Insights from CE - Drug Interaction (Alert) Overload
In a nutshell, not all computerizes / automated drug interaction alerts are of clinical importance, this resulted in so-called "alert fatigue". Currently most software systems could not function more specifically based on factors like dose, timing, age, gender, pharmacogenetics, comorbidity, or the duration of drug therapy. What are some ways to avoid this problem of "alert fatigue"?
Source: http://pharmacistsletter.therapeuticresearch.com/ce/cecourse.aspx?pc=12-216
Examples:
- Reduce topical medicines that are unlikely to pose risk. With exception of example, timolol eye drops as it can worsen bradycardia when given with other drugs that slow cardiac conduction, like verapamil or digoxin, especially in patients with heart failure or who already have a slow heart rate.
- Identify formulation-specific interactions. Example, potassium pills are not to be given with anticholinergic drugs. The concern is that anticholinergic drugs reduce gastrointestinal (GI) motility, making it more likely that potassium chloride pills will adhere to the GI mucosa and cause ulceration. This interaction can confuse software systems. Potassium chloride solutions and powders may get flagged as a problem although they are not of concern. And of course inhaled anticholinergics are not of concern too.
- In a VA study, 20% of overridden warfarin interaction alerts were for an interaction between warfarin and vitamin E. All of these alerts were triggered by prescriptions for a multivitamin containing 60 iu of vitamin E. But, vitamin E doses less than 400 iu are not expected to interact with warfarin.
- Drug interactions can occur because of effects that persist after a long-acting drug has been discontinued or because discontinuation of a drug alters hepatic metabolism of the victim drug.
"The effects of some drugs may be present after they are discontinued. For example, most monoamine oxidase (MAO) inhibitors bind to monoamine oxidase for the life of the enzyme, so it takes several weeks after discontinuing an MAO inhibitor for the enzyme to reaccumulate. This is why a 14-day washout period is recommended between discontinuing an MAO inhibitor and starting another serotonergic drug. Some drugs with extremely long half life are of concern as well.
Discontinuation of a cytochrome P450 (CYP) enzyme inhibitor or inducer can lead to loss of efficacy or toxicity of a CYP substrate. For example, dosage increases of some atypical antipsychotics (risperidone [Risperdal], quetiapine [Seroquel], etc) may be necessary during coadministration of carbamazepine (Tegretol) because it is a powerful inducer of multiple CYP enzymes and P-glycoprotein. Subsequent discontinuation of carbamazepine can increase exposure to the atypical antipsychotic and put the patient at risk for adverse effects like akathisia and Parkinsonism. Clinicians may fail to detect this interaction.19 "Uninduction" after discontinuation of carbamazepine can take one to two weeks.20 The ideal drug interaction alert for discontinuation of carbamazepine would provide options for managing the interaction."
Hard-stop alerts problems
A few as described below which I have extracted from the article.
"One institution experienced unintended consequences when they initiated a study to evaluate a new hard-stop rule for the interaction between trimethoprim/sulfamethoxazole (TMP/SMX, Bactrim, etc) and warfarin.24 This interaction was considered a good candidate for a hard-stop alert because it reliably increases the INR and leads to bleeding complications. The study found that the hard-stop was effective in reducing coadministration of warfarin and TMP/SMX. However, the study was stopped early after the hard-stop alert was linked to important delays in treatment for both warfarin and TMP/SMX."
"Even the interaction between phosphodiesterase inhibitors and nitroglycerin may have situations in which it may be appropriate for patients to have access to both drugs. In the inpatient setting, coadministration of IV nitroglycerin and sildenafil might be indicated in patients with severe pulmonary hypertension and angina in an intensive care setting with monitoring.26 In the outpatient setting, a patient who has a prescription for as-needed use of sildenafil (Viagra) for erectile dysfunction might also have a prescription for sublingual nitroglycerin for use in case angina ever occurs."
"One institution set a Level 2 alert requiring a response from the clinician after initial research indicated that proton pump inhibitors (PPIs) might reduce the efficacy of clopidogrel (Plavix). As more conflicting research results were published, the interaction became more controversial. The interaction was downgraded to a Level 3 information-only alert. At that point, analysis of alert data found that the alert had led some clinicians to discontinue clopidogrel rather than the PPI, an unintended consequence that might place the patient at risk of a cardiovascular event. Clinicians were notified so that appropriate care could be ensured for patients affected by the alert. This vignette should be a reminder of the need to continually reassess alert advice as new data becomes available."
