Drug Interactions 

In studies conducted with Valcyte:

No in vivo drug-drug interaction studies were conducted with valganciclovir. However, because valganciclovir is rapidly and extensively converted to ganciclovir, interactions associated with ganciclovir will be expected for Valcyte tablets.

In studies conducted with ganciclovir:

Binding of ganciclovir to plasma proteins is only about 1% to 2%, and drug interactions involving binding site displacement are not anticipated.

Drug-drug interaction studies were conducted in patients with normal renal function. Patients with impaired renal function may have increased concentrations of ganciclovir and the co-administered drug following concomitant administration of Valcyte tablets and drugs excreted by the same pathway as ganciclovir. Therefore, these patients should be closely monitored for toxicity of ganciclovir and the co-administered drug.

There are potential drug interactions with Valcyte that are of importance to both the AIDS-treating physician and the transplant physician. Please see accompanying tables.

Results of Drug Interaction Studies With Ganciclovir: Effects of Coadministered Drug on Ganciclovir Plasma AUC and Cmax Values⁴

Coadministered Drug	Ganciclovir Dosage	n	Ganciclovir Pharmacokinetic (PK) Parameter	Clinical Comment
Zidovudine 100 mg every 4 hours	1000 mg every 8 hours	12	AUC ↓17 ± 25%(range: -52% to 23%)	Zidovudine and Valcyte each have the potential to cause neutropenia and anemia. Some patients may not tolerate concomitant therapy at full dosage.
Didanosine 200 mg every 12 hours administered 2 hours before ganciclovir	1000 mg every 8 hours	12	AUC ↓21 ± 17% (range: -44% to 5%)	Effect not likely to be clinically significant.
Didanosine 200 mg every 12 hours simultaneously administered with ganciclovir	1000 mg every 8 hours	12	No effect on ganciclovir PK parameters observed	No effect expected.
	IV ganciclovir 5 mg/kg twice daily	11	No effect on ganciclovir PK parameters observed	No effect expected.
	IV ganciclovir 5 mg/kg once daily	11	No effect on ganciclovir PK parameters observed	No effect expected.
Probenecid 500 mg every 6 hours	1000 mg every 8 hours	10	AUC ↑53 ± 91% (range: -14% to 299%) Ganciclovir renal clearance ↓22 ± 20% (range: -54% to -4%)	Patients taking probenecid and Valcyte should be monitored for evidence of ganciclovir toxicity.
Zalcitabine 0.75 mg every 8 hours administered 2 hours before ganciclovir	1000 mg every 8 hours	10	AUC ↑13%	Effect not likely to be clinically significant.
Trimethoprim 200 mg once daily	1000 mg every 8 hours	12	Ganciclovir renal clearance ↓ 16.3% Half-life ↑15%	Effect not likely to be clinically significant.
Mycophenolate Mofetil 1.5 g single dose	IV ganciclovir 5 mg/kg single dose	12	No effect on ganciclovir PK parameters observed (patients with normal renal function)	Patients with renal impairment should be monitored carefully as levels of metabolites of both drugs may increase.

Results of Drug Interaction Studies With Ganciclovir: Effects of Ganciclovir on Plasma AUC and Cmax Values of Coadministered Drug⁴

Coadministered Drug	Ganciclovir Dosage	N	Ganciclovir Pharmacokinetic (PK) Parameter	Clinical Comment
Zidovudine 100 mg every 4 hours	1000 mg every 8 hours	12	AUC0-4 ↑ 19 ± 27% (range: -11% to 74%)	Zidovudine and Valcyte each have the potential to cause neutropenia and anemia. Some patients may not tolerate concomitant therapy at full dosage.
Didanosine 200 mg every 12 hours when administered 2 hours prior to or concurrent with ganciclovir	1000 mg every 8 hours	12	AUC0-12 ↑111 ± 114% (range: 10% to 493%)	Patients should be closely monitored for didanosine toxicity.
Didanosine 200 mg every 12 hours	IV ganciclovir 5 mg/kg twice daily	11	AUC0-12 ↑70 ± 40% (range: 3% to 121%) Cmax↑49 ± 48% (range: -28% to 125%)	Patients should be closely monitored for didanosine toxicity.
Didanosine 200 mg every 12 hours	IV ganciclovir 5 mg/kg once daily	11	AUC0-12 ↑50 ± 26% (range: 22% to 110%) Cmax ↑36 ± 36% (range: -27% to 94%)	Patients should be closely monitored for didanosine toxicity.
Zalcitabine 0.75 mg every 8 hours administered 2 hours before ganciclovir	1000 mg every 8 hours	10	No clinically relevant PK parameter changes	No effect expected.
Trimethoprim 200 mg once daily	1000 mg every 8 hours	12	Increase (12%) in Cmin	Effect not likely to be clinically significant.
Mycophenolate Mofetil (MMF) 1.5 g single dose	IV ganciclovir 5 mg/kg single dose	12	No PK interaction observed (patients with normal renal function)	Patients with renal impairment should be monitored carefully as levels of metabolites of both drugs may increase.

  Safety Information

 

Reference:

⁴Valcyte® [product information]. Nutley, NJ: Roche Laboratories Inc.; January 2006.