James B. Ray, PharmD, CPE The James A. Otterbeck Professor of Hospice & Palliative Care University of Iowa College of Pharmacy 11/18/2015 Deprescribing at the End-of-Life: Less is More

Deprescribing – systematic process of identifying and discontinuing drugs in instances in which existing or potential harms outweigh existing or potential benefits in the context of an individual patients’ care Brief background - definitions and statistics

Packet of patient cases Task – Identify which medications you would deprescribe – Share rationale – Prioritize….which would you DC first? CASES –

Remaining Life Expectancy Time Until Benefit Goals of Care Treatment Target

Clinical judgement and patient guided decision making – Ongoing discussion Standards of care and practice guidelines can be momentarily forgotten Goals of Care

Hyperlipidemia increases with age However, very old, severely ill patients, and actively dying patients may having declining LDL and TC levels Too low of TC may be a marker of poor outcomes Time-to-benefit for statins – 2-6 years Burdens of statins: – Myopathy and myalgias – Fatigue – Pill burden – Lab testing – Cost Statins

Proven benefit for fracture prevention in osteoporosis and for women on anti-estrogen therapies Correct duration of therapy is unknown Risks of bisphosphonates include: Short term » Headache, dyspepsia, abdominal pain, gastrointestinal ulcers, muscle cramps Long term » Bone fractures, chronic bone/joint/muscle pain, osteonecrosis of the jaw, severe hypocalcemia Issues at the end-of-life – Administration – Cost – Adverse effects – Quality of life – Extended efficacy? Bisphosphonates

Primary prevention of cardiovascular disease and kidney disease BP is used as a surrogate marker for control Guideline driven care with specific BP targets – often >1 drug Issues at the end-of-life Fatigue Hypotension Orthostasis Falls Cognitive impairment Anti-hypertensives

Evidence-based recommendations: How do I stop it? The how?

If used daily for more than 3-4 weeks then: Reduce dose by 25% every week (i.e. week 1-75%, week 2-50%, week 3-25%) If intolerable withdrawal symptoms occur (usually 1-3 days after a dose change), go back to the previously tolerated dose until symptoms resolve and plan for a more gradual taper with the patient Dose reduction may need to slow down as one gets to smaller doses (i.e. 25% of the original dose) The rate of discontinuation needs to be controlled by the person taking the medication. Benzodiazepines

Symptoms to monitor for: – Rebound insomnia – Tremor – Anxiety – Hallucinations – Seizures – Delirium Benzodiazepines

If used daily for more than 3-4 weeks then: Reduce the dose by 25% every 3 to 4 days Once at 25% of the original dose and no withdrawal symptoms have been seen, stop the drug If any withdrawal symptoms occur, go back to approximately 75% of the previously tolerated dose. Opioids

Symptoms to monitor for: – Restlessness – Runny nose – Goose flesh – Sweating – Muscle cramps – Insomnia – Pain – Secretion of tears – Dilation of the pupils – Breathlessness – Decrease or impairment in daily function Opioids

If used daily for more than 3weeks: – Reduce dose by 50% every 1 to 2 weeks (7-10 days) – May stop once at 25% if not symptomatic – Metoprolol and atenolol Symptoms to monitor for: – Chest pain – Pounding heart – Blood pressure – does it need to be re-measured? – Anxiety – Tremor Beta Blockers

If used for >1 week: – Reduce dose by 50% every week – May taper over 2-4 days – Oral versus patch? Symptoms to monitor for: – Rebound hypertension – Headache – Insomnia – Tachycardia – Hiccups – Salivation Clonidine

Depends on the agent! – Paroxetine and venlafaxine – Fluoxetine Taper over several months – reduce the dose by 25% every 4 to 6 weeks Symptoms to monitor for: – Insomnia – Flu-like symptoms – Imbalance – Sensory experiences (electric shock-like feelings) – Hyperarousal – N/V/D – Agitation Anti-depressants

Taper over 2-4 weeks Decrease dose by 25% every week Symptoms to monitor for: – High fever – Altered mental status – Muscle rigidity – Muscle cramps and pain Re-initiate therapy if symptoms are intolerable at 75% of the original dose Baclofen

Tizanidine Corticosteroids Anti-psychotics Gabapentin Anti-epileptics Carisoprodol Nitrates Others

Help patients understand WHY a medication may not be appropriate any longer Discuss how they may feel after stopping the medication Tell them HOW you are going to stop the medication WHAT are you going to do if symptoms come back? Use conversation to help understand your patient’s treatment target, goals of care, and overall wishes about medications Be an advocate for your patients