Ofloxacin is an antimicrobial drug in the fluoroquinolone family that is effective in treating a wide variety of bacterial infections. It received FDA approval in 1990 as a “1C" drug, categorizing it as a new molecular entity offering little or no therapeutic advantage over existing therapies, namely, ciprofloxacin. Yet, despite its insignificant therapeutic benefit, ofloxacin earned support for its improved oral bioavailability, longer half-life, and expanded applications to certain sexually transmitted infections compared to its counterpart, ciprofloxacin.
The following are FDA-approved indications for ofloxacin use:
As with other second-generation fluoroquinolone drugs, ofloxacin is a broad-spectrum antibiotic that exhibits a bactericidal effect. It works by binding to and inhibiting bacterial topoisomerase II (DNA gyrase), an enzyme that relaxes supercoiled DNA, and topoisomerase IV, an enzyme that separates linked daughter chromosomes following replication. These inhibitory effects interrupt DNA replication, transcription, and repair, thereby preventing cell division in bacterial cells.
Ofloxacin administration can be in oral, intravenous, or topical forms. General infections receive oral or intravenous ofloxacin. In instances of severe infection, intravenous administration is preferable as it allows higher dosing that leads to higher drug concentrations, ultimately leading to an increase in clinical cure rates.
Topical preparations exist for specific cases. For otitis externa and otitis media, patients have treatment with an ofloxacin otic drop solution. Topical ofloxacin penetrates the tympanic membrane, achieving similar middle ear concentrations through topical or by systemic administration. For bacterial conjunctivitis and corneal ulcers, patients can receive an ofloxacin ophthalmic drop solution. An animal study demonstrated that topical ofloxacin permeates the cornea, achieving therapeutic levels in the anterior and posterior chambers of the eye while sparing the retina from any toxic effects.
Fluoroquinolones chelate di- and trivalent metal cations, thus antacids or vitamins containing calcium, magnesium, aluminum, iron, and zinc should be avoided during ofloxacin therapy, as these reduce the amount of drug that gets absorbed.
The most characteristic adverse effect of ofloxacin treatment, along with other fluoroquinolone treatments, is tendinopathy, typically presenting as pain or swelling along a tendon’s path. Such injury has been observed both during drug administration and up to several months after. In patients receiving corticosteroid therapy or engaging in strenuous physical activity with concurrent ofloxacin administration, there is a particularly high risk of tendon rupture. This injury primarily affects the Achilles tendon and necessitates surgical repair.
It is also possible for ofloxacin treatment to cause increased intracranial pressure and toxic psychosis. As ofloxacin may stimulate the central nervous system, neurological effects such as seizures, lightheadedness, hallucinations, restlessness, tremors, anxiety, depression, confusion, difficulty sleeping, nightmares, paranoia, or suicidal thoughts or acts may also occur. These effects may develop after as little as one dose and call for immediate termination of treatment. Caution is necessary when considering therapy for patients with preexisting conditions or risk factors that predispose to seizures or other CNS effects.
Hypersensitivity reactions are another adverse effect occasionally observed with ofloxacin treatment, most frequently following the initial dose. This Type I hypersensitivity reaction is the result of some patients possessing preformed serum IgE against ofloxacin. Reported signs of a hypersensitivity reaction include seizure, cardiovascular collapse, shock, loss of consciousness, airway obstruction, dyspnea, tingling, angioedema, urticaria, itching, and other allergic skin manifestations. On rare occasion and following multiple doses, other serious and sometimes fatal hypersensitivity-associated events have been observed, involving fever, rash, severe dermatologic reactions, vasculitis, serum sickness, arthralgia, myalgia, allergic pneumonitis, interstitial nephritis, acute renal insufficiency or failure, acute hepatic necrosis or failure, hepatitis, jaundice, hemolytic or aplastic anemia, thrombocytopenia, leukopenia, agranulocytosis, pancytopenia, and other hematologic disorders. As with other hypersensitivity reactions, the earliest indication of these clinical manifestations calls for immediate discontinuation of treatment.
Though uncommon, ofloxacin treatment has also led to reports of peripheral neuropathy, as manifest by pain, burning, tingling, numbness, weakness, and altered sensation. Exacerbation of muscle weakness in a patient with myasthenia gravis is a dangerous possibility. The earliest indication of these clinical manifestations calls for immediate discontinuation of treatment.
Other rare and serious adverse effects include prolongation of the QT interval and aortic aneurysm.
Ofloxacin use is contraindicated in patients with a history of quinolone-associated hypersensitivity reactions, myasthenia gravis, and prolonged QT interval. Unless there is no other option, it is also contraindicated in patients with a history of or at increased risk for aortic aneurysm, Marfan syndrome, or Ehlers-Danlos syndrome.
In general, ofloxacin is regarded as a safe drug with a considerable safety margin. For patients with an increased risk of adverse effects or in cases with a prolonged treatment course, useful values and tests for monitoring include creatinine levels, CBC, and liver function tests. The therapeutic index for ofloxacin varies by bacterial agent and indication.
Orally administered ofloxacin has a bioavailability of approximately 98% and reaches peak serum concentration one to two hours after administration. Elimination occurs primarily through renal excretion, although a small portion (4 to 8%) of the drug is excreted fecally as bile.
In cases of overdose, gastric lavage and sufficient hydration are recommended interventions. No antidotes yet exist, and dialysis treatments are not effective in reversing toxicity. Activated charcoal may decrease ofloxacin absorption and reduce the likelihood of systemic toxicity.
By supporting patients with diverse interprofessional teams of healthcare providers, many severe adverse effects of ofloxacin treatment are avoidable. A nurse or physician taking the patient’s history may identify patients at high risk due to previous histories of hypersensitivity reactions, tendon disorders, cardiovascular disorders, Marfan syndrome, Ehlers-Danlos syndrome, or risk factors that lower the seizure threshold. Pharmacists may notice red flags for patients who are already taking corticosteroids, antiarrhythmics, or CNS medications whose adverse effects would be compounded by ofloxacin treatment. In these cases, the patients benefit from proactive interprofessional teams capable of working together to devise alternative drug treatment plans or ensuring that proper monitoring was available to ensure successful treatment and avoid adverse effects. The pharmacist should assist the team by verifying dosing, and in severe cases, and infectious disease board-certified pharmacist can provide antibiogram data to direct agent selection. Nursing can monitor for adverse events and treatment effectiveness. This type of interprofessional team paradigm enhances positive results while minimizing adverse effects. [Level 5]
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