Ciprofloxacin Ophthalmic solution USP 0.3%w/v Taj Pharma

1. Name of the medicinal product

Ciprofloxacin Ophthalmic solution USP 0.3%w/v Taj Pharma

2. Qualitative and quantitative composition

Each ml contains:
Ciprofloxacin Hydrochloride USP 3.5mg
Equivalent to Ciprofloxacin USP (Base) 3mg
Excipients: Q.S.

Excipients with known effect: One ml of solution contains 0.06mg of benzalkonium chloride.

For a full list of excipients, see Section 6.1.

3. Pharmaceutical form

Eye drops, solution. A clear and colourless to pale yellow solution.

4. Clinical particulars

Therapeutic indications

Adults, newborn infants (0-27 days), infants and toddlers (28 days to 23 months), children (2-11 years) and adolescents (12-16 years).

Ciprofloxacin Taj Pharma is indicated for the treatment of corneal ulcers and superficial infections of the eye and adnexa caused by susceptible strains of bacteria.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Posology and method of administration

Adults, newborn infants (0-27 days), infants and toddlers (28 days to 23 months), children (2-11 years) and adolescents (12-16 years).

Corneal Ulcers:

Ciprofloxacin Taj Pharma must be administered in the following intervals, even during night time:

On the first day, instil 2 drops into the affected eye every 15 minutes for the first six hours and then 2 drops into the affected eye every 30 minutes for the remainder of the day.

On the second day, instil 2 drops in the affected eye hourly.

On the third through the fourteenth day, place two drops in the affected eye every 4 hours. If the patient needs to be treated longer than 14 days, the dosing regimen is at the discretion of the attending physician.

Superficial Ocular Infection:

The usual dose is one or two drops in the affected eye(s) four times a day. In severe infections, the dosage for the first two days may be one or two drops every two hours during waking hours.

For either indication a maximum duration of therapy of 21 days is recommended.

The dosage in children above the age of 1 year is the same as for adults.

Use in children

Safety and effectiveness of Ciprofloxacin Taj Pharma Eye Drops were determined in 230 children between the ages of 0 and 12 years of age. No serious adverse drug reaction was reported in this group of patients.

Use in renal and hepatic impairment

No studies have been performed using Ciprofloxacin Taj Pharma Eye Drops in patients with kidney or liver problems.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1.
• Hypersensitivity to quinolones.

Special warnings and precautions for use

After cap is removed, if tamper evident snap collar is loose, remove before using product.

For ocular use only.

The clinical experience in children less than one year old, particularly in neonates is very limited. The use of Ciprofloxacin Taj Pharma eye drops in neonates with ophthalmia neonatorum of gonococcal or chalamydial origin is not recommended as it has not been evaluated in such patients. Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition.

When using Ciprofloxacin Taj Pharma eye drops one should take into account the risk of rhinopharyngeal passage which can contribute to the occurrence and the diffusion of bacterial resistance.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, were observed in patients receiving treatment based on systematically administered quinolones. 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 (see section 4.8).

Serious acute hypersensitivity reactions to ciprofloxacin may require immediate emergency treatment. Oxygen and airway management should be administered where clinically indicated.

Ciprofloxacin Taj Pharma should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

As with all antibacterial preparations prolonged use may lead to overgrowth of non-susceptible bacterial strains or fungi. If superinfection occurs, appropriate therapy should be initiated.

Tendon inflammation and rupture may occur with systemic fluoroquinolone therapy including ciprofloxacin, particularly in elderly patients and those treated concurrently with corticosteroids. Therefore, treatment with Ciprofloxacin Taj Pharma Eye Drops should be discontinued at the first sign of tendon inflammation (see section 4.8).

In patients with corneal ulcer and frequent administration of Ciprofloxacin Taj Pharma Eye Drops, white topical ocular precipitates (medication residue) have been observed which resolved after continued application of Ciprofloxacin Taj Pharma Eye Drops. The precipitate does not preclude the continued application of Ciprofloxacin Taj Pharma Eye Drops nor does it adversely affect the clinical course of the recovery process. The onset of the precipitate was within 24 hours to 7 days after starting therapy. Resolution of the precipitate varied from immediately to 13 days after therapy commencing.

Contact lens wear is not recommended during treatment of an ocular infection. Therefore, patients should be advised not to wear contact lenses during treatment with Ciprofloxacin Taj Pharma eye drops.

Ciprofloxacin Taj Pharma Eye Drops contains benzalkonium chloride which may cause irritation and is known to discolour soft contact lenses.

