Details of Drug-Drug Interaction
| Drug General Information (ID: DDI7JBCKXT) | |||||||||
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| Drug Name | Pravastatin | Drug Info | Dabrafenib | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Statins/Antihyperlipidemic Agents | Multikinase Inhibitors | |||||||
| Structure | |||||||||
| Mechanism of Pravastatin-Dabrafenib Interaction (Severity Level: Moderate) | |||||||||
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| Transporter inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Pravastatin | Dabrafenib | |||||||
| Mechanism 1 | OATP1B1 substrate | OATP1B1 inhibitor | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Liver organic anion transporter 1 |
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Structure
Sequence
MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFEISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGYYRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNMLRGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYVDLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLETNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVFKYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLSFYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGITYISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAIQVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCIKWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASENGSVMDEANLESLNKNKHFVPSAGADSETHC
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| 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.
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| Mechanism Description |
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| Mechanism 2 | OATP1B3 substrate | OATP1B3 inhibitor | |||||||
| Key Mechanism Factor 2 | |||||||||
| Factor Name | Liver organic anion transporter 2 |
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Structure
Sequence
MDQHQHLNKTAESASSEKKKTRRCNGFKMFLAALSFSYIAKALGGIIMKISITQIERRFDISSSLAGLIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCLLMGTGSILTSLPHFFMGYYRYSKETHINPSENSTSSLSTCLINQTLSFNGTSPEIVEKDCVKESGSHMWIYVFMGNMLRGIGETPIVPLGISYIDDFAKEGHSSLYLGSLNAIGMIGPVIGFALGSLFAKMYVDIGYVDLSTIRITPKDSRWVGAWWLGFLVSGLFSIISSIPFFFLPKNPNKPQKERKISLSLHVLKTNDDRNQTANLTNQGKNVTKNVTGFFQSLKSILTNPLYVIFLLLTLLQVSSFIGSFTYVFKYMEQQYGQSASHANFLLGIITIPTVATGMFLGGFIIKKFKLSLVGIAKFSFLTSMISFLFQLLYFPLICESKSVAGLTLTYDGNNSVASHVDVPLSYCNSECNCDESQWEPVCGNNGITYLSPCLAGCKSSSGIKKHTVFYNCSCVEVTGLQNRNYSAHLGECPRDNTCTRKFFIYVAIQVINSLFSATGGTTFILLTVKIVQPELKALAMGFQSMVIRTLGGILAPIYFGALIDKTCMKWSTNSCGAQGACRIYNSVFFGRVYLGLSIALRFPALVLYIVFIFAMKKKFQGKDTKASDNERKVMDEANLEFLNNGEHFVPSAGTDSKTCNLDMQDNAAAN
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| 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.
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Until more information is available, caution is advised when dabrafenib is prescribed with HMG-Coa reductase inhibitors. Clinical and laboratory monitoring are recommended whenever dabrafenib is added to or withdrawn from therapy, and the statin dosage adjusted as necessary. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. | ||||||||