers is not recommended. If concurrent use is necessary, closely monitor for treatment response.(1)

DISCUSSION: In vitro data shows that maribavir is metabolized by CYP3A4. A study in 14 subjects with concurrent maribavir 400 mg twice daily and rifampin 600 mg daily resulted in a decrease in maribavir area-under-curve (AUC) and maximum concentration (Cmax) by 60% and 39%, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, encorafenib, enzalutamide, ivosidenib, lumacaftor, mitotane, rifampin, rifapentine, and St. John's wort.(2-3)

Weak Cyp3a4 Inhibitors/Lomitapide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of lomitapide.(1) Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Thus even weak CYP3A4 inhibitors may affect lomitapide exposure (AUC, area-under-curve).

CLINICAL EFFECTS: Concurrent use of a weak inhibitor of CYP3A4 may result in 2-fold increases in lomitapide levels and toxicity from lomitapide.(1)

PREDISPOSING FACTORS: This interaction may be more severe in patients with hepatic impairment or with end-stage renal disease.(1)

PATIENT MANAGEMENT: When initiating lomitapide in patients taking a stable dose of a weak CYP3A4 inhibitor, follow the recommended dose and titration schedule per labeling. When initiating a weak CYP3A4 inhibitor in patients taking lomitapide, decrease the dose of lomitapide by 50%. The maximum recommended lomitapide dose with concurrent weak CYP3A4 inhibitors should be: -Adults (age 18 years and older): 30 mg daily, -Age group 11 to 17 years: 20 mg daily, -Age group 2 to 10 years: 10 mg daily. Due to lomitapide's long half-life, it may take 1 to 2 weeks to see the full effect of this interaction.(1) For patients on avapritinib: this interaction applies only to gastrointestinal stromal tumor (GIST) patients on avapritinib 200 mg or 300 mg.(2)

DISCUSSION: Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Based upon interactions with stronger inhibitors, weak inhibitors of CYP3A4 are predicted to increase lomitapide area-under-curve(AUC) 2-fold.(1) Weak CYP3A4 inhibitors linked to this interaction include: amiodarone, amlodipine, anamorelin, asciminib, atorvastatin, avapritinib, azithromycin, Baikal skullcap, belumosudil, bicalutamide, blueberry juice, brodalumab, camizestrant, cannabidiol, capivasertib, cilostazol, cimetidine, ciprofloxacin, chlorzoxazone, clotrimazole, cranberry juice, cyclosporine, daridorexant, delavirdine, diosmin, elinzanetant, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lurasidone, maribavir, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, resveratrol, roxithromycin, rucaparib, selpercatinib, sevabertinib, sitaxsentan, skullcap, teriflunomide, ticagrelor, tolvaptan, trofinetide, vepdegestrant, viloxazine, vonoprazan, ziftomenib, and zileuton.(1-3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Maribavir/Rifabutin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Rifabutin, a moderate CYP3A4 inducer, may accelerate the metabolism of maribavir.(1)

CLINICAL EFFECTS: The concurrent administration of rifabutin may result in decreased levels and effectiveness of maribavir.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The manufacturer of maribavir states that concurrent use with rifabutin requires a dose adjustment of maribavir. Increase the dosage of maribavir to 800 mg (four 200 mg tablets) twice daily.(1) If concurrent use is necessary, closely monitor for treatment response.(1)

DISCUSSION: Maribavir is metabolized by CYP3A4. A PBPK model predicted that the area-under-curve (AUC) and maximum concentration (Cmax) of maribavir was comparable when maribavir 800 mg twice daily was coadministered with rifabutin 300 mg daily versus maribavir 400 mg twice daily given alone (AUC ratio 1.38, Cmax ratio 1.52).(1)

Maribavir/Selected Immunosuppressants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The metabolism of cyclosporine, everolimus, sirolimus, tacrolimus and temsirolimus by CYP3A4 may be inhibited by maribavir.

CLINICAL EFFECTS: Concurrent administration of maribavir may result in elevated levels of and toxicity from cyclosporine, everolimus, sirolimus, tacrolimus or temsirolimus.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Cyclosporine, everolimus, sirolimus, tacrolimus or temsirolimus levels and renal function should be monitored frequently during therapy with maribavir. Monitor immunosuppressant levels closely during initiation and after discontinuation of maribavir. The dosage of cyclosporine, everolimus, sirolimus, tacrolimus or temsirolimus may need to be adjusted.

DISCUSSION: In a study in 20 patients, maribavir increased the area-under-curve (AUC), concentration maximum (Cmax), and Ctau of tacrolimus by 51%, 38%, and 57%, respectively. In a multiple-dose study, concomitant administration of ketoconazole with sirolimus oral solution increased the sirolimus Cmax, time to Cmax (Tmax), and AUC by 4.3-fold, 38%, and 10.9-fold, respectively. Single-dose sirolimus did not affect steady-state 12-hour plasma ketoconazole concentrations. In a study in 6 patients, ketoconazole was successfully used to augment sirolimus levels. Patients were able to receive one-eight to one-fourth (0.25 - 0.50 mg daily) of the usual sirolimus dose while taking 100 to 200 mg of ketoconazole daily. Concurrent administration of ketoconazole had no effects on temsirolimus AUC or Cmax; however, sirolimus AUC and Cmax increased 3.1-fold and 2.2-fold, respectively. Dosage adjustment of temsirolimus to 12.5 mg/week in the presence of strong CYP3A4 inhibitors is expected to adjust levels to the range observed without inhibitors; however, there are no data available with this dose adjustment.

