Archive - 2017

Opioids and Allergies
Increasing Awareness of Melatonin
Make Sure the Pharmacist Knows…
Safe Medication Practices
Options for Switching Antipsychotics
Medication Discontinuation in Dementia Patients By Corina Reyna, PharmD, BCGP
When Discontinuing Medications is Continuing Compassionate Care
Tramadol in the Hospice Setting

Opioids and Allergies

Hospice patients often communicate allergies to medications.  When the medication is an opioid, hospice staff often have to determine whether the reaction that the patient believed to be an allergy is truly an allergy and whether the reaction necessitates the avoidance of certain opioids.  True allergies involve an immune response; other reactions can fall into the category of either side effects or pseudoallergy, which is generally the result of histamine release but no actual immune response.  Given a patient’s reaction history, sometimes it can be difficult to determine which medications are safe and which are not, but some simple collection of reaction information can provide some guidance.


Pseudoallergy: If the following symptoms occur with respect to opioid administration, they are likely related to a pseudoallergy rather than a true drug allergy:

  • Generalized flushing, itching, and/or sweating
  • Mild hypotension
  • Itching, flushing, or hives at injection/application site

Such reactions can be managed with the following:

  • Try nonopioid analgesics for mild pain
  • Avoid codeine, morphine, and meperidine
  • Use a more potent opioid at appropriate doses (drugs listed below from least to most potent):
    • Meperidine < codeine < morphine < hydrocodone < oxycodone < hydromorphone  < fentanyl
  • If opioid in question is effective against pain and symptoms are mild, consider administering it with an antihistamine
  • Consider a reduction in dose, if tolerated
  • Avoid parenteral administration and/or slow down the rate of administration


Allergy: A true allergy to an opioid often displays one or more of the following:

  • Bronchospasm
  • Breathing, speaking, and/or swallowing difficulties
  • Angioedema
  • Severe hypotension
  • Urticaria

When there is a history of such symptoms related to a certain opioid:

  • Do not administer the offending agent
  • Try a nonopioid analgesic if pain is mild
  • Try an opioid from a different chemical class and monitor closely (see below for general opioid drug classes)


Drug Class Specific Agent Brand Names




Demerol®Duragesic®, Sublimaze®
Diphenylheptane Methadone Dolophine®
Phenanthrines MorphineCodeine



Oxymorphone Hydromorphone

MS Contin®, Roxanol®Tylenol #3®

Vicodin®, Lortab®, Norco®

Percocet®, OxyContin®, Oxyfast®

Numorphan®, Opana®


Increasing Awareness of Melatonin

The ever-increasing awareness of the dangers of hypnotic use in the elderly leaves many patients, prescribers, and caregivers hesitant to initiate prescription medications to treat insomnia.  Combined with the increased awareness and use of natural vitamins and supplements amongst hospice patients, many hospices are finding it desirable to utilize melatonin in certain patients having difficulty sleeping.

Melatonin is a hormone naturally produced by the pineal gland as part of the sleep-wake cycle, with its blood level being highest at night. Many proponents of its use believe that it provides benefit in sleep disorder or, more specifically, sleep disorder involving circadian rhythm.  Melatonin is a body clock regulator and not a sleep initiator.  It does not increase the body’s drive for sleep but, rather, tells the brain when it is time to sleep.

Though its adverse effects are typically mild, the most common side effects include daytime sleepiness, dizziness, and headaches, with abdominal discomfort, mild anxiety, irritability, confusion, and short-lasting feelings of depression possibly occurring.  Mobile patients who take melatonin should be advised to not engage in activities requiring alertness for four to five hours after taking melatonin.

Melatonin can potentially interact with various medications.  For instance, since it slows clotting, it should be used with caution with blood thinners.  Melatonin stimulates the immune system, so its use should be avoided in patients on immunosuppressants.  Due to its effect of increasing blood sugar levels, diabetic patients may need closer monitoring while on melatonin.  Taking melatonin along with sedative medications can cause excessive sleepiness.

Though research is mostly inconclusive regarding the efficacy of melatonin, there also is no conclusive evidence of dangers of its use at reasonable doses for short periods of time.

