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 2001Linjakumpu et al 2002Kaufman 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

long-acting 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.

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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.

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symptom control, polypharmacy, and adverse reactions. Am J Hosp Palliat Care

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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.