Simvastatin Systemic Exposure Coadministered Drug
or Grapefruit Juice Dosing of Coadministered Drug or Grapefruit Juice Dosing of
Simvastatin Geometric Mean Ratio
(Ratio* with / without
coadministered drug)
No Effect = 1.00
AUC Cmax
* Results based on a chemical assay except results with propranolol as indicated. † Results could be representative of the following CYP3A4 inhibitors: ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, and nefazodone. ‡ Simvastatin acid refers to the β-hydroxyacid of simvastatin. § The effect of amounts of grapefruit juice between those used in these two studies on simvastatin pharmacokinetics has not been studied. ¶ Double-strength: one can of frozen concentrate diluted with one can of water. Grapefruit juice was administered TID for 2 days, and 200 mL together with single dose simvastatin and 30 and 90 minutes following single dose simvastatin on Day 3. # Single-strength: one can of frozen concentrate diluted with 3 cans of water. Grapefruit juice was administered with breakfast for 3 days, and simvastatin was administered in the evening on Day 3. Þ Because Chinese patients have an increased risk for myopathy with simvastatin coadministered with lipid-modifying doses (≥1 gram/day niacin) of niacin-containing products, and the risk is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products [see Warnings and Precautions (5.1) and Drug Interactions (7.4)].
Contraindicated with simvastatin [see Contraindications (4) and Warnings and Precautions (5.1)]
Telithromycin† 200 mg QD for 4 days 80 mg simvastatin acid‡
simvastatin 12
8.9 15
5.3
Nelfinavir† 1250 mg BID for 14 days 20 mg QD for 28 days simvastatin acid‡
simvastatin
6
6.2
Itraconazole† 200 mg QD for 4 days 80 mg simvastatin acid‡
simvastatin 13.1
13.1
Posaconazole 100 mg (oral suspension)
QD for 13 days
200 mg (oral suspension)
QD for 13 days 40 mg
40 mg
simvastatin acid
simvastatin
simvastatin acid
simvastatin
7.3
10.3
8.5
10.6 9.2
9.4
9.5
11.4
Gemfibrozil 600 mg BID for 3 days 40 mg simvastatin acid
simvastatin 2.85
1.35 2.18
0.91
Avoid grapefruit juice with simvastatin [see Warnings and Precautions (5.1)]
Grapefruit Juice§
(high dose) 200 mL of double-strength TID¶ 60 mg single dose simvastatin acid
simvastatin 7
16
Grapefruit Juice§
(low dose) 8 oz (about 237 mL) of single-strength# 20 mg single dose simvastatin acid
simvastatin 1.3
1.9
Avoid taking with >10 mg simvastatin, based on clinical and/or postmarketing experience [see Warnings and Precautions (5.1)]
Verapamil SR 240 mg QD Days 1-7 then 240 mg BID on Days 8-10 80 mg on Day 10 simvastatin acid
simvastatin 2.3
2.5 2.4
2.1
Diltiazem 120 mg BID for 10 days 80 mg on Day 10 simvastatin acid
simvastatin 2.69
3.10 2.69
2.88
Diltiazem 120 mg BID for 14 days 20 mg on Day 14 simvastatin 4.6 3.6
Dronedarone 400 mg BID for 14 days 40 mg QD for 14 days simvastatin acid
simvastatin 1.96
3.90 2.14
3.75
Avoid taking with >20 mg simvasta
