Videx (Didanosine) - Drug Interactions, Contraindications, Overdosage

Drug Interactions: Ribavirin has been shown in vitro to increase intracellular triphosphate levels of didanosine, which could cause or worsen clinical toxicities (see PRECAUTIONS: Drug Interactions).

Tables 3 and 4 summarize the effects on AUC and C_MAX, with a 90% or 95% confidence interval (CI) when available, following coadministration of VIDEX (didanosine) with a variety of drugs. For most of the listed drugs, no clinically significant pharmacokinetic interactions were observed. Clinical recommendations based on drug interaction studies for drugs in bold font are included in PRECAUTIONS: Drug Interactions and DOSAGE AND ADMINISTRATION (for tenofovir).

Table 3: Results of Drug Interaction Studies with VIDEX: Effects of Coadministered Drug on Didanosine Plasma AUC and C_MAX Values

↑ indicates increase.
↓ indicates decrease.
↔ indicates no change, or mean increase or decrease of <10%.
a HIV-infected patients.
b 90% CI.
c Parallel-group design; entries are subjects receiving combination and control regimens, respectively.
d tenofovir disoproxil fumarate.
e For results of drug interaction studies between the enteric-coated formulation of didanosine (VIDEX EC) and tenofovir, see the complete prescribing information for VIDEX EC.
f patients <60 kg with creatinine clearance ≥60 mL/min.
NA Not available.
Drugs With Clinical Recommendations Regarding Coadministration ( see PRECAUTIONS: Drug Interactions)
Drug	Didanosine Dosage	n	AUC of Didanosine (95% CI)	CMAX of Didanosine (95% CI)
allopurinol renally impaired, 300 mg/day	200 mg single dose	2	↑ 312%	↑ 232%
healthy volunteer, 300 mg/day for 7 days	400 mg single dose	14	↑ 113%	↑ 69%
ciprofloxacin, 750 mg q12h for 3 days, 2 h before didanosine	200 mg q12h for 3 days	8a	↓ 16%	↓ 28%
ganciclovir,1000 mg q8h, 2 h after didanosine	200 mg q12h	12	↑ 111%	NA
indinavir, 800 mg single dose simultaneous 1 h before didanosine	200 mg single dose 200 mg single dose	16 16	↔ ↓ 17% (-27, - 7%)b	↔ ↓ 13% (-28, 5%)b
ketoconazole, 200 mg/day for 4 days, 2 h before didanosine	375 mg q12h for 4 days	12a	↔	↓ 12%
methadone, chronic maintenance dose	200 mg single dose	16, 10c	↓ 57%	↓ 66%
tenofovir,d,e 300 mg once daily, 1 h after didanosine	250f or 400 mg once daily for 7 days	14	↑ 44% (31, 59%)b	↑ 28% (11, 48%)b
No Clinically Significant Interaction Observed
Drug	Didanosine Dosage	n	AUC of Didanosine (95% CI)	CMAX of Didanosine (95% CI)
loperamide, 4 mg q6h for 1 day	300 mg single dose	12a	↔	↓ 23%
metoclopramide, 10 mg single dose	300 mg single dose	12a	↔	↑ 13%
ranitidine, 150 mg single dose, 2 h before didanosine	375 mg single dose	12a	↑ 14%	↑ 13%
rifabutin, 300 or 600 mg/day for 12 days	167 or 250 mg q12h for 12 days	11	↑ 13% (-1, 27%)	↑ 17% (-4, 38%)
ritonavir, 600 mg q12h for 4 days	200 mg q12h for 4 days	12	↓ 13% (0, 23%)	↓ 16% (5, 26%)
stavudine, 40 mg q12h for 4 days	100 mg q12h for 4 days	10	↔	↔
sulfamethoxazole, 1000 mg single dose	200 mg single dose	8a	↔	↔
trimethoprim, 200 mg single dose	200 mg single dose	8a	↔	↑ 17% (-23, 77%)
zidovudine, 200 mg q8h for 3 days	200 mg q12h for 3 days	6a	↔	↔

Table 4: Results of Drug Interaction Studies with VIDEX: Effects of Didanosine on Coadministered Drug Plasma AUC and C_MAX Values

↑ indicates increase.
↓ indicates decrease.
↔ indicates no change, or mean increase or decrease of <10%.
a HIV-infected patients.
b tenofovir disoproxil fumarate.
c patients <60 kg with creatinine clearance ≥60 mL/min.
NA Not available.
Drugs With Clinical Recommendations Regarding Coadministration (see PRECAUTIONS: Drug Interactions)
Drug	Didanosine Dosage	n	AUC of Coadministered Drug (95% CI)	CMAX of Coadministered Drug (95% CI)
ciprofloxacin 750 mg q12h for 3 days, 2 h before didanosine	200 mg q12h for 3 days	8a	↓ 26%	↓ 16%
750 mg single dose	buffered placebo tablet	12	↓ 98%	↓ 93%
delavirdine, 400 mg single dose simultaneous 1 h before didanosine	125 or 200 mg q12h 125 or 200 mg q12h	12a 12a	↓ 32% ↑ 20%	↓ 53% ↑ 18%
ganciclovir, 1000 mg q8h, 2 h after didanosine	200 mg q12h	12a	↓ 21%	NA
indinavir, 800 mg single dose simultaneous 1 h before didanosine	200 mg single dose 200 mg single dose	16 16	↓ 84% ↓ 11%	↓ 82% ↓   4%
ketoconazole, 200 mg/day for 4 days, 2 h before didanosine	375 mg q12h for 4 days	12a	↓ 14%	↓ 20%
nelfinavir, 750 mg single dose, 1 h after didanosine	200 mg single dose	10a	↑ 12%	↔
No Clinically Significant Interaction Observed
Drug	Didanosine Dosage	n	AUC of Coadministered Drug (95% CI)	CMAX of Coadministered Drug (95% CI)
dapsone, 100 mg single dose	200 mg q12h for 14 days	6a	↔	↔
ranitidine, 150 mg single dose, 2 h before didanosine	375 mg single dose	12a	↓ 16%	↔
ritonavir, 600 mg q12h for 4 days	200 mg q12h for 4 days	12	↔	↔
stavudine, 40 mg q12h for 4 days	100 mg q12h for 4 days	10a	↔	↑ 17%
sulfamethoxazole, 1000 mg single dose	200 mg single dose	8a	↓ 11% (-17, -4%)	↓ 12% (-28, 8%)
tenofovir,b 300 mg once daily 1 h after didanosine	250c or 400 mg once daily for 7 days	14	↔	↔
trimethoprim, 200 mg single dose	200 mg single dose	8a	↑ 10% (-9, 34%)	↓ 22% (-59, 49%)
zidovudine, 200 mg q8h for 3 days	200 mg q12h for 3 days	6a	↓ 10% (-27, 11%)	↓ 16.5% (-53, 47%)