Livtencity
(maribavir)Dosage & Administration
400 mg (two 200 mg tablets) orally twice daily with or without food.
By using PrescriberAI, you agree to the AI Terms of Use.
Livtencity Prescribing Information
LIVTENCITY is indicated for the treatment of adults and pediatric patients (12 years of age and older and weighing at least 35 kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet [see Use in Specific Populations (8.4) and Clinical Studies (14)].
Recommended Dosage
The recommended dosage in adults and pediatric patients (12 years of age and older and weighing at least 35 kg) is 400 mg (two 200 mg tablets) taken orally twice daily with or without food [see Use in Specific Populations (8.4), Clinical Pharmacology (12.3) and Clinical Studies (14)].
Dosage Adjustment When Coadministered with Anticonvulsants
If LIVTENCITY is coadministered with carbamazepine, increase the dosage of LIVTENCITY to 800 mg (four 200 mg tablets) twice daily [see Drug Interactions (7.3)].
If LIVTENCITY is coadministered with phenytoin or phenobarbital, increase the dosage of LIVTENCITY to 1,200 mg (six 200 mg tablets) twice daily [see Drug Interactions (7.3)].
Administration
The immediate-release tablets can be taken as whole, dispersed or crushed tablets by mouth, or as dispersed tablets through a nasogastric or orogastric tube (French size 10 or larger). The suspension may be prepared ahead of time and stored at room temperature for up to 8 hours.
Administration of Dispersed Tablets 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 (other liquids have not been tested) to make a suspension (see Table 1 below).
Table 1: Number of Tablets and Volume of Drinking Water Needed to Make a Suspension for Administration of Dispersed or Crushed Tablets by Mouth Recommended Dosage Number of 200 mg Tablets Volume of Drinking Water 400 mg Two 30 mL 800 mg Four 60 mL 1,200 mg Six 90 mL - Swirl the container gently to keep the particles from settling, and administer the suspension before it settles. The mixture will have a bitter taste.
- Rinse the container with 15 mL of drinking water and administer the rinse water.
- Repeat Step 3. Visually confirm that no particles are left in the container. If particles remain, repeat Step 3.
Administration of Dispersed Tablets through a Nasogastric (NG) or Orogastric (OG) Tube
- Remove the cap (if applicable) and plunger out of a 50 or 60 mL catheter-tip compatible syringe or equivalent. Add two tablets into the syringe body and place the plunger back in the syringe. Only two tablets can be administered via NG or OG tube at a time.
- Draw 30 mL of drinking water (other liquids have not been tested) into the syringe and hold the syringe with the tip pointing upward. Pull the plunger further to a higher volume position to have some air space in the syringe. Place the cap back on the syringe (if applicable). Shake the syringe well (careful not to spill the contents) 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 Step 4 and make sure no particles are left in the syringe by visual inspection. If particles remain, repeat Step 4.
- For doses of 800 mg (four 200 mg tablets) and 1,200 mg (six 200 mg tablets) [see Dosage and Administration (2.2)], repeat Steps 1-5 until prescribed dose is reached. The same syringe, NG or OG tube can be used.
Tablet: 200 mg, blue, oval shaped convex tablet debossed with "SHP" on one side and "620" on the other side.
Pregnancy
Risk Summary
No adequate human data are available to establish whether LIVTENCITY poses a risk to pregnancy outcomes. In animal reproduction studies, embryo-fetal survival was decreased in rats, but not in rabbits, at maribavir exposures less than those observed in humans at the recommended human dose (RHD) (see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
In a combined fertility and embryofetal development study, maribavir was administered to male and female rats at oral doses of 100, 200, or 400 mg/kg/day. Females were dosed for 15 consecutive days prior to pairing, throughout pairing, and up to gestation day (GD) 17, while males were dosed 29 days prior to mating and throughout mating. A decrease in the number of viable fetuses and increase in early resorptions and post-implantation losses were observed at ≥100 mg/kg/day (at exposures approximately half the human exposure at the RHD). Intermittent reduced body weight gain was observed in pregnant animals at ≥200 mg/kg/day. Maribavir had no effect on embryo-fetal growth or development at dose levels up to 400 mg/kg/day, at exposures similar to those observed in humans at the RHD.
No significant toxicological effects on embryo-fetal growth or development were observed in rabbits when maribavir was administered at oral doses up to 100 mg/kg/day from GD 8 to 20, at exposures approximately half the human exposure at the RHD.
