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
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 [ see Warnings and Precautions (5.2); Drug Interactions (7.4)].
Contraindicated with JUVISYNC [see Contraindications (4); Warnings and Precautions (5.2)]
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 40 mg simvastatin acid
simvastatin 7.3
10.3 9.2
9.4
200 mg (oral suspension)
QD for 13 days 40 mg simvastatin acid
simvastatin 8.5
10.6 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 [see Warnings and Precautions (5.2)]
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 (100 mg/10 mg or 50 mg/10 mg JUVISYNC), based on clinical and/or postmarketing experience [see Warnings and Precautions (5.2)]
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 simvastatin (100 mg/20 mg or 50 mg/20 mg JUVISYNC), based on clinical and/or postmarketing experience [see Warnings and Precautions (5.2)]
Amlodipine 10 mg QD for 10 days 80 mg on Day 10 simvastatin acid
simvastatin 1.58
1.77 1.56
1.47
Ranolazine SR 1000 mg BID for 7 days 80 mg on Day 1 and Days 6-9 simvastatin acid
simvastatin 2.26
1.86 2.28
1.75
Amiodarone 400 mg QD for 3 days 40 mg on Day 3 simvastatin acid
simvastatin 1.75
1.76 1.72
1.79
No dosing adjustments required for the following:
Fenofibrate 160 mg QD for 14 days 80 mg QD on Days 8-14 simvastatin acid
simvastatin 0.64
0.89 0.89
0.83
Niacin extended-release Þ 2 g single dose 20 mg single dose simvastatin acid
simvastatin 1.6
1.4 1.84
1.08
Propranolol 80 mg single dose 80 mg single dose total inhibitor
0.79
↓ from 33.6 to 21.1 ng∙eq/mL
active inhibitor 0.79 ↓ from 7.0 to 4.7 ng∙eq/mL
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Sitagliptin
A two-year carcinogenicity study was co
