Atorvastatin Calcium (Page 5 of 11)

Combination of Protease Inhibitors

Atorvastatin AUC was significantly increased with concomitant administration of atorvastatin calcium tablets with several combinations of protease inhibitors [see Clinical Pharmacology (12.3)]. In patients taking tipranavir plus ritonavir or glecaprevir plus pibrentasvir, concomitant use of atorvastatin calcium tablets should be avoided. In patients taking lopinavir plus ritonavir, or simeprevir, use the lowest necessary atorvastatin calcium tablet dose. In patients taking saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, or elbasvir plus grazoprevir, the dose of atorvastatin calcium tablets should not exceed 20 mg. In patients taking nelfinavir the dose of atorvastatin calcium tablets should not exceed 40 mg and close clinical monitoring is recommended [see Dosage and Administration (2.6) and Warnings and Precautions (5.1)].

Itraconazole

Atorvastatin AUC was significantly increased with concomitant administration of atorvastatin calcium tablets 40 mg and itraconazole 200 mg [see Clinical Pharmacology (12.3)]. Therefore, in patients taking itraconazole, caution should be used when the atorvastatin calcium tablet dose exceeds 20 mg [see Dosage and Administration (2.6) and Warnings and Precautions (5.1)].

7.2 Grapefruit Juice

Contains one or more components that inhibit CYP 3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (> 1.2 liters per day).

7.3 Cyclosporine

Atorvastatin is a substrate of the hepatic transporters. Atorvastatin-metabolites are substrates of the OATP1B1 transporter. Inhibitors of the OATP1B1 (e.g., cyclosporine) can increase the bioavailability of atorvastatin. Atorvastatin AUC was significantly increased with concomitant administration of atorvastatin calcium tablets 10 mg and cyclosporine 5.2 mg/kg/day compared to that of atorvastatin calcium tablets alone [see Clinical Pharmacology (12.3)].

The co-administration of atorvastatin calcium tablets with cyclosporine should be avoided [see Warnings and Precautions (5.1)].

7.4 Letermovir

Concomitant administration of atorvastatin 20 mg and letermovir 480 mg daily resulted in an increase in exposure to atorvastatin (ratio of AUC: 3.29) [see Clinical Pharmacology (12.3)]. Letermovir inhibits efflux transporters P-gp, BCRP, MRP2, OAT2 and hepatic transporter OATP1B1/1B3, thus it increases exposure to atorvastatin. Do not exceed 20 mg atorvastatin calcium tablets daily [see Dosage and Administration (2.6)].

The magnitude of CYP3A- and OATP1B1/1B3-mediated drug interactions on co-administered drugs may be different when letermovir is co-administered with cyclosporine. Use of atorvastatin calcium tablets is not recommended in patients taking letermovir co-administered with cyclosporine.

7.5 Glecaprevir and Pibrentasvir; Elbasvir and Grazoprevir

Concomitant administration of glecaprevir and pibrentasvir or elbasvir and grazoprevir may lead to increased plasma concentrations of atorvastatin and an increased risk of myopathy.

Coadministration of glecaprevir and pibrentasvir with atorvastatin increase plasma concentrations of atorvastatin by 8.3-fold due in part to BCRP, OATP1B1/1B3, and CYP3A inhibition; therefore, coadministration of atorvastatin calcium tablets in patients receiving concomitant medications with products containing glecaprevir and pibrentasvir is not recommended.

Coadministration of elbasvir and grazoprevir with atorvastatin increase plasma concentrations of atorvastatin by 1.9-fold due in part to BCRP, OATP1B1/1B3, and CYP3A inhibition; therefore, the dose of atorvastatin calcium tablets should not exceed 20 mg daily in patients receiving concomitant medications with products containing elbasvir and grazoprevir [see Dosage and Administration (2.6), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].

7.6 Gemfibrozil

Due to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are co-administered with gemfibrozil, concomitant administration of atorvastatin calcium tablets with gemfibrozil should be avoided [see Warnings and Precautions (5.1)].

7.7 Other Fibrates

Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of other fibrates, atorvastatin calcium tablets should be administered with caution when used concomitantly with other fibrates [see Warnings and Precautions (5.1)].

7.8 Niacin

The risk of skeletal muscle effects may be enhanced when atorvastatin calcium tablets are used in combination with niacin; a reduction in atorvastatin calcium tablet dosage should be considered in this setting [see Warnings and Precautions (5.1)].

7.9 Rifampin or Other Inducers of Cytochrome P450 3A4

Concomitant administration of atorvastatin calcium tablets with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampin) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, simultaneous co-administration of atorvastatin calcium tablets with rifampin is recommended, as delayed administration of atorvastatin calcium tablets after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.

7.10 Digoxin

When multiple doses of atorvastatin calcium tablets and digoxin were co-administered, steady state plasma digoxin concentrations increased [see Clinical Pharmacology (12.3)]. Patients taking digoxin should be monitored appropriately.

7.11 Oral Contraceptives

Co-administration of atorvastatin calcium tablets and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking atorvastatin calcium tablets.

7.12 Warfarin

Atorvastatin calcium tablets had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.

7.13 Colchicine

Cases of myopathy, including rhabdomyolysis, have been reported with atorvastatin co-administered with colchicine, and caution should be exercised when prescribing atorvastatin with colchicine.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Atorvastatin calcium tablets are contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit of lipid lowering drugs during pregnancy. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, atorvastatin calcium tablets may cause fetal harm when administered to a pregnant woman. Atorvastatin calcium tablets should be discontinued as soon as pregnancy is recognized [see Contraindications (4)]. Limited published data on the use of atorvastatin are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies in rats and rabbits there was no evidence of embryo-fetal toxicity or congenital malformations at doses up to 30 and 20 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 80 mg, based on body surface area (mg/m2). In rats administered atorvastatin during gestation and lactation, decreased postnatal growth and development was observed at doses ≥ 6 times the MRHD (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.