PHARMACEUTICAL INFORMATION CHEMISTRY

Drug Substance: Travoprost

Description: Travoprost is a synthetic prostaglandin F analog. Its chemical name is [1R-[1α(Z),2β(1E,3R*),3α,5α]]- 7-[3,5 Dihydroxy-2-[3-hydroxy-4-[3-(trifluoromethyl) phenoxy]-1-butenyl]cyclopentyl]-5-heptenoic acid, 1 methylethylester. It has a molecular formula of C₂₆H₃₅F₃O₆ and a molecular weight of 500.55. The chemical structure of travoprost is:

Composition:
Each ml contains:
Travoprost I.P. …………………………………. 0.04 mg
Stabilized Oxychloro Complex ………. 0.005% w/v
(As Preservative)
Sterile Aqueous Base ……………………………… q.s.

INDICATIONS
Travoprost Eye Drops is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

DOSAGE AND ADMINISTRATION
The recommended dosage is one drop in the affected eye(s) once daily in the evening. Travoprost Eye Drops should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 2 hours after the first administration with maximum effect reached after 12 hours. Travoprost Eye Drops may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

CONTRAINDICATIONS
Hypersensitivity to the active substance or to any of the excipients.

WARNINGS
Pigmentation: Travoprost Eye Drops has been reported to cause changes to pigmented tissues.

Eyelash Changes: Travoprost Eye Drops may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes.

Intraocular Inflammation: Travoprost Eye Drops should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. 

Angle-closure, Inflammatory or Neovascular Glaucoma: Travoprost Eye Drops has not been evaluated for the treatment of angle-closure, inflammatory or neovascular glaucoma.

PREGNANCY
Pregnancy Category C: There are no adequate and well-controlled studies of Travoprost Eye Drops administration in pregnant women. Because animal reproductive studies are not always predictive of human response, Travoprost Eye Drops should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: A study in lactating rats demonstrated that radiolabeled travoprost and/or its metabolites were excreted in milk. It is not known whether this drug or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when travoprost.

Pediatric Use: Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

SYMPTOMS AND TREATMENT OF OVERDOSAGE
No cases of overdose have been reported. A topical overdose of Travoprost may be flushed from the eye(s) with lukewarm water. Treatment of a suspected oral ingestion is symptomatic and supportive.

SPECIAL INSTRUCTIONS
Patients should be advised to avoid contamination of the dispensing tip.

STORAGE
Store in a cool & dark place below 30°C.

PRESENTATION
Travneal is available in 3ml RISHPHARM R2 Teal Green vials with Tamper Evident ring retention feature, Compliant to US FDA regulatory requirements and exactly delivers a calibrated 30μl drop size, with Outer Packs colour coding adapted from American Academy of Ophthalmology Color Codes guidelines for Topical Ocular Medications.

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance,
S. G. Highway, Ahmedabad 380015,
Gujarat, INDIA

R0423-00

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY

Drug Substance: Brimonidine Tartrate & Timolol Maleate
Brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5%, sterile, is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor (topical intraocular pressure lowering agent).

The structural formulae are:
Brimonidine tartrate:

5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate; Molecular weight = 442.24

Timolol maleate:

(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)-oxy]-2-propanol maleate (1:1) (salt); Molecular weight = 432.50 as the maleate salt.

Composition:
Each ml contains:
Brimonidine Tartrate I.P…………………….. 2 mg
Timolol Maleate I.P.
equivalent to Timolol …………………………….5 mg
Stabilized Oxychloro Complex ……………….. 0.005% w/v
(As Preservative)
Sterile Aqueous Base …………………………… q.s.

INDICATIONS
Brimonidine Tartrate & Timolol Maleate Ophthalmic Solution reduces intraocular pressure (IOP) in patients with chronic open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers.

DOSAGE AND ADMINISTRATION
To avoid contamination of the eye or eye drops do not allow the dropper tip to come into contact with any surface.

Recommended dosage in adults (including the elderly): The recommended dose is one drop of Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution in the affected eye(s) twice daily, approximately 12 hours apart. If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart.

MECHANISM OF ACTION
Brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5% is comprised of two components: Brimonidine Tartrate and Timolol Maleate. Each of these two components decreases elevated intraocular pressure, whether associated with glaucoma or not. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage.

Brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5% is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor. Both brimonidine and timolol have a rapid onset of action, with peak ocular hypotensive effect seen at two hours post-dosing for brimonidine and one to two hours for timolol.

Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. Timolol maleate is a beta1 and beta2 adrenergic receptor inhibitor that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.

CONTRAINDICATIONS
Brimonidine Tartrate & Timolol Maleate Ophthalmic Solution is hypersensitivity to the active substances or to any of the excipients. It is reactive airway disease including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease. Sinus bradycardia, sick sinus syndrome sino-atrial block, second- or third-degree atrioventricular block not controlled with a pace-maker, overt cardiac failure, cardiogenic shock. Use in neonates and infants (less than 2 years of age). Patients receiving monoamine oxidase (MAO) inhibitor therapy. Patients on antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin).

WARNINGS
Like other topically applied ophthalmic agents, Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution may be absorbed systemically. No enhancement of the systemic absorption of the individual active substances has been observed. Due to beta-adrenergic component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration.

DRUG INTERACTIONS
No interaction studies have been performed with the brimonidine timolol fixed combination. Although specific drug interactions studies have not been conducted with Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution, the theoretical possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anaesthetics) should be considered. 

Mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally. Beta- blockers may increase the hypoglycaemic effect of anti-diabetic agents. Beta-blockers can mask the signs and symptoms of hypoglycaemia. Although specific drug interactions studies have not been conducted with Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution, the theoretical possibility of an additive IOP lowering effect with prostamides, prostaglandins, carbonic anhydrase inhibitors and pilocarpine should be considered.

PREGNANCY
Pregnancy Category C: There are no adequate data for the use of the brimonidine timolol fixed combination in pregnant women. Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution should not be used during pregnancy unless clearly necessary. 

Nursing Mothers: It is not known if brimonidine is excreted in human milk but it is excreted in the milk of the lactating rat. Beta-blockers are excreted in breast milk. However, at therapeutic doses of timolol in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant. Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution should not be used by women breast-feeding infant. 

Pediatric Use: The safety and effectiveness of Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution in children and adolescents (2 to 17 years of age) have not been established and therefore, its use is not recommended in children or adolescents.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.

SYMPTOMS AND TREATMENT OF OVERDOSAGE
Rare reports of overdosage with Brimonidine Tartrate and Timolol Maleate Ophthalmic Solution in humans resulted in no adverse outcome. Treatment of an overdose includes supportive and symptomatic therapy; a patient’s airway should be maintained. 

Ophthalmic overdose (Adults): In those cases received, the events reported have generally been those already listed as adverse reactions.

Systemic overdose resulting from accidental ingestion (Adults): There is very limited information regarding accidental ingestion of brimonidine in adults. The only adverse event reported to date was hypotension. It was reported that the hypotensive episode was followed by rebound hypertension. Oral overdoses of other alpha-2-agonists have been reported to cause symptoms such as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnoea, hypotonia, hypothermia, respiratory depression and seizure.

Paediatric population: Symptoms of systemic timolol overdose include: bradycardia, hypotension, bronchospasm, headache, dizziness and cardiac arrest. A study of patients showed that timolol did not dialyse readily.

CLINICAL STUDIES
Clinical studies were conducted to compare the IOP-lowering effect over the course of the day of Brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5% administered twice a day (BID) to individually-administered brimonidine tartrate ophthalmic solution, 0.2% administered three times per day (TID) and timolol maleate ophthalmic solution, 0.5% BID in patients with glaucoma or ocular hypertension. Brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5% BID provided an additional 1 to 3 mm Hg decrease in IOP over brimonidine treatment TID and an additional 1 to 2 mm Hg decrease over timolol treatment BID during the first 7 hours post dosing. However, the IOP-lowering of Brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5% BID was less (approximately 1-2 mm Hg) than that seen with the concomitant administration of 0.5% timolol BID and 0.2% brimonidine tartrate TID. Brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5% administered BID had a favorable safety profile versus concurrently administered brimonidine TID and timolol BID in the self-reported level of severity of sleepiness for patients over age 40.

SPECIAL INSTRUCTIONS
Patients should be advised to avoid contamination of the dispensing tip.

STORAGE
Store in a cool & dark place below 30°C. Do not allow to freeze.

PRESENTATION
Britneal Ophthalmic Solution is available in 5ml RISHPHARM R2 Teal Green vials with Tamper Evident ring retention feature, Compliant to US FDA regulatory requirements and exactly delivers a calibrated 30μl drop size, with Outer Packs colour coding adapted from American Academy of Ophthalmology Color Codes guidelines for Topical Ocular Medications.