Fall risk, psychiatric conditions, and concurrent drug therapy can make the use of traditional hypnotics undesirable.  In such patients, it may be reasonable to consider a conservative dose of melatonin.  Doses of 3 to 5 mg are commonly used, but research indicates that lower doses in the range of 0.3 to 1 mg are more effective and possibly safer.  Regardless of the dose used, it is typically advised to administer melatonin about 90 minutes prior to the desired bedtime.

Make Sure the Pharmacist Knows…

Meeting the Conditions of Participations (CoPs) medication review requirements is important.  However, even more important is ensuring that the pharmacist performing the reviews is aware of all pertinent patient co-morbidities.  A complete list of co-morbidities is valuable in order to ensure that all potential disease-state/medication interactions are detected and the appropriate interventions are made.  Nursing staff can greatly assist in this transmission of information.  If staff is conscientious to double check patient charts for several of the most common disease states that interact with medications, patient care can be significantly improved.  Some of the most important disease states to communicate to the individual performing the medication review(s) are:

  • Renal disease (include disease stage or renal lab values)
  • Hepatic disease (type and severity)
  • Congestive heart failure (include stage, if available)
  • Heart block (include degree of heart block)
  • Benign prostate hyperplasia (BPH)
  • Asthma
  • Parkinson’s disease
  • Arrhythmias
  • Hypertension

Safe Medication Practices

The Institute for Safe Medication Practices (ISMP) has long recognized the frequency of mix-ups resulting from the non-standardization of units utilized in measuring volume of oral liquid medications.  Since 2009, ISMP has strongly encouraged all practitioners to solely utilize the metric system for measuring oral liquid doses.

The National Council for Prescription Drug Programs (NCPDP) supports the use of the milliliter (mL) as the standard unit of liquid measure for prescription oral liquid medications.  In addition to encouraging the use of the milliliter unit alone for such products, NCPDP stresses that dose amounts should always include leading zeros before the decimal point when the amount is less than one milliliter and should not include trailing zeros after a decimal point.  For instance, directions for eight tenths of a milliliter should be written as 0.8 mL and never .8 mL where the decimal point can be overlooked and the dose misinterpreted as 8 mL.  Similarly, utilize 2 mL rather than 2.0 mL which can be confused as 20 mL.  Altogether avoid the use of the teaspoon or other non-metric measurements for all patient instructions.

Always ensure that patients have a measuring device marked clearly in milliliters only to prevent errors.  For further patient safety, ISMP recommends that patients and/or caregivers be coached on use and cleaning of oral liquid measuring devices, utilizing the “teach back” approach to ascertain whether or not training is understood.


  1. NCPDP recommendations and guidance for standardizing the dosing designations on prescription container labels of oral liquid medications. March 2014
  2. ISMP 2014-15 targeted medication safety best practices for hospitals, best practice 5.

Options for Switching Antipsychotics

Medication cost, adverse effects, and poor therapeutic response often necessitate switching a hospice patient from one antipsychotic to another.  Prescribers can choose among several options when a switch is necessary.

Abrupt switch:

Often preferred by hospice prescribers, one antipsychotic can be abruptly discontinued with the immediate start of a new antipsychotic at a therapeutic dose.

Gradual tapering:

The initial antipsychotic dosage can be decreased by 25 to 50% of the total daily dose every 4 or 5 half-lives with concurrent up-titration of the new antipsychotic.  Refer to the chart of half-lives of common antipsychotics.


When overlapping products, the initial antipsychotic is continued at full dose while titrating the patient’s new antipsychotic.  When the new antipsychotic is at a therapeutic dose, the initial antipsychotic is tapered for discontinuation.

Since no one option is universally superior to another, prescribers must select the best switch method on a patient-by-patient basis.  Patient prognosis, patient stability, clinical status, efficacy of current medication(s), type of side effect(s) present, potential side effects of the new antipsychotic, and caregiver limitations are important factors that must be considered.

Problems occurring early after a switch can include psychotic symptoms, insomnia, anxiety, agitation, and extrapyramidal effects.  Since these effects can be either a response to the new medication or a result of withdrawal of the previous medication, they can be managed in various ways.  Watchful waiting is often preferred when symptoms are mild.  A slow restart of the initial antipsychotic may be necessary if severe rebound effects or withdrawal symptoms are present.  When the switch results in anxiety and restlessness, the addition of a benzodiazepine can provide temporary benefit of withdrawal effects, allowing clinicians to wait to see how the patient tolerates the switch once withdrawal dissipates.

