Options for treating postherpetic neuralgia in the medically complicated patient

Figures & data

Table 1 Drugs recommended as therapy for postherpetic neuralgia

	American academy of neurology 2004^Citation12	Canadian pain society 2007^Citation14	International association for the study of pain 2010^Citation10	European federation of neurological societies 2010^Citation13
Tricyclic antidepressants	First-line	First-line	First-line	First-line
Anticonvulsants
Gabapentin	First-line	First-line	First-line	First-line
Pregabalin	First-line	First-line	First-line	First-line
Lidocaine patch 5%	First-line	Second-line	First-line	First-line
Tramadol	First-linea	Third-line	Second-line	Not recommended
Opioids	First-line	Third-line	Second-line	Second-line
Capsaicin 8% patch	Second line	No recommendation	Third-line	Second-line
Capsaicin cream	Second-line	No recommendation	No recommendation	Second-line

Note:

a Grouped with opioids.

Table 2 Potential drug–drug interactions of drugs commonly prescribed for postherpetic neuralgia

Drug	Metabolic pathwaya	Pharmacokinetic interactions	Pharmacodynamic interactions
Generally first-line therapies
Tricyclic antidepressants
Amitriptyline	CYP2D6^Citation49,Citation50	CYP2D6 substrates, CYP3A4 inhibitor^Citation49,Citation50	Anticholinergic drugs (additive) Sympathomimetic drugs (additive) CNS depressants (additive) MAOis, guanethidine, thyroid medications, disulfiram (additive)^Citation71
Nortriptyline	CYP2D6^Citation49,Citation50	CYP2D6 substrates, CYP3A4 inhibitor^Citation49,Citation50	Anticholinergic drugs (additive) Sympathomimetic drugs (additive) Chlorpropamide (hypoglycemia)^Citation72
Desipramine	CYP2D6^Citation49,Citation50	CYP2D6 substrates, CYP3A4 inhibitor^Citation49,Citation50	Anticholinergic drugs (additive) Sympathomimetic drugs (additive) CNS depressants (additive)^Citation73
Clomipramine	CYP2D6^Citation49,Citation50	CYP2D6 substrates^Citation49	Anticholinergic drugs (additive) Sympathomimetic drugs (additive) CNS depressants (additive) Highly protein-bound drugs (eg, warfarin, digoxin)^Citation80
Calcium channel α2-δ ligands
Gabapentin^Citation60	None	Hydrocodone (reverse) Morphine (↑ gabapentin concentrations)	Minimal interaction potential
Pregabalin^Citation59	None	Minimal interaction potential	Oxycodone (additive) Lorazepam (additive) Thiazolidinedione (additive)
Lidocaine patch 5%^Citation69	None	None	Antiarrhythmics (additive)b
Generally second-line therapies
Opioids^Citation64
Codeine	CYP2D6/ glucuronidation	CYP2D6 substrates, inhibitors, and inducers	Anticoagulants (additive) CNS depressants (additive)
Fentanyl	CYP3A4	CYP3A4 substrates, inhibitors, and inducers	CNS depressants (additive)
Hydrocodone	CYP2D6/ glucuronidation	CYP2D6 substrates, inhibitors, and inducers	CNS depressants (additive)
Hydromorphone	Glucuronidation	Minimal interaction potential	CNS depressants (additive)
Methadone	CYP2B6 CYP2C8 CYP2C19 CYP2D6 CYP2C9 CYP3A4	CYP substrates, inhibitors, and inducers	CNS depressants (additive) Arrhythmogenic agents – Class i and ii (additive) TCAs, CCBs, antipsychotics – selected (additive) Diuretics and laxatives
Morphine	Glucuronidation	Minimal interaction potential	CNS depressants (additive)
Oxycodone	CYP3A4/ CYP2D6	CYP3A4 substrates, inhibitors, and inducers/ CYP2D6 substrates, inhibitors, and inducers	CNS depressants (additive)
Oxymorphone	Glucuronidation	Minimal interaction potential	CNS depressants (additive)
Tramadol	CYP3A4, 2D6, 2B6	CYP3A4 substrates, inhibitors, and inducers CYP2D6 substrates, inhibitors, and inducers	CNS depressants (additive) SSRis, TCAs, SNRIs, MAOIs, cyclobenzaprine, triptans (additive)
Capsaicin patch^Citation45	None	None	None

Notes:

a Several opioids undergo CYP-mediated metabolism to metabolites that require glucuronidation. For example, codeine is metabolized to morphine, which then undergoes glucuronidation;

b this warning is for all formulations of lidocaine, including injectable formulations.