Source: http://pharmacistsletter.therapeuticresearch.com/ce/cecourse.aspx?pc=12-216
Examples:
- Reduce topical medicines that are unlikely to pose risk. With exception of example, timolol eye drops as it can worsen bradycardia when given with other drugs that slow cardiac conduction, like verapamil or digoxin, especially in patients with heart failure or who already have a slow heart rate.
- Identify formulation-specific interactions. Example, potassium pills are not to be given with anticholinergic drugs. The concern is that anticholinergic drugs reduce gastrointestinal (GI) motility, making it more likely that potassium chloride pills will adhere to the GI mucosa and cause ulceration. This interaction can confuse software systems. Potassium chloride solutions and powders may get flagged as a problem although they are not of concern. And of course inhaled anticholinergics are not of concern too.
- In a VA study, 20% of overridden warfarin interaction alerts were for an interaction between warfarin and vitamin E. All of these alerts were triggered by prescriptions for a multivitamin containing 60 iu of vitamin E. But, vitamin E doses less than 400 iu are not expected to interact with warfarin.
- Drug interactions can occur because of effects that persist after a long-acting drug has been discontinued or because discontinuation of a drug alters hepatic metabolism of the victim drug.
"The effects of some drugs may be present after they are discontinued. For example, most monoamine oxidase (MAO) inhibitors bind to monoamine oxidase for the life of the enzyme, so it takes several weeks after discontinuing an MAO inhibitor for the enzyme to reaccumulate. This is why a 14-day washout period is recommended between discontinuing an MAO inhibitor and starting another serotonergic drug. Some drugs with extremely long half life are of concern as well.
Discontinuation of a cytochrome P450 (CYP) enzyme inhibitor or inducer can lead to loss of efficacy or toxicity of a CYP substrate. For example, dosage increases of some atypical antipsychotics (risperidone [Risperdal], quetiapine [Seroquel], etc) may be necessary during coadministration of carbamazepine (Tegretol) because it is a powerful inducer of multiple CYP enzymes and P-glycoprotein. Subsequent discontinuation of carbamazepine can increase exposure to the atypical antipsychotic and put the patient at risk for adverse effects like akathisia and Parkinsonism. Clinicians may fail to detect this interaction.19 "Uninduction" after discontinuation of carbamazepine can take one to two weeks.20 The ideal drug interaction alert for discontinuation of carbamazepine would provide options for managing the interaction."
Hard-stop alerts problems
A few as described below which I have extracted from the article.
"One institution experienced unintended consequences when they initiated a study to evaluate a new hard-stop rule for the interaction between trimethoprim/sulfamethoxazole (TMP/SMX, Bactrim, etc) and warfarin.24 This interaction was considered a good candidate for a hard-stop alert because it reliably increases the INR and leads to bleeding complications. The study found that the hard-stop was effective in reducing coadministration of warfarin and TMP/SMX. However, the study was stopped early after the hard-stop alert was linked to important delays in treatment for both warfarin and TMP/SMX."
"Even the interaction between phosphodiesterase inhibitors and nitroglycerin may have situations in which it may be appropriate for patients to have access to both drugs. In the inpatient setting, coadministration of IV nitroglycerin and sildenafil might be indicated in patients with severe pulmonary hypertension and angina in an intensive care setting with monitoring.26 In the outpatient setting, a patient who has a prescription for as-needed use of sildenafil (Viagra) for erectile dysfunction might also have a prescription for sublingual nitroglycerin for use in case angina ever occurs."
"One institution set a Level 2 alert requiring a response from the clinician after initial research indicated that proton pump inhibitors (PPIs) might reduce the efficacy of clopidogrel (Plavix). As more conflicting research results were published, the interaction became more controversial. The interaction was downgraded to a Level 3 information-only alert. At that point, analysis of alert data found that the alert had led some clinicians to discontinue clopidogrel rather than the PPI, an unintended consequence that might place the patient at risk of a cardiovascular event. Clinicians were notified so that appropriate care could be ensured for patients affected by the alert. This vignette should be a reminder of the need to continually reassess alert advice as new data becomes available."
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| Drug Interactions in Assessment Tool for Drug Interaction Software37 |
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