Otic Drop Research Articles

Rising Costs of Otic Drops: Review of a National Database.

US prescription drug prices have increased substantially during the past decade and now account for approximately 17% of total US health expenditures. Otic drop prices are of particular interest given their common use in otolaryngologic clinical practice. We hypothesized that otic drop prices increased at a rate significantly higher than the overall inflation rate. We considered potential causes for otic drop price fluctuations during this period and whether they could be correlated with corporate restructuring events. Publicly available data on otic antibiotic drop pricing was assessed from 2012 to 2020 and were correlated with contemporaneous publicly available information about corporate and political events. CiproHC (Alcon Laboratories, Inc., Fort Worth, TX, US), Ciprodex (Alcon Laboratories, Inc., Fort Worth, TX, US), Cortisporin-TC (Endo Pharmaceuticals, Dublin, Ireland), Coly-Mycin S (JHP Pharmaceuticals, LLC, Rochester, MI, US), generic neomycin-polymixin-HC otic drop, ciprofloxacin otic drop, and ofloxacin otic had overall change in cost between January 2014 and January 2020 of 69.9%, 63%, 268.9%, 219.5%, 232.5%, 13%, and 62.4%, respectively. Generic ofloxacin otic drop showed the most price fluctuation, temporarily rising 945% from July 2015 to its peak price of $26/mL in October 2016. Otic drop prices have been volatile, with overall price increases higher than overall inflation. Drug pricing is not transparent, making it difficult for prescribers and patients alike to be cost conscious when choosing the best therapy. We outline six factors that contribute to high US medication prices and also highlight two examples of otic drops that underwent significant price fluctuation during the studied period. V Laryngoscope, 131:E1069-E1075, 2021.

Tube patency: Is there a difference following otic drop administration?

PurposeMany surgeons instill peri-operative otic drops to maintain tube patency. A post-hoc analysis of three randomized, controlled studies involving a one-time administration of ciprofloxacin (OTO-201) given instead of otic drops perioperatively was conducted to evaluate tube patency in patients who did and did not receive otic drops as defined within the study protocol. Materials and methodsPost-hoc, retrospective analysis from three prospective, randomized, double-blind trials, (Phase 1b study [n = 83] and two Phase 3 studies [n = 532]) which enrolled children with confirmed middle ear effusion on the day of tympanostomy tube surgery and then randomized to placebo/sham (tubes alone) or OTO-201 and studied over a 28-day observation period. Patients with observed otorrhea post-tube were provided otic drops in the studies. An analysis was performed on the combined studies to evaluate tube patency, determined by pneumatic otoscopy and tympanometry, at four defined study visits over 28 days after the initial tube placement. ResultsThe analysis included 591 total patients with similar baseline demographics across groups. Tube patency ranged from 87 to 95% for patients who received otic drops, and from 96 to 99% for patients who did not receive otic drops. ConclusionBased on a retrospective post-hoc analysis from three randomized controlled trials in nearly 600 patients, tympanostomy tube occlusion rates was not increased in patients who did not receive otic drops. From this analysis, occlusion is likely caused primarily by peri-operative otorrhea since patency rates approached 99% in the absence of this complication.

Ototoxicity associated with topical administration of diclofenac sodium as an otic drop: An experimental animal study

ObjectivesThe aim of the study is to evaluate the ototoxicity of topical diclofenac sodium in comparison to positive and negative controls prior to the investigation of analgesic and anti-inflammatory efficacy of the agent in otic administration. MethodsTwenty four ears of 12 guinea pigs were included in the study. Wide myringotomy was performed on all tympanic membranes under general anesthesia and auditory brainstem responses (ABR) were evaluated. The subjects were separated into four groups, two groups received diclofenac sodium at low and high doses, positive controls received gentamicin and negative controls received isotonic sodium chloride topically for 14 days and ABRs were reevaluated. ResultsNo significant difference were observed between the pre and post-treatment click response, 1 kHz and 8 kHz response threshold levels after isotonic sodium chloride administration. All threshold levels were elevated in the positive control group. In the low and high dose diclofenac sodium groups, click response, 1 kHz and 8 kHz response threshold levels were significantly higher compared to the baseline values. Pre and post-treatment mean threshold level changes were not significantly different between the low and high dose diclofenac sodium groups. Pre and post-treatment mean threshold level changes in the gentamicin group were not significantly different from low or high dose diclofenac sodium groups. ConclusionDiclofenac sodium, considered as an analgesic and anti-inflammatory otic preparation, is shown to be as ototoxic as gentamicin in chronic use which may lead to loss of hearing especially when used topically in chronic otitis cases with tympanic membrane damage.

