Source: Health Products and Food Branch (CA) Revision Year: 2017
CIPRODEX is contraindicated in patients with:
FOR TOPICAL OTIC USE ONLY.
NOT FOR OPHTHALMIC USE.
NOT FOR INJECTION.
CIPRODEX should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolones. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticarial and itching. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.
Corticosteroids may reduce resistance to and aid in the establishment of non-susceptible bacterial, fungal, parasitic or viral infections and mask the clinical signs of infection.
If the infection is not improved after one week of treatment, alternate therapy should be considered.
If otorrhea persists after a full course of therapy, or if 2 or more episodes of otorrhea occur within 6 months, further evaluation is recommended to exclude an underlying condition, such as cholesteatoma, foreign body, or a tumor.
The systemic administration of quinolones, including ciprofloxacin at doses much higher than given or absorbed by the otic route, has led to lesions or erosions of the cartilage in weightbearing joints and other signs of arthropathy in immature animals of various species.
Tendon inflammation and rupture may occur with systemic fluoroquinolone therapy, including ciprofloxacin, particularly in elderly patients and in those treated concurrently with corticosteroids. Therefore, treatment with CIPRODEX should be discontinued at the first sign of tendon inflammation.
Spontaneous extrusion of tympanostomy tubes is not unexpected and occurred at an incidence of 1.8% in the CIPRODEX treatment group in the clinical trials.
CIPRODEX contains the preservative benzalkonium chloride, which may be an irritant and cause skin reactions.
Studies have not been performed to evaluate the effect of topical administration of the combination of ciprofloxacin and dexamethasone on human fertility. Topical dermal studies in animals have shown effects on male sex organs following long-term use of dexamethasone at high doses (see TOXICOLOGY, Reproduction & Teratology).
Reproduction studies have been performed in rats and mice using oral doses of up to 100 mg/kg and IV doses up to 30 mg/kg and have revealed no evidence of harm to the fetus as a result of ciprofloxacin. In rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, but no teratogenicity was observed at either dose. After intravenous administration of doses up to 20mg/kg, no maternal toxicity was produced in the rabbit, and no embryotoxicity or teratogenicity was observed.
Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. The teratogenic potential of dexamethasone after topical (ophthalmic) treatment has been investigated in New Zealand white rabbits. Treatment with a 0.1% suspension of dexamethasone into the conjunctival sac on days 6 through 18 of gestation resulted in a 15.6% and 32.3% incidence of fetal anomalies in two groups of rabbits.
Animal reproduction studies have not been conducted with CIPRODEX. No adequate and well controlled studies have been performed in pregnant women. Prolonged or repeated systemic corticoid use during pregnancy has been associated with an increased risk of intra-uterine growth retardation. Infants born of mothers who received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism. Caution should be exercised when CIPRODEX is used by a pregnant woman.
Ciprofloxacin and corticosteroids, as a class, appear in milk following oral administration. Dexamethasone in breast milk could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical otic administration of ciprofloxacin or dexamethasone could result in sufficient systemic absorption to produce detectable quantities in human milk. Because of the potential for unwanted effects in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and the low dose used in topical otic therapy.
The safety and effectiveness of CIPRODEX have not been established in pediatric patients 6 months of age.
The safety and efficacy of CIPRODEX have been established in pediatric patients 6 months and older (937 patients) in clinical trials.
No clinically relevant changes in hearing function were observed in 69 pediatric patients (age 4 to 12 years) treated with CIPRODEX and tested for audiometric parameters.
Although ciprofloxacin and other quinolones cause arthropathy in immature animals after oral administration, topical ocular administration of ciprofloxacin to immature dogs did not cause any arthropathy and there is no evidence that the otic dosage form has any effect on the weight bearing joints.
Prescribing CIPRODEX in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development of resistant drug-resistant bacteria.
As with other antibacterial preparations, prolonged use of CIPRODEX may result in overgrowth of non-susceptible organisms, including yeast and fungi. If superinfection occurs, discontinue use and institute alternative therapy.
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
In Phase II and III clinical trials, a total of 937 patients were treated with CIPRODEX. This included 400 patients with acute otitis media with otorrhea and 537 patients with acute otitis externa. The reported treatment-related adverse events are listed below:
The following treatment-related adverse events occurred in 0.5% or more of the patients with non-intact tympanic membranes.
| Adverse Event | Incidence (N=400) |
|---|---|
| Ear discomfort | 3.0% |
| Ear pain | 2.3% |
| Ear precipitate (residue) | 0.5% |
| Irritability | 0.5% |
| Taste perversion | 0.5% |
The following treatment-related adverse events were each reported in a single patient: tympanostomy tube blockage; ear pruritus; tinnitus; candidiasis; crying; dizziness; and erythema.
The following treatment-related adverse events occurred in 0.4% or more of the patients with intact tympanic membranes.
| Adverse Event | Incidence (N=537) |
|---|---|
| Ear pruritus | 1.5% |
| Ear debris | 0.6% |
| Superimposed ear infection | 0.6% |
| Ear congestion | 0.4% |
| Ear pain | 0.4% |
| Erythema | 0.4% |
The following treatment-related adverse events were each reported in a single patient: ear discomfort; decreased hearing; and ear disorder (tingling).
Adverse reactions identified from subsequent clinical trials are listed below.
Ear and labyrinth disorders: ear infection fungal, otorrhea;
Gastrointestinal disorders: vomiting;
General disorders and administration site conditions: device occlusion;
Nervous system disorders: headache;
Skin and subcutaneous tissue disorders: skin exfoliation.
Adverse reactions identified via spontaneous reporting are listed below.
Ear and labyrinth disorders: auricular swelling;
Immune system disorders: hypersensitivity.
Specific drug interaction studies have not been conducted with CIPRODEX administered in the ear.
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