tegravir
Dabigatran etexilate/ Rilpivirine
Dolutegravir ↔
(Not studied)
Rilpivirine ↔
Not studied. Dabigatran etexilate ↑
A risk for increases in dabigatran plasma concentrations cannot be excluded
(inhibition of intestinal P-gp).
The combination of Juluca and dabigatran etexilate should be used with caution.
HMG CO-A reductase inhibitors
Atorvastatin/ Dolutegravir
Atorvastatin/ Rilpivirine1,2
Dolutegravir ↔
(Not studied)
Rilpivirine
AUC ↔
Cmin ↔
Cmax ↓ 9%
Atorvastatin
AUC ↔
Cmin ↓ 15%
Cmax ↑ 35%
No dose adjustment is required.
Phosphodiesterase type 5 (PDE-5) inhibitors
Sildenafil / Dolutegravir
Sildenafil/ Rilpivirine1,2
Dolutegravir ↔
Rilpivirine
AUC ↔
Cmin ↔
Cmax ↔
Sildenafil
AUC ↔
Cmin NA
Cmax ↔
No dose adjustment is required.
Vardenafil
Tadalafil/ Dolutegravir
Vardenafil
Tadalafil/ Rilpivirine
Dolutegravir ↔
(Not studied)
Rilpivirine ↔
(Not studied)
No dose adjustment is required.
1 The interaction between dolutegravir and/or rilpivirine and the medicinal product was eva luated in a clinical study. All other drug-drug interactions shown are predicted.
2 This interaction study has been performed with a dose higher than the recommended dose for rilpivirine assessing the maximal effect on the co-administered drug.
NA = Not applicable
QT prolonging medicinal products
There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and medicinal products that prolong the QTc interval of the ECG. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the ECG (see section 5.1). Juluca should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
Women of childbearing potential (WOCBP) should undergo pregnancy testing before initiation of Juluca. WOCBP who are taking Juluca should use effective contraception throughout treatment.
Pregnancy
There are limited data from the use of rilpivirine in pregnant women. Preliminary data from a surveillance study has suggested an increased incidence of neural tube defects (0.9%) in mothers exposed to dolutegravir at the time of conception compared with mothers exposed to non-dolutegravir containing regimens (0.1%).
The incidence of neural tube defects in the general population ranges from 0.5-1 case per 1,000 live births (0.05-0.1%). As neural tube defects occur within the first 4 weeks of foetal development (at which time the neural tubes are sealed) this potential risk would concern women exposed to dolutegravir at the time of conception and in early pregnancy. Due to the potential risk of neural tube defects, dolutegravir should not be used during the first trimester unless there is no alternative.
More than 1000 outcomes from second and third trimester exposure to dolutegravir in pregnant women indicate no evidence of increased risk of malformative and foeto/neonatal negative effects. However, as the mechanism by which dolutegravir may interfere in human pregnancy is unknown, the safety in use during the second and third trimester cannot be confirmed.
In animal reproductive toxicology studies with dolutegravir, no ad |