Abbreviations: CCBs, calcium channel blockers; CNS, central nervous system; CYP, cytochrome P450; MAOIs, monoamine oxidase inhibitors; SNRIs, serotonin– norepinephrine reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants.

Table 3 Risks associated with drugs for postherpetic neuralgia: patients with renal or hepatic impairment or failure

Relative risk	Renal impairment/failure		Hepatic impairment/failure
	First-line therapies	Second-line therapies	First-line therapies	Second-line therapies
Low risk	Amitriptyline^Citation71 Nortriptyline^Citation72 Lidocaine patch 5%^Citation69	Fentanyla,^Citation64 Capsaicin patch/cream^Citation45	Desipramine^Citation73 Nortriptyline^Citation72 Gabapentin^Citation60 Pregabalin^Citation59	Fentanyla,^Citation64 Capsaicin patch/cream^Citation45
Use with caution	Clomipramine^Citation80 Desipramine^Citation73 Gabapentinb,^Citation60 Pregabalinb,^Citation59	Tramadol^Citation64 Methadone^Citation64	Amitriptyline^Citation71 Clomipramine^Citation80 Lidocaine patch 5%c,^Citation69	Hydromorphone^Citation64 Morphine^Citation64 Oxycodone^Citation64 Methadone^Citation64
Avoid	NA	Codeine^Citation64 Hydrocodone^Citation64 Morphine^Citation64 Tapentadold,^Citation37	NA	Codeine^Citation64 Oxymorphone^Citation64 Tramadol^Citation64 Tapentadold,^Citation37
Limited information	NA	Hydromorphone^Citation64 Oxycodone^Citation64 Oxymorphone^Citation64	NA	Hydrocodone^Citation64

Notes:

a Not recommended in opioid-naive patients;

b dose should be adjusted based on creatinine clearance in older patients suspected of having renal impairment;

c patients with severe hepatic disease are at greater risk of developing toxic blood concentrations of lidocaine because of their inability to metabolize lidocaine normally;

d not recommended in patients with severe renal or hepatic impairment; may use with caution in patients with moderate hepatic impairment, and no dose adjustment is needed in patients with mild hepatic impairment.

Abbreviation: NA, not applicable.

Table 4 Drugs for postherpetic neuralgia: relative risk in patients with cardiovascular or respiratory disease, cerebrovascular disease, or brain disorders

Relative risk	First-line therapies	Second-line therapies
Cardiovascular or respiratory disease
Low risk	Gabapentin^Citation60 Pregabalin^Citation59 Lidocaine patch 5%^Citation69	Tramadol^Citation64,Citation109
Use with caution	TCAsa,^Citation71^–^Citation73,Citation80	Morphine^Citation64 Oxycodone^Citation64 Oxymorphone^Citation64 Fentanylb,^Citation64 Capsaicin patch^Citation42,Citation45,Citation99
Avoid	NA	Methadone^Citation64 Codeine^Citation64
Cerebrovascular disease/brain disorders
Relative risk	First-line therapies	Second-line therapies
Low risk	Lidocaine patch 5%^Citation69
Use with caution	TCAs^Citation32,Citation111	Capsaicin patch^Citation45
	Gabapentin^Citation24 Pregabalin^Citation23	Most opioids^Citation113^–^Citation116
Avoid	NA	Morphine^Citation114^–^Citation116 Hydromorphone^Citation113,Citation117

Notes:

a Avoid in patients with heart failure;

b not recommended in opioid-naive patients.

Abbreviations: NA, not applicable; TCA, tricyclic antidepressant.

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