Impact of a terbinafine-florfenicol-betamethasone acetate otic gel on the quality of life of dogs with acute otitis externa and their owners.

Treatment of canine otitis externa with owner-administered products can be difficult. To evaluate otic treatment administered by a veterinarian on quality of life (QoL) of dogs with otitis externa and their owners, and on clinical and cytology parameters of otitis; compared to an owner-administered treatment. Fifty client-owned dogs randomly randomized into two groups and treated for 2 weeks. Veterinarians treated Group A dogs with a veterinary licensed otic gel on two occasions at a 1 week interval; owners treated Group B dogs once daily with a veterinary licensed otic drop based product along with twice weekly cleaning. Veterinarians evaluated otitis with the OTI-3 scale and semi-quantitative cytological examination on days 0, 7, 14 and 28. At each visit, owners assessed QoL with a validated questionnaire and pruritus with a Visual Analog Scale. Scores before and after treatment of each group, and differences between groups were analysed statistically. In both groups, all parameters improved significantly. There was a significantly higher improvement of QoL scores, for dogs and owners, in Group A, compared to Group B at all time points (P < 0.05), except for owner QoL on Day 28. There was no difference in improvement of OTI-3 between groups at any time point, whereas Group A cytology scores and pruritus improved significantly more by Day 7 (P = 0.0026 and P = 0.0294, respectively). A veterinarian-administered otic gel provided equivalent efficacy and higher QoL to dogs with otitis externa and their owners, compared to an owner-administered topical otic therapy.

Differences in Acetic Acid Ototoxicity in Guinea Pigs are Dependent on Maturity

Objectives: The objective was to study if the difference exist in drug ototoxicity between less mature and mature guinea pigs. Methods: The matured animal group had a body weight of 400 g and the less mature animal group had a body weight of 200 g. After compound action potential of the eight cranial nerves was measured, the middle ear cavity was filled with acetic acid. Results: The less mature animal group was more sensitive to the acetic acid treatment than the more mature animal group. Conclusion: We suggest that a difference in ototoxicity of certain otic drop treatments may exist between pediatric and adult patients.

Risk factors associated with postoperative tympanostomy tube obstruction.

Myringotomy and tympanostomy tube placement for chronic otitis media with effusion is the most common reason for a child to undergo anesthesia in the United States. Postoperative tube obstruction occurs in 1.4% to 36.0% of cases and remains a challenge in achieving middle ear ventilation. To identify risk factors associated with tube obstruction. Retrospective medical record review of 248 patients, mean age 2.54 years, seen between March 2007 and June 2011 in a tertiary care pediatric hospital. Tympanostomy tube placement and postoperative otic drop therapy. Tube patency at postoperative visit, number of tube removals and revisions, age, sex, body mass index (BMI), middle ear fluid type at time of surgery, and time between surgery and first postoperative visit were examined. Type of surgery (tympanostomy tube placement alone, adenoidectomy + tympanostomy tube placement, tympanostomy tube placement + adenoidectomy + tonsillectomy) and its effect on tube patency were also reviewed. At first follow-up, 10.6% of patients had occlusion of one or both tubes. No significant association was found between tube patency and a patient's BMI percentile, sex, or procedure type. Patients with no middle ear fluid were more likely to have patent tubes than those who had serous fluid (odds ratio [OR], 3.5; 95% CI, 1.2-10.6; P = .02). A significant inverse correlation was found between patency and time between surgery and follow-up in that patients who had longer follow-up after surgery were less likely to have patent tubes (OR per day of follow-up delay, 0.990; 95% CI, 0.981-0.999; P = .01). Tympanostomy tube obstruction was seen in 10.6% of patients. Serous fluid and increased time to postoperative visit were statistically significant indicators for tube occlusion.

