Key takeaways
- This gel pairs three mechanism classes in one preparation: an NSAID, a muscle relaxant and a local anesthetic.
- The three agents do not have equal evidence behind them when applied topically. That distinction is worth knowing.
- Topical ketoprofen carries a recognized photosensitivity risk. Patients should keep the treated area out of sunlight.
- There is no FDA approved topical ketoprofen or topical cyclobenzaprine product in the US, so this combination requires compounding.
- Compounded preparations are not FDA approved and require a valid prescription. The prescriber decides what fits.
What this article covers
Pain in a shoulder or a lower back rarely has one clean cause. There is often inflammation, some degree of muscle guarding, and irritated tissue all contributing at once. A three agent topical gel is an attempt to address more than one of those at the same place, at the same time.
That is the reasoning, and it is a sensible one. What follows is a closer look at each of the three agents, what the research supports for each, and a safety point about ketoprofen that deserves far more attention than it usually gets.
Why these three agents
Each one is doing a different job. Prescribers who write for this combination are generally trying to cover three contributors with a single application rather than asking a patient to layer products or take several oral medications.
The appeal of a topical route is straightforward. Concentrate the drug where the problem is and keep systemic exposure lower than an equivalent dose taken by mouth.
Agent by agent, with the evidence
Ketoprofen
A nonsteroidal anti inflammatory agent. Topical NSAIDs as a class have the strongest evidence of anything in this gel. Cochrane reviews support their use for localized musculoskeletal pain, and they produce lower systemic drug levels than the same NSAID taken orally, with fewer gastrointestinal adverse events in comparative reviews.
Two things to know specifically about ketoprofen, though. There is no FDA approved topical ketoprofen product in the United States, which is a large part of why this ends up at a compounding pharmacy. And it carries a photosensitivity concern that gets its own section below.
Cyclobenzaprine
A centrally acting muscle relaxant, structurally related to tricyclic antidepressants, and FDA approved as an oral medication. Prescribers include it topically when muscle guarding or spasm seems to be contributing to the picture.
Being straightforward about it: cyclobenzaprine works centrally, and evidence for topical application is limited. There is no FDA approved topical cyclobenzaprine product. Its inclusion rests more on clinical reasoning and prescriber experience than on a body of topical trial data.
Lidocaine
A local anesthetic that blocks sodium channels in nerve endings near the application site, producing numbing where it is applied. Of the three, lidocaine has the clearest topical track record, and FDA approved topical lidocaine products exist in several strengths and formats including over the counter creams and prescription patches.
In a compounded gel, it is generally included for its local effect alongside the other agents rather than as the primary component.
Reading that honestly
One agent has solid topical class evidence, one has well established topical use with approved products available, and one is included largely on clinical reasoning. That is not an argument against the formulation. It is the information a prescriber should have when deciding whether it is the right call for a particular patient.
The photosensitivity issue nobody mentions
☀️ Ketoprofen and sun exposure
Topical ketoprofen has a recognized association with photosensitivity and photoallergic contact dermatitis. European regulators reviewed this and required specific warnings on topical ketoprofen products, and it remains one of the more notable adverse effects of this particular NSAID applied to skin.
Reactions can appear at the application site and can be significant. General precautions used with topical ketoprofen include:
- Keep the treated area covered and out of direct sunlight while using it
- Continue that protection for a period after stopping, per your prescriber's direction
- Wash hands thoroughly after application
- Avoid sunlamps and tanning beds during use
- Stop and contact your prescriber if a rash develops at the application site
Follow the specific directions your prescriber and prescription label give you. This applies year round, and in Southern California that is not a small footnote.
What combining them does and does not do
Here is where we have to be careful, because this is where marketing usually gets ahead of the evidence.
Combining agents from different mechanism classes is a reasonable clinical strategy. What has not been established is that the combination performs better than the individual pieces. In 2019, a randomized, placebo controlled trial published in Annals of Internal Medicine evaluated compounded topical pain creams for localized chronic pain and did not find them superior to placebo across the categories studied.
That result belongs in any honest discussion of these products. It does not mean no patient benefits, and prescribers continue to use multi agent topicals based on individual judgment. It does mean that a promise of relief from a custom gel goes past what anyone can support.
| Agent | Class | Topical evidence | FDA approved topical product? |
|---|---|---|---|
| Ketoprofen | NSAID | Class evidence reasonably strong for topical NSAIDs | No US approved topical product |
| Cyclobenzaprine | Muscle relaxant | Limited for topical application | No. Oral products are approved. |
| Lidocaine | Local anesthetic | Well established for local numbing | Yes, several formats |
| The combination | Multi agent | Mixed. A 2019 RCT found no benefit over placebo. | No |
The base carrying it all
Three actives in one preparation puts real demands on the vehicle. It has to hold all of them stably, help them move through skin, and feel good enough that someone applies it consistently. A preparation that separates, or that feels unpleasant enough to abandon, fails regardless of what is in it.
As a PCCA member pharmacy, we match the base to the actives and the route on your prescription.
Bases suited to multi agent topicals
Lipoderm®
PCCA's flagship permeation enhancing transdermal base. Designed to carry actives through skin, accommodates multiple actives, and has a smooth finish patients tolerate well.
PermE8™
An anhydrous permeation enhancing gel with water activity below 0.6. Supports extended default beyond use dates and holds multiple actives including salt forms.
Pharmacist's choice
Write that on the prescription and we will select a base suited to these three actives, or call and we will work through it with you.
Practical notes for the prescription
A few things that reduce back and forth and get the preparation out faster.
| Include | Why it matters |
|---|---|
| Concentration for each active | Three actives means three numbers. A percentage without a unit, or a missing one, means a call back. |
| Base preference | Name Lipoderm®, PermE8™, or simply write pharmacist's choice. |
| Quantity in grams or mL | Matched to the dosage form and the expected duration of use. |
| Application site in the Sig | Where to apply, how much, and how often. Useful for the patient and for our label. |
| Sun precaution counseling | Given the ketoprofen component, worth reinforcing at the visit as well as on the label. |
Important regulatory information
Please read this part
This compounded gel is not an FDA approved drug product. It is prepared pursuant to a valid, patient specific prescription. There is no FDA approved topical ketoprofen or topical cyclobenzaprine product in the United States. FDA approved topical options including diclofenac gel and lidocaine products are available and are appropriate for many patients.
No promise of results. Under federal law, promotion of prescription drugs, including compounded drugs, must be truthful, non misleading and accurate. Nothing in this article claims this gel will relieve pain or produce any particular outcome, or that a compounded preparation is safer or more effective than an FDA approved product.
On side effects. Topical NSAIDs produce lower systemic exposure than oral NSAIDs and comparative reviews report fewer GI adverse events, but systemic absorption still occurs and NSAID cautions still apply. Skin reactions at the application site are the most common adverse effect, and topical ketoprofen specifically carries a photosensitivity risk.
FDA recommends that patients talk with their health care professional about their specific circumstances before taking any medication.
For licensed prescribers. Cyclobenzaprine is structurally related to tricyclic antidepressants and prescribers assess interaction considerations accordingly, including with serotonergic agents and MAO inhibitors. NSAID cautions relating to gastrointestinal, renal and cardiovascular risk apply to topical NSAIDs as well, at reduced systemic exposure. Compounded preparations are used at the prescriber's clinical discretion and are not a substitute for clinical judgment. Mixwell is a non sterile compounding pharmacy in Chino, CA.
Sending a prescription to Mixwell
- Note the three concentrations, base preference or pharmacist's choice, quantity and directions including the application site.
- Fax or e prescribe to our Chino, CA pharmacy.
- Call (909) 378-7301 if you want to talk through concentrations, base selection or turnaround time.
- Your patient can pick up in Chino, or we can deliver. We serve patients across California.
Related from Mixwell
- Ketoprofen, cyclobenzaprine and lidocaine customized topical gel
- Compounded topical pain creams and what the evidence shows
- Topical pain compounding for orthopedic specialties
- Pain management compounding services
- Fibromyalgia support formulations
- A prescriber's guide to writing compounded prescriptions
Common questions
Why can I not just buy a ketoprofen gel?
There is no FDA approved topical ketoprofen product in the United States, though topical ketoprofen products are available in some other countries. In the US it is available only as a compounded preparation, prepared pursuant to a prescription.
Do I really need to stay out of the sun?
Topical ketoprofen has a recognized association with photosensitivity and photoallergic reactions, and European regulators required specific warnings on topical ketoprofen products. Keep the treated area covered and out of direct sunlight while using it and for a period afterward, per your prescriber's direction, and contact them if a rash appears.
Does combining three agents work better than one?
That has not been established. A 2019 randomized controlled trial of compounded topical pain creams did not find them superior to placebo. Prescribers still use multi agent topicals based on individual clinical judgment, but nobody should be promising results.
Is topical cyclobenzaprine well studied?
Not particularly. Cyclobenzaprine is FDA approved as an oral medication and acts centrally. Evidence for topical application is limited, and there is no FDA approved topical cyclobenzaprine product. Its inclusion rests largely on clinical reasoning.
Are there approved topical options I should consider first?
Often, yes, and we would say so. FDA approved topical diclofenac gel and topical lidocaine products are available. Compounding becomes relevant when a prescriber wants a combination, concentration or base that no manufactured product provides.
Should I talk to my provider first?
Yes. FDA recommends that patients talk with their health care professional about their specific circumstances before taking any medication, including compounded preparations.
Does Mixwell take insurance?
We do not accept insurance. Call (909) 378-7301 and we can go over current pricing with you.
Want to talk through concentrations or base selection?
Mixwell Compounding Pharmacy
13788 Roswell Ave, Ste 158, Chino, CA 91710
PCCA Member · CA Licensed · USP <795> · Non Sterile Compounding · Delivery Across California
Call (909) 378-7301References: Derry S, Moore RA, Gaskell H, et al. Topical NSAIDs for acute and chronic musculoskeletal pain in adults. Cochrane Database of Systematic Reviews. | Brutcher RE, Kurihara C, Bicket MC, et al. Compounded Topical Pain Creams to Treat Localized Chronic Pain: A Randomized Controlled Trial. Ann Intern Med. 2019;170(5):309-318. | European Medicines Agency review of topical ketoprofen containing medicines and photosensitivity reactions, with resulting product information warnings. | Cyclobenzaprine and lidocaine product labeling, U.S. FDA. | Lipoderm® and PermE8™ are permeation enhancing compounding bases from PCCA; base characteristics per manufacturer technical documentation. | This article is educational information and is not a substitute for clinical judgment or medical advice, and is not a promise of results. Reviewed by the Mixwell Compounding Pharmacy compounding team, Chino, CA.