Half-Lives of Common Antipsychotic Medications

Haloperidol 15-37 hours
Olanzapine 21-54 hours
Quetiapine 6 hours
Risperidone 3 hours in extensive metabolizers;20 hours in poor metabolizers
Ziprasidone 7 hours



Martin, C. Reducing antipsychotic medications: developing a systematic process. Consult Pharm 2015;30:378-84.

Bobo, W. (2013, Mar 13). Switching anitpsychotics: why, when, and how? Psychiatric Times. Retrieved from

Medication Discontinuation in Dementia Patients By Corina Reyna, PharmD, BCGP

Understanding the progressive nature of dementia can help in the decision to continue or discontinue dementia medications in patients on hospice care for end-stage dementia.  Goals change as patient’s progress from mild to severe dementia.  In mild to moderate dementia, the primary goal is to slow the progression of the disease.  As dementia nears its end stages, the goal of care generally shifts to the control of dementia symptoms.

Neither the cholinesterase inhibitors nor the NMDA receptor antagonists have been proven helpful in end-stage dementia.  Both classes of dementia medications have the potential to cause significant adverse effects in declining patients whose bodies are less able to efficiently metabolize these medications.  Diarrhea, loss of appetite, nausea, symptomatic slow heart rate, and fainting are all potential side effects of cholinesterase inhibitors.  Interactions with other medications increase the risk for symptoms such as worsening of mental status, urinary retention, constipation, and dry mouth.  Though some patients gain a small benefit from the continuation of dementia medications, the potential dangers of continuing dementia medications must be considered.

The decision to continue or discontinue dementia medications can seem difficult until it is realized that a simple discontinuation plan can guide therapy options and ease caregiver concerns.  A prudent plan is to gradually discontinue dementia medications, monitoring patients for any new or worsening symptoms.  Some symptoms are better managed with other medications commonly used to manage dementia symptoms at end of life.  More often than not, patients do well with the discontinuation of medications, have less risk of adverse effects from their remaining medications, and are well managed with conventional symptom management.

When Discontinuing Medications is Continuing Compassionate Care

If ever there is a time for compassionate medicine, it is when a patient is nearing the end of life.  Unfortunately, when hospice becomes involved in patient care and recommendations are made for the discontinuation of medications, patients and caregivers alike can feel abandoned.  They may feel as though the discontinuations will hasten death, worsen symptoms, or imply the patient is not worth treating any longer.

The difficulty of appropriately communicating rationale for drug discontinuation often results in continuation of unnecessary polypharmacy in order to avoid those difficult discussions.  However, if approached appropriately, these discontinuations can be made while assuring patients and caregivers of a desire to improve quality of life.

Careful consideration must be made when determining what medications to discontinue in hospice patients.  Helpful questions to ask include:

–Does a medication’s risks outweigh its benefits?

–Is the therapeutic benefit diminished to the extent that the medication no longer provides benefit?

–Is there a lack of evidence to support the continuation of therapy?

–Does this medication help meet goals of care for this patient?

–If the medication was recently added, is the time to benefit longer than life expectancy?

–Is there a clear indication for the medication?

–Has the medication been effective?

–Does the medication interact with other products or disease states?

–Are there therapeutic duplications in the patient’s drug regimen?

–Could the medication be treating a side effect of another medication?

–Is the patient and/or caregiver over-burdened with current drug regimen?

When there is no time to taper medications, ensure staff and caregivers are aware to monitor patients for withdrawal symptoms, such as rebound hypertension when blood pressure medications are discontinued or agitation when antipsychotics are stopped.

Discussions regarding discontinuation of medications can be intimidating for case managers to initiate, but educating staff on the benefits of appropriate discontinuation can give them more confidence in their presentation of such recommendations.  As hospice staff knowledge increases regarding issues surrounding the continuation versus discontinuation of risky medications, case managers are more likely to seize the opportunity to discuss the benefits of timely discontinuation.  Are family members recognizing the patient’s decline?  Consider discontinuing unnecessary medications.  Is the patient experiencing troublesome side effects that decrease quality of life?  Consider discontinuation of offending medications.  Are medications becoming ineffective?  Consider stopping those drugs that are no longer providing benefit.

