(25 mg once daily)
 Rilpivirine

↔ Cmax 1.05 (0.97, 1.15)

↔ AUC 1.06 (1.02, 1.09)

↔ Cmin 0.99 (0.94, 1.04)

Sofosbuvir

↑ Cmax 1.21 (0.90, 1.62)

↔ AUC 1.09 (0.94, 1.27)

Cmin (NA)

GS-331007

↔ Cmax 1.06 (0.99, 1.14)

↔ AUC 1.01 (0.97, 1.04)

Cmin (NA)
 No dose adjustment of sofosbuvir or rilpivirine is required when sofosbuvir and rilpivirine are used concomitantly.
 
HIV ANTIVIRAL AGENTS: HIV PROTEASE INHIBITORS
 
Darunavir boosted with ritonavirf

(800/100 mg once daily)
 Darunavir

↔ Cmax 0.97 (0.94, 1.01)

↔ AUC 0.97 (0.94, 1.00)

↔ Cmin 0.86 (0.78, 0.96)

Sofosbuvir

↑ Cmax 1.45 (1.10, 1.92)

↑ AUC 1.34 (1.12, 1.59)

Cmin (NA)

GS-331007

↔ Cmax 0.97 (0.90, 1.05)

↔ AUC 1.24 (1.18, 1.30)

Cmin (NA)
 No dose adjustment of sofosbuvir or darunavir (ritonavir boosted) is required when sofosbuvir and darunavir are used concomitantly.
 
HIV ANTIVIRAL AGENTS: INTEGRASE INHIBITORS
 
Raltegravirf

(400 mg once daily)
 Raltegravir

↓ Cmax 0.57 (0.44, 0.75)

↓ AUC 0.73 (0.59, 0.91)

↔ Cmin 0.95 (0.81, 1.12)

Sofosbuvir

↔ Cmax 0.87 (0.71, 1.08)

↔ AUC 0.95 (0.82, 1.09)

Cmin (NA)

GS-331007

↔ Cmax 1.09 (0.99, 1.20)

↔ AUC 1.03 (0.97, 1.08)

Cmin (NA)
 No dose adjustment of sofosbuvir or raltegravir is required when sofosbuvir and raltegravir are used concomitantly.
 
ORAL CONTRACEPTIVES
 
Norgestimate/ethinyl estradiol
 Norgestromin

↔ Cmax 1.06 (0.93, 1.22)

↔ AUC 1.05 (0.92, 1.20)

Cmin (NA)

Norgestrel

↔ Cmax 1.18 (0.99, 1.41)

↔ AUC 1.19 (0.98, 1.44)

Cmin (NA)

Ethinyl estradiol

↔ Cmax 1.14 (0.96, 1.36)

↔ AUC 1.08 (0.93, 1.25)

Cmin (NA)
 No dose adjustment of norgestimate/ethinyl estradiol is required when sofosbuvir and norgestimate/ethinyl estradiol are used concomitantly.

NA = not available/not applicable

a. Mean ratio (90% CI) of co-administered drug pharmacokinetics with/without sofosbuvir and mean ratio of sofosbuvir and GS-331007 with/without co-administered drug. No effect = 1.00

b. All interaction studies conducted in healthy volunteers

c. Comparison based on historical control

d. Administered as Atripla

e. Bioequivalence boundary 80%-125%

f. Equivalence boundary 70%-143%

Medicinal products that are potent P-gp inducers in the intestine (rifampicin, St. John's wort, carbamazepine and phenytoin) may significantly decrease sofosbuvir plasma concentration leading to reduced therapeutic effect. For this reason, sofosbuvir should not be co-administered with known inducers of P-gp.
4.6 Fertility, pregnancy and lactation
 Women of childbearing potential / contraception in males and females

When Sovaldi is used in combination with ribavirin or peginterferon alfa/ribavirin, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Significant teratogenic and/or embryocidal