For further details, please write to:
Amneal Healthcare Pvt. Ltd. 
9th Floor, 901 to 905, Iscon Elegance,
S.G. Highway, Ahmedabad 380015,
Gujarat, INDIA

R0423-00

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY

Drug Substance: Brinzolamide

Structural Formula:

Molecular Formula: C₁₂H₂₁N₃O₅S₃

Molecular Weight: 383.51
Chemical Name: 2H-Thieno[3,2-e]-1,2-thiazine-6-sulfonamide, 4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-, 1,1-dioxide, (R)-; (R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfo amide 1,1-dioxide

Drug Substance: Brimonidine tartrate

Structural Formula:

Molecular Formula: C₁₅H₁₆BrN₅O₆

Molecular Weight: 442.22
Chemical Name: 6-Quinoxalinamine, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1); 5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline L-tartrate (1:1).

Composition:
Each ml contains:
Brimonidine Tartrate I.P. ………………………….. 2 mg
Brinzolamide I.P. ………………………………………….. 10 mg
Benzalkonium Chloride Solution I.P. ……………….. 0.02% v/v
(As Preservative)
Sterile Aqueous Base …………………………………… q.s.

ACTIONS & CLINICAL PHARMACOLOGY:
Brinzolamide
Brinzolamide is a medicine that treats high pressure inside the eye (ocular hypertension) and helps with glaucoma. High pressure can happen when too much fluid builds up inside your eye. Brinzolamide helps the eye to produce less fluid.

Brimonidine: 
Ophthalmic brimonidine is used to lower pressure in the eyes in patients who have glaucoma (high pressure in the eyes that may damage nerves and cause vision loss) and ocular hypertension (pressure in the eyes that is higher than normal but not high enough to cause vision loss).

INDICATIONS:
Decrease of elevated intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction.

DOSAGE AND ADMINISTRATION:
One drop of Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension in the affected eye(s) two to three times daily or as recommended by prescribing clinician.

SIDE EFFECT:
Blurred vision, taste change, sleepiness, Dizziness, ocular hyperemia, eye discomfort.

WARNINGS:
Talk to your doctor, optometrist (optician) or pharmacist before using Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension, if you have now or have had in the past:

• liver problems
• a type of high pressure in the eyes called narrow-angle glaucoma
• dry eyes or cornea problems

If you wear soft contact lenses, do not use the drops with your lenses on.

PREGNANCY:
Pregnant women:
Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension should be used during pregnancy only if, potential benefit justifies the potential risk to the fetus.

Nursing Mothers:
It is unknown whether topical Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension is excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown that following oral administration, minimal levels of brinzolamide are excreted in breast milk. Brimonidine administered orally is excreted in breast milk. Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension should not be used by women who are breast-feeding.

Paediatric Use:
The safety and efficacy of Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension in children and adolescents aged 2 to 17 years have not been established. Symptoms of brimonidine overdose (including loss of consciousness, hypotension, hypotonia, bradycardia, hypothermia, cyanosis and apnoea) have been reported in neonates and infants receiving brimonidine eye drops as part of medical treatment of congenital glaucoma. Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension is therefore contraindicated in children below 2 years of age.

Treatment of children 2 years and above (especially those in the 2-7 age range and/or weighing <20 kg) is not recommended because of the potential for central nervous system-related side effects.

Fertility:
Non-clinical data do not show any effects of brinzolamide or brimonidine on fertility. There are no data on the effect of topical ocular administration of Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension on human fertility.

TREATMENT OF OVERDOSAGE
If overdose with Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension occurs, treatment should be symptomatic and supportive. The patient’s airway should be maintained.

SPECIAL INSTRUCTIONS:
Patients should be advised to avoid contamination of the dispensing tip.

STORAGE:
Store in a cool & dark place below 30°C.
Keep out of reach of children.
Use the suspension within one month after opening the container.

DRUG INTERACTIONS
Oral Carbonic Anhydrase Inhibitors: There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and brinzolamide ophthalmic suspension 1%, a component of Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension. The concomitant administration of Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension and oral carbonic anhydrase inhibitors is not recommended.

High-Dose Salicylate Therapy: Carbonic anhydrase inhibitors may produce acid-base and electrolyte alterations. These alterations were not reported in the clinical trials with brinzolamide ophthalmic suspension 1%. However, in patients treated with oral carbonic anhydrase inhibitors, rare instances of acid-base alterations have occurred with high-dose salicylate therapy. Therefore, the potential for such drug interactions should be considered in patients receiving Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension.

