NAV

Drug Interactions Structure & Example

In this example we will review the interaction between Clarithromycin (DB01211) and Atorvastatin (DB01076)

{
    "interactions": [
        {
            "ingredient": {
                "drugbank_id": "DB01211",
                "name": "Clarithromycin"
            },
            "affected_ingredient": {
                "drugbank_id": "DB01076",
                "name": "Atorvastatin"
            },
            "description": 
"The risk or severity of rhabdomyolysis can be increased when Clarithromycin is combined with Atorvastatin."
,
            
"extended_description"
: "Clarithromycin is a potent inhibitor of the CYP3A family of enzymes, including CYP3A4, and has demonstrated a similar inhibitory potential on the hepatic influx transporter OATP1B1. Atorvastatin's metabolism is primarily mediated by CYP3A4, and OATP1B1 is considered the most important influx transporter related to statin drugs - given these multiple avenues of potential interaction, the co-administration of clarithromycin and atorvastatin can result in markedly increased serum concentrations of atorvastatin. Both _in vitro_ and _in vivo_ studies have estimated that clarithromycin may increase the AUC of co-administered atorvastatin by 2- to 6-fold, although documented inter-individual variability exists due to genetic polymorphisms associated with OATP1B1 activity. Statins, including atorvastatin, have been associated with skeletal muscle toxicity ranging from mild myalgia to rhabdomyolysis, and the risk of these adverse effects appear tied to serum concentrations of the statin and its metabolites. The risk of severe manifestations of this adverse effect, such as rhabdomyolysis, may therefore be significantly increased when atorvastatin is co-administered with clarithromycin.",
            "action": "increase_specific_adverse_effects",
            
"severity": "moderate",

            "subject_dosage": "",
            "affected_dosage": "",
            
"evidence_level": "level_1",

            "management": "Prescribing information for both atorvastatin and clarithromycin recommend limiting the dose of atorvastatin to 20mg daily in patients requiring concomitant therapy, though other mitigation strategies exist. The use of a statin metabolized with less involvement from CYP3A (e.g. fluvastatin or rosuvastatin) may also be considered. Patients should be monitored closely for signs of developing skeletal muscle toxicity (e.g. muscle pain, tenderness) and therapy adjusted or discontinued should these symptoms arise. In the context of short-term antibiotic therapy, it may be more prudent to adjust the antibiotic in question. For patients maintained on atorvastatin requiring short-term antibiotic therapy, consider the use of an alternative (i.e. non-macrolide) antibiotic where appropriate. If a macrolide antibiotic is necessary, azithromycin may be considered due to a more favorable interaction profile, though this regimen is still not without its risks. If no suitable alternative exists and clarithromycin must be used, atorvastatin should be withheld for the duration of antibiotic therapy and for two weeks after completing the course."
        }
    ],
    "total_results": 1
}
By reading this structure we can see that there is a moderate interaction which increases the severity of the adverse effect rhabdomyolysis when taking Clarithromycin - DB01211 and Atorvastatin - DB01076. The extended description that follows, is more detailed and is mostly meant for healthcare professionals. This interaction is a level 1 interaction since it is found directly on the label of the drug product. The best way to manage the interaction would be to limit the dose of atorvastatin to 20mg daily in patients requiring concomitant therapy, though other mitigation strategies exist. Patients should be monitored closely for signs of developing skeletal muscle toxicity (e.g. muscle pain, tenderness) and therapy adjusted or discontinued should these symptoms arise.