Details of Drug-Drug Interaction
| Drug General Information (ID: DDIE5GP6J8) | |||||||||
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| Drug Name | Amiodarone | Drug Info | Sofosbuvir | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antiarrhythmic Agents | Antiviral Agents | |||||||
| Structure | |||||||||
| Mechanism of Amiodarone-Sofosbuvir Interaction (Severity Level: Major) | |||||||||
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| Transporter inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Amiodarone | Sofosbuvir | |||||||
| Mechanism 1 | P-gp inhibitor | P-gp substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | P-glycoprotein 1 |
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Structure
Sequence
MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAIIHGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSGIGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVSKINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFTDKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSGQTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLFATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRSSLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAIINGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKAGEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEAIENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFGAYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDSYSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVVSQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTKRQ
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| Gene Name | ABCB1 | ||||||||
| Uniprot ID | MDR1_HUMAN | ||||||||
| KEGG Pathway | hsa:5243 | ||||||||
| Protein Family | ABC transporter superfamily | ||||||||
| Protein Function |
Translocates drugs and phospholipids across the membrane (PubMed:8898203, PubMed:2897240, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:9038218).
Click to Show/Hide
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| Mechanism Description |
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| Increased risk of bradycardia Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Amiodarone | Sofosbuvir | |||||||
| Mechanism 2 | Bradycardia | Bradycardia | |||||||
| Key Mechanism Factor 2 | |||||||||
| Factor Name | Bradycardia | ||||||||
| Factor Description | Bradycardia is a slow heart rate in which the heart beats less than 60 times per minute. If the heart rate is very slow and the heart is not pumping enough oxygen-rich blood to the body, and you may feel dizzy, very tired or weak, and short of breath. | ||||||||
| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Concomitant use of amiodarone with sofosbuvir-containing hepatitis C antiviral treatment is not recommended. However, if coadministration is unavoidable, some authorities recommend cardiac monitoring in an inpatient hospital setting for the first 48 hours, followed by subsequent cardiac monitoring every day for at least the first 2 weeks of treatment. Similar cardiac monitoring is recommended for patients in whom amiodarone was discontinued just prior to starting hepatitis C antiviral treatment due to the long half-life of amiodarone. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate symptomatic bradycardia such as dizziness, lightheadedness, confusion, memory problems, fainting, malaise, weakness, excessive tiredness, palpitation, chest pain, irregular heart rhythm, shortness of breath, or syncope. | ||||||||