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The contents of this blog contain topics relevant to end of life care written by our own hospice clinical pharmacists. Continue to check this site regularly for the newest post or subscribe to the RSS feed below.

Dr. Shane Donnelly is a PGY2 Pain and Palliative Care Pharmacy Resident at Delta Care Rx. He received his doctorate of pharmacy degree with a specialty certificate in Medication Therapy Management from Duquesne University in May of 2015. Dr. Donnelly’s areas of focus in residency training with Delta Care Rx include palliative therapeutics, pain management, academia, and infectious diseases. He started his professional career with Delta Care Rx as the PGY1 Pharmacy Practice Resident in June of 2015.

Shane Donnelly, PharmD

Estimating Risk for Thromboembolism in Atrial Fibrillation: The ATRIA Risk Score

2016 06 28 9 45 57Atrial fibrillation, or Afib, is essentially a temporary, semi-permanent, or permanent change in the electrophysiology of the atria of the heart. Afib is the abnormal rapid contraction of the atria, resulting in an irregular atrioventricular contraction rhythm. This decreases the heart’s ability to eject blood through the body efficiently (decreased cardiac output), thus increasing stasis of pooled blood within the chambers of the heart. Patients with atrial fibrillation are at an increased risk for arterial thromboembolic events because of the procoagulant effect of hemostasis.

The most common arterial thromboembolic event correlated with atrial fibrillation is ischemic stroke. Determining the risk for thromboembolism in these patients is multifactorial and risk factors such as concurrent valvular heart disease (i.e. mitral valve stenosis, prosthetic valves etc.), significantly increase the risk for thromboembolism.1 In patients with valvular heart disease, the risk for thromboembolism high and anticoagulation or antiplatelet therapy should be utilized, barring significant contraindications to either warfarin (Coumadin) or aspirin. Hospice patients with prosthetic valves, mechanical valves, or significant valvular stenosis should maintain anticoagulation or antiplatelet therapy until the patient loses the ability to swallow, or a bleeding diathesis poses a greater risk to the patient and family than the benefit of preventing an ischemic stroke.

In patients with non-valvular atrial fibrillation, the risk of stroke is less significant and warrants an investigation into the patient’s risk of having an ischemic event. There are several modalities by which to estimate risk for thromboembolism in patients with non-valvular atrial fibrillation. The CHADS2 and CHA2DS2-VASc scores are the most common scoring tools utilized by clinicians. Each scoring system is briefly described below.2

CHADS2 - Assigns points to patients based upon risk factors proven in various trials to increase the risk for ischemic stroke in patients with atrial fibrillation. Does not take into account previous history of arterial vascular disease (aortic plaque, myocardial infarction, peripheral arterial disease, etc.) or sex. Assigns 1 point for: congestive heart failure, hypertension, age greater than 74, or the presence of diabetes mellitus. Assigns 2 points to patients with a history of stroke/TIA. In this scoring system, patients with a score of 0 are considered low risk, a score of 1 equates to a moderate risk, and 2 or greater indicates a high risk patient.

CHA2DS2-VASc - Broadens stroke risk assessment for patients between the ages of 65-74, adds increased risk points for age greater than 74, and includes history of arterial vascular disease and female sex as additional risk factors. Assigns 1 point for: congestive heart failure, hypertension, presence of diabetes mellitus, arterial vascular disease, age between 65-74, or female sex. Assigns 2 points for an age greater than 74 years and history of stroke/TIA. This risk estimation system utilizes the same risk score-based anticoagulation parameters as CHADS2.

The 2014 AHA/ACC/HRS guidelines recommends utilizing vitamin K antagonists (i.e. warfarin) or novel oral anticoagulants (rivaroxaban [Xarelto ®] or apixaban [Eliquis ®]) with a CHADS2 or CHA2DS2-VASc score of 2 or greater (moderate-high risk).3 The downfall to utilizing these risk assessments is the underestimation of low risk in patients who fit parameters for high risk of stroke.

