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6 Interactions found for:

Plavix and atorvastatin
Interactions Summary
  • 4 Major
  • 2 Moderate
  • 0 Minor
  • Plavix
  • atorvastatin

Drug Interactions

Moderate
Atorvastatin + Plavix

The following applies to the ingredients: Atorvastatin and Clopidogrel (found in Plavix)

MONITOR: The concomitant administration of atorvastatin may reduce the metabolic activation of the prodrug clopidogrel and its antiplatelet effects. The proposed mechanism is competitive inhibition of CYP450 3A4 enzymatic activity, which is responsible for the conversion of clopidogrel to its active metabolite. However, data have been conflicting. In a trial with coronary stent implant patients receiving clopidogrel 75 mg/day (n=44), the percent platelet aggregation was 34% with no atorvastatin, 58% with atorvastatin 10 mg, 74% with 20 mg, and 89% with 40 mg. Results from an in vitro study suggest that equimolar concentrations of atorvastatin inhibit clopidogrel metabolism by more than 90 %. However, in a post hoc analysis of a trial with percutaneous coronary intervention patients, no statistical differences in the incidence of bleeding, stroke, myocardial infarction, or death were found at 1 year with concomitant administration of clopidogrel 75 mg/day and CYP450 3A4-metabolized HMG-CoA reductase inhibitors (n=1001, atorvastatin, lovastatin, simvastatin, cerivastatin) or other statins (n=158, pravastatin, fluvastatin).

MANAGEMENT: Until more information is available, monitoring for altered efficacy of clopidogrel may be advisable if atorvastatin is coadministered with clopidogrel. Pravastatin, fluvastatin, and rosuvastatin are not metabolized by CYP450 3A4 and are theoretically not expected to interact with clopidogrel.

References

  1. Lau WC, Waskell LA, Watkins PB, et al. "Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction." Circulation 107 (2003): 32-7
  2. Serebruany VL, Steinhubl SR, Hennekens CH "Are antiplatelet effects of clopidogrel inhibited by atorvastatin? A research question formulated but not yet adequately tested." Circulation 107 (2003): 1568-9
  3. Shechter M "Atorvastatin and the ability of clopidogrel to inhibit platelet aggregation." Circulation 107 (2003): e210; author reply e210
  4. Saw J, Steinhubl SR, Berger PB, et al. "Lack of Adverse Clopidogrel-Atorvastatin Clinical Interaction From Secondary Analysis of a Randomized, Placebo-Controlled Clopidogrel Trial." Circulation 108 (2003): 921-924
  5. Neubauer H, Gunesdogan B, Hanefeld C, Spiecker M, Mugge A "Lipophilic statins interfere with the inhibitory effects of clopidogrel on platelet function - a flow cytometry study." Eur Heart J 24 (2003): 1744-1749
  6. Damkier P "Atorvastatin and clopidogrel." Circulation 108 (2003): e96; author reply e96
  7. Clarke TA, Waskell LA "The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin." Drug Metab Dispos 31 (2003): 53-9

Drug and Food Interactions

Moderate
Atorvastatin + Food

The following applies to the ingredients: Atorvastatin

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 40 mg dose of atorvastatin was coadministered with 240 mL of grapefruit juice, atorvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 16% and 37%, respectively. Greater increases in Cmax (up to 71%) and/or AUC (up to 2.5 fold) have been reported with excessive consumption of grapefruit juice (>=750 mL to 1.2 liters per day). Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

MANAGEMENT: Patients receiving therapy with atorvastatin should limit their consumption of grapefruit juice to no more than 1 liter per day. Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, patients should either refrain from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times by at least 2 to 4 hours.

References

  1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706
  2. McMillan K "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a reductase inhibitors." Am J Health Syst Pharm 53 (1996): 2206-14
  3. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  4. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos 25 (1997): 321-31
  5. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  7. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74

Drug and Pregnancy Interactions

The following applies to the ingredients: Atorvastatin

According to some authorities: Use is contraindicated during pregnancy or in patients of childbearing potential not using contraception.

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned

Risk summary: Based on its mechanism of action, this drug may cause fetal harm when administered during pregnancy.
-Available data on the use of statins in pregnant women have not identified a drug-related risk of major congenital malformations and are insufficient to inform a drug-related risk of miscarriage.

Comments:
-If the patient becomes pregnant while taking this drug, therapy should be discontinued and the patient should be apprised of the potential harm to the fetus.
---According to some authorities: Alternatively, the ongoing needs of the individual patient should be considered.
-According to some authorities: Patients of childbearing potential should use effective contraception during therapy; this drug should be used in patients of childbearing potential only when they are highly unlikely to conceive and have been informed of the potential.

