Topical Analgesics for Persistent (Chronic) Pain

Chapter outline

IT is important to distinguish between the terms topical and transdermal (Stanos, 2007). Although both routes require a drug to cross the stratum corneum to produce analgesia (Figure 24-1), transdermal drug delivery (e.g., long-acting transdermal fentanyl patch) requires absorption to achieve systemic effects, whereas topical agents (e.g., lidocaine patch 5% and other local anesthetics, capsaicin) are intended to produce effects in the tissues immediately under the site of application (Stanos, 2007). Transdermal analgesic drugs provide systemic analgesia, and topical analgesics provide what is referred to as “targeted peripheral analgesia,” or pain relief achieved by “dampening” pain mechanisms within the peripheral nervous system (Argoff, 2003). Transdermal delivery systems typically have a slow onset and extended duration of analgesia. Topical analgesics are faster acting and dissipate relatively soon after removal of the drug.

Figure 24-1 Anatomy and physiology of the skin: potential analgesic action sites. Adapted from Brown, M. B., Martin, G. P., Jones, S. A., et al. (2006). Dermal and transdermal drug delivery systems: Current and future prospects. Drug Deliv, 13(3), 175-187. In S. P. Stanos. (2007). Topical agents for the management of musculoskeletal pain. J Pain Symptom Manage, 33(3), 345.

There are significant benefits to using topical analgesics, including patient acceptance, ease of administration, reductions in systemic adverse effects, and fewer drug interactions (Argoff, 2003; McCleane, 2008; Stanos, 2007). Some preparations (e.g., capsaicin, L.M.X.4) can be obtained without a prescription; others (e.g., lidocaine patch 5%, clonidine, EMLA, diclofenac patch) require a prescription. Some topical analgesics (e.g., antidepressants, anticonvulsants, ketamine) are not commercially available but may be prepared by a compounding pharmacy. The topical therapies discussed here are those used primarily for persistent pain and include the lidocaine patch 5% and other local anesthetics, capsaicin, antidepressants, anticonvulsants, clonidine, and ketamine. A bupivacaine patch (Eladur) was under development at the time of publication. Local anesthetics used for procedural pain are discussed in Chapter 28. Topical formulations containing aspirin or NSAIDs are discussed in Chapter 7. A list of topical agents can be found in Table 24-1.

Guidelines

Table 24-1

Topical Analgesics

Type	Example	Indications/Comments
Local anesthetics	Lidocaine patch 5% (Lidoderm) Eutectic mixture of local anesthetics (EMLA) (2.5 mg lidocaine + 2.5 mg prilocaine) Lidocaine 4% cream (L.M.X.4) Lidocaine 70 mg + tetracaine 70 mg (Synera) J-tip Benzocaine 20% Spray (Hurricaine)	Approved for postherpetic neuralgia; used for a wide variety of types of persistent (chronic) and acute pain Cream used primarily for dermal procedural local anesthesia; some data on long-term use Cream for dermal procedural local anesthesia Patch for dermal procedural local anesthesia Needless delivery under pressure of local anesthetic for dermal procedures Associated with methemoglobinemia
Capsaicin	Qutenza 8% patch, Arthritis Formula Capiscum, Capzasin, Trixaicin, Zostrix, and others	Patient must be warned of burning sensation on application and that this will subside with regular, uninterrupted applications; patch requires a prescription, and supervised application is recommended
Antidepressants	Tricyclic antidepressants (amitriptyline, doxepin)	No commercially available preparations
Anticonvulsants	Clonazepam (Klonopin)	No commercially available preparations
Clonidine	Catapres TTS	Transdermal formulation
Ketamine	Ketalar	No commercially available preparations

This table provides guidelines for the use of the several of the topical analgesics.

From Pasero, C., & McCaffery, M. Pain assessment and pharmacologic management, p. 685, St. Louis, Mosby. Pasero C, McCaffery M. May be duplicated for use in clinical practice.

Lidocaine Patch 5%

The topical lidocaine patch 5% (Lidoderm) is 10 cm by 14 cm and contains 700 mg of lidocaine in an aqueous base. After removing a polyethylene terephthalate film release liner, the patch is placed directly over or adjacent to the painful area (Pasero, 2003b) (see Box 24-1 for guidelines on the use of the lidocaine patch 5%). The patch is not sterile so should not be placed in wounds, but they are often placed around painful wounds. They may be cut to fit smaller areas as well. For example, a patch can be cut into strips and wrapped around painful fingers or toes. A trial period of three weeks is recommended to determine effectiveness of lidocaine patch 5% (Dworkin, O’Connor, Backonja, et al., 2007).

