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Drug Interactions between pravastatin and rifampin

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

rifAMPin pravastatin

Applies to: rifampin and pravastatin

MONITOR: Rifampin may have variable effects on the pharmacokinetics of pravastatin depending on the circumstances and duration of administration. In one study, concurrent administration of a single oral dose each of pravastatin and rifampin resulted in nearly 3-fold increases in pravastatin peak plasma concentration (Cmax) and systemic exposure (AUC), presumably due to rifampin inhibition of the hepatic uptake of pravastatin via organic anion transporting polypeptide (OATP) 1B1 and 1B3. In another study conducted in 10 healthy nonsmoking volunteers, pretreatment with rifampin 600 mg orally once daily for 5 days decreased the mean AUC of a single 40 mg oral dose of pravastatin by 31% compared to placebo. However, there were large interindividual differences in the effect of rifampin, as pravastatin AUC decreased in 7 subjects (by more than 50% in 5 of them) but increased in 3 subjects when compared to placebo. Rifampin also decreased the Cmax of pravastatin on average by 21%, although the difference was not statistically significant. The mechanism by which rifampin decreases pravastatin exposures is unknown but may involve reduced absorption as well as increased first-pass biliary excretion of pravastatin due to rifampin induction of canalicular multispecific organic anion transporter (cMOAT or MRP2), an efflux transporter expressed in the kidney, liver, and intestine and of which pravastatin is a substrate. It is possible that pravastatin exposures may increase initially following coadministration with rifampin but decrease after chronic coadministration, since induction effects generally take longer to manifest than inhibition.

MANAGEMENT: Caution is advised when pravastatin is prescribed with rifampin. Some authorities recommend separating their administration by at least two hours. Dosage adjustment for pravastatin may be necessary during long-term treatment with rifampin.

References (3)
  1. Kyrklund C, Backman JT, Neuvonen M, Neuvonen PJ (2004) "Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects." Br J Clin Pharmacol, 57, p. 181-7
  2. (2024) "Product Information. Pravastatin (pravastatin)." Milpharm Ltd
  3. (2024) "Product Information. Pravastatin Sodium (Sandoz) (pravastatin)." Sandoz Pty Ltd

Drug and food interactions

Moderate

rifAMPin food

Applies to: rifampin

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References (6)
  1. (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
  2. (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
  3. (2023) "Product Information. Rifadin (rifampicin)." Sanofi
  4. (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE (2024) Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/
  6. (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.
Moderate

pravastatin food

Applies to: pravastatin

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

References (9)
  1. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  2. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  3. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  4. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  5. (2002) "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals
  6. (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  8. Cerner Multum, Inc. "Australian Product Information."
  9. (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)

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.


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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.