Medication Errors Focus on the HIV-Infected Patient Nimish Patel, Pharm.D., Ph.D., AAHIVP Associate Professor Albany College of Pharmacy & Health Sciences
I do not have any conflict of interest in relation to this program or presentation.
Objectives List common causes of medication errors Describe common examples of medication errors that have occurred in the HIV and non-hiv population List common methods to reduce incidence of medication errors.
Medication Errors Medication errors affect over 1.5 million persons in the United States Excess cost of $3.5 billion annually Every hospitalized patient may be subjected to as much as one medication error per day 33,000 trademarked medication names 8,000 nonproprietary medication names Unsurprising that medication names are mixed up
Categories of Medication Errors Prescribing error Omission error Wrong time error Unauthorized drug error Improper dose error Wrong dosage form error Wrong drug preparation error Wrong administrationtechnique error Deteriorated drug error Monitoring error Adherence error Other Am J Hosp Pharm. 1993; 50:305 14
More Generally Prescribing errors Wrong dose written Drug interactions not accounted for Dispensing errors Wrong drug dispensed Drug interactions not caught Patient errors Patient takes the wrong medications Patient takes meds at the wrong dose or frequency
Implications of Errors in HIV Early discontinuation of medications Virologic Failure / Drug Resistance Drug Toxicity Finding the Balance
Percent Medication Errors on the Rise Year Clin Infect Dis. 2006; 43:933 8 Ann Pharmacother 2000; 34:833 8. Am J Health Syst Pharm 2007; 64:2064 8. HIV Med 2011; 12:494 9.
Contemporary estimate of medication errors Retrospective cohort study Johns Hopkins Hospital HIV Clinic Implemented the Eclipsys Sunrise Clinical Manager CPOE system equipped to Calculate creatinine clearance at time of order entry Alert providers to potential drug-drug interactions Eclipsys does NOT: Flag incomplete antiretroviral regimens Identify ART medication dosing or scheduling errors Yehia BR. Clin Infect Dis. 2012 May 31. [Epub ahead of print]
Contemporary estimate of med errors Collected data on: Demographics Labs Inpatient service utilization Inpatient medication use Medication errors 2 clinical pharmacists reviewed med profiles to identify: ART medication errors Drug interaction errors Yehia BR. Clin Infect Dis. 2012 May 31. [Epub ahead of print]
Contemporary estimate of med errors Errors were classified as: 1. Incomplete ART regimen 2. Incorrect dosage 3. Incorrect schedule 4. Non-recommended drug-drug combinations Per DHHS list of contraindicated or do not coadminister medications Yehia BR. Clin Infect Dis. 2012 May 31. [Epub ahead of print]
Results: 702 hospital admissions 388 HIV-infected patients 188 with ART medications prescribed and 24h admission 145 ART medication errors identified 83 patients (29% of hospital admissions) Nature of the errors: Incomplete regimen: 58% Incorrect dosage: 38% Incorrect schedule: 23% Non-recommended drug combinations: 13% Distribution of errors involving ARTs: PI: 61%, NRTI: 26%, NNRTI: 13% RTV + fluticasone 46% Yehia BR. Clin Infect Dis. 2012 May 31
Medication Errors Study Kaiser Permanente Northern California Study derived from the HIV-infected members of the Kaiser Permanente Northern California Serves 30% of resident population in N. California Approximately 5550 HIV-infected patients received health care at KPNC during the surveillance period of 2001 2002 Able to compare written prescriptions with medications dispensed to patients DeLorenze G. et al. Medical Care. 2005;43:63-68
Error Categories Explored 1. Co-administration of contraindicated drugs 2. Incorrect dosing Excluded PI s due to multiple dosing options for PIs 3. Co-administration of duplicative medications 4. Sound-alike / Look-alike drug names 5. Antiretroviral Monotherapy DeLorenze G. et al. Medical Care. 2005;43:63-68
Error Rates Type of Error Contraindicated Medications No. of potential errors seen No. of errors reviewed No. of errors confirmed 207 167 134 Incorrect Dosing 396 100 58 Duplicative Medication 27 27 16 Sound-alike / Lookalike Antiretroviral Monotherapy 23 23 10 1379 202 4 Number of errors seen in 5473 HIV-infected patients studied DeLorenze G. et al. Medical Care. 2005;43:63-68
Adverse events and catches Type of Error Contraindicated Medications Proportion of confirmed errors associated with adverse events Proportion of confirmed errors identified by clinical staff 10% 8% Incorrect Dosing 0 40% Duplicative Medication Sound Alike / Lookalike Antiretroviral Monotherapy 0 25% 0 0 0 0 DeLorenze G. et al. Medical Care. 2005;43:63-68
Case example A patient was recently hospitalized and was discharged and is now returning to your facility. You receive the following medication order Atazanavir 300mg by mouth daily Ritonavir 100mg by mouth daily Abacavir 600mg by mouth daily Any concerns?
Simple 3 drug rule For the VAST majority of patients, at least 3 antiretroviral agents should be used at one time For treatment-experienced patients, more than 3 drugs may be used Ritonavir or cobicistat is NOT considered an individual agent and should not be counted as one of the 3 agents
Simple 3 drug rule Suggestions: If you see a patient who is prescribed less than 3 antiretroviral agents, question it or look at note (if you have access). Possible consequences detrimental Incomplete virologic suppression ARV resistance
Case example 2 A patient was admitted to your facility. The medication reconciliation team provides you with the following: Darunavir 600mg by mouth daily Tenofovir 300mg by mouth daily Emtricitabine 200mg by mouth daily Any concerns?
The Boosters Should ritonavir be used in the regimen or perhaps not? Depends upon the protease inhibitor Every protease inhibitor can be boosted EXCEPT for nelfinavir Some can be un-boosted and some always must be boosted Less of an issue as cobicistat slowly replaces ritonavir as the preferred booster and is coformulated with many of the products that it boosts
The Ritonavir Rule PIs that can be given without ritonavir: Atazanavir Fosamprenavir Indinavir PIs that MUST be given with ritonavir: Darunavir Saquinavir Lopinavir (built-in) Tipranavir (higher dose) -Cobicistat coformulated with atazanavir (Evotaz) and darunavir (Prezcobix) -Cobicistat also found in Genvoya and Stribild
Drug Duplication Order written for: Lopinavir/RTV + zidovudine + Combivir Problem: Combivir contains both zidovudine and lamivudine Overdosage of zidovudine (1200mg per day) Potential adverse effects: risks for anemia, lactic acidosis, neuropathy, etc. **Likely to become a bigger issue as many ART become generic while others remain branded**
Therapeutic confusion TWO formulations of tenofovir exist Tenofovir disoproxil fumarate (TDF) ~2001 Tenofovir alafenamide (TAF) ~2015 TAF concentrations are 80-90% higher intracellularly and 90% lower in renal tubules Lower rate of GFR changes
Therapeutic confusion Formulations containing TDF Viread Truvada Complera Atripla Stribild Formulations containing TAF Genvoya Odefsey Descovey
Antiretroviral Dosing Errors Why is the prescribed dose not matching up with the dose listed in the package insert? Example? Prescription written for etravirine 400mg PO daily FDA approved dose is 200mg PO twice daily You can t get in touch with the presriber
Stuck between a rock and a hard place
Reasons for different dosing Off-label dosing that has yet to be FDA approved Once daily dosing of twice daily dosed agent Usually done for adherence concerns Renal or hepatic disease Reduced dosing may be recommended certain patients Drug-drug interactions Sometimes may alter dose to overcome drug-drug interactions
Drugs currently being dosed off label for some patients Once daily dosed etravirine 400mg PO daily Usually dosed 200mg PO twice daily Once daily dosed raltegravir 800mg PO daily Usually dosed 400mg PO twice daily
Dosage Adjustments for Organ Impairment Renal dysfunction: didanosine stavudine zidovudine tenofovir lamivudine emtricitabine Combivir (AZT+3TC) Trizivir (AZT+3TC+ABC) Epzicom (3TC+ABC) Truvada (FTC+TDF) Atripla (TDF + FTC + EFV) Complera (TDF + FTC + RPV) And others Liver dysfunction fosamprenavir indinavir amprenavir abacavir efavirenz DHHS guidelines. http://aidsinfo.nih.gov.
Drug interactions and dose adjustments What we know: Drug-drug interactions are common with antiretroviral agents Management consequences: Closer monitoring required Co-administration of agents contraindicated Dose alterations recommended to help normalize drug levels
Common Examples Atazanavir + Tenofovir Atazanavir should always be boosted with ritonavir Tenofovir + Didanosine Reduce dose of didanosine 400 to 250mg for patients >=60kg 250 to 200mg for patients <60kg Kaletra (lopinavir/ritonavir) + efavirenz Increase Kaletra dose from 2 tablets to 3 tablets twice daily
Examples Raltegravir + rifampin Increase raltegravir dose from 400mg to 800mg BID Protease inhibitors + rifabutin Reduce rifabutin dose to 150mg daily or 3 times weekly Atazanavir and acid suppressants Ensure appropriate spacing of administration times
Maraviroc Dosing Concomitant Medications Maraviroc Dosing CYP3A inhibitors (with or without a CYP3A inducer) including: -protease inhibitors Other concomitant medications 150mg twice daily 300mg twice daily CYP3A inducers (without a strong CYP3A inhibitor) including 600mg twice daily
Drug Interaction Update Numerous drug interactions exist between antiretroviral agents These interactions increase the risk for: Underdosing Poor efficacy Antiretroviral resistance Overdosing Increase the risk for toxicity and side effects Decrease tolerability
Harvoni TDF & boosted PIs In the presences of boosted protease inhibitors: Tenofovir exposures (AUC) are increased ~30% Potential for increase in renal adverse events In HIV/HCV coinfected patients using Harvoni, TDF and PIboosted regimen Even higher increases in tenofovir exposure Potential for renal adverse events Increase renal monitoring Harvoni not an issue with TAF containing products
Harvoni Amiodarone In HIV/HCV coinfected patients using amiodarone AVOID HARVONI Life-threatening reports of bradyarrythmias Contraindicated drug-drug interaction
Rilpivirine Acid Suppressants Rilpivirine Omeprazole interaction study 40% reduction in rilpivirine concentrations PPI co-administration considered a contraindication with rilpivirine H2 antagonists Use with caution with rilpivirine Administer at least 12 hours before or 4 hours after rilpivirine TMC278 Investigator s Brochure, edition 6. Tibotec Pharmaceuticals Ltd., November 2006. Edurant prescribing information. Johnson and Johnson. 2011
Salmeterol - Ritonavir Ritonavir shown to cause significant increase in salmeterol concentrations The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia. Combination not recommended Take home message: Additional reasons not to co-prescribe fluticasone-salmeterol (Advair) along with protease inhibitors WWW.FDA.GOV
Antiretroviral Check-List 1. Are they prescribed a complete antiretroviral regimen or does it look like a drug is missing 2. Are duplicate medications present? Look closely at combination products 3. Are the doses appropriate? If they are not using standard doses, are there reasons why? 4. Always consider drug interactions Can they be managed?
Example 1 The following prescription comes to your pharmacy: Darunavir 600mg BID Ritonavir 100mg BID Any concerns?
Example 1 The following prescription comes to your pharmacy: Darunavir 600mg BID Ritonavir 100mg BID Any concerns? Incomplete regimen Additional agents are necessary
Example 2 The following prescription comes your way: Darunavir 600mg BID Ritonavir 100mg BID Abacavir 600mg/d Lamivudine 50mg/d Any concerns?
Example 2 The following prescription comes your way: Darunavir 600mg BID Ritonavir 100mg BID Abacavir 600mg/d Lamivudine 50mg/d Any concerns? Lamivudine should be dosed 150mg/d at a CrCL > 40mL/min
Example 3 The following prescription comes to your pharmacy: Evotaz 1 tablet daily Ritonavir 100mg daily Truvada 1 tablet daily Any concerns?
Example 3 The following prescription comes to your pharmacy: Evotaz 1 tablet daily Ritonavir 100mg daily Truvada 1 tablet daily Any concerns? Booster duplication with ritonavir Evotaz already had cobicistat built into product (atazanavir/cobicistat)
Example 4 The following prescription comes your way: Atazanavir 300mg/d Ritonavir 100mg/d Truvada 1 tablet daily Fluticasone 1 inhalation daily Any concerns?
Example 4 The following prescription comes your way: Atazanavir 300mg/d Ritonavir 100mg/d Truvada 1 tablet daily Fluticasone 1 inhalation daily Any concerns? Coadministration ritonavir-boosted PIs with fluticasone can cause Cushing s syndrome and is not recommended
Thank You!