OTO-201

HypothesisOTO-201 can provide sustained release to the middle ear and effectively treat otitis media, when compared with FDA-approved ciprofloxacin otic drop formulations.BackgroundThere is an unmet medical need for antibiotic therapy that can provide a full course of treatment from a single administration by an otolaryngologist at the time of tympanostomy tube placement, obviating the need for twice daily multiday treatment with short-acting otic drops.MethodsStudies in guinea pigs and chinchillas were conducted. OTO-201 was administered as a single intratympanic injection and compared with the twice daily multi-day treatment with Ciprodex or Cetraxal otic drops.ResultsOTO-201 demonstrated sustained release of ciprofloxacin in the middle ear compartment for days to approximately 2 weeks depending on the dose. The substantial Cmax values and steady drug exposure yielded by OTO-201 were in contrast to the pulsatile short lasting exposure seen with Ciprodex and Cetraxal. OTO-201 was also effective in a preclinical chinchilla model of Streptococcus pneumoniae–induced otitis media. The degree of cure was comparable to that afforded by Ciprodex and Cetraxal. There was no evidence of middle or inner ear pathology in guinea pigs treated with OTO-201, unlike Ciprodex and Cetraxal, which both demonstrated mild cochlear ototoxicity. No adverse effects of the poloxamer 407 vehicle were noted.ConclusionIntratympanic injection of OTO-201 constitutes an attractive treatment option to twice daily multiday dosing with ciprofloxacin ear drops for the treatment of otitis media, as evidenced by superior middle ear drug exposure, efficacy in an acute otitis media model, safety of administration, and convenience of a single dose regimen.

Factors of the blockage of ventilation tubes in the immediate postoperative period

Postoperative ventilation tube (VT) blockage is relatively common with a reported incidence of 0.0-13.1%. The purpose of this study was to evaluate the factors that contribute to postoperative VT blockage. A retrospective chart review was carried out to compare rates of VT blockage within 2 weeks postsurgery. Analyzed factors included: otic drop, nature, and amount of middle ear (ME) effusion, presence of ME mucosa edema or granulation, bleeding during surgery, number of prior VT insertion, and the status of the tympanic membrane (TM). One hundred and twenty-eight ears from 79 patients were enrolled in this study. Eleven VTs (8.6%) were obstructed within 2 weeks postsurgery. Ears using ciprobay and tarivid otic drops showed a significantly higher rate of tube blockage (14.1%) compared to ears that were not exposed to otic drops (1.8%). Glue effusion caused the highest rates (14.8%) of tube blockage compared to mucoid (9.6%) and serous (3.0%) effusions. The amount of effusion, the presence of mucosal edema or granulation, bleeding during surgery, number of prior VT insertions and the status of the TM were not associated with postoperative VT blockage. The results of this study suggest that the routine use of antibiotic-containing otic drops after the insertion of VT may not be useful. Viscosity of the effusion appears to have an effect on the postoperative VT blockage. Thus, more attention should be focused on the ears with glue or mucoid effusions after surgery.

Ofloxacin Otic Drops vs Neomycin–Polymyxin B Otic Drops as Prophylaxis Against Early Postoperative Tympanostomy Tube Otorrhea

To evaluate the incidence of tympanostomy tube (TT) sequelae, tube otorrhea, and tube obstruction immediately postoperatively in patients receiving TT for otitis media and to compare patients receiving postoperative otic drops with controls. Blinded randomized control trial. A tertiary pediatric otolaryngology practice. The study population comprised 306 patients undergoing TT placement. The 306 patients were enrolled into the following 3 groups: (1) those receiving no postoperative otic drop prophylaxis (control group), (2) those receiving ofloxacin otic drops (FLOX group), and (3) those receiving neomycin sulfate-polymyxin B sulfate-hydrocortisone otic drops (COS group). Overall otorrhea rates postoperatively were 14.9% for the control group, 8.1% for the FLOX group, and 5.5% for the COS group. When controlling for disease severity, the rate of otorrhea was significantly higher for the control group than for both the FLOX (P = .04) and COS (P = .01) groups. Nonpatent, plugged, tube rates were added to otorrhea rates for a TT failure analysis postoperatively. The control group demonstrated a significantly greater failure rate (29.9%) than both the FLOX (12.1%) and COS (7.7%) groups. The only differences between the patients in the 2 groups receiving drops were that ofloxacin was more well liked by patients (P = .04) and caused less pain (P = .004). Nonpatency and otorrhea are the most frequent sequelae immediately following TT placement. Few studies have compared different treatment regimens in a randomized controlled trial. These results demonstrate that otic drops clearly provide benefit postoperatively in preventing TT plugging and otorrhea but primarily in patients who have middle ear fluid at the time of TT placement. In addition, consideration of drop choice should be based on patient tolerance and medication safety profiles.