The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) risk score is a novel tool designed to more accurately define high risk versus low risk patients.4 The ATRIA score includes risk factors addressed with CHADS2/CHA2DS2-VASc and adds the presence of renal dysfunction as an additional risk factor (eGFR < 45 mL/min or ESRD and proteinuria). The ATRIA risk score, however, stratifies patients into two categories based on the presence/absence of stroke/TIA in the past medical history. This unique feature of ATRIA may provide additional clinical significance in avoiding anticoagulation when it may actually not be clinically necessary.

In hospice patients, the need for anticoagulation is a clinical conundrum that frequently leaves clinicians wondering if anticoagulation is necessary. Patients may or may not be able to swallow, which complicates matters further. The ATRIA risk score may provide hospice clinicians a better picture as to whether anticoagulation is necessary. The scoring system is more time-intensive in comparison to the CHADS2/CHA2DS2-VASc stroke risk scores, but in the end may be able to help prevent adverse bleeding events and can become a cost-effective approach to anticoagulation in hospice patients. The scoring system is as follows:4

Risk Factor Points without prior stroke Points with prior stroke
Age (years)
            85 or greater 6 9
               75-84 5 7
               65-74 3 7  
               Less than 65 0 8
Female 1 1
Diabetes 1 1
CHF 1 1
Hypertension 1 1
Proteinuria 1 1
eGFR less than 45 mL/min 1 1

In patients with an ATRIA risk score of 6 or below, the risk of stroke per 100 patient years is approximately that of a CHADS2/CHA2DS2-VASc stroke risk score or 0-1.2 In patients scoring above a 6, the benefits of stroke prevention most likely outweigh the risk of major bleeding with anticoagulation. In patients with a score less than 6, it may be feasible to discontinue anticoagulation or downgrade the intensity of anticoagulation. Downgrading anticoagulation could include discontinuing warfarin or the novel oral anticoagulants, discontinuing clopidogrel, and switching the patient to low-dose aspirin (81 mg orally once daily). If the patient’s ATRIA scores are as low as 2, anticoagulation is most likely unnecessary.

Most clinicians are familiar with the CHADS2/CHA2DS2-VASc stroke risk scores. Some hospice patients may require a more rigorous assessment of stroke risk, and the benefits of anticoagulation should be weighed versus the risks of adverse bleeding events, drug interactions, and the evolving issue of polypharmacy. It may be advantageous to consider utilizing the ATRIA risk score to assist with anticoagulation decision making at the end-of-life in patients with non-valvular atrial fibrillation. Populations that may particularly benefit from an ATRIA risk assessment include patients with no history of stroke/TIA and those at an older age without renal dysfunction or other significant comorbidities.


References:
1. Nishimura R, Otto C, Bonow R et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-2492. Accessed December 14th 2015.
2. Friberg L, Rosenqvist M, Lip G. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. European Heart Journal. 2012;33(12):1500-1510. Accessed December 14th 2015.
3. January C, Wann L, Alpert J et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary.Journal of the American College of Cardiology. 2014;64(21):2246-2280. Accessed December 15th 2015.
4. Singer D, Chang Y, Borowsky L et al. A New Risk Scheme to Predict Ischemic Stroke and Other Thromboembolism in Atrial Fibrillation: The ATRIA Study Stroke Risk Score. Journal of the American Heart Association. 2013;2(3):e000250-e000250. Accessed December 17th 2015.

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Shane Donnelly, PharmD

Renal Dosing for Commonly Used Oral Antibiotics

The kidneys are one of the most important organs responsible for eliminating substances from the body. Structural damage to the excretion mechanisms of the kidneys slows the filtration and elimination process down, allowing drug metabolites to stay in the body for longer periods of time. For some medications with inactive and harmless metabolites, this is not a relevant issue. However, for medications with active metabolites or medications that are not completely metabolized by the liver, this poses a potentially significant problem. The inability to efficiently eliminate active drug molecules puts patients at risk for harmful adverse effects. Antibiotics are particularly interesting in this regard. When dosed appropriately and efficiently eliminated by the body, side effect profiles are often mild and harmless. However, when dosed inappropriately in a patient with renal impairment, active drug molecules or metabolites can build up and may induce or exacerbate neurological, cardiac, or pulmonary comorbid conditions.

The table below provides a foundation for dosing common antibiotics in patients with renal impairment. It is important to utilize this table in the manner in which it was intended; purely as a reference point. Individualize treatment based on the patient and the indication that is being treated.

