Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI3ZG8XFC)
  Drug Name Pravastatin Drug Info Clarithromycin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Statins/Antihyperlipidemic Agents Antibiotics
  Structure

 Mechanism of Pravastatin-Clarithromycin Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Pravastatin Clarithromycin
      Mechanism 1 OATP1B1 substrate OATP1B1 inhibitor
      Key Mechanism Factor 1
Factor Name Liver organic anion transporter 1
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Structure Sequence
MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFEISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGYYRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNMLRGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYVDLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLETNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVFKYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLSFYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGITYISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAIQVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCIKWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASENGSVMDEANLESLNKNKHFVPSAGADSETHC
Gene Name OATP1B1
Uniprot ID SO1B1_HUMAN
KEGG Pathway hsa:10599
Protein Family Organo anion transporter (TC 2.A.60) family
Protein Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Pravastatin due to the transporter inhibition by Clarithromycin 
      Mechanism 2 OATP1B3 substrate OATP1B3 inhibitor
      Key Mechanism Factor 2
Factor Name Liver organic anion transporter 2
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Structure Sequence
MDQHQHLNKTAESASSEKKKTRRCNGFKMFLAALSFSYIAKALGGIIMKISITQIERRFDISSSLAGLIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCLLMGTGSILTSLPHFFMGYYRYSKETHINPSENSTSSLSTCLINQTLSFNGTSPEIVEKDCVKESGSHMWIYVFMGNMLRGIGETPIVPLGISYIDDFAKEGHSSLYLGSLNAIGMIGPVIGFALGSLFAKMYVDIGYVDLSTIRITPKDSRWVGAWWLGFLVSGLFSIISSIPFFFLPKNPNKPQKERKISLSLHVLKTNDDRNQTANLTNQGKNVTKNVTGFFQSLKSILTNPLYVIFLLLTLLQVSSFIGSFTYVFKYMEQQYGQSASHANFLLGIITIPTVATGMFLGGFIIKKFKLSLVGIAKFSFLTSMISFLFQLLYFPLICESKSVAGLTLTYDGNNSVASHVDVPLSYCNSECNCDESQWEPVCGNNGITYLSPCLAGCKSSSGIKKHTVFYNCSCVEVTGLQNRNYSAHLGECPRDNTCTRKFFIYVAIQVINSLFSATGGTTFILLTVKIVQPELKALAMGFQSMVIRTLGGILAPIYFGALIDKTCMKWSTNSCGAQGACRIYNSVFFGRVYLGLSIALRFPALVLYIVFIFAMKKKFQGKDTKASDNERKVMDEANLEFLNNGEHFVPSAGTDSKTCNLDMQDNAAAN
Gene Name OATP1B3
Uniprot ID SO1B3_HUMAN
KEGG Pathway hsa:28234
Protein Family Organo anion transporter (TC 2.A.60) family
Protein Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Pravastatin due to the transporter inhibition by Clarithromycin 

Recommended Action
      Management The benefits of using pravastatin in combination with clarithromycin or erythromycin should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. A lower dosage of pravastatin should be considered if concomitant use is required. The product labeling for pravastatin recommends that dosage not exceed 40 mg daily when used in combination with clarithromycin. No dosage recommendations are available for use with erythromycin. All patients receiving statin therapy 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.

References
1 Jacobson TA "Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors." Am J Cardiol 94 (2004): 1140-6. [PMID: 15518608]
2 Product Information. Pravachol (pravastatin). Bristol-Myers Squibb, Princeton, NJ.
3 Seithel A, Eberl S, Singer K, et al. "The influence of macrolide antibiotics on the uptake of organic anions and drugs mediated by OATP1B1 and OATP1B3." Drug Metab Dispos 35 (2007): 779-86. [PMID: 17296622]