Educating Pharmacists on Ophthalmic- and Otic-Drop Administration Techniques Using Internet-Based Video Clips

In 2003, 3.22 billion prescriptions were dispensed in U.S. community pharmacies, including more than 39 million prescriptions dispensed for 19 different ophthalmic and otic drops.1 Patients must use ophthalmic and otic medications correctly to achieve optimal outcomes. One factor in ensuring proper use is provison of patient counseling. Pharmacists need to know how to administer drops correctly so that they can teach these skills to their patients. We developed Internet-based multimedia video clips to teach ophthalmic and otic drop administration techniques. These video clips have been shown to be useful in teaching student pharmacists the correct techniques.2 In doing so, our focus was to demonstrate how an Internet-based multimedia video clip could efficiently augment the knowledge base of pharmacists, providing an opportunity to improve their ability to counsel patients on the administration of ophthalmic and otic products. The 3.22 billion prescriptions dispensed in 2003 represents a significant increase from the 2.8 billion prescriptions dispensed 1999, and a 47% projected increase to 4.5 billion prescriptions is expected by 2010.3,4 In 2003, an estimated 132,289 community pharmacists were in practice (24,341 prescriptions per pharmacist), and the number of community pharmacists is expected to rise only 9.2% to 144,508 by 2010.4 In view of the current pharmacist shortage and the projected increase in prescription volume in the coming years, pharmacists face increased time constraints for patient counseling over what they currently experience. Efficient patient counseling will become even more important than it is now. Objectives

Educating Pharmacists on Ophthalmic- and Otic-Drop Administration Techniques Using Internet-Based Video Clips

In 2003, 3.22 billion prescriptions were dispensed in U.S. community pharmacies, including more than 39 million prescriptions dispensed for 19 different ophthalmic and otic drops.1 Patients must use ophthalmic and otic medications correctly to achieve optimal outcomes. One factor in ensuring proper use is provison of patient counseling. Pharmacists need to know how to administer drops correctly so that they can teach these skills to their patients. We developed Internet-based multimedia video clips to teach ophthalmic and otic drop administration techniques. These video clips have been shown to be useful in teaching student pharmacists the correct techniques.2 In doing so, our focus was to demonstrate how an Internet-based multimedia video clip could efficiently augment the knowledge base of pharmacists, providing an opportunity to improve their ability to counsel patients on the administration of ophthalmic and otic products. The 3.22 billion prescriptions dispensed in 2003 represents a significant increase from the 2.8 billion prescriptions dispensed 1999, and a 47% projected increase to 4.5 billion prescriptions is expected by 2010.3,4 In 2003, an estimated 132,289 community pharmacists were in practice (24,341 prescriptions per pharmacist), and the number of community pharmacists is expected to rise only 9.2% to 144,508 by 2010.4 In view of the current pharmacist shortage and the projected increase in prescription volume in the coming years, pharmacists face increased time constraints for patient counseling over what they currently experience. Efficient patient counseling will become even more important than it is now. Objectives

Protection against aminoglycoside otic drop–induced ototoxicity by a spin trap: I. Acute effects

