Polypharmacy Approach for Pain Management

Polypharmacy Approach for
Pain Management
Tracy M. Hagemann, Pharm.D., FCCP, FPPAG
October 5, 2012
• Define polypharmacy as it relates to pain
• Identify patients at high risk for adverse effects
with polypharmacy
• Identify indications for the rational use of
polypharmacy in treating acute and chronic pain
What is it?
polypharmacy /poly·phar·ma·cy/ (-fahr´mah-se)
• 1. administration of many drugs together.
• 2. administration of excessive medication.
– Duplication
– Potentially inappropriate medications
Dorland's Medical Dictionary for Health Consumers. © 2007
Polypharmacy and Pain
• Multiple medications to treat a single condition
• Using multiple drugs from the same class or
multiple drugs with a similar mechanism of
action to treat different conditions
• Generally the RULE rather than the exception,
especially for chronic pain
When is it appropriate?
• Not all polypharmacy is inappropriate
– Co-morbidities
– Different mechanistic pathways
– Treatment of side effects
Who is at risk for adverse events?
• Those with co-morbidities
• Older patients
• Patients who are non-adherent to their
medication/treatment regimens
Rational Polypharmacy
• Multimodal approach – achieve pain relief with minimal
• Goals:
– Use lower doses of > 1 drug to minimize adverse effects
– Increase adherence
– Maintain analgesic efficacy to prevent pain
– Increase efficacy using > 2 drugs with different mechanisms of
– Target different but associated symptoms
– Target different locations of the disease process
Barriers to Rational Polypharmacy
• Drug-Drug Interactions
• Drug-Disease Interactions
• Medication abuse, misuse and addiction
Pain Medication Arsenal
– Anti-anxiety
– Anti-depressant
– Neuropathic pain treatments
Anticonvulsants (i.e. gabapentin)
– Steroids
– Topicals
Side effect management
– Constipation
– Nausea/vomiting
– Sedation
Considerations for Rational
• Know drug toxicities
• Avoid overlapping/additive toxicities
• Know drug mechanisms of action
• Understand drug pharmacokinetics
• Have convincing evidence that the combination
is more effective than monotherapy
Patient Factors
• Age
• Gender
• Ethnicity
• Physiologic aging impacts pharmacokinetics
• Increased risk of drug-drug interactions with
multiple drug use
• Aging affects pharmacodynamics
– Affects at receptor sites
– Number of receptors binding capacity and
biochemical reactions
Age - Recommendations
• Initiate treatment at lowest effective dose
• Give as small a dose as possible for long-term
therapeutic effect
• Make SLOW changes in medications and
• Women use more medications
– 4.8 Rx meds vs. 3.8 Rx meds
– 81% vs. 74%
– 12% of women over 65 years of age take at least
10 medications
• 23% take at least 5 prescription medications
Jorgensen et al 2001
Linjakumpu et al 2002
Kaufman et al 2002
• Associations
– Ethnicity and other diseases like HTN, CV, malignancy
– Ethnicity and drug metabolism (CYP 2D6)
• 5-10% of Caucasians and 1-2% of African Americans and Asians are
poor metabolizers
– More likely to have frequent adverse events with standard doses
• Fast Metabolizers
– 10-15% Ethiopians and Saudi Arabians
– 1-5% Caucasians
– 2% African Americans
– 0-2% Asians
– More likely to have subtherapeutic effects with standard doses
Drug-Related Variables
• Mechanism of action/pharmacodynamics
• Efficacy
• Dosage forms available
• Pharmacokinetics
• Adverse effects
• Drug Interactions
• Cost
Indications and Examples
Indication #1
• To reduce drug intolerance by using a 2nd drug
that allows a lower dose of 1st drug
• May lead to increased adherence
• Provide analgesic efficacy at certain times of day
(giving IR with long-acting drugs)
– Control breakthrough pain in a patient taking longacting opioids
Indication #2
• To use a lower dose of a drug by using a 2nd
– Example: opioid-sparing strategies, addition of
Indication #3
• To address partial or non-response to 1 drug by
adding a 2nd drug to increase efficacy
– Example: use 2 medications with different
mechanisms of action
– Example: use a medication that has synergy with the
1st medication
• Add an NMDA-type medication to a regimen containing an
Indication #4
• To target different symptom clusters that are
a product of the disease or a comorbid
– Example: pain associated with depression
– Example: pain worsened by anxiety
Indication #5
• To treat the comorbid disease by aggressively
treating the index disease
– Example: treat diabetes aggressively thereby
reducing peripheral neuropathy severity
Indication #6
• To address different locations of the disease
– Example: pain that has peripheral AND central
mechanisms may require medications that use each
– Example: topical lidocaine patch with an
Indication #7
• To treat an adverse effect
– Nausea/vomiting
– Itching
– Sedation
– Constipation
Approach to Rational Polytherapy
• Consider:
– Pain and non-pain medications
– Prescription, OTC and homeopathies/others
– PK/PD profile of all used medications
– Therapeutic index of each medication
– Route of elimination of the medications
– Patient’s health status
5 Principles for Pain-Associated
• Use drugs for comorbid disease that have proven analgesic
• Your 1st target symptom should always be PAIN
• Target all possible pain mechanisms
• Do not shoot for absolute pain relief
– Aim for tolerable pain levels (QoL)
• Use drugs to address more than one comorbidity
– Example: Sedating antidepressant for pain, sleep and
Prescribing Guidelines for
• Anticipate the impact of adding the new
• Avoid
– Prescribing medications that significantly inhibit
or induce CYP450 enzymes
Prescribing Guidelines for
• Prescribe medications that:
– Are eliminated through multiple pathways
– Do not have serious consequences if their
metabolism is prolonged
– With different mechanisms of action from the
patient’s existing medications
Prescribing Guidelines for
• Remind patients to tell you when other
physicians prescribe medications for them
• Remember
– Metabolism can create active or more active
compounds that the parent drug
– Generally, the older the medication, the less is known
about it’s metabolism
• SIMPLIFY the drug regimen as much as possible
• Know the ADVERSE EFFECTS of each drug and the
drug-drug interactions
• Each medication should have a clear INDICATION and
well-developed therapeutic goal
• LIST the name and dosage of each medication in the
chart and provide this information to the patient.
Selected References
Werder SF, Preskorn SH. Managing polypharmacy: walking the line between help and harm. J
Fam Prac 2003;2(2)
Maggiore RJ, Gross CP, Hurria A. Polypharmacy in older adults with cancer. The Oncologist
Chaparro LE, Wiffen PJ, Moore RA, Gilron I. Combination pharmacotherapy for the treatment of
neuropathic pain in adults. Cochrane Database 2012;7:Article #:CD008943
Gallagher RM. Rational integration of pharmacologic, behavioral, and rehabilitation strategies in
the treatment of chronic pain. Am J Phys Med Rehabil 2005;84(3Suppl):S64-76.
Al-Shahri MZ, Molina EH, Oneschuk D. Medication-focused approach to total pain: poor symptom
control, polypharmacy, and adverse reactions. Am J Hosp Palliat Care 2003;20:307-310.
Smith H, Bruckenthal P. Implications of opioid analgesia for medically complicated patients.
Drugs Aging 2010;27(5):417-33.
Pergolizzi JV, Labhsetwar SA, Puenpatom RA, et al. Exposure to potential CYP450
pharmacokinetic drug-drug interactions among osteoarthritis patients: incremental risk of
multiple prescription. Pain Practice 2011;11(4):325-36.

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