esketamine otic

Esketamine otic is a medication being investigated for the treatment of ringing in the inner ears (inner ear tinnitus). Esketamine otic is a hyaluronic acid gel formulation that is injected through the eardrum into the middle ear and the active drug component oozes through the membrane into the inner ear (cochlea). In July 2016, the FDA granted Fast Track designation to esketamine otic, however, two Phase III clinical trials failed to meet the primary endpoint for the drug’s efficacy, and further investigations continue.

Inner ear tinnitus is a perception of sound in the ears with no external stimuli, which may be transient or become permanent. Tinnitus can seriously impact a person’s ability to concentrate, relax or sleep, which can lead to fatigue, irritability, frustration and depression. Inner ear tinnitus may be caused by exposure to very loud noise (acute acoustic trauma), middle ear infection (otitis media), idiopathic sudden sensorineural hearing loss (ISSNHL), or injury to the ear.

Trauma to the ear from injury or infections may trigger excessive release of glutamate, the primary stimulatory chemical (neurotransmitter) in the auditory nervous system. Glutamate enables hearing by activating N-methyl-D-aspartate (NMDA) receptors, ion channels in the nerve cells in the cochlea, a spiral-shaped organ responsible for hearing. Excessive stimulation of the auditory nerve causes abnormal firing of the nerve cells that results in tinnitus.

Esketamine otic is an NMDA antagonist that binds to NMDA receptors and is believed to suppress the abnormal excitation of the auditory nerve and reduce the loudness of tinnitus. Although esketamine otic was well-tolerated in clinical trials, the efficacy in reducing the annoyance and loudness of tinnitus is yet to be established.

Warnings

• Esketamine otic is an investigational drug and information is not available on the drug’s contraindications, warnings and precautions.

Esketamine otic is still in clinical trials and there is insufficient information on side effects. Some side effects include:

• Ear pain
• Transient increase in tinnitus loudness
• Muffled hearing
• Reduced hearing acuity
• Headache

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Esketamine otic is in clinical trials and recommended dosages are not available. Dosages used during clinical trials were:

Gel

• 0.27 mg/ml
• 0.81 mg/ml

Inner Ear Tinnitus

• Administered in clinical trials in patients aged 16 to 65 on 3 consecutive days as intratympanic injection into the middle ear to diffuse into the cochlea
• The drug is delivered in a hyaluronic acid gel formulation

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• There is no information available on interactions of esketamine otic with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Esketamine otic is still in clinical trials and no information is available on its use during pregnancy and breastfeeding.