Guidelines

Box 24-1

Use of Topical Lidocaine Patch 5%¹

Description

10 cm by 14 cm patch containing 700 mg of lidocaine in an aqueous base

Indications

Targeted peripheral neuropathic and other pains (see text for research on specific types of pain and Figure 24-1 for action site)

Contraindications

• Allergy to amide local anesthetics

• Lack of skin integrity at site of application

Safety warning: May produce additive effects in patients taking antiarrhythmic medications (e.g., mexiletine, IV lidocaine)

Dosing recommendations

Up to 3 patches worn for 12 hours, then removed and followed by a period of wearing no patch for 12 hours (12 hours on, 12 hours off). This application process may be repeated as needed for continued analgesia.

Note: Although the manufacturer recommends no more than 3 patches in a 24-hour period, up to 4 patches worn continuously for 24 hours has been shown to be safe. Further, long-term use of 3 to 4 patches for 12 to 24 hours has been shown to be safe (see text).

Trial period to determine effectiveness

3 weeks

Patch storage

• Keep patch at room temperature of 15° to 30° C (59° to 86° F).

• Keep patch in sealed package until ready to use.

• Apply promptly after removal from sealed package.

Application instructions

1. Ensure that area of application is clean and dry.

Note: Application of the patch after daily hygiene activities (e.g., bathing or showering) is recommended. Do not apply cream or powder to the targeted area prior to application. Protect patch from becoming wet during wear (e.g., cover with waterproof material such as ordinary plastic [polyethylene] wrap if bathing is necessary while patch is in place). Patients should be told to avoid putting heat (e.g., heating pads, hot packs) directly on the patch as this increases absorption of the lidocaine and can lead to toxicity.

2. Slowly remove the film release liner from the back of the patch.

Note: The patch may be cut before removal of the release liner to fit the targeted area. Cutting the patch does not affect absorption of the drug.

3. Warn the patient that the patch may feel cool when first applied.

4. Place the patch (or patches) directly on or beside (e.g., around wound) the painful area.

Note: The patch is not sterile and should be placed on intact skin only. Although the patch may be used in patients with acute herpes zoster (near affected area), it should not be placed on open vesicles.

5. Smooth out the patch over the targeted area making sure all edges adhere.

6. The patch may be covered with clothing to prevent accidental displacement, e.g., patches placed on a foot or calf may be covered with a sock or stocking.

7. After 12 to 24 hours, remove the patch.

8. Repeat application process for continued pain relief.

Disposal instructions

1. Fold the used patch on top of itself.

Note: Only 2% of the drug in the patch is absorbed; at least 95% is left in the patch when removed after 12 hours. Proper disposal is essential to prevent exposure to others, such as children and pets.

2. Discard in the same manner as other pharmaceutical waste in health care institutions.

Note: Most health care institutions do not consider the lidocaine patch 5% to be hazardous waste.

¹ The lidocaine patch 5% should not be confused with other patch systems such as the fentanyl transdermal patch (see text for distinction between topical and transdermal delivery systems).

From Pasero, C., & McCaffery, M. Pain assessment and pharmacologic management, p. 686, St. Louis, Mosby. Pasero C, McCaffery M. May be duplicated for use in clinical practice.

Lidocaine and other local anesthetics relieve pain primarily by suppressing the activity of peripheral sodium channels thereby reducing ectopic, paroxysmal discharges and pathologic pain transmission (see Section I and Figure I-2 on pp. 4-5). A major advantage of analgesics such as the lidocaine patch 5% is that they work peripherally rather than systemically, and thus are associated with a low incidence of systemic adverse effects (Stanos, 2007). Although lidocaine is a local anesthetic, penetration of the drug following topical application is sufficient to produce an analgesic effect but not a sensory block. Patients should be told to expect pain relief, not anesthesia. At this time, the lidocaine patch 5% is available only by prescription. (See lidocaine patch 5% patient medication information, Form V-8 on pp. 773-774, at the end of Section V.)

Guidelines on the treatment of neuropathic pain recommend the lidocaine patch 5% as a first-line (Dubinsky, Kabbani, El-Chami, et al., 2004; Dworkin, O’Connor, Backonja, et al., 2007) or second-line (Moulin, Clark, Gilron, et al., 2007) drug for postherpetic neuralgia. However, a Cochrane Collaborative Review called for further research comparing it with other medications for the treatment of this condition (Khaliq, Alam, Puri, 2007). Nevertheless, it is approved for postherpetic neuralgia, and the safety, effectiveness, and convenience of this drug for treatment of this condition led to its use for a wide variety of other types of pain and pain syndromes. Below is a list of case reports, reviews, and research.