Tonmya for the Treatment of Fibromyalgia
In August 2025, the US Food and Drug Administration (FDA) approved Tonmya (cyclobenzaprine hydrochloride sublingual tablets; Tonix Pharmaceuticals) for the treatment of fibromyalgia in adults.
While its exact mechanism of action in fibromyalgia is unknown, cyclobenzaprine is structurally related to tricyclic antidepressants. In pharmacology studies, cyclobenzaprine has demonstrated functional antagonism of 5-HT2A, α1-adrenergic, H1-histaminergic, and M1-muscarinic acetylcholine receptors.
Clinical Trials
The approval of Tonmya for fibromyalgia was based on data from 3 randomized, 2-arm, parallel-group, double-blind, placebo-controlled, multicenter trials (ClinicalTrials.gov Identifier: Trial 1 [NCT04172831], Trial 2 [NCT04508621], and Trial 3 [NCT05273749]), which included a total of 1474 patients aged 18 to 65 years who met the 2016 American College of Rheumatology (ACR) criteria for diagnosis of fibromyalgia (Figure 1).
Study participants were randomly assigned to receive bedtime sublingual treatment with either Tonmya 2.8 mg nightly for the first 2 weeks, then 5.6 mg beginning on the evening of day 15 through week 14 (n=735), or placebo nightly for 14 weeks (n=739).
The primary endpoint in all 3 trials was the change from baseline to week 14 in the weekly average of daily 24-hour recall pain intensity scores, as measured by the 11-point numeric rating scale (NRS).
To be enrolled, patients were required to have a minimum baseline pain score of 4. Baseline mean weekly averages of daily diary pain scores were similar between the Tonmya and placebo groups.
Findings from Trials 1 and 3 showed a statistically significant reduction in pain intensity scores with Tonmya compared with placebo at week 14. However, no statistically significant difference was observed in Trial 2.
In Trial 1, the mean change from baseline in the weekly average of daily 24-hour recall pain intensity scores was -1.9 in the Tonmya group vs -1.5 in the placebo group (difference in least squares mean: -0.4 [95% CI, -0.7, -0.1]; P =.010). At week 14, 47% of patients who received Tonmya achieved at least a 30% improvement from baseline in their weekly average of daily 24-hour recall pain intensity score.
Similarly in Trial 3, the mean change from baseline in the weekly average of daily 24-hour recall pain intensity scores was -1.8 in the Tonmya arm vs -1.2 in the placebo arm (difference in least squares mean: -0.7 [95% CI, -1.0, -0.3]; P <.001). At week 14, 46% of Tonmya-treated patients achieved at least a 30% improvement from baseline in their weekly average of daily 24-hour recall pain intensity score.
Safety Data
The safety of Tonmya for fibromyalgia was supported by 3 randomized, 2-arm, parallel-group, double-blind, placebo-controlled, multicenter trials (Trials 1 , 2, and 3). In these trials, 580 patients completed 14 weeks of treatment with Tonmya, while 602 received placebo.
Adverse reactions reported in at least 2% of Tonmya-treated patients and at a higher incidence than placebo included oral hypoesthesia (23%), oral discomfort (9%), abnormal product taste (9%), somnolence (6%), oral paresthesia (6%), oral pain (5%), fatigue (4%), dry mouth (3%), and aphthous ulcer (2%). Forty-three percent of patients treated with Tonmya experienced at least 1 treatment emergent oral mucosal adverse reaction, compared with 8% of those who received placebo. Eighty-two percent of these oral mucosal adverse reactions occurred within minutes of dosing, with 88% occurring after nearly every dose. Two-thirds of these reactions lasted less than 60 minutes, while a third lasted longer than 60 minutes, with some present the following morning (63%).
There were five patients (0.7% of Tonmya-treated patients) who experienced severe oral mucosal adverse reactions, including paresthesia, glossitis, hypoesthesia, oral pain, and dry mouth. Most reactions resolved within days after discontinuing Tonmya.
Dosage and Administration
Tonmya is supplied as a sublingual tablet containing 2.8 mg of cyclobenzaprine hydrochloride. It is administered by placing the tablet under the tongue and allowing it to dissolve completely.
The starting dosage of Tonmya is 2.8 mg (1 sublingual tablet) once daily at bedtime on days 1 to 14. On day 15 and thereafter, the dosage is 5.6 mg (2 sublingual tablets) once daily at bedtime. The maximum recommended dosage is 5.6 mg once daily.
For geriatric patients and those with mild hepatic impairment, the maximum recommended dosage is 2.8mg once daily at bedtime. Tonmya is not recommended for patients with moderate to severe hepatic impairment.
Prior to administration, females of reproductive potential should be tested for pregnancy as Tonmya may cause neural tube defects based on animal data.
