Polypharmacy Approach for
Pain Management
Tracy M. Hagemann, Pharm.D., FCCP, FPPAG
October 5, 2012
Objectives
• Define polypharmacy as it relates to pain
management
• 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?
Definition
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
toxicity
• 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
action
– 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
•
Non-opioids
•
Opioids
•
Adjuvants
– Anti-anxiety
– Anti-depressant
– Neuropathic pain treatments
•
Anticonvulsants (i.e. gabapentin)
– Steroids
– Topicals
•
Side effect management
– Constipation
– Nausea/vomiting
– Sedation
Considerations for Rational
Polypharmacy
• 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
Age
• 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
doses
Gender
• 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
Ethnicity
• 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
drug
– Example: opioid-sparing strategies, addition of
anti-inflammatories
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
opioid
Indication #4
• To target different symptom clusters that are
a product of the disease or a comorbid
disease
– 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
process
– Example: pain that has peripheral AND central
mechanisms may require medications that use each
pathway
– Example: topical lidocaine patch with an
antidepressant
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
Comorbidity
• Use drugs for comorbid disease that have proven analgesic
efficacy
• 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
depression
Prescribing Guidelines for
Polypharmacy
• Anticipate the impact of adding the new
medication
• Avoid
– Prescribing medications that significantly inhibit
or induce CYP450 enzymes
Prescribing Guidelines for
Polypharmacy
• 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
Polypharmacy
• 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
S.A.I.L.
• 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
2010;15:507-22.
•
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.