P-Glycoprotein (P-Gp) Inhibitors/Digoxin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: P-glycoprotein (P-gp) inhibitors may inhibit cellular efflux of digoxin at the levels of intestinal absorption, renal tubular secretion, and biliary-intestinal secretion.(1)

CLINICAL EFFECTS: Concurrent administration of a P-gp inhibitor may result in elevated levels and toxicities of digoxin.(1) Symptoms of digoxin toxicity can include anorexia, nausea, vomiting, headache, fatigue, malaise, drowsiness, generalized muscle weakness, disorientation, hallucinations, visual disturbances, and arrhythmias.

PREDISPOSING FACTORS: Low body weight, advanced age, impaired renal function, hypokalemia, hypercalcemia, and/or hypomagnesemia may increase the risk of digoxin toxicity.

PATIENT MANAGEMENT: Monitor digoxin concentrations before initiating concomitant use with P-gp inhibitors and continue monitoring serum digoxin concentrations as recommended in the prescribing information for digoxin.(1) When digoxin levels are expected to be increased by over 50%, the manufacturer of digoxin recommends decreasing the dose of digoxin by approximately 30-50% or by modifying the dosing frequency to reduce digoxin concentrations.(1) When digoxin levels are expected to be increased by less than 50%, the manufacturer of digoxin recommends decreasing the dose of digoxin by approximately 15-30% or by modifying the dosing frequency to reduce digoxin concentrations.(1) For patients on daraxonrasib, the manufacturer of daraxonrasib states that it should be taken at least 4 hours apart from P-gp substrates.(2)

DISCUSSION: Digoxin is a known substrate of P-gp. Inhibitors of P-gp may increase toxicity of digoxin.(1) In a clinical study, elacestrant increased the area-under-curve (AUC) and maximum concentration (Cmax) of digoxin by 1.1-fold and 1.3-fold, respectively.(3,4) In another clinical study, imlunestrant increased the area-under-curve (AUC) and maximum concentration (Cmax) of digoxin by 1.4-fold and 1.6-fold, respectively.(5) In another clinical study, maribavir increased the AUC and Cmax of digoxin by 1.2-fold and 1.25-fold, respectively.(6) Inhibitors of P-gp linked to this monograph include: abrocitinib, aumolertinib, capmatinib, daraxonrasib, elacestrant, enzalutamide, imlunestrant, maribavir, selpercatinib, sparsentan, sotorasib, vepdegestrant, and vibegron.(2-8)

Weak Cyp3a4 Inhibitors/Ubrogepant (<= 50 Mg)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of ubrogepant.(1)

CLINICAL EFFECTS: Concurrent use of ubrogepant with weak CYP3A4 inhibitors may result in an increase in exposure of ubrogepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when used concomitantly with weak CYP3A4 inhibitors. Initial dose of ubrogepant should not exceed 50 mg when used concomitantly with weak inhibitors of CYP3A4. A second dose may be given within 24 hours but should not exceed 50 mg when used concurrently with weak CYP3A4 inhibitors.(1) For patients on avapritinib: this interaction applies only to gastrointestinal stromal tumor (GIST) patients on avapritinib 200 mg or 300 mg.(2)

DISCUSSION: Coadministration of ubrogepant with verapamil, a moderate CYP3A4 inhibitor, resulted in a 3.5-fold and 2.8-fold increase in area-under-curve (AUC) and concentration maximum (Cmax), respectively. No dedicated drug interaction study was conducted to assess concomitant use with weak CYP3A4 inhibitors. The conservative prediction of the maximal potential increase in ubrogepant exposure with weak CYP3A4 inhibitors is not expected to be more than 2-fold.(1) Weak inhibitors of CYP3A4 include: amiodarone, amlodipine, anamorelin, asciminib, avapritinib, azithromycin, Baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, camizestrant, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, delavirdine, deutivacaftor, dihydroberberine, diosmin, elinzanetant, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, maribavir, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, pirtobrutinib, propiverine, propofol, ranitidine, ranolazine, resveratrol, roxithromycin, simeprevir, sitaxsentan, skullcap, teriflunomide, ticagrelor, tolvaptan, trofinetide, vepdegestrant, viloxazine, vonoprazan, and ziftomenib.(3,4)

*The manufacturer states that there are no known contraindications to the use of maribavir.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

Adverse reactions reported in >=10% of patients receiving maribavir include taste disturbance, nausea, diarrhea, vomiting, and fatigue.

Less Frequent

• Anemia
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Neutropenic disorder

More Frequent

• Diarrhea
• Dysgeusia
• Fatigue
• Nausea
• Vomiting

No enhanced messaging available.

Safety and efficacy of maribavir have not been established in pediatric patients <12 years of age. Pharmacokinetics have not been evaluated in patients <18 years of age.

Use of maribavir for the treatment of CMV disease in pediatric transplant recipients is based on pharmacokinetic modeling and simulation, and further supported by extrapolated data from studies in adults.

Course of the disease and exposure of maribavir in pediatric patients are expected to be similar to those observed in adults.

There are no adequate and well-controlled studies in pregnant women to inform a drug-associated risk of adverse developmental outcomes with maribavir.

In animal studies, embryofetal toxicity (e.g., increased resorptions, post-implantation loss) was observed in rats receiving maribavir in dosages resulting in exposures less than the systemic exposures achieved in humans at the recommended human dose.

It is not known whether maribavir is distributed into human milk, affects milk production, or has any effects on breast-fed infants.

Consider the benefits of breast-feeding and the importance of maribavir to the woman along with any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

No dosage adjustment is necessary in patients >65 years of age.

In the principal efficacy trial, 23% of patients who received maribavir were >=65 years of age. No overall differences in safety and efficacy were observed between these geriatric patients and younger adults.