Contraindications, Warnings, Precautions, and Adverse Reactions
Tonmya is contraindicated in patients with a hypersensitivity to cyclobenzaprine, with concomitant use of monoamine oxidase inhibitors (MAOI) or within 14 days of discontinuation of an MAOI, during the acute recovery phase of myocardial infarction, in patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure, and in those with hyperthyroidism.
Embryofetal Toxicity
According to animal reproduction studies, Tonmya has been associated with an increased risk of neural tube defects when administered to a pregnant female 2 weeks prior to conception and during the first trimester of pregnancy. Due to this risk, females of reproductive potential should avoid use of Tonmya 2 weeks prior to conception and during the first trimester of pregnancy.
Prior to initiating treatment, a pregnancy test should be performed to exclude use of Tonmya during the first trimester of pregnancy. Females of reproductive potential should be advised to use effective contraception during Tonmya treatment and for 2 weeks after the last dose.
Serotonin Syndrome
Cyclobenzaprine has been associated with a risk for potentially life-threatening serotonin syndrome when taken with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors.
Tonmya and any concomitant serotonergic agents should be discontinued immediately if symptoms of serotonin syndrome develop and supportive treatment should be initiated. If concomitant use of Tonmya and serotonergic agents is clinically unavoidable, patients should be closely monitored especially during treatment initiation or dosage increases.
Tricyclic Antidepressant-like Adverse Reactions
As cyclobenzaprine is structurally related to tricyclic antidepressants (TCAs), caution should be used when given to patients with a history of seizure disorder, as TCAs may lower the seizure threshold. Additional adverse events that have been reported with TCAs include arrhythmias, sinus tachycardia, and prolongation of the conduction time leading to myocardial infarction and stroke.
Discontinuation of Tonmya should be considered if clinically significant central nervous system symptoms develop.
Atropine-like Adverse Reactions
Tonmya should be administered with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in those taking anticholinergic drugs due to its atropine-like action.
CNS Depression
Tonmya can cause CNS depression, which may be increased if the medication is taken with alcohol, barbiturates, or other CNS depressants. As somnolence can occur with treatment, patients should avoid operating a motor vehicle or dangerous machinery until they are reasonably certain that Tonmya does not impair their ability to perform these activities.
Oral Mucosal Adverse Reactions
Treatment with Tonmya can result in oral mucosal reactions (eg, sensory changes [numbness, tingling], discomfort, pain, irritation, inflammation, lesions). These reactions typically occurred within minutes of administration, with most resolving within 60 minutes.
In all trials, there were a total of 5 patients who experienced severe oral mucosal adverse reactions, including sensory changes (paresthesia, hypoesthesia), inflammation (glossitis), oral pain, and dry mouth. Most of these reactions had resolved within days after discontinuing treatment.
To reduce the risk of oral sensory changes (hypoesthesia), patients should be instructed to moisten their mouth with sips of water prior to taking Tonmya. Severe oral mucosal adverse reactions should be reported to a health care provider as this may require discontinuing therapy.
Drug Interactions
Due to its structural similarity to TCAs, the concomitant use of Tonmya with the following medications is either contraindicated or strongly cautioned against as it may increase the risk for adverse reactions.
Considerations for Specific Populations
According to animal data, Tonmya may cause fetal harm when administered to pregnant women. Females of reproductive potential should avoid use of Tonmya 2 weeks prior to conception and through the first trimester of pregnancy. Pregnancies while on Tonmya should be reported to the Tonix Medicines, Inc, Adverse Event reporting line at 1-888-869-7633 (1-888-TNXPMED).
No data currently exist on the effects of cyclobenzaprine on a breastfed child, or its effect on milk production. Clinicians should consider the benefits and risks of Tonmya treatment in patients who are lactating.
Before initiating Tonmya therapy, it is recommended that females of reproductive potential undergo pregnancy testing. It is also advised that these patients use effective contraception during treatment and for 2 weeks after the last dose.
The efficacy and safety of Tonmya have not been established in pediatric patients. Regarding older patients, it is unclear whether they would respond differently to Tonmya than younger adult patients as there were no participants aged 65 years and older treated with the drug in clinical trials. The recommended dosage of Tonmya in patients aged 65 years and older is 2.8 mg once daily at bedtime because of the risk for higher cyclobenzaprine exposure in this patient population.
Tonmya is not recommended for patients with moderate to severe hepatic impairment because of the risk for higher cyclobenzaprine exposure in this patient population. The recommended dosage of Tonmya in patients with mild hepatic impairment is 2.8 mg once daily at bedtime.
Key Takeaways
Tonmya is a sublingual formulation of cyclobenzaprine indicated for the treatment of fibromyalgia in adults.
Clinical trials supporting approval showed Tonmya statistically significantly reduced pain intensity scores compared with placebo.
Prior to initiating treatment, pregnancy testing is recommended for females of reproductive potential.
Dosage modification is recommended for geriatric patients and in those with mild hepatic impairment; Tonmya is not recommended for patients with moderate or severe hepatic impairment.
