Comparing Prescription and Over-the-counter Lidocaine Patches

This month, we revisit a topic previously covered in a 2022 clinical feature, providing an updated comparison of prescription (Rx) and over-the-counter (OTC) lidocaine patches in response to the frequently asked question, “Do OTC lidocaine patches require the same “off time” as Rx Lidoderm® 5% patches?”

LOCALIZED PAIN

Acute and chronic pain are significant sources of suffering in advanced illness. Adverse effects from systemic analgesics (e.g., via oral or parenteral routes) contribute to and often exacerbate suffering and limit dose titration, thus hindering effectiveness. Topical analgesics, like lidocaine, offer a solution to limit systemic adverse effects and should be considered whenever pain is localized, and the severity allows for achievable pain relief with topical application.¹

Acute ailments include strains, sprains, tendonitis, acute back pain, and muscle aches. Chronic conditions, however, are more common in the hospice and palliative population and may respond to local lidocaine application. These include arthralgia (e.g., osteoarthritis, rheumatoid arthritis), low back pain, and neuropathic pain (e.g., diabetic neuropathy, localized peripheral neuropathic pain, post-herpetic neuralgia).^2-4

Lidocaine is available in creams, ointments, gels, lotions, and patches.⁴

PRESCRIPTION (RX) TRANSDERMAL PATCHES (E.G., LIDODERM® 5%, ZTLIDO® 1.8%)

The transdermal route is defined as “administration through the dermal layer of the skin to the systemic circulation by diffusion.”⁵ Although many literature sources and drug information databases categorize prescription lidocaine patches as transdermal, they are technically FDA-approved as topical,^6-7 delivering medication to the outer surface of the body. Dose and application limitations in the product prescribing information exist to prevent systemic lidocaine toxicity, however lidocaine systemic absorption when used according to package instructions is low and several pharmacokinetic studies have shown that systemic lidocaine levels remain safe, even with extended dosing (18-24 hours) and up to 4 patches per application.^8-10

Lidoderm® 5% and ZTlido® 1.8% patches are FDA-approved for postherpetic neuralgia, however, are used off-label for general topical anesthesia of skin.⁴ These products have a drug-in-adhesive (DIA) system with two layers, a backing layer (furthest from the skin) and the drug-in-adhesive layer. A release liner covers the DIA layer and is removed before application.¹¹ Prescribing instructions include:

• Apply patch to intact skin to cover the most painful area. Up to 3 patches may be applied in a single application. Patch(es) may remain in place for up to 12 hours in any 24-hour period, leaving a patch-free period of at least 12 hours.^4,12,13
• Patches may be cut into smaller sizes with scissors prior to removal of the release liner.^4,13

A single 5% Lidoderm patch contains 700 mg lidocaine. When used according to the recommended dosing instructions, approximately 3% of the dose applied is expected to be absorbed. At least 95% (665 mg) of lidocaine will remain in a used patch.¹³ In comparison, a single 1.8% ZTlido patch contains 36 mg lidocaine yet provides equivalent lidocaine absorption as the 5% patch.¹⁴ ZTlido is designed with a more efficient delivery of lidocaine with less residual left in the patch after normal use¹⁵ – it is also promoted as having improved adhesion to skin compared to Lidoderm.¹⁶

OVER-THE-COUNTER (OTC) TOPICAL PATCHES (E.G., LIDOCARE® 4%, SALONPAS® 4%)

OTC products are not regulated by the FDA and usually have not been subject to the same clinical trials required for prescription products. As such, they lack individual pharmacokinetic and efficacy data as well as comparative trial data with prescription products. The FDA revisited the underlying regulations that allow external analgesics to be marketed over the counter without a new drug application (NDA) approval in 2003, and formally designated topical patches as Category III (safety and efficacy unknown).^11,17

Nevertheless, OTC products are used widely by patients and may be recommended by clinicians for less severe symptoms as a less costly and easier to access alternative. Instructions for use vary, making it important to refer to the manufacturer’s labeling for product-specific recommendations. General guidance includes:^12,16

• Apply 1 patch to painful area
• Frequency varies from 1 to 4 times daily in a 24-hour period
• Duration of application varies from 8 to 24 hours

Despite absence of guidance on the necessity of allowing a patch-free (i.e., lidocaine-free) period, it is accepted that the OTC lidocaine patch products do not need the “off time” like prescription Lidoderm® 5% patches. Rule of thumb – for the OTC patch containing only lidocaine, up to 3 times a day is appropriate, however, some products may allow use up to 4 times daily on the package label.^18,19

Keep in mind, Lidoderm 5% patches are transdermal, and employ a different method of medication delivery compared to topicals such as lidocaine cream, ointment, jelly, and OTC patches. The OTC patches may provide slightly longer pain relief than cream, ointment, and jelly; however, all these products must be managed with the same application frequency recommendations.

Also, frequency recommendations for OTC patches vary among products by different manufacturers, leading to discrepancies in drug information. Recognize that several OTC lidocaine patches contain additional ingredients, like menthol, camphor, and methyl salicylate, which may limit patient tolerance and application frequency. Be mindful of the manufacturer’s labeling and monitor for safety (e.g., application site irritation/lesions) and pain relief.

TAKE AWAY POINTS

• Efficacy and safety data exists for the Rx patches only
• Scarcity of literature comparing Rx and OTC patches
• OTC patches are usually less costly
• OTC patches are more accessible to patients, making them useful alternatives for mild symptoms
• Rx and OTC patches have different dosing frequencies, application durations, and patch-free requirements¹⁶

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CITATIONS

1. Portenoy RK, Krotova E, Lussier D. Chapter 45: Adjuvant analgesic drugs. In: Textbook of palliative medicine and supportive care. Boca Raton: Taylor & Francis Group, LLC; 2015.
2. Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults – an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017 May; 2017(5): CD008609.
3. Tauben D, Stacey BR. Approach to the management of chronic non-cancer pain in adults. In: UpToDate, Fishman S, Swenson S, Nussmeier NA (Eds), Wolters Kluwer. (Accessed Aug 7, 2026).
4. Clinical Pharmacology [database online]. Tampa, FL: Elsevier/Gold Standard, Inc.; 2026.
5. Food & Drug Administration (FDA). Routes of administration. Accessed Aug 7, 2026. Site link
6. Lidoderm 5% NDA. In: Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food & Drug Administration. Accessed Aug 7, 2026. Site link
7. ZTLido 1.8% NDA. In: Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food & Drug Administration. Accessed Aug 7, 2026. Site link
8. Rosielle DA. The Lidocaine Patch. In: Palliative Care Network of Wisconsin (PCNOW) Fast Facts. Jul 3, 2025. Article link
9. Gammaitoni AR, Davis MW. Pharmacokinetics and tolerability of lidocaine patch 5% with extended dosing. Ann Pharm. 2002; 36:236-240.
10. Gammaitoni AR, Alvarez NA, Galer BS. Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: A review of the literature. J Clin Pharmacol. 2003;43:111-117.
11. Nalamachu S, Gudin J. Characteristics of Analgesic Patch Formulations. J Pain Res. 2020:13. Article link
12. UpToDate Lexidrug [database online]. Wolters Kluwer; 2026.
13. Lidocaine patch 5%. Rochester, MI: Par Health USA; Dec 2025. Resource link
14. ZTLido (lidocaine topical system 1.8%). Palo Alto, CA: Scilex Pharmaceuticals Inc.; Revised Nov 2024. Resource link
15. Gudin J, Argoff C, Fudin J, et al. A randomized, open-label, bioequivalence study of lidocaine topical system 1.8% and lidocaine patch 5% in healthy subjects. J Pain Res. 2020 Jun 22;13:1485–1496. Article link
16. Clinical Resource, Characteristics of Transdermal Patches (United States). Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. November 2024.
17. Food & Drug Administration. Marketed Unapproved Drugs – Compliance Policy Guide. Sec. 440.100 Marketed New Drugs Without Approved NDAs or ANDAs. September 19, 2011. Article link
18. Clinical Resource, Topicals for Pain Relief. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. May 2024.
19. Article, Consider OTC Alternatives to Lidoderm, Pharmacist’s Letter, November 2017.