CNS Depressants: Although specific drug interaction studies have not been conducted with Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension, the possibility of an additive or potentiating effect with CNS depressants (alcohol, opiates, barbiturates, sedatives, or anesthetics) should be considered. 

Antihypertensives/Cardiac Glycosides: Because brimonidine tartrate, a component of Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension, may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension is advised.

Tricyclic Antidepressants: Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with Brimonidine Tartrate and Brinzolamide Ophthalmic Suspension in humans can lead to resulting interference with the IOP lowering effect. Caution is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

Monoamine Oxidase Inhibitors: Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine tartrate and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

PHARMACOKINETICS:
Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its affinity for CA-II, brinzolamide distributes extensively into the RBCs and exhibits a long half-life in whole blood (approximately 111 days). In humans, the metabolite N-desethyl brinzolamide is formed, which also binds to CA and accumulates in RBCs. This metabolite binds mainly to CA-I in the presence of brinzolamide. In plasma, both parent brinzolamide and N-desethyl brinzolamide concentrations are <10 ng/mL. Binding to plasma proteins is approximately 60%. Brinzolamide is eliminated predominantly in the urine as an unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N desmethoxypropyl and O-desmethyl metabolites.

After ocular administration of a 0.2% solution of brimonidine tartrate, plasma concentrations peaked within 1 to 4 hours and declined with a systemic half-life of approximately 3 hours. In humans, systemic metabolism of brimonidine is extensive. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites. Approximately 87% of an orally administered radioactive dose was eliminated within 120 hours, with 74% found in the urine.

PRESENTATION:
Brinzneal Ophthalmic Suspension is available in 5 ml RISHPHARM R2 White vials with Tamper Evident ring retention feature, compliant to US FDA regulatory requirements and exactly delivers a calibrated 30μl drop size.

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S.G. Highway, Ahmedabad 380015
Gujarat, INDIA

R0423-00

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

GENERIC NAME
Netarsudil Ophthalmic Solution 0.02% w/v

QUALITATIVE AND QUANTITATIVE COMPOSITION
Composition:
Each ml contains:
Netarsudil Mesylate Eq. to
Netarsudil ……………………………………….. 0.2 mg
Benzalkonium Chloride I.P. ……………….. 0.15 mg
(As Preservative)
Sterile Aqueous Vehicle …………………………… q.s.

DOSAGE FORM AND STRENGTH
Ophthalmic Solution
Netarsudil Mesylate Eq. to Netarsudil 0.2 mg

CLINICAL PARTICULARS
Therapeutic indications
It is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

DOSAGE AND ADMINISTRATION
Dosage:
As directed by the Physician.

Method of administration: For topical ocular use only.
If one dose is missed, treatment should continue with the next dose in the evening. Twice a day dosing is not well tolerated and is not recommended. If Netarsudil 0.02% is to be used concomitantly with other topical ophthalmic drug products to lower IOP, administer each drug product at least 5 minutes apart.

Contraindications
Netarsudil Ophthalmic Solution 0.02% w/v is contraindicated in patients with known hypersensitivity to Netarsudil or any other component of this formulation.

Special warnings and precautions for use
Bacterial Keratitis:
There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.

Use with Contact Lenses:
Contact lenses should be removed prior to instillation of Netarsudil Ophthalmic Solution 0.02% w/v and may be reinserted 15 minutes following its administration.

Drugs interactions
No information available.

Use in special populations
Pregnancy:
Risk Summary: There are no available data on Netarsudil Ophthalmic Solution 0.02% w/v use in pregnant women to inform any drug associated risk; however, systemic exposure to Netarsudil from ocular administration is low. Intravenous administration of Netarsudil to pregnant rats and rabbits during organogenesis did not produce adverse embryo fetal effects at clinically relevant systemic exposures.

Data
Animal Data: Netarsudil administered daily by intravenous injection to rats during organogenesis caused abortions and embryo fetal lethality at doses ≥0.3 mg/kg/day (126-fold the plasma exposure at the recommended human ophthalmic dose [RHOD], based on C_max). The no-observed-adverse-effect-level (NOAEL) for embryo fetal development toxicity was 0.1 mg/kg/day (40-fold the plasma exposure at the RHOD, based on C_max). Netarsudil administered daily by intravenous injection to rabbits during organogenesis caused embryofetal lethality and decreased fetal weight at 5 mg/kg/day (1480-fold the plasma exposure at the RHOD, based on C_max), Malformations were observed at ≥3 mg/kg/day (1330-fold the plasma exposure at the RHOD, based on C_max), including thoracogastroschisis, umbilical hernia and absent intermediate lung lobe. The NOAEL for embryofetal development toxicity was 0.5 mg/kg/day (214-fold the plasma exposure at the RHOD, based on C_max).

