Menthol is a monocyclic terpenoid alcohol obtained from various mint oils or prepared synthetically. The compound has a peppermint-like odor and is the primary active agent in peppermint oil. Menthol is used on the skin as a single agent and within various combination products for external analgesia. It may also be used in oral lozenges for the treatment of cough or pharyngitis. Menthol has been marketed for over-the-counter use; as such, the FDA has not formally evaluated the safety and efficacy of the drug.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Liquid Formulations
Lozenges:
-Dissolve slowly in mouth.
Topical Administration
-Do not apply to open wounds, infections, irritated, or sensitive skin.
-Avoid contact with eyes and mucous membranes. If eye contact occurs, immediately wash out the eye with water or saline, and consult a physician if irritation persists.
-Do not apply external heat or occlusive dressings to treated areas.
-If medication comes in contact with hands, wash hands with soap and water after application.
Transdermal Patch Formulations
-Apply directly to the site of pain.
-Apply according to product-specific package instructions.
Other Topical Formulations
Foam, gel, liquid, or spray:
-Apply generously to affected area. Massage into skin until absorbed.
-Avoid sunlight exposure of treated area.
-Avoid application of the topical spray into skin folds.
-The topical foam and spray products are flammable; avoid heat, flame, or smoking during and immediately following application of the foam or spray.
Use of menthol has been associated with transient erythema, skin irritation, and/or paresthesias (e.g., burning, stinging, warm sensation) at the site of application. This sensitivity generally diminishes with continued use. However, more serious hypersensitivity reactions may also occur. Contact dermatitis with disseminated pruritus and erythema multiforme lesions have been attributed to the topical application of menthol in one published case report. Resolution of symptoms occurred following hospitalization and a 10-day taper of systemic corticosteroid therapy. Advise patients to promptly discontinue use if pronounced symptoms occur and seek medical attention if condition persists. In September 2012, the FDA warned healthcare providers and consumers about the rare risk of serious skin injuries, including first to third degree burns, with the use of over the counter topical analgesics used for mild muscle and joint pain. Post-marketing surveillance and medical literature review detected 43 cases of burns on application sites with the use of topical analgesic patches, balms, and creams. Few cases have been reported with capsaicin containing products; most cases occurred with the use of single-ingredient products containing menthol and in those containing both menthol and methyl salicylate in concentrations of greater than 3% and greater than 10%, respectively. Many burns appeared in areas where the product was applied following 1 application, with severe burning or blistering occurring within 24 hours. Some burns resulted in hospitalization. Patients should not apply topical analgesics such as menthol to wounds or broken, irritated skin, and the area should not be tightly wrapped or bandaged. Contact with mucous membranes and application of heat to the affected area should be avoided. Items such as heating pads, lamps, or hot water bags and bottles may increase the risk of burns. Discuss the risk of burns with patients, as warnings on over the counter topical analgesics for joint or muscle pain are not required. Patients who experience pain, skin blistering, or swelling should stop use and contact their healthcare provider for treatment.
Toxicity including full-thickness skin necrosis, superficial muscle necrosis, transitory elevated hepatic enzymes, and persistent interstitial nephritis has been reported following the use of topical cream containing 18.3% methyl salicylate and 16% menthol to multiple sites. Upon presentation, the patient stated that periodic application of a heating pad was used on each treated area for no more than 15 to 20 minutes. Clinicians attributed effects to excessive percutaneous absorption and subsequent drug toxicity due in part to the application of heat. Similar reactions may be possible following use of single-ingredient menthol products. Menthol package labels include warnings to avoid use of heat and occlusive dressings. Advise patients accordingly.
Adverse events have been noted in premature infants following the nasal inhalation of menthol fumes. In a clinical trial design to test the protective reactivity of the respiratory system in premature infants, investigators placed an open vial of menthol crystals approximately one centimeter from the nose of sleeping neonates. This chemical stimulation resulted in apnea with a mean duration of 4.7 seconds (+/- 0.4 seconds) in 42.8% of the 50 cases conducted on 21 infants. Sneezing was reported following 3 cases of menthol inhalation. Other indicators of infant arousal were noted including an increase in heart rate, licking, grimacing, opening the eyes, and stretching.
Some menthol topical products are flammable. Store and use with appropriate caution.