In the pre-and post-natal developmental toxicity study, maribavir was administered to pregnant rats at oral doses of 50, 150, or 400 mg/kg/day from GD 7 to post-natal day (PND) 21. A delay in developmental milestones was observed, including pinna detachment at doses ≥150 mg/kg/day and eye opening and preputial separation associated with reduced bodyweight gain of the offspring at 400 mg/kg/day. In addition, decreased fetal survival and litter loss was observed due to maternal toxicity and poor maternal care, respectively, at doses ≥150 mg/kg/day. No effects were observed at 50 mg/kg/day (which is estimated to be less than the human exposure at the RHD). No effects on number of offspring, proportion of males, number of live pups, or survival to PND 4 were observed at any dose in the offspring born to the second generation.
Lactation
Risk Summary
It is not known whether maribavir or its metabolites are present in human or animal milk, affect milk production, or have effects on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LIVTENCITY and any potential adverse effects to the breast-fed child.
Pediatric Use
The recommended dosing regimen in pediatric patients 12 years of age and older and weighing at least 35 kg is the same as that in adults. Use of LIVTENCITY in this age group is based on the following:
- Evidence from controlled studies of LIVTENCITY in adults
- Population pharmacokinetic (PK) modeling and simulation demonstrating that age and body weight had no clinically meaningful effect on plasma exposures of LIVTENCITY
- LIVTENCITY exposure is expected to be similar between adults and children 12 years of age and older and weighing at least 35 kg
- The course of the disease is similar between adults and pediatric patients to allow extrapolation of data in adults to pediatric patients [see Dosage and Administration (2.2), Clinical Pharmacology (12.3) and Clinical Studies (14)]
The safety and effectiveness of LIVTENCITY have not been established in children younger than 12 years of age.
Geriatric Use
No dosage adjustment is required for patients over 65 years of age based on the results from population pharmacokinetics analysis [see Clinical Pharmacology (12.3)] and efficacy and safety data from the clinical studies. In the clinical Study 303, 54 patients aged 65 years and over were treated with LIVTENCITY. Safety, effectiveness, and pharmacokinetics were consistent between elderly patients (≥65 years) and younger patients (<65 years).
Impaired Renal Function
No dose adjustment of LIVTENCITY is needed for patients with mild, moderate, or severe renal impairment [see Clinical Pharmacology (12.3)]. Administration of LIVTENCITY in patients with end stage renal disease (ESRD), including patients on dialysis, has not been studied.
Impaired Hepatic Function
No dose adjustment of LIVTENCITY is needed for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment [see Clinical Pharmacology (12.3)]. Administration of LIVTENCITY in patients with severe hepatic impairment has not been studied.
None.
Risk of Reduced Antiviral Activity When Coadministered with Ganciclovir and Valganciclovir
LIVTENCITY may antagonize the antiviral activity of ganciclovir and valganciclovir by inhibiting human CMV pUL97 kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir. Coadministration of LIVTENCITY with ganciclovir or valganciclovir is not recommended [see Drug Interactions (7.1) and Microbiology (12.4)].
Virologic Failure During Treatment and Relapse Post-Treatment
Virologic failure due to resistance can occur during and after treatment with LIVTENCITY. Virologic relapse during the post-treatment period usually occurred within 4-8 weeks after treatment discontinuation. Some maribavir pUL97 resistance-associated substitutions confer cross-resistance to ganciclovir and valganciclovir. Monitor CMV DNA levels and check for maribavir resistance if the patient is not responding to treatment or relapses [see Microbiology (12.4) and Clinical Studies (14.1)].
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
The concomitant use of LIVTENCITY and certain drugs may result in potentially significant drug interactions, some of which may lead to reduced therapeutic effect of LIVTENCITY or adverse reactions of concomitant drugs [see Drug Interactions (7)].
See Table 4 for steps to prevent or manage these possible or known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during LIVTENCITY therapy; review concomitant medications during LIVTENCITY therapy and monitor for adverse reactions.
Maribavir is primarily metabolized by CYP3A4. Drugs that are strong inducers of CYP3A4 are expected to decrease maribavir plasma concentrations and may result in reduced virologic response; therefore, coadministration of LIVTENCITY with these drugs is not recommended, except for selected anticonvulsants [see Dosage and Administration (2.2) and Drug Interactions (7.3)].
Use with Immunosuppressant Drugs
LIVTENCITY has the potential to increase the drug concentrations of immunosuppressant drugs that are CYP3A4 and/or P-glycoprotein (P-gp) substrates where minimal concentration changes may lead to serious adverse events (including tacrolimus, cyclosporine, sirolimus and everolimus). Frequently monitor immunosuppressant drug levels throughout treatment with LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY and adjust the immunosuppressant dose, as needed [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].