Animal studies have failed to reveal evidence of embryofetal toxicity or teratogenicity; however, at maternally toxic doses, increased postimplantation loss and decreased fetal body weights have been observed. No adverse developmental effects were observed in pregnant rats or rabbits administered oral doses that resulted in 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 this drug during gestation and lactation, decreased postnatal growth and development delay were observed at doses at least 6 times the MRHD. This drug crosses the rat placenta and reaches levels in the fetal liver equivalent to that of maternal plasma. A study of statin-exposed pregnant women compared to controls did not find a significant teratogenic effect from maternal use of statins in the first trimester, after adjusting for potential confounders. Rare cases of congenital anomalies after intrauterine exposure to HMG-CoA reductase inhibitors have been reported. There are no controlled data in human pregnancy.

Cholesterol and other products of cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell membranes). Because this drug decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol, it may cause fetal harm when used during pregnancy.

Treatment of hyperlipidemia is not generally necessary during pregnancy. Since atherosclerosis is a chronic process, discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term primary hypercholesterolemia therapy for most patients.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

References

  1. "Product Information. Lipitor (atorvastatin)." Viatris Specialty LLC SUPPL-81 (2024):
  2. "Product Information. Atorvaliq (atorvastatin)." Carolina Medical Products Company SUPPL-2 (2024):
  3. "Product Information. Lipitor (atorvastatin)." Aspen Pharmacare Australia Pty Ltd (2023):
  4. "Product Information. Lorstat (atorvastatin)." Alphapharm Pty Ltd (2024):
  5. "Product Information. Lipitor (atorvastatin)." Viatris UK Healthcare Ltd (2024):
  6. "Product Information. Atorvastatin (atorvastatin)." Rosemont Pharmaceuticals Ltd (2024):

The following applies to the ingredients: Clopidogrel (found in Plavix)

Use is not recommended. When possible, discontinue this drug 5 to 7 days prior to labor, delivery, or neuraxial blockade.

AU TGA pregnancy category: B1
US FDA pregnancy category: Not assigned.

Risk Summary: Available data from cases reported in published literature and postmarketing surveillance have not identified an association with use of this drug in pregnancy and major birth defects, miscarriage, or adverse fetal outcomes.

While this drug is known to cross the placenta, animal studies have failed to reveal evidence of fetal harm. Reproduction studies performed in rats and rabbits at doses of 500 and 300 mg/kg/day (65 and 78 times the recommended daily human dose, respectively, on a mg/m2 basis) revealed no evidence of impaired fertility or fetotoxicity. There are no controlled data in human pregnancy.

Use of this drug during labor or delivery will increase the risk of maternal bleeding and hemorrhage. Avoid neuraxial blockade during use of this drug.

AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

References

  1. "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

Drug and Breastfeeding Interactions

The following applies to the ingredients: Atorvastatin

Until more data are available, an alternate agent may be preferred, particularly while breastfeeding newborn or preterm infants.
-According to some authorities: Breastfeeding is not recommended during use of this drug.
-According to some authorities: Use is contraindicated.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-Another drug in this class is excreted into human milk.
-Statins (including this drug) decrease synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; they may cause harm to the breastfed infant.
-The effects in the nursing infant are unknown; based on the mechanism of action, there is the potential for serious adverse reactions in nursing infants.

Due to a concern over disruption of infant lipid metabolism, it is generally agreed that women taking a statin should not breastfeed; however, others have argued that children homozygous for familial hypercholesterolemia are treated with statins starting at 1 year of age, statins have low oral bioavailability, and risks to the breastfed infant are low. Some evidence indicates that this drug can be taken by nursing mothers with no obvious developmental problems in their infants.

In cases of patients with homozygous familial hypercholesterolemia, 6 patients breastfed 11 infants after restarting statin therapy postpartum; the specific statin was not reported, but most of the women on statin therapy were using this drug (40 or 80 mg/day). Normal early child development was reported for all offspring; children started school at the appropriate age with no learning difficulties reported.

References

  1. Bethesda (MD): National Institute of Child Health and Human Development (US) "Atorvastatin - Drugs and Lactation Database (LactMed) https://www.ncbi.nlm.nih.gov/books/NBK501361/" (2024):
  2. "Product Information. Lipitor (atorvastatin)." Viatris Specialty LLC SUPPL-81 (2024):
  3. "Product Information. Atorvaliq (atorvastatin)." Carolina Medical Products Company SUPPL-2 (2024):
  4. "Product Information. Lipitor (atorvastatin)." Aspen Pharmacare Australia Pty Ltd (2023):
  5. "Product Information. Lorstat (atorvastatin)." Alphapharm Pty Ltd (2024):
  6. "Product Information. Lipitor (atorvastatin)." Viatris UK Healthcare Ltd (2024):
  7. "Product Information. Atorvastatin (atorvastatin)." Rosemont Pharmaceuticals Ltd (2024):

The following applies to the ingredients: Clopidogrel (found in Plavix)

This drug has been used without apparent harmful effects. However, use is not recommended or contraindicated per some authorities. Benefit should outweigh risk in case of use during lactation.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments: The effects in the nursing infant are unknown.

References

  1. "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

Therapeutic Duplication Warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

Switch to: Consumer Interactions

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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