Additional education regarding optimal discontinuation methods can prevent undesirable withdrawal symptoms.  Tapering may be necessary, especially in discontinuation of:

Paroxetine and venlafaxine



Anti-seizure medications


Baclofen and tizanidine




Ultimately, goals of care should always center around providing the most excellent care for the hospice patient.  As medication decisions are made, ensure that both the patient’s and physician’s goals of care are met.  Honest, open communication with the patient, family, and caregivers as well as among participants of IDG will help guide decision-making and result in the  medication regimen most appropriate for the compassionate care of each patient.

Tramadol in the Hospice Setting

Tramadol is frequently prescribed for the treatment of pain in the palliative care setting.  Various reasons for its popularity include its low cost and ease of prescribing as it is a Schedule IV medication rather than a more highly regulated Schedule II product.  However, prescribers do have to consider its pharmacology and adverse effects in order to make prudent decisions regarding its use in the hospice setting.

The mechanism of action attributed to tramadol involves both activity as a  mu-opioid agonist and as a weak inhibitor of reuptake of norepinephrine and serotonin.    Though its side effect profile is fairly similar to other opioids, its pharmacology makes it less likely to cause respiratory depression and be abused but necessitates that several cautions be taken into consideration when it is being considered for use in a hospice patient.

Caution #1: Consider Hepatic and Renal Status

Recommendations are that tramadol dosing be adjusted in patients with significant renal impairment and/or hepatic impairment.  When patients’ creatinine clearance falls below 30 mL/min, it is prudent to increase the dosing interval to 12 hours and not exceed the maximum daily dose of 200 mg.  Dosing in cirrhosis patients should not exceed 50 mg every 12 hours.  Regardless of whether or not renal and hepatic statuses are known, patients over 75 years of age should not exceed a total of 300 mg per day due to the greater risk for adverse effects.

Caution #2: Consider Potential Drug Interactions Affecting Metabolism

Tramadol functions as a prodrug, with the majority of its effects being from its pharmacologically active metabolite O-desmethyltramadol (M1).  Because the metabolism of tramadol to M1 depends upon CYP2D6, tramadol interacts significantly with other CYP2D6 inhibitors (such as fluoxetine, paroxetine, bupropion, and quinidine).  Such inhibitors decrease the plasma concentrations of M1.  Though the clinical significance of this interaction is not known, it may lead to a decrease in therapeutic response to tramadol since M1 demonstrates 6 times the analgesic effects of tramadol.

Interactions with CYP3A4 inhibitors (such as clarithromycin, verapamil, and diltiazem) are also significant as such inhibition increases plasma concentrations of tramadol and M1, increasing the risk of seizures and serotonin syndrome.

It may be appropriate to adjust dosing and clinical effects of tramadol when drugs altering its metabolism are added or withdrawn.

Caution #3: Consider Seizure Risk

Higher than recommended dosing of tramadol can result in seizure, as can concomitant use of other medications that lower the seizure threshold, such as SSRIs, SNRIs, and MAOIs.  Use caution in patients with a history of seizures or with a risk of seizures related to other medical conditions (i.e. head trauma, CNS malignancy, or drug/ethanol withdrawal).

Caution #4: Consider Risk for Serotonin Syndrome

When tramadol is concomitantly used with other serotonergic drugs, serotonin syndrome can occur.  The characteristic changes in cognitive, neuromuscular, and autonomic function typically occur within six to eight hours of an increase in dose or initiation of a serotonergic medication.

Caution #5: Risk of Clinically Significant Hypoglycemia

A large UK study found a significant increase in risk of hospitalization for hypoglycemia in those patients taking tramadol compared with those utilizing codeine.  Ensure that caregivers are aware to report any signs of hypoglycemia regardless of whether diabetic medications are being used or not.


1) Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008 Jul; 54(7): 988–992.

2) Fournier J, et. al. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. JAMA Intern Med. 2015;175(2):186-193.

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