Lactation:
Risk Summary: There are no data on the presence of Netarsudil Ophthalmic Solution 0.02% w/v in human milk, the effects on the breastfed infant, or the effects on milk production. However, systemic exposure to Netarsudil following topical ocular administration is low, and it is not known whether measurable levels of Netarsudil would be present in maternal milk following topical ocular administration.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Netarsudil Ophthalmic Solution 0.02% w/v and any potential adverse effects on the breast-fed child from Netarsudil Ophthalmic Solution 0.02% w/v.

Paediatric Use:
Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Geriatric Use:
No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Effects on ability to drive and use medicines:
There’re no reports of Netarsudil effect on the ability to drive and use machines. However, Netarsudil may cause transient blurring of vision on instillation. Therefore, warn patients not to drive or operate hazardous machinery until vision is clear.

Undesirable effects
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most common ocular adverse reaction observed in controlled clinical studies with Netarsudil Ophthalmic Solution 0.02% w/v dosed once daily was conjunctival hyperemia which was reported in 53% of patients. Other common (approximately 20%) ocular adverse reactions reported were: corneal verticillata, instillation site pain, and conjunctival hemorrhage. Instillation site erythema, corneal staining, blurred vision, increased lacrimation, erythema of eyelid, and reduced visual acuity were reported in 5-10% of patients. 

Corneal Verticillata Corneal verticillata occurred in approximately 20% of the patients in controlled clinical studies. The corneal verticillata seen in Netarsudil Ophthalmic Solution 0.02% w/v treated patients were first noted at 4 weeks of daily dosing. This reaction did not result in any apparent visual functional.

The most frequent adverse event (AE) was generally mild conjunctival hyperemia, the severity of which did not increase with continued dosing. Netarsudil was associated with minimal treatment-related serious or systemic AEs, likely due to the lack of systemic exposure.

Overdose
No information available.

Supportive therapy should be given as required or rush to the nearest hospital or contact physician.

PHARMACOLOGICAL PROPERTIES

Mechanism of Action
Netarsudil is a rho kinase inhibitor, which is believed to reduce IOP by increasing the outflow of aqueous humor through the trabecular meshwork route. The exact mechanism is unknown.

Pharmacokinetics properties
Absorption
The systemic exposures of Netarsudil and its active metabolite, AR-13503, were evaluated in 18 healthy subjects after topical ocular administration of Netarsudil Ophthalmic Solution 0.02% w/v once daily (one drop bilaterally in the morning) for 8 days. There were no quantifiable plasma concentrations of Netarsudil (lower limit of quantitation (LLOQ) 0.100 ng/mL) post dose on Day 1 and Day 8. Only one plasma concentration at 0.11 ng/mL for the active metabolite; was observed for one subject on Day 8 at 8 hours post-dose.

Metabolism
After topical ocular dosing, Netarsudil is metabolized by esterase’s in the eye.

NON-CLINICAL PROPERTIES
Animal toxicology or Pharmacology
Carcinogenesis, Mutagenesis, Impairment of Fertility. Longterm studies in animals have not been performed to evaluate the carcinogenic potential of Netarsudil. Netarsudil was not mutagenic in the Ames test, in the mouse lymphoma test, or in the in vivo rat micronucleus test. Studies to evaluate the effects of Netarsudil on male or female fertility in animals have not been performed.

DESCRIPTION
Netarsudil Ophthalmic Solution 0.02% w/v is a Rho kinase inhibitor indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Its chemical name is (S)-4-(3-amino-1-(isoquinolin-6-yl-amino)- 1oxopropan-2-yl) benzyl 2,4-dimethylbenzoate dimesylate. The molecular formula of the free base is C₂₈H₂₇N₃O₃ and the molecular formula of the dimesylate is C₃₀H₃₅N₃O₉S₂. The molecular weight of the free base is 453.54 and the molecular weight of the dimesylate is 645.74.