Avoid contact with soft contact lenses. In case patients are allowed to wear contact lenses they should be instructed to remove them prior to application of Ciprofloxacin Taj Pharma Eye Drops and wait at least 15 minutes before reinsertion.

• Interaction with other medicinal products and other forms of interaction

Specific drug interaction studies have not been conducted with ophthalmic ciprofloxacin. Given the low systemic concentration of ciprofloxacin following topical ocular administration of the product, drug interactions are unlikely to occur.

If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.

• Fertility, pregnancy and lactation

Fertility

Studies have not been performed in humans to evaluate the effect of topical administration of ciprofloxacin on fertility. Oral administration in animals does not indicate direct harmful effects with respect to fertility.

Pregnancy

There are no adequate data from the use of Ciprofloxacin Taj Pharma in pregnant woman. Animal studies do not indicate direct harmful effects with respect to reproductive toxicity. Systemic exposure to ciprofloxacin after topical use is expected to be low.

As a precautionary measure, it is preferable to avoid the use of Ciprofloxacin Taj Pharma during pregnancy, unless the therapeutic benefit is expected to outweigh the potential risk to the fetus.

Breastfeeding

Orally administered ciprofloxacin is excreted in the human milk. It is unknown whether ciprofloxacin is excreted in human breast milk following topical ocular or otic administration. A risk to the suckling child cannot be excluded. Therefore, caution should be exercised when Ciprofloxacin Taj Pharma is administered to nursing women.

• Effects on ability to drive and use machines

This product has no or negligible influence on the ability to drive or use machines.

Temporarily blurred vision or other visual disturbances may affect the ability to drive or use machines. If transient blurred vision occurs upon instillation, the patient must wait until the vision clears before driving or using machinery.

• Undesirable effects

In clinical trials, the most frequently reported adverse drug reactions were ocular discomfort, dysgeusia and corneal deposits occurring approximately in 6%, 3% and 3% of patients respectively.

Tabulated summary of adverse reactions

The adverse reactions listed below are classified according to the following convention: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), or not known (cannot be estimated from the available data). Within each frequency-grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions have been observed during clinical trials and post-marketing experience.

The following undesirable effects were reported in association with the ophthalmic use of Ciprofloxacin Taj Pharma:

Description of selected adverse events

With locally applied fluoroquinolones (generalized) rash, toxic epidermolysis, dermatitis exfoliative, Stevens-Johnson syndrome and urticaria occur very rarely.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolone therapy (see section 4.4). Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial oedema, dyspnoea, urticaria, and itching.

Ruptures of the shoulder, hand, Achilles, or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving systemic fluoroquinolones. Studies and post marketing experience with systemic fluoroquinolones indicate that the risk of these ruptures may be increased in patients receiving corticosteroids, especially geriatric patients and in tendons under high stress, including the Achilles tendon. To date, clinical and post marketing data have not demonstrated a clear association between Ciprofloxacin Taj Pharma and musculoskeletal and connective tissue adverse reactions.

In isolated cases blurred vision, decreased visual acuity and medication residue have been observed with ophthalmic ciprofloxacin (see section 4.4).

Moderate to severe phototoxicity has been observed in patients treated with systemic quinolones. Nevertheless, phototoxic reactions to ciprofloxacin are uncommon.

Paediatric population

Safety and effectiveness of Ciprofloxacin Taj Pharma 3mg/ml eye drops were determined in 230 children between the ages of 0 and 12 years of age. No serious adverse drug reaction was reported in this group of patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

• Overdose

A topical overdose of Ciprofloxacin Taj Pharma may be rinsed out from the eye(s) with lukewarm tap water. Due to the characteristics of this preparation no toxic effects are to be expected with an ocular overdose of this product, or in the event of accidental ingestion of the contents of one bottle.

5. Pharmacological properties
   • Pharmacodynamic properties

Pharmacotherapeutic Group – Ophthalmologicals, Other Antiinfectives.

Mechanism of Action

Ciprofloxacin Taj Pharma eye drops, solution contains the fluoroquinolone ciprofloxacin. The cidal 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 Taj Pharma has in vitro activity against a wide range of Gram-positive and Gram-negative bacteria.

Mechanism of Resistance

Fluoroquinolone resistance, particularly ciprofloxacin, requires significant genetic changes in one or more of five major bacterial mechanisms: a) enzymes for DNA synthesis, b) protecting proteins, c) cell permeability, d) drug efflux, or e) plasmid-mediated aminoglycoside 6′-N-acetyltransferase, AAC (6′)-Ib.

Fluoroquinolones, including ciprofloxacin, differ in chemical structure and mode of action from aminoglycosides, β-lactam antibiotics, macrolides, tetracyclines, sulfonamides, trimethoprim, and chloramphenicol. Therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin.