Use menthol topical products as intended. Do not use in areas with skin abrasion, irritation, infection, inflammation, or sensitivity. Do not apply occlusive dressing or heating pad to treated area. Avoid application of topical menthol into skin folds. Further, advise patients to avoid sunlight (UV) exposure of treated skin after application of this medication. Transient, self-limiting burning sensation may occur following application; this sensitivity generally diminishes with continued use. Advise patients to promptly discontinue use if severe burning sensation occurs and seek medical attention if condition persists. When used for self-medication, if a person's condition worsens or if symptoms persist for more than 7 days, or clear up and occur again within a few days, menthol therapy should be discontinued and a physician should be consulted.
Menthol is an irritant. Topical menthol products are for external use only. Avoid mucous membrane and ocular exposure to external products. External products have a potential for overdose or poisoning if ingested. If a topical menthol formulation is swallowed, patients should seek medical help or contact a Poison Control Center.
Generally, use of external menthol topical products is not recommended in children less than 12 years of age except under the direction of a physician. Some over-the-counter menthol liquids and gels may be used for children as young as 2 years of age; refer to specific package directions. Topical menthol is not indicated for use in neonates or infants. The safety and efficacy of menthol topical patch has not been established in patients less than 12 years of age. Oral lozenges may be used in patients down to 5 years of age; refer to specific package directions as the recommendations may differ between products.
Adequate and well controlled study of topical menthol use during pregnancy has not been conducted. Further, manufacturers do not provide specific recommendations for such use. Consider the potential for risks and benefits to both mother and fetus.
Menthol lozenges and topical patches may be used during breast-feeding. Only a limited amount of menthol is absorbed systemically from the topical application. Menthol is metabolized rapidly at first-pass metabolism to menthol glucuronide; only 0.063% of the maternal dose is transferred to the breast milk. Patients should be instructed not use menthol on or near the breast where baby might ingest it, and to use care not to make contact with the skin of an infant or very young child. There have been cases where the direct application of menthol topical products (for example, Vicks VapoRub) to an infant's skin resulted in severe breathing difficulties or other problems.
Because some transdermal systems (i.e., patches) contain aluminum or other metal components, patients should be instructed to remove menthol topical patch before undergoing magnetic resonance imaging (MRI). Metal components contained in the backing of some transdermal systems can overheat during an MRI scan and cause skin burns in the area where the patch is adhered.
The topical foam and spray menthol formulations are flammable, as are certain topical gel menthol formulations. Avoid use of the preparations near a fire or flame, including tobacco smoking, during or immediately after application.
For the temporary relief of mild pain associated with arthritis, simple backache, muscle strains, sprains, or bruises:
Topical dosage (2.5%, 3.1%, 4%, 4.4%, 5%, 5.5%, 7%, 10%, and 16% gel):
Adults: Apply to affected area as needed up to 3 to 4 times daily.
Adolescents and Children 12 years: Apply to affected area as needed up to 3 to 4 times daily.
Topical dosage (2% and 3.5% gel):
Adults: Apply to affected area as needed up to 3 to 4 times daily.
Adolescents and Children 2 years and older: Apply to affected area as needed up to 3 to 4 times daily.
Topical dosage (16% liquid):
Adults: Apply to affected area as needed up to 3 to 4 times daily.
Adolescents and Children 12 years: Apply to affected area as needed up to 3 to 4 times daily.
Topical dosage (up to 4% liquid, Absorbine Jr):
Adults: Apply to affected area as needed up to 3 to 4 times daily.
Adolescents and Children 2 years and older: Apply to affected area as needed up to 3 to 4 times daily.
Topical dosage (patch):
Adults: Apply to affected area as needed up to 4 times daily.
Adolescents and Children 12 years: Apply to affected area as needed up to 4 times daily.
Topical dosage (cream):
Adults: Apply to the affected area as needed up to 3 to 4 times daily.
Adolescents and Children 12 years: Apply to the affected area as needed up to 3 to 4 times daily.
Topical dosage (spray):
Adults: Spray affected area 1 to 4 times daily, as needed.
Adolescents and Children 12 years: Spray affected area 1 to 4 times daily, as needed.
Topical dosage (liquid foam):
Adults: Apply to affected area 1 to 4 times daily, as needed.
Adolescents and Children 12 years: Apply to affected area 1 to 4 times daily, as needed.
For the treatment of cough or sore throat (pharyngitis):
Oral dosage (lozenges containing menthol 5 mg or more):
Adults: Dissolve 1 lozenge in the mouth. Repeat every 2 hours as needed.
Adolescents and Children 5 years and older: Dissolve 1 lozenge in the mouth. Repeat every 2 hours as needed.
Oral dosage (lozenges containing less than 5 mg menthol):
Adults: Dissolve 2 lozenges in the mouth, 1 at a time. Repeat every 2 hours as needed.
