statin and simvastatin may predispose patients to myopathies, including rhabdomyolysis, the combination of these medicinal products with ritonavir is contraindicated (see section 4.3). Atorvastatin is less dependent on CYP3A for metabolism. While rosuvastatin elimination is not dependent on CYP3A, an elevation of rosuvastatin exposure has been reported with ritonavir co-administration. The mechanism of this interaction is not clear, but may be the result of transporter inhibition. When used with ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent, the lowest possible doses of atorvastatin or rosuvastatin should be administered. The metabolism of pravastatin and fluvastatin is not dependent on CYP3A, and interactions are not expected with ritonavir. If treatment with an HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.
Hormonal contraceptive
Ethinyl estradiol
50 µg, single dose
500 q12h
40%
32%
Due to reductions in ethinyl estradiol concentrations, barrier or other non-hormonal methods of contraception should be considered with concomitant ritonavir use when dosed as an antiretroviral agent or as a pharmacokinetic enhancer. Ritonavir is likely to change the uterine bleeding profile and reduce the effectiveness of estradiol-containing contraceptives (see section 4.4).
Immunosupressants
Cyclosporine, tacrolimus, everolimus
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of cyclosporine, tacrolimus or everolimus. Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with ritonavir.
Phosphodiesterase inhibitors
Sildenafil
100, single dose
500 q12h
↑ 11-fold
↑ 4-fold
Concomitant use of sildenafil for the treatment of erectile dysfunction, with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer should be used with caution and in no instance should sildenafil doses exceed 25 mg in 48 hours (see also section 4.4). Concomitant use of sildenafil with ritonavir is contraindicated in pulmonary arterial hypertension patients (see section 4.3).
Tadalafil
20, single dose
200 q12h
↑ 124%
↔
The concomitant use of tadalafil for the treatment of erectile dysfunction with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer should be with caution at reduced doses of no more than 10 mg tadalafil every 72 hours with increased monitoring for adverse reactions (see section 4.4).
When tadalafil is used concurrently with ritonavir in patients with pulmonary arterial hypertension, refer to the tadalafil SmPC or prescribing information
Vardenafil
5, single dose
600 q12h
↑ 49-fold
↑ 13-fold
The concomitant use of vardenafil and ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer should be with caution at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions (see section 4.4).
Sedatives/hynoptics
Clorazepate, diazepam, estazolam, flurazepam, oral and parenteral midazolam and triazolam
Ritonavir co-administrati |
