t to represent induction of bupropion metabolism. However, because ritonavir has also been shown to inhibit CYP2B6 in vitro, the recommended dose of bupropion should not be exceeded. In contrast to long-term administration of ritonavir, there was no significant interaction with bupropion after short-term administration of low doses of ritonavir (200 mg twice daily for 2 days), suggesting reductions in bupropion concentrations may have onset several days after initiation of ritonavir co-administration.
Steroids
Fluticasone propionate aqueous nasal spray
200 µg qd
100 q12h
↑ ~350-fold
↑ ~ 25-fold
Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression (plasma cortisol levels were noted to be decreased 86% in the above study) have been reported in patients receiving ritonavir and inhaled or intranasal fluticasone propionate; similar effects could also occur with other corticosteroids metabolised by CYP3A eg, budesonide. Consequently, concomitant administration of ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4). A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (eg, beclomethasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may be required over a longer period.
Dexamethasone
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A and as a result is expected to increase the plasma concentrations of dexamethasone. Careful monitoring of therapeutic and adverse effects is recommended when dexamethasone is concomitantly administered with ritonavir.
Prednisolone
20
200 q12h
↑ 28%
↑ 9%
Careful monitoring of therapeutic and adverse effects is recommended when prednisolone is concomitantly administered with ritonavir. The AUC of the metabolite prednisolone increased by 37 and 28% after 4 and 14 days ritonavir, respectively.
ND: Not determined
1. Based on a parallel group comparison
2. Sulfamethoxazole was co-administered with trimethoprim.
Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide, mexiletine or nefazadone. The possibility of medicinal product interaction cannot be excluded.
In addition to the interactions listed above, as ritonavir is highly protein bound, the possibility of increased therapeutic and toxic effects due to protein binding displacement of concomitant medicinal products should be considered.
Ritonavir dosed as a pharmacokinetic enhancer
Important information regarding medicinal product interactions when ritonavir is used a pharmacokinetic enhancer is also contained in the Summary of Product Characteristics of the co-administered protease inhibitor.
Proton pump inhibitors and H2-receptor antagonists: proton pump inhibitors and H2-receptor antagonists (e.g. omeprazole or ranitidine) may reduce concentrations for co-administered protease inhibitors. For specific information regarding the impact of co-administration of acid reducing agents, refer to t |