The chemical structure is:

PHARMACEUTICAL PARTICULARS
Incompatibilities
Not applicable

Shelf life
As per Carton

Packaging information
Netarsudil Ophthalmic Solution 0.02% w/v is available in 2.5 ml pack.

Storage and handling instruction
Store at 2°-8°C. Protect from light & moisture. Do not freeze.

Keep out of reach of children.

PATIENT COUNSELLING INFORMATION
Read this entire leaflet carefully before you are given this medicine because it contains important information for you. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or pharmacist or nurse. If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

Before you take Netarsudil Ophthalmic Solution 0.02% w/v, tell your Healthcare provider (HCP) about other conditions you have and medications you may be taking: do not take if you have an allergy to this drug. This product should not be used by patients who are hypersensitive to any of the ingredients.

Handling the Container
Instruct patients to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to minimize contamination of the solution. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

When to Seek Physician Advice
Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use of Netarsudil Ophthalmic Solution 0.02% w/v.

Use with Contact Lenses
Advise patients that Netarsudil Ophthalmic Solution 0.02% w/v contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of Netarsudil Ophthalmic Solution 0.02% w/v and may be reinserted 15 minutes following its administration.

Use with Other Ophthalmic Drugs
Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between applications. 

If Netarsudil Ophthalmic Solution 0.02% w/v is to be used concomitantly with other topical ophthalmic drug products to lower IOP, administer each drug product at least 5 minutes apart.

Missed Dose
Advise patients that if one dose is missed, treatment should continue with the next dose in the evening. Twice a day dosing is not well tolerated and is not recommended.

General information about the safe and effective use of Netarsudil Ophthalmic Solution 0.02% w/v

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use Netarsudil

Ophthalmic Solution 0.02% w/v for a condition for which it was not prescribed. Do not give Netarsudil Ophthalmic Solution 0.02% w/v to other people, even if they have the same symptoms you have. It may harm them. If you would like more information, talk with your healthcare provider.

DETAILS OF MANUFACTURER

Presentation:
Netaneal is available in 2.5 ml white vials with Outer Packs colour coding adapted from American Academy of Ophthalmology Color Codes guidelines for Topical Ocular Medications.

Manufactured in India By:
Pure & Cure Healthcare Pvt. Ltd.
(A subsidiary of Akums Drugs & Pharmaceuticals Ltd.)
Plot No. 26A, 27-30, Sector-8A, I.I.E., SIDCUL, Ranipur
Haridwar-249 403, Uttarakhand.

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S.G. Highway, Ahmedabad 380015
Gujarat, INDIA

DETAILS OF PERMISSION OR LICENCE NUMBER WITH DATE
Mfg. Lic. No.: 51/UA/SC/P-2013 (Date: 08/09/2021)

DATE OF REVISION
R0523-00 (Date: 09/05/2023)

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

Drug Substance: Sodium Hyaluronate 

Structure: 

Molecular formula: (C₁₄H₂₂NNa0₁₁) n  

Composition: 
Sodium Hyaluronate BP……………0.1% w/v 
Other Ingredients: L-ProIine USP, L-Lysine Hydrochloride USP, L-Leucine USP, Glycine I.P., Water for Injections I.P. q.s. 

DESCRIPTION 
Sodium Hyaluronate, a natural polymer which is also present in ttie structures of the human eye. The particular physical characteristics of Sodium Hyaluronate confer to this formulation its viscoelastic and water retaining properties. Sodium Hyaluronate provides a stable coating on the surface of the eye, which is slowly eliminated by blinking. Therefore, Sodium Hyaluronate Eye Drops combines long lasting relief with maximum comfort. It is well tolerated due to its unique composition. 

Mechanism of Action: Sodium Hyaluronate may promote adhesion and migration of corneal epithelial cells by binding to fibronectin and has superior water retention property. 

CLINICAL PARTICULARS
Indication:
0.1% sodium hyaluronate, ophthalmic solution are used for treatment of dry eyes and burning sensations due to environmental conditions.

Dosage and Method of Administration:
Posology:
Usually, instill one drop of Sodium Hyaluronate Ophthalmic 0.1% Solution at a time into the eye five to six times daily. The dosage may be adjusted according to the patients’ symptoms. 

Sodium Hyaluronate Ophthalmic Solution can be used while wearing contact lenses. Wearing soft or hard contact lenses can be more comfortable by using Sodium Hyaluronate Ophthalmic Solution as it does not form crusts or residues. 

Sodium Hyaluronate Ophthalmic Solution is