Clinical Overview: Ciprofloxacin/Dexamethasone for Acute Otitis Media, Acute Otitis Externa

The FDA approved ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension (Ciprodex) in 2003 for the treatment of ear infections, acute otitis media, and acute otitis externa.¹ The product combines ciprofloxacin, a fluoroquinolone antibiotic, with dexamethasone, an anti-inflammatory corticosteroid. Generic products became available as of 2020.²

Ciprofloxacin/dexamethasone is indicated to treat acute otitis media caused by Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa in pediatric patients age 6 months and older with tympanostomy tubes.¹ Health care providers most commonly prescribe antibacterial agents for children with otitis media, or middle ear infections, in the United States.³

Providers may insert tympanostomy tubes in the eardrum to allow fluid drainage within the inner ear of patients with recurrent ear infections.⁴ Ciprofloxacin/dexamethasone is also indicated to treat acute otitis externa caused by the most common pathogens, Staphylococcus aureus and Pseudomonas aeruginosa in adult and pediatric patients 6 months of age and older.^1,5

Otitis externa, also known as swimmer’s ear, is an outer ear canal infection.⁵

Clinical Studies¹

When researchers compared treatments of acute otitis media with tympanostomy tubes in a clinical trial, ciprofloxacin/dexamethasone administered 2 times daily for 7 days clinically cured 86% of patients compared to 79% for ofloxacin 0.3% solution administered 2 times daily for 10 days. For patients with positive cultures, ciprofloxacin/dexamethasone had a 90% cure rate compared to 79% for ofloxacin.

Microbiological eradication rates were 91% for ciprofloxacin/dexamethasone compared to 82% for ofloxacin.

Researchers conducted 2 clinical trials for acute otitis externa. Ciprofloxacin/dexamethasone administered twice daily for 7 days clinically cured 87% and 94% of patients compared to 84% and 89% of patients treated with neomycin 0.35%, polymyxin B 10,000 units/mL, and hydrocortisone 1.0% (neo/poly/HC) otic suspension.

For patients with positive cultures, ciprofloxacin/dexamethasone had 86% and 92% cure rates, respectively, compared to 84% and 89%, respectively, for neo/poly/HC. Microbiological eradication rates were 85% and 92%, respectively, for ciprofloxacin/dexamethasone compared to 85% and 85%, respectively, for neo/poly/HC.

Mechanism of Action¹

Ciprofloxacin is a fluoroquinolone antibacterial agent. Ciprofloxacin works as a bactericide by interfering with DNA gyrase, an enzyme essential for the synthesis of bacterial DNA.

Dexamethasone, a corticosteroid, suppresses inflammation that often accompanies bacterial infection. Dexamethasone inhibits multiple inflammatory cytokines resulting in decreased edema, redness, and pruritus.

Dosage and Administration¹

Pharmacists should counsel patients to shake the bottle well immediately before use. Patients can warm the suspension by holding the bottle in the hands for 1 or 2 minutes prior to administration, as instilling a cold suspension may cause dizziness. The usual dose is to instill 4 drops of ciprofloxacin/dexamethasone, which contain 0.42 mg ciprofloxacin and 0.14 mg dexamethasone, into the affected ear twice daily for 7 days.

The patient should lie with the affected ear upward before instilling the drops and should stay in the same position for 60 seconds. They should repeat, if necessary, for the opposite ear.

For acute otitis media, the patient or caregiver should press the tragus (the small projection in front of the ear canal) 5 times with a pumping motion to allow the drops to enter the middle ear. For acute otitis externa, patients should gently pull the outer ear lobe upward and backward to allow the drops to enter the ear canal.

Ciprofloxacin/dexamethasone is for otic use (ears) only and should not be administered to the eyes or by injection. Counsel patients to avoid contamination of the bottle tip with material from the ear, fingers, or other sources. The patient should complete the full treatment regimen, even if symptoms improve before 7 days, and discard unused portions.

Adverse Effects (AEs)¹

The most common AEs reported during clinical trials include ear discomfort, ear pain, and ear pruritus.

Contraindications¹

Ciprofloxacin/dexamethasone is contraindicated in patients with a history of hypersensitivity to ciprofloxacin, other quinolones, or any excipients. The medication is also contraindicated in viral infections of the external canal, including herpes simplex infections and fungal otic infections.

Warning and Precautions¹

Patients should discontinue use if any allergic reaction occurs with ciprofloxacin/dexamethasone. Possible symptoms include urticaria and facial swelling.

Prolonged use may lead to overgrowth of non-susceptible bacteria and fungi. If the infection does not improve after 1 week, the health care provider should obtain cultures to guide further treatment, discontinue ciprofloxacin/dexamethasone use, and implement alternative therapy.

If otorrhea persists after a full therapy course, or if 2 or more episodes of otorrhea occur within 6 months, providers should evaluate further to exclude an underlying condition, such as cholesteatoma, foreign body, or a tumor.

Pregnancy and Lactation¹

No data are available on ciprofloxacin/dexamethasone use in pregnant women to evaluate for teratogenicity, miscarriage or adverse maternal, or fetal outcomes. This product is expected to be of minimal risk for maternal and fetal toxicity when administered to pregnant women, due to the minimal systemic absorption of ciprofloxacin and dexamethasone following topical otic administration.

The effects of ciprofloxacin and dexamethasone following topical otic administration in terms of human milk production and presence in human milk are unknown. Systemically administered corticosteroids have appeared in human milk and caused AEs to the breastfeeding child.

The health care provider should consider the health benefits of breastfeeding, the mother’s clinical need for ciprofloxacin/dexamethasone, and possible AEs for the breastfeeding child before prescribing the medication.

About the Author

Wendy La, PharmD, is a clinical pharmacist at Elixir, a pharmacy benefits subsidiary of Rite Aid.

References

1. Ciprodex. Prescribing information. Novartis Pharmaceuticals Corporation; 2020. Accessed May 9, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e2cf3ea-a8f2-42e3-8424-9a6d6f0a4cb3&audience=professional
2. 2020 First Generic Drug Approvals. U.S. Food and Drug Administration (FDA). Updated February 23, 2021. Accessed May 9, 2022. https://www.fda.gov/drugs/first-generic-drug-approvals/2020-first-generic-drug-approvals
3. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media [published correction appears in Pediatrics. 2014 Feb;133(2):346. Dosage error in article text]. Pediatrics. 2013;131(3):e964-e999. doi:10.1542/peds.2012-3488
4. Schilder AG, Chonmaitree T, Cripps AW, et al. Otitis media. Nat Rev Dis Primers. 2016;2(1):16063. Published 2016 Sep 8. doi:10.1038/nrdp.2016.63
5. Rosenfeld RM, Schwartz SR, Cannon CR, et al. Clinical practice guideline: acute otitis externa [published correction appears in Otolaryngol Head Neck Surg. 2014 Mar;150(3):504] [published correction appears in Otolaryngol Head Neck Surg. 2014 Mar;150(3):504]. Otolaryngol Head Neck Surg. 2014;150(1 Suppl):S1-S24. doi:10.1177/0194599813517083