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VIEKIRA XR(dasabuvir, ombitasvir, paritaprevir, and ritonavir)extended-release tablets(十四)
orphine
↑ norbuprenorphine
(metabolite of
buprenorphine) Patients should be closely monitored for sedation and cognitive effects.
PROTON PUMP INHIBITORS
omeprazole ↓ omeprazole Monitor patients for decreased efficacy of omeprazole. Consider increasing the omeprazole dose in patients whose symptoms are not well controlled; avoid use of more than 40 mg per day of omeprazole.
SEDATIVES/HYPNOTICS
alprazolam ↑ alprazolam Contraindicated Sedatives/Hypnotics [see Contraindications (4)].
Alprazolam:
Clinical monitoring of patients is recommended. A decrease in alprazolam dose can be considered based on clinical response.
diazepam ↓ diazepam
↓ nordiazepam
(metabolite of
diazepam) Increase dose if clinically indicated.
See Clinical Pharmacology, Tables 7 and 8.
The direction of the arrow indicates the direction of the change in exposures (Cmax and AUC) (↑ = increase of more than 20%, ↓ = decrease of more than 20%, ↔ = no change or change less than 20%).
*not studied.
7.4 Drugs without Clinically Significant Interactions with VIEKIRA XR
No dosage adjustments are recommended when VIEKIRA XR is co-administered with the following medications: abacavir, dolutegravir, digoxin, duloxetine, emtricitabine/tenofovir disoproxil fumarate, escitalopram, lamivudine, methadone, progestin only contraceptives, raltegravir, sofosbuvir, sulfamethoxazole, trimethoprim, warfarin and zolpidem.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
If VIEKIRA XR is administered with ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant. Refer to the ribavirin prescribing information for more information on use in pregnancy.
No adequate human data are available to establish whether or not VIEKIRA XR poses a risk to pregnancy outcomes. In animal reproduction studies, no adverse developmental effects were observed when the components of VIEKIRA XR were administered separately during organogenesis and lactation. During organogenesis, the exposures were up to 28 and 4 times (mice and rabbits, respectively; ombitasvir), 8 and 98 times (mice and rats, respectively; paritaprevir, ritonavir), and 24 and 6 times (rats and rabbits, respectively; dasabuvir) exposures at the recommended clinical dose of VIEKIRA XR. In rodent pre/postnatal developmental studies, maternal systemic exposures (AUC) to ombitasvir, paritaprevir and dasabuvir were approximately 25, 17 and 44 times, respectively, the exposure in humans at the recommended clinical dose [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% to 4% and 15% to 20%, respectively.
Data
Animal data
Dasabuvir
Dasabuvir was administered orally to pregnant rats (0, 60, 300 and 800 mg/kg/day) and rabbits (0, 100, 200 or 400 mg/kg/day) during the period of organogenesis (on GD 6 to 17 and GD 7 to 20, respectively). There were no test article-related embryofetal effects (malformations or fetal toxicity) at any dose level in either species. The highest systemic exposure of dasabuvir was 24-times higher (rats) and 6-times higher (rabbits) than the exposures in humans at the recommended cl |
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