Renal Dosing Guide for Commonly Used Oral Antibiotics  
 
Antibiotic Renal-Dosing Special Considerations  
Amoxicillin (Amoxil) Amoxicillin + Clavulanate Potassium (Augmentin)

Severe Impairment (CKD Stage 4) give 250-500 mg amoxicillin q12h

End-Stage Disease (CKD Stage 5) give  250-500 mg amoxicillin q24h

All products containing

875 mg of Amoxicillin or extended-release formulations should be avoided in patients with severe impairment.

 
Azithromycin (Z-Pack, Zithromax) None. Use with caution. No specific renal dosing required in manufacturer's labeling.  
Cefaclor (Ceclor) None. Use with caution. No specific renal dosing required in manufacturer’s labeling.  
Cefuroxime (Ceftin)

Severe Impairment (CKD Stage 4) give the indicated dose q24h

End-Stage Disease (CKD Stage 5) give the indicated dose q48h

Alternatively, may dose at 15 mg/kg/dose q24h in patients with End-Stage Disease.  
Cephalexin (Keflex)

Moderate-Severe Impairment (CKD Stage 3-4) give 500 mg q8-12h

End-Stage Disease (CKD Stage 5) give 500 mg q12-24h

Cost-effective option for treating skin and soft tissue infections and may be used as an alternative agent for uncomplicated UTIs.  
Ciprofloxacin (Cipro)

Moderate Impairment (CKD Stage 3) give 250-500 mg q12h

Severe Impairment (CKD Stage 4) give 250-500 mg q18h

End-Stage Disease (CKD Stage 5) give 250-500 mg q24h

If using extended-release formulation, dose at 500 mg q24h with Severe Impairment.  
Clarithromycin (Biaxin) Severe Impairment (CKD Stage 4) decrease the dose by 50% Many drug interactions. May need to decrease dose with certain HIV medication.  
Clindamycin (Cleocin) None Potential alternative to penicillin due to allergy.  
Doxycycline Monohydrate (Vibramycin) None Potential safe alternative for community-acquired pneumonia or MRSA in patients with renal dysfunction.  
Erythromycin (Ery-Tab) None Medication can be used to induce gastric motility.  
Levofloxacin (Levaquin)

Moderate Impairment (CKD Stage 3) give 250 mg q24h +/- 500 mg loading dose (or) 750 mg q48h

Severe Impairment (CKD Stage 4) give 250-500 mg q48h +/- 500-750 mg loading dose

Dosing largely depends on indication. Utilize dose of that fits the suspected organism/infection.  
Metronidazole (Flagyl) None. Use with caution. Metabolites may accumulate in patients with End-Stage Renal Disease.  
Nitrofurantoin (Macrobid, Macrodantin) Moderate Impairment (CKD Stage 3) note that use is contraindicated Some literature1 suggests nitrofurantoin can be used safely in patients with a CrCl >40 mL/min for short-term treatment of uncomplicated UTI's (<1 week).  
Penicillin V Potassium (Pen VK) Use with caution. Excretion of penicillin is prolonged in patients with renal impairment.  
Sulfamethoxazole/ Trimethoprim (Bactrim, Septra)

Severe Impairment (CKD Stage 4) decrease the dose by 50%

End-Stage Disease (CKD Stage 5) note that use is not recommended

Dosing is highly dependent on indication.

*Per LexiComp, Wolters Kluwer Health 2
**Degree of Impairment and estimated Glomerular Filtration Rate: Moderate Impairment (CKD Stage 3): CrCl < 60 mL/min; Severe Impairment (CKD Stage 4): CrCl < 30 mL/min; End-Stage Disease (CKD Stage 5): CrCl < 15 mL/min

Age over 65 years old, hypertension, cardiovascular disease, diabetes, tobacco use, and obesity are all risk factors for developing chronic kidney disease 4. Many patients admitted to hospice have at least one of these risk factors. Awareness of the common signs of chronic kidney disease (known risk factors, consistent itching, changes in urine output, etc.4 can help the team to safely utilize medication.

Ultimately, the decision to treat and effectively dose antibiotics relies on the constant vigilance of the palliative care/hospice team. Awareness of the common dosing of antibiotics, the indications, and dosing for renal impairment can lead to better outcomes for patients who experience the uncomfortable reality of their diseases.


