Drug for deprescription | Substrate | Possible adverse drug reaction from stopping an enzyme inducer or inhibitor | Prevention or amelioration of potential rebound adverse drug event |
---|---|---|---|
Ritonavir (Strong inhibitor) | Fluticasone, budesonide | Decreased level of corticosteroids → adrenal insufficiency | Monitor for signs and symptoms of adrenal insufficiency; perform an ACTH stimulation test if symptoms of adrenal insufficiency present; depending on symptoms and duration of adrenal axis suppression, supplemental cortisone may be required |
Pioglitazone | Decreased level of pioglitazone → hyperglycemia | Monitor for glycemia; increase pioglitazone if symptomatic hyperglycemia develops or switch to an alternative agent | |
Candesartan | Increased level of candesartan → hypotension or acute kidney injury | Monitor blood pressure and renal function; decrease dose of candesartan if blood pressure decreases or creatinine increases | |
Phenytoin (Strong inducer) | Simvastatin | Increased level of simvastatin → rhabdomyolysis, acute liver injury | Monitor for symptoms of myalgia and weakness; monitor for symptoms of right upper quadrant pain and jaundice; decrease dose of simvastatin or stop drug if adverse effects occur |
Carbamazepine (Strong inducer) | Olanzapine | Increased level of olanzapine → increased sedative effect, orthostatism, extrapyramidal effects | Monitor for adverse effects and decrease dose of olanzapine |
Cyclosporine | Increased level of cyclosporine → risk of acute calcineurin inhibitor nephrotoxicity | Monitor renal function and electrolytes; consult transplant service to adjust cyclosporine if toxicity develops | |
Apixaban, rivaroxaban | Increased therapeutic effect of apixaban or rivaroxaban → bleeding events | Monitor for signs of bleeding; counsel patient to seek medical attention if bleeding complication occurs | |
Propranolol | Increased level of propranolol → bradycardia | Monitor for bradycardia/arrhythmia and adjust dose | |
Fluoxetine, paroxetine, bupropion (Strong inhibitors) | Repaglinide | Decreased level of repaglinide → hyperglycemia | Monitor for hyperglycemia; increase dose of repaglinide or add a second agent if symptomatic hyperglycemia develops |
Gemfibrozil (Inhibitor) | Repaglinide | Decreased level of repaglinide → hyperglycemia | Monitor for hyperglycemia; increase dose of repaglinide if symptomatic hyperglycemia develops |
Verapamil, diltiazem (Inhibitors) St. John’s wort (Inducer) | Fentanyl | Decreased level of fentanyl → pain crisis | Monitor for symptoms of pain crisis; counsel patient to seek medical attention if symptoms of opioid withdrawal develop |
Warfarin | Increased level of warfarin → supratherapeutic INR and bleeding events | Monitor INR more frequently; decrease warfarin dose |
Note: ACTH = adrenocorticotropic hormone, INR = international normalized ratio.
* Important concept: patients taking multiple drugs can be in a state of relative homeostasis. Clinicians should be aware that stopping a strong inducer or inhibitor may affect the metabolism of some substrate drugs, whether increasing (inducer stopped) or decreasing (inhibitor stopped) their therapeutic effect.