Topical administration of aminoglycoside antibiotic drops containing neomycin and polymyxin B disrupts cochlear structure and function in rodents, possibly as a result of reactive oxygen species generation. This study investigated the ability of a spin trap, α-phenyl- tert -butyl-nitrone (PBN), to prevent acute aminoglycoside antibiotic drop–induced cochlear dysfunction. Guinea pigs were monitored for compound action potential thresholds and 1.0 μV root-mean-square cochlear microphonic isopotential curve values, then injected intraperitoneally with PBN (60 mg/kg) or saline solution. After 10 minutes, 50 μl of PBN (100 mmol/L) or artificial perilymph was applied to the round window membrane, followed after 10 minutes with artificial perilymph or aminoglycoside antibiotic drops (50 μl). From 10 to 60 minutes after exposure, mean compound action potential thresholds progressively increased in the artificial perilymph–aminoglycoside antibiotic drop group, beginning with high frequencies and later including ever-lower frequencies. These threshold shifts in compound action potentials were significantly greater ( p < 0.05) than those seen in the artificial perilymph–artificial perilymph or PBN–aminoglycoside antibiotic drop groups. This finding indicates that PBN provided protection against acute aminoglycoside antibiotic drop–induced compound action potential threshold sensitivity loss. Mean cochlear microphonic shift values at 60 minutes in the artificial perilymph–aminoglycoside antibiotic drop group significantly exceeded those of the other groups only at the highest frequencies. These data suggest that acute aminoglycoside antibiotic drop–induced cochlear disruption primarily affects high frequency compound action potential function and may be partially reactive oxygen species–mediated and preventable. (Otolaryngol Head Neck Surg 1998;119:581-7.)

Acute and chronic effects of alpha-phenyl-tert-butylnitrone against single dose aminoglycoside otic drop induced ototoxicity

Acute and chronic effects of alpha-phenyl-tert-butylnitrone against single dose aminoglycoside otic drop induced ototoxicity

Otoacariasis in Bengal goats of Bangladesh

The clinical findings and therapy of otoacariasis, caused by Psoroptes cuniculi, were studied in 12 Bengal goats. The major presenting signs included marked discomfort, rubbing of the ears against fixed objects or scratching by the toes, ear twitching and head shaking. In some severe cases violent head dashing against fixed objects was also noticed. Crackling sounds were detectable by gentle digital pressure on the ear base. In all cases, external auditory meatuses were found to be filled with yellowish-brown laminated scabs or waxy materials. Ten animals recovered after three to five applications of Lorexane cream 1% (ICI Ltd.) applied at an interval of 7 days. Two animals died after 2–3 days of treatment. Terramycin Otic Drop (Pfizer) was also applied to inhibit secondary bacterial infections and to promote the healing process. It is suggested that otoacariasis should be included in the list of differential diagnoses of brain diseases in goats.

Therapeutic management of chronic suppurative otitis media with otic drops

The use of potentially ototoxic topical drugs is controversial. Few experimental reports of audiometric data from human subjects exist. The purpose of this study is to determine if a significant difference between bone conduction hearing sensitivity before and after otic drop treatment for children with chronic suppurative otitis media and patent ventilation tubes exists. A statistical analysis of sensorineural threshold status after treatment of chronic suppurative otitis media with otic drops is presented.

The preparation of acetic acid for use in otic drops and its effect on endocochlear potential and pH in inner ear fluid

The ototoxicity of an otic drop preparation containing 2% acetic acid and 3% propylene glycol (VoSol, Denver Chemical Co., Humacao, PR) was investigated according to measurements of endocochlear potential (EP) and inner ear fluid pH. The application of this preparation to the round window membrane for 30 minutes caused a depression in EP from 80.5 ± 2.5 mV (mean ± SD; n = 6) to 11.7 ± 7.7 mV, and lowered inner ear fluid pH from 7.55 ± 0.09 to 5.06 ± 0.19 (n = 6) in perilymph and from 7.52 ± 0.07 to 5.88 ± 0.63 (n = 6) in endolymph. Two percent acetic acid produced similar changes after 30 minutes: EP was reduced from 83.0 ± 2.2 mV to 34.0 ± 2.9 mV and endolymphatic pH from 7.49 ± 0.04 to 6.83 ± 0.21 (n = 4). However, the application of artificial perilymph of pH 4 titrated with HCl induced no significant changes in either EP or endolymphatic pH. We suggest that the mechanisms of ototoxicity in the otic drop preparation are Na + and K +-ATPase inhibition, and that such inhibition is due to the intracellular acidification of strial cells resulting from the penetration of acetic acid across the cell membrane, and to the direct and synergistic actions of propylene glycol.