Breakpoints:

There are no official topical ocular breakpoints for ciprofloxacin and although systemic breakpoints have been used, their relevance to topical therapy is doubtful. The EUCAST clinical MIC breakpoints used for this antibiotic are the following:

Susceptibility to Ciprofloxacin Taj Pharma:

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. The presentation below lists bacterial species recovered from external ocular infections of the eye.

• Pharmacokinetic properties

Ciprofloxacin Taj Pharma eye drops, solution is rapidly absorbed into the eye following topical ocular administration. Systemic levels are low following topical administration. Plasma levels of ciprofloxacin in human subjects following 2 drops of 0.3% ciprofloxacin solution every 2 hours for two days and then every four hours for 5 days ranged from non-quantifiable (<1.0 ng/mL) to 4.7 ng/mL. The mean peak ciprofloxacin plasma level obtained in this study is approximately 450-fold less than that seen following a single oral dose of 250 mg ciprofloxacin. The systemic pharmacokinetic properties of ciprofloxacin have been well studied. Ciprofloxacin Taj Pharma widely distributes to tissues of the body. The apparent volume of distribution at steady state is 1.7 to 5.0 l/kg. Serum protein binding is 20-40%. The half-life of ciprofloxacin in serum is 3-5 hours. Both ciprofloxacin and its four primary metabolites are excreted in urine and faeces. Renal clearance accounts for approximately two-thirds of the total serum clearance with biliary and faecal routes accounting for the remaining percentages. In patients with impaired renal function, the elimination half-life of ciprofloxacin is only moderately increased due to extrarenal routes of elimination. Similarly, in patients with severely reduced liver function the elimination half-life is only slightly longer.

There are no pharmacokinetic data available in respect of use in children.

• Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. Non-clinical developmental toxicity was observed only at exposures considered sufficiently in excess of the maximum human exposure, indicating little relevance to clinical use.

6. Pharmaceutical particulars

List of excipients

Benzalkonium chloride, disodium edetate, mannitol, glacial acetic acid, sodium acetate, hydrochloric acid/sodium hydroxide, purified water.

Incompatibilities

Incompatible with alkaline solutions.

Shelf life

Unopened 24 months, after opening 28 days.

Special precautions for storage

Store upright. Do not store above 25°C.

Do not refrigerate or freeze

Nature and contents of container

5ml Drop-Tainer LDPE bottle and plug with a polystyrene or polypropylene cap.

Special precautions for disposal and other handling

Discard product 28 days after first opening.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com

Ciprofloxacin Ophthalmic solution USP 0.3%w/v Taj Pharma

Package Leaflet – Information for the User
Ciprofloxacin Taj Pharma (as hydrochloride)

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or your pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

IN THIS LEAFLET

1. What Ciprofloxacin Taj Pharma is and what it is used for
2. Before you use Ciprofloxacin Taj Pharma
3. How to use Ciprofloxacin Taj Pharma
4. Possible side effects
5. How to store Ciprofloxacin Taj Pharma
6. Further information

1.WHAT Ciprofloxacin Taj Pharma® IS AND WHAT IT IS USED FOR

Ciprofloxacin Taj Pharma belongs to a group of medicines known as quinolone antibiotics.

It is used for the treatment of corneal ulcers and some other bacterial infections of the eye(s).

2. BEFORE YOU USE Ciprofloxacin Taj Pharma®
   Do not use Ciprofloxacin Taj Pharma

• If you are allergic (hypersensitive) to ciprofloxacin or any other quinolone antibiotic or to any of the other ingredients listed in section 6.

Ask your doctor for advice.

Take special care…

• Only use Ciprofloxacin Taj Pharma in your eyes.
• Only use Ciprofloxacin Taj Pharma in children younger than 1 year if prescribed by your doctor.
• As with any antibiotic, use of Ciprofloxacin Taj Pharma for a long time may lead to other infections. If your symptoms get worse or suddenly return tell your doctor. You may become more susceptible to other infections with the use of this medicine, especially after prolonged use.
• If you notice the first signs of a skin rash or any other allergic reaction, including hives, itching, breathing problems stop treatment and immediately contact your doctor. If you have a serious allergic reaction then you may need emergency treatment.
• 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 Ciprofloxacin Taj Pharma. If you experience any inflammation or inflammatory condition, stop treatment and immediately consult your doctor.

Pregnancy and breast-feeding

If you are pregnant or might get pregnant, or if you are breast-feeding a baby, talk to your doctor before you use Ciprofloxacin Taj Pharma.

