Details of Drug-Drug Interaction
| Drug General Information (ID: DDIIV05ML6) | |||||||||
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| Drug Name | Carteolol (ophthalmic) | Drug Info | Dronedarone | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antihypertensive Agents | Group Iii Antiarrhythmics | |||||||
| Structure | |||||||||
| Mechanism of Carteolol (ophthalmic)-Dronedarone Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Carteolol (ophthalmic) | Dronedarone | |||||||
| Mechanism 1 | CYP450 2D6 substrate | CYP450 2D6 inhibitor | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 2D6 |
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Structure
Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
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| Gene Name | CYP2D6 | ||||||||
| Uniprot ID | CP2D6_HUMAN | ||||||||
| KEGG Pathway | hsa:1565 | ||||||||
| Protein Family | Cytochrome P450 family | ||||||||
| Protein Function |
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
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| Mechanism Description |
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| Increased risk of atrioventricular block Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Carteolol (ophthalmic) | Dronedarone | |||||||
| Mechanism 2 | Delay atrioventricular conduction | Delay atrioventricular conduction | |||||||
| Key Mechanism Factor 2 | |||||||||
| Factor Name | Atrioventricular block | ||||||||
| Factor Description | Atrioventricular block is a type of cardiac conduction block that occurs when the electrical signal from the atria to the ventricles is impaired. In an Atrioventricular block, this electrical signal is either delayed or completely blocked. When the signal is completely blocked, the ventricles produce their own electrical signal to control the heart rate. The heart rate produced by the ventricles is much slower than that produced by the sinus node. | ||||||||
| Mechanism Description |
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| Increased risk of bradycardia Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Carteolol (ophthalmic) | Dronedarone | |||||||
| Mechanism 3 | Bradycardia | Bradycardia | |||||||
| Key Mechanism Factor 3 | |||||||||
| 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 | Caution is advised if dronedarone is coadministered with a beta-blocker, including ophthalmic formulations. The dosage of the beta-blocker should start low and increased only after ECG verification of good tolerability. Patients should be advised to promptly report potential symptoms of toxicity such as excessive fatigue, fainting, difficulty breathing, chest pain or tightness, bradycardia, or arrhythmia. | ||||||||
| References | |||||||||||||||||||
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| 1 | Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ. | ||||||||||||||||||