Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
Drug interactions with valganciclovir
In-vivo drug interaction studies with Valganciclovir have not been performed.
Since valganciclovir is extensively and rapidly metabolised to ganciclovir; drug interactions associated with ganciclovir will be expected for valganciclovir.

Drug interactions with ganciclovir

Pharmacokinetic interactions
Probenecid
Probenecid given with oral ganciclovir resulted in statistically significantly decreased renal clearance of ganciclovir (20 %) leading to statistically significantly increased exposure (40 %). These changes were consistent with a mechanism of interaction involving competition for renal tubular secretion.
Therefore, patients taking probenecid and valganciclovir should be closely monitored for ganciclovir toxicity.

Didanosine
Didanosine plasma concentrations were found to be consistently raised when given with IV ganciclovir. At intravenous doses of 5 and 10 mg/kg/day, an increase in the AUC of didanosine ranging from 38 to 67% has been observed confirming a pharmacokinetic interaction during the concomitant administration of these drugs. There was no significant effect on ganciclovir concentrations. Patients should be closely monitored for didanosine toxicity e.g. pancreatitis (see section 4.4).

Other antiretrovirals
Cytochrome P450 isoenzymes play no role in ganciclovir pharmacokinetics.
As a consequence, pharmacokinetic interactions with protease inhibitors and non-nucleoside reverse transcriptase inhibitors are not anticipated.

Pharmacodynamic interactions
Imipenem-cilastatin
Seizures have been reported in patients taking ganciclovir and imipenem- cilastatin concomitantly and a pharmacodynamic interaction between these two drugs cannot be discounted. These drugs should not be used concomitantly unless the potential benefits outweigh the potential risks (see section 4.4).

Zidovudine
Both zidovudine and ganciclovir have the potential to cause neutropenia and anaemia. A pharmacodynamic interaction may occur during concomitant administration of these drugs. Some patients may not tolerate concomitant therapy at full dosage (see section 4.4).

Potential drug interactions
Toxicity may be enhanced when ganciclovir/valganciclovir is co-administered with other drugs known to be myelosuppressive or associated with renal impairment. This includes nucleoside (e.g. zidovudine, didanosine, stavudine) and nucleotide analogues (e.g. tenofovir, adefovir), immunosuppressants (e.g.
ciclosporin, tacrolimus, mycophenolate mofetil), antineoplastic agents (e.g.
doxorubicin, vinblastine, vincristine, hydroxyurea) and anti-infective agents (trimethoprim/sulphonamides, dapsone, amphotericin B, flucytosine,
pentamidine). Therefore, these drugs should only be considered for concomitant use with valganciclovir if the potential benefits outweigh the potential risks (see section 4.4).