References:
1. Oplinger M and Andrews CO. “Drug Information Rounds: Nitrofurantoin Contraindication in Patients With a Creatinine Clearance Below 60 mL/min: Looking for the Evidence,” Ann Pharmacother, 2013, 47(1):106-11. 
2. LexiComp. Hudson, Ohio: Wolters Kluwer Health; c1978-2015. https://online.lexi.com/lco/action/home. 
3. The National Kidney Foundation. GFR. 2014. Available at: https://www.kidney.org/kidneydisease/siemens_hcp_gfr. 
4. Mayoclinic.org. Chronic kidney disease Risk factors - Mayo Clinic. 2015. Available at: http://www.mayoclinic.org/diseases-conditions/kidney-disease/basics/risk-factors/con-20026778.

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Shane Donnelly, PharmD

Prescription Drug Misuse, Dependence, and Abuse in the Elderly

Older adults are often left out of the discussion when it comes to prescription drug misuse, dependence, and abuse. Prescription drug abuse is an epidemic in this country, and it’s not just confined to the younger patient population. It is estimated that 11% of elderly patients abuse prescription medication.1

The elderly consume roughly one quarter of the prescriptions sold in the United States.1 Elderly patients often have chronic pain, anxiety, or insomnia that requires the use of potentially addictive medication. Additionally, elderly patients may not be adequately treated with their current therapies. These risk factors, along with social isolation, depression, and limited functionality, make the geriatric population particularly at risk for substance misuse and abuse.

Providing safe and effective care for elderly patients requires that signs of prescription misuse, dependence, and abuse are recognized quickly. The medications that are often abused can lead to events such as falls and accidents that require these patients to be admitted to inpatient units or nursing homes. To effectively manage prescription medication misuse and abuse in this population, the definition of substance misuse, dependence, tolerance, and abuse should be addressed.

Misuse- Prescription medication misuse is the improper taking of medication by the patient. It is most commonly by accident, but can also be intentional. Assess your patient’s ability to take medication correctly. It may be necessary to provide pharmaceutical education to your patient.  Examples include.2

• Taking medication differently than directed on the label due to poor eyesight or reading ability

• Doubling up on doses

• Borrowing medication from friends or family members

• Acquiring medication online to treat self-diagnosed conditions

Physical dependence and Tolerance- Physical dependence evolves from the continued regular use of a substance that results in withdrawal symptoms upon discontinuation. Tolerance to medication occurs when patients need higher doses of medication to achieve adequate symptomatic relief. Patients with physical dependence and tolerance may display drug-seeking behavior that can be misconstrued as psychological dependence (addiction).2 Assess the patient’s current condition and medication profile. The patient’s therapy may be inadequate due to tolerance or lack of efficacy. Communicate concerns with the patient’s physician. The patient may then cease to engage in drug-seeking behavior.

Psychological dependence (addiction)- Psychological dependence is a state that demonstrates loss of control and/or compulsive drug-seeking behavior.3 These patients engage in medication use despite the potential for adverse consequences. These patients need professional help to overcome both physical and psychological dependence. At this point, it is important to understand that these patients are potentially putting themselves and others in immediate danger.

In hospice, it is rare for a patient to become psychologically dependent on medication. It is important to be aware of any signs of substance abuse among family members or caregivers. Recognizing signs of caregiver abuse is important to protect patients and provide the best possible care for the end-of-life stage. It’s important to listen your patient’s concerns regarding their medication and to assess the root cause of medication discrepancies.


References:

1 Culbertson JW, Ziska, M. Prescription drug misuse/abuse in the elderly. Geriatrics. 2008; 63(9): 22-31.

2 Agins, A. Prescription drug abuse: from bad to worse. CEdrugstorenews.com March/April 2012. Retrieved July 5, 2012 at: http://www.cedrugstorenews.com/userapp//lessons/lesson_view_ui.cfm?lessonuid=401-000-12-201-H01.

3 American Psychiatric Association. Diagnostic and Statistical Methods of Mental Disorders (Fourth Edition, Text Revision). Washington, DC: American Psychiatric Association. 2000;199-273

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