TO, is present in human milk. It is not known whetherdolutegravir, a component of DOVATO, is present in human milk. When administered to
lactating rats, dolutegravir was present in milk (see Data). There is no information on the effectsof DOVATO or the components of DOVATO on the breastfed infant or the effects of the drugson milk production.
Because of the potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developingviral resistance (in HIV-positive infants), and (3) adverse reactions in a breastfed infant similarto those seen in adults, instruct mothers not to breastfeed if they are receiving DOVATO.
Data
Animal Data: Dolutegravir was the primary drug-related component excreted into the milk oflactating rats following a single oral dose of 50 mg/kg on Lactation Day 10, with milkconcentrations of up to approximately 1.3 times that of maternal plasma concentrations observed
8 hours postdose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Perform pregnancy testing in individuals of childbearing potential before initiation of DOVATO.
Contraception
Individuals of childbearing potential should avoid use of DOVATO at the time of conceptionthrough the first trimester of pregnancy because of the potential risk of neural tube defects [seeUse in Specific Populations (8.1)].
Advise individuals of childbearing potential who are taking DOVATO to consistently useeffective contraception.
8.4 Pediatric Use
The safety and efficacy of DOVATO have not been established in pediatric patients.
8.5 Geriatric Use
Clinical trials of DOVATO did not include sufficient numbers of subjects aged 65 and over todetermine whether they respond differently from younger subjects. In general, caution should beexercised in the administration of DOVATO in elderly patients reflecting the greater frequencyof decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy[see Clinical Pharmacology (12.3)].
8.6 Renal Impairment
DOVATO is not recommended for patients with creatinine clearance <50 mL/min becauseDOVATO is a fixed-dose combination and the dosage of the individual components cannot beadjusted. If a dose reduction of lamivudine, a component of DOVATO, is required for patientswith creatinine clearance <50 mL/min, then the individual components should be used.
8.7 Hepatic Impairment
No dosage adjustment of DOVATO is necessary in patients with mild or moderate hepaticimpairment (Child-Pugh Score A or B). Dolutegravir has not been studied in patients with severehepatic impairment (Child-Pugh Score C); therefore, DOVATO is not recommended for patientswith severe hepatic impairment.
10 OVERDOSAGE
There is no known specific treatment for overdose with DOVATO. If overdose occurs, thepatient should be monitored and standard supportive treatment applied as required.
Dolutegravir
As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantlyremoved by dialysis.
Lamivudine
Because a negligible amount of lamivudine was removed via (4-hour) hemodialysis, continuousambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuoushemodialysis would provide clinical benefit in a lamivudine overdose event.
11 DESCRIPTION
DOVATO is a fixed-dose combination tablet containing dolutegravir (as dolutegravir sodium),an INSTI, and lamivudine (also known as |
