CIPLOX D Eye Ointment (Ciprofloxacin + Dexamethasone)

Table of Content

Qualitative and Quantitative Composition

CIPLOX D Eye Ointment

Ciprofloxacin Hydrochloride equivalent to Ciprofloxacin….................................0.3% w/w

Dexamethasone Sodium Phosphate IP equivalent to Dexamethasone………..0.1% w/v Benzalkonium Chloride IP……………………………………………………………0.01% w/w

Dosage Form and Strength

Ciprofloxacin 0.3% Dexamethasone 0.1% Ophthalmic Ointment.

Clinical Particulars

Therapeutic Indications

CIPLOX D Eye Ointment is indicated for the treatment of post-operative inflammatory condition of the eye.

Posology and Method of Administration

Apply a half-inch ribbon of ointment into the conjunctival sac three times a day on the first 2 days; then, for the next 5 days, apply a half-inch ribbon of ointment two times a day.

Contraindications

  • A history of hypersensitivity to ciprofloxacin and/or dexamethasone or any other component of the medication is a contraindication to its use.
  • A history of hypersensitivity to other quinolones may also contraindicate the use of ciprofloxacin.
  • Use is contraindicated in epithelial herpes simplex keratitis (dendritic keratitis); fungal diseases of ocular structures; acute infectious stages of vaccinia, varicella and many other viral disease of the cornea and conjunctiva; mycobacterial infection of the eye and in those persons who have shown hypersensitivity to any component of this preparation.

Special Warnings and Precautions for Use

FOR TOPICAL OPHTHALMIC USE ONLY.

NOT FOR INJECTION INTO THE EYE.

Ciprofloxacin

Serious, and occasionally fatal, hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial oedema, dyspnoea, urticaria, and itching. Only a few patients had a history of hypersensitivity reactions. Serious anaphylactic reactions require immediate emergency treatment with epinephrine and other resuscitation measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated.

General

As with other antibacterial preparations, prolonged use of ciprofloxacin may result in overgrowth of non-susceptible organisms, including fungi. If super-infection occurs, appropriate therapy should be initiated. Whenever clinical judgement dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy and, where appropriate, fluorescein staining. Ciprofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction. Ophthalmic ointments may retard corneal healing and cause visual blurring. Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.

Dexamethasone

Prolonged use may result in ocular hypertension and/or glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and posterior subcapsular cataract formation. Prolonged use may suppress the host response and thus increase the hazard of secondary ocular infections. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical corticosteroids. In acute purulent conditions of the eye, corticosteroids may mask infection or enhance existing infection. If these products are used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Employment of corticosteroid medication in the treatment of herpes simplex other than epithelial herpes simplex keratitis, in which it is contraindicated, requires great caution; periodic slit-lamp microscopy is essential.

The possibility of persistent fungal infections of the cornea should be considered after prolonged corticosteroid dosing.

Drugs Interactions

Specific drug interaction studies have not been conducted with ophthalmic ciprofloxacin. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, enhance the effects of the oral anticoagulant, warfarin, and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.

Use in Special Populations

Pregnant Women

Category C

Reproduction studies have been performed in rats and mice at doses up to 6 times the usual daily human oral dose and have revealed no evidence of impaired fertility or harm to the foetus due to ciprofloxacin. In rabbits, as with most antimicrobial agents, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion. No teratogenicity was observed at either dose. After intravenous administration, at doses up to 20 mg/kg, no maternal toxicity was produced and no embryotoxicity or teratogenicity was observed.

Dexamethasone has been shown to be teratogenic in mice and rabbits following topical ophthalmic application in multiples of the therapeutic dose.

In the mouse, corticosteroids produce fetal resorptions and a specific abnormality, cleft palate. In the rabbit, corticosteroids have produced fetal resorptions and multiple abnormalities involving the head, ears, limbs, palate, etc.

There are no adequate or well-controlled studies in pregnant women. CIPLOX D Eye Ointment should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the embryo or fetus. Infants born of mothers who have received substantial doses of quinolones and corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism.

Lactating Women

It is not known whether topically applied ciprofloxacin is excreted in human milk. However, it is known that orally administered ciprofloxacin is excreted in the milk of lactating rats and oral ciprofloxacin has been reported in human breast milk after a single 500 mg dose.

Topically applied steroids are absorbed systemically. Therefore, because of the potential for serious adverse reactions in nursing infants from dexamethasone sodium phosphate, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother. Caution should be exercised when CIPLOX D Eye Ointment is administered to a nursing mother.

Paediatric Patients

Safety and effectiveness of CIPLOX D Eye Ointment in paediatric patients below the age of 2 years have not been established. Although ciprofloxacin and other quinolones may cause arthropathy in immature Beagle dogs after oral administration, topical ocular administration of ciprofloxacin to immature animals did not cause any arthropathy and there is no evidence that the ophthalmic dosage form has any effect on the weight bearing joints.

Safety and effectiveness of dexamethasone in children have not been established.

Geriatric Patients

No overall clinical differences in safety or effectiveness have been observed between the elderly and other adult patients.

Effects on Ability to Drive and Use Machines

CIPLOX D Eye Ointment may cause side effects which could affect your ability to drive.

CIPLOX D Eye Ointment may cause dizziness (vertigo). Changes in your eyesight or muscle weakness may also happen. This may affect your driving ability.

Undesirable Effects

The following adverse reactions (incidence) were reported in 2% of the patients in clinical studies for ciprofloxacin ophthalmic ointment: discomfort, keratopathy.

Other reactions associated with ciprofloxacin therapy occurring in less than 1% of patients included allergic reactions, blurred vision, corneal staining, decreased visual acuity, dry eye, oedema, epitheliopathy, eye pain, foreign body sensation, hyperaemia, irritation, keratoconjunctivitis, lid erythema, lid margin hyperaemia, photophobia, pruritus, and tearing.

Systemic adverse reactions related to ciprofloxacin therapy occurred at an incidence below 1% and included dermatitis, nausea and taste perversion.

Systemic Absorption of fluoroquinolones has been reported to cause following adverse effects:

The drug may cause low blood sugar and mental health related side effects. Low blood sugar levels, also called hypoglycemia, can lead to coma. The mental health side effects more prominent and more consistent across the systemic fluoroquinolone drug class are as mentioned below;

  • Disturbances in attention
  • Disorientation
  • Agitation
  • Nervousness
  • Memory impairment
  • Serious disturbances in mental abilities called delirium

The following adverse reactions have been reported with dexamethasone: glaucoma with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infections from pathogens including herpes simplex, and perforation of the globe. Rarely, filtering blebs have been reported when topical steroids have been used following cataract surgery. Rarely, stinging or burning may occur.

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the National Pharmacovigilance Programme of India (PvPI) by calling on 1800 267 7779 (Cipla number) or you can report to PvPI on 1800 180 3024. By reporting side effects, you can help provide more information on the safety of this product.

Overdose

Not known.

Pharmacological Properties

Mechanism of Action

Ciprofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive organisms. The bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase, which is needed for the synthesis of bacterial DNA.

Dexamethasone sodium phosphate suppresses the inflammatory response to a variety of agents.

Pharmacodynamic Properties

Ciprofloxacin: Pharmacotherapeutic Group – Ophthalmologicals, Other Antiinfectives. ATC Code: S01A X13.

Dexamethasone: Pharmacotherapeutic group: Corticosteroids, plain, ATC code: S01 BA01

CIPLOX D Eye Ointment contain the fluoroquinolone, ciprofloxacin. The bactericidal and inhibitory activity of ciprofloxacin against bacteria results from an interference with the DNA gyrase, an enzyme needed by the bacterium for the synthesis of DNA. Thus, the vital information from the bacterial chromosomes cannot be transcribed which causes a breakdown of the bacterial metabolism. Ciprofloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative bacteria.

Microbiology

Ciprofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive organisms. The bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase, which is needed for the synthesis of bacterial DNA.

Ciprofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections.

Aerobic Gram-positive Microorganisms

Staphylococcus aureus (methicillin-susceptible strains)

Staphylococcus epidermidis (methicillin-susceptible strains)

Streptococcus pneumoniae

Streptococcus Viridans group

Aerobic Gram-negative microorganisms

Haemophilus influenzae

The following in vitro data are available; but their clinical significance in ophthalmologic infections is unknown. The safety and effectiveness of ciprofloxacin in treating conjunctivitis due to these microorganisms have not been established in adequate and well controlled trials.

The following organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. Ciprofloxacin exhibits in vitro minimal inhibitory concentrations (MIC’s) of 1 mcg/mL or less (systemic susceptible breakpoint) against most (greater than or equal to 90%) strains of the following ocular pathogens.

Aerobic Gram-positive Microorganisms

Bacillus species

Corynebacterium species

Staphylococcus haemolyticus

Staphylococcus hominis

Aerobic Gram-negative Microorganisms

Acinetobacter calcoaceticus

Enterobacter aerogenes

Escherichia coli

Haemophilus parainfluenzae

Klebsielle pneumoniae

Moraxella catarrhalis

Neisseria gonorrhoeae

Proteus mirabilis

Pseudomonas aeruginosa

Serratia marcesens

Most strains of Burkholderia cepacia and some strains of Stenotrophomonas maltophilia are resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.

The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2. Resistance to ciprofloxacin in vitro usually develops slowly (multiple-step mutation). Ciprofloxacin does not cross-react with other antimicrobial agents such as beta-lactams or aminoglycosides; therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin. Organisms resistant to ciprofloxacin may be susceptible to beta-lactams or aminoglycosides.

Clinical Studies: In multi-centre clinical trials, approximately 75% of the patients with signs and symptoms of bacterial conjunctivitis and positive conjunctival cultures were clinically cured and approximately 80% had presumed pathogens eradicated by the end of treatment (Day 7).

CIPLOX D Eye Ointment also contain dexamethasone, a highly potent and long-acting glucocorticoid. It has an approximately 7 times greater anti-inflammatory potency than prednisolone, another commonly prescribed corticosteroid.

The actions of corticosteroids are mediated by the binding of the corticosteroid molecules to receptor molecules located within sensitive cells. Corticosteroid receptors are present in human trabecular meshwork cells and in rabbit iris ciliary body tissue.

Corticosteroids will inhibit phospholipase A2, thereby preventing the generation of substances that mediate inflammation, e.g. prostaglandins. Corticosteroids also produce a marked, though transient, lymphocytopaenia. This depletion is due to redistribution of the cells, with the T lymphocytes being affected to a greater degree than the B lymphocytes. Lymphokine production is reduced, as is the sensitivity of macrophages to activation by lymphokines.

Corticosteroids also retard epithelial regeneration, diminish post-inflammatory neo- vascularisation and reduce the excessive permeability of inflamed capillaries to normal levels.

The actions of corticosteroids, as described above, are exhibited by dexamethasone and they all contribute to its anti-inflammatory effect.

Pharmacokinetic Properties

Systemic Absorption: Absorption studies in humans with the ciprofloxacin ointment have not been conducted, however, based on studies with ciprofloxacin solution, 0.3%, mean maximal concentrations are expected to be less than 2.5 ng/mL.

Dexamethasone

Absorption

When administered topically into the eye, dexamethasone is absorbed into the aqueous humour, cornea, iris, choroid, ciliary body and retina. Systemic absorption occurs but may be significant only at higher dosages or in extended paediatric therapy. Up to 90% of dexamethasone is absorbed when given by mouth; peak plasma levels are reached between 1 and 2 hours after ingestion and show wide individual variations.

Distribution

Tissue distribution studies in animals show a high uptake of dexamethasone by the liver, kidneys and adrenal glands; a volume of distribution has been quoted as 0.58 l/kg. In man, over 60% of circulating steroids are excreted in the urine within 24 hours, largely as unconjugated steroid.

Biotransformation

Dexamethasone sodium phosphate is rapidly converted to dexamethasone within the circulation. Up to 77% of dexamethasone is bound to plasma proteins, mainly albumin. This percentage, unlike cortisol, remains practically unchanged with increasing steroid concentrations. The mean plasma half-life of dexamethasone is 3.6 ± 0.9 hours.

Elimination

Dexamethasone also appears to be cleared more rapidly from the circulation of the foetus and neonate than in the mother; plasma dexamethasone levels in the foetus and the mother have been found in the ratio of 0.32:1.

Non-Clinical Properties

Animal Toxicology or Pharmacology

Ciprofloxacin and related drugs have been shown to cause arthropathy in immature animals of most species tested following oral administration. However, a 1-month topical ocular study using immature Beagle dogs did not demonstrate any articular lesions.

Dexamethasone

Repeat-dose topical ocular safety studies with dexamethasone in rabbits have shown systemic corticosteroid effects. Such effects are considered to be unlikely when dexamethasone eye drops are used as recommended.

Dexamethasone was clastogenic in the in vitro human lymphocyte assay and in vivo in the mouse micronucleus assay at doses in excess of those obtained following topical application. Conventional carcinogenicity studies with dexamethasone have not been performed.

Dexamethasone has been found to be teratogenic in animal models. Dexamethasone induced abnormalities of foetal development, including cleft palate, intra-uterine growth retardation and effects on brain growth and development.

Description

CIPLOX D Eye Ointment contains 0.3% ciprofloxacin, a fluoroquinolone antibacterial and 0.1% dexamethasone a corticosteroid which suppresses the inflammatory response. It is a synthetic, sterile, multiple-dose, antimicrobial for topical use.

Pharmaceutical Particulars

Incompatibilities

Not known.

Shelf-Life

As on the pack.

Packaging Information

CIPLOX D Eye Ointment…………. tube of 5 gm

Storage and Handling Instructions

Store in a cool place.

Sterile until opened. Use within one month after opening the tube.

Patient Counselling Information

  • What is CIPLOX D Eye Ointment?

CIPLOX D Eye Ointment contains 0.3% ciprofloxacin, a fluoroquinolone antibacterial and 0.1% dexamethasone a corticosteroid which suppresses the inflammatory response. It is indicated to use for post-operative inflammatory condition of eyes.

  • Do not use if you have an allergy to CIPLOX D Eye Ointment

Do not use if you have an allergy to ciprofloxacin and/or dexamethasone and/or any other quinolone antibiotic or any other part of ciprofloxacin eye ointment.

  • Before you use CIPLOX D Eye Ointment, tell your HCP about other medication.

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. If you are using more than one type of eye medicine

  • How should I use CIPLOX D Eye Ointment?

Always use CIPLOX D Eye Ointment exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

  • What are the possible side effects?

Like all medicines, CIPLOX D Eye Ointment can cause side effects, although not everybody gets them.

Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

You may experience some or all the following effects in your eye(s):

Common (1 to 10 users in 100)

  • White deposits on the eye surface (cornea)
  • Discomfort (stinging or burning, gritty feeling in the eye, irritation)
  • Redness, watering of the eyes

Uncommon (1 to 10 users in 1,000)

  • Damage to the eye surface (cornea)
  • Sensitivity to light
  • Blurred vision
  • Swelling of the eye or eyelid, pain
  • Dry eye
  • Itchiness
  • Eye discharge
  • Eyelid crusting
  • Eyelids scales
  • Eyelid redness
  • Poor vision
  • Watery eyes
  • Red eyes

Rare (1 to 10 users in 10,000)

  • Damage of the eye
  • Inflammation
  • Double vision
  • Decreased eye sensation
  • Tired eyes, stye

Topical corticosteroids should not be used for longer than 1 week except under ophthalmic supervision.

If you notice white particles in your eyes, continue to use CIPLOX D Eye Ointment but tell your doctor immediately.

You may also experience effects in other areas of your body such as the following:

Common: bad taste.

Uncommon: headache, nausea.

Rare: hypersensitivity, dizziness, ear pain, inflammation inside the nose, nasal sinus discharge, diarrhoea, abdominal pain, skin inflammation, tendon disorder.

If you experience an allergic reaction, stop using CIPLOX D Eye Ointment and tell your doctor.

  • How should I store CIPLOX D Eye Ointment?
  • Store at room temperature. Do not freeze.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Keep the bottle tightly closed.
  • Do not use the drops after the expiry date on the bottle and the carton. The expiry date refers to the last day of that month.
  • Use within one month after opening the tube
  • General information about safe and effective use of CIPLOX D Eye Ointment.

CIPLOX D Eye Ointment is indicated in the treatment of external ocular infection of the eyes.    

  • Tell all of your healthcare providers that you use ciprofloxacin eye ointment. This includes your doctors, nurses, pharmacists, and dentists.
  • Use care when driving or doing other tasks that call for clear eyesight.
  • Bright lights may bother you. Wear sunglasses.
  • Do not use longer than you have been told.
  • If you feel pain, swelling or inflammation while or shortly after taking this medicine, stop treatment and contact your doctor.
  • If you are elderly or if you are taking medicines called ‘corticosteroids’ used to treat conditions such as pain and inflammation, asthma or skin problems, then you have a higher risk of getting tendon problems during treatment with CIPLOX D Eye Ointment. If you experience any inflammation or inflammatory condition, stop treatment and immediately consult your doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using ciprofloxacin eye ointment while you are pregnant.
  • Tell your doctor if you are breastfeeding. You will need to talk about any risks to your baby.
  • What are the ingredients in CIPLOX D Eye Ointment?

CIPLOX D Eye Ointment contains 0.3% ciprofloxacin and 0.1% Dexamethasone along with Benzalkonium Chloride, NF 0.01% as preservative.

  • Any other information

Do not touch tip to any surface as this may contaminate the ointment.

Do not use the product if the imprinted carton seals have been damaged, or removed.

Details of the Manufacturer

Mfd. by Okasa Pharma Pvt. Ltd.

T-68, M.I.D.C. Tarapur, Boisar,

Dist. Thane 401 502

Details of Permission or Licence Number with Date

M.L. KD-2150-A

Date of Revision

13/11/2019