Driving and using machines

If your sight is temporarily blurred or affected in any way following use of Ciprofloxacin Taj Pharma you should not drive or operate machinery until your vision is clear again.

Using other medicines

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, the medicines must be used at least 5 minutes apart. Eye ointments should be used last.

Important information if you wear Contact Lenses

There is a preservative in Ciprofloxacin Taj Pharma (benzalkonium chloride) that may cause eye irritation and can discolour soft contact lenses. Do not wear contact lenses (hard or soft) during treatment with Ciprofloxacin Taj Pharma. If you do continue to wear your lenses, you must remove them before using Ciprofloxacin Taj Pharma and wait at least 15 minutes after use before putting your lenses back in.

3. HOW TO USE Ciprofloxacin Taj Pharma®

The usual dose

This will depend on whether you are being treated for corneal ulcers or for some other bacterial infection in your eye.

Corneal Ulcers

Dosing is continued during the night time. Day 1-2 drops every 15 minutes for the first 6 hours and then 2 drops every 30 minutes.

Day 2-2 drops every hour.

Day 3 to Day 14 – 2 drops every 4 hours.

Your doctor will tell you if treatment needs to be continued for longer than 14 days. Other bacterial infections 1 or 2 drops 4 times a day. For severe infections the dose for the first 2 days may be increased to 1 or 2 drops every 2 hours, while you are awake.

It is important that you continue to use Ciprofloxacin Taj Pharma for the full treatment period as advised by your doctor even if your symptoms improve. If you stop using this medicine too early, your symptoms may re-occur.

You should not use Ciprofloxacin Taj Pharma for more than 21 days, unless your doctor says otherwise.

Remove the loose collar from the cap when the bottle is first opened.

Always use Ciprofloxacin Taj Pharma exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Continued over >3. HOW TO USE Ciprofloxacin Taj Pharma® (continued)

How to use

• Wash your hands before you start.
• Twist off the bottle cap.
• Hold the bottle pointing down, between your thumb and fingers.
• Tilt your head back.
• Pull down your lower eyelid with a finger, until there is a ‘pocket’ between the eyelid and your eye.
• The drop will go in here (picture 1).
• Bring the bottle tip close to the eye. Do this in front of a mirror if it helps.
• Do not touch your eye or eyelid, surrounding areas or other surfaces with the dropper. It could infect the drops.
• Gently press on the base of the bottle to release one drop at a time (picture 2).
• Do not squeeze the bottle, only a gentle press on the bottom is needed.
• If you use drops in both eyes, repeat the steps for your other eye. Put the bottle cap firmly back on immediately after use.
• If a drop misses your eye, try again.
• If you forget to use Ciprofloxacin Taj Pharma, do not worry, just use it when it is next due. Do not take a double dose to make up.
• If you use more Ciprofloxacin Taj Pharma than you should it can be washed out of your eye with lukewarm water.
• If this medicine is accidentally swallowed, it is not likely to cause any serious problems, but contact your doctor.

If you have any further questions on the use of Ciprofloxacin Taj Pharma, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Ciprofloxacin Taj Pharmacan cause side effects, although not everybody gets them.

• You may experience some or all of 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.

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.

If you notice white particles in your eyes, continue to use Ciprofloxacin Taj Pharma but tell your doctor immediately.

• You may also experience effects in other areas of your body including:

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.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

By reporting side effects you can help provide more information on the safety of this medicine.

If you experience an allergic reaction, stop using Ciprofloxacin Taj Pharma and tell your doctor.

5. HOW TO STORE Ciprofloxacin Taj Pharma

• Keep out of the reach and sight of children.
• Do not store above 25°C.
• Do not refrigerate or freeze.
• Keep the bottle tightly closed.
• Do not use the drops after the expiry date (marked ‘Exp’) on the bottle and the carton. The expiry date refers to the last day of that month.
• Stop using the bottle 28 days after first opening, to prevent infections.
• Medicines should not be disposed of via waste water or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help toprotect the environment.
• Do not pass this medicine on to others. It may harm them, even if their symptoms are the same as yours

6. FURTHER INFORMATION

What Ciprofloxacin Taj Pharma contains

• The active substance is ciprofloxacin 3 mg/ml (as the hydrochloride).
• The other ingredients are sodium acetate, acetic acid, mannitol, edetate disodium, benzalkonium chloride, hydrochloric acid and/or sodium hydroxide (to adjust pH) and purified water.

What Ciprofloxacin Taj Pharma looks like and contents of the pack

Ciprofloxacin Taj Pharma is a clear, colourless liquid supplied in a pack containing a 5ml plastic bottle with a screw cap.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com