Children and Adolescents 5 to 17 years: Dissolve 2 lozenges in the mouth, 1 at a time. Repeat every 2 hours as needed.
Oral dosage (drops, emulsion):
Adults: Dissolve 2 lozenges in the mouth, 1 at a time. Repeat every 2 hours as needed.
Children and Adolescent age 6 to 17 years: Dissolve 2 lozenges in the mouth, 1 at a time. Repeat every 2 hours as needed.
Maximum Dosage Limits:
-Adults
Gel, liquid, cream, liquid foam, spray, and patch: 4 topical applications/day. Oral lozenges containing menthol 5 mg or more: 12 lozenges/day. Oral lozenges containing less than 5 mg of menthol: 24 lozenges/day.
-Geriatric
Gel, liquid, cream, liquid foam, spray, and patch: 4 topical applications/day. Oral lozenges containing menthol 5 mg or more: 12 lozenges/day. Oral lozenges containing less than 5 mg of menthol: 24 lozenges/day.
-Adolescents
Gel, liquid, cream, liquid foam, spray, and patch: 4 topical applications/day. Oral lozenges containing menthol 5 mg or more: 12 lozenges/day. Oral lozenges containing less than 5 mg of menthol: 24 lozenges/day.
-Children
12 years or older: Gel, liquid, cream, spray, liquid foam, and patch: 4 topical applications/day. Oral lozenges containing menthol 5 mg or more: 12 lozenges/day. Oral lozenges containing less than 5 mg of menthol: 24 lozenges/day.
5 to 11 years: 2% gel, 3.5% gel, and 4% or less liquid: 4 topical applications/day. Safety and efficacy have not been established for liquid greater than 4%; 2.5%, 3.1%, 4%, 4.4%, 5%, 7%, 10%, and 16% gel; topical cream; topical patch; topical liquid foam, and topical spray. Oral lozenges containing menthol 5 mg or more: 12 lozenges/day. Oral lozenges containing less than 5 mg of menthol: 24 lozenges/day.
2 to 4 years: 2% gel, 3.5% gel, and 4% or less liquid: 4 topical applications/day. Safety and efficacy have not been established for liquid greater than 4%; 2.5%, 3.1%, 4%, 4.4%, 5%, 7%, 10%, and 16% gel; topical cream; topical patch; topical liquid foam; topical spray; and oral lozenges.
Younger than 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Menthol products.
Local effects including mild analgesia, cooling sensation, irritant/counter-irritant effect, and vasodilation have been attributed to topical menthol application. The exact mechanism of these actions is not well defined and primarily based on observation. Analgesia may occur directly through interaction with kappa-opioid receptors or indirectly through nociceptor activation and resultant counter-irritant effect. Further, experts have theorized that menthol-induced activation of cold thermoreceptors in the skin may account for the sensation of cool, while activation of nociceptors evokes irritation or burning, and vasodilation. On a cellular level, menthol appears to alter calcium efflux from nerve-cell membranes of cold receptors. Investigators have termed these neurosensory receptors cold- and menthol-sensitive receptor-1 (CMR1), a subfamily of transient receptor potential channel M8 (TRPM8) receptors. The literature is unclear if menthol stimulation of nociceptors is mediated by alterations in cell wall calcium conduction or by, as yet, undefined mechanisms. However, the results of clinical study may explain the dose-dependent sensory effects of menthol. At low concentrations, menthol has been shown to have relative selectivity for CMR1, cold receptors, as compared to nociceptors, pain receptors, while at higher concentrations this selectivity is overcome and menthol acts at both.
Menthol is administered topically.
-Route-Specific Pharmacokinetics
Topical Route
Limited pharmacokinetic study has been conducted with cutaneous menthol. However, low levels of systemic exposure have been demonstrated following the use of menthol; camphor; methyl salicylate combination topical patches. Eight hour application of various numbers of patches resulted in menthol systemic exposure in all study patients. Average maximum menthol plasma concentrations of 7.6 +/- 2.6 ng/mL, 19 +/- 5.4 ng/mL, and 31.9 +/- 8.8 ng/mL were measured following the use of 74.88 mg, 149.76 mg, and 299.52 mg of menthol. Menthol was no longer detectable 8 to 12 hours after patch removal following the use of 74.88 mg of menthol, a normal dose for this product. Based on data from each of the 3 administered doses, a menthol terminal half-life of 3 to 6 hours was estimated. Percutaneous penetration has been shown to increase with increasing menthol concentrations. Further, local and systemic toxicity has been reported following use of large doses of menthol; methyl salicylate and heat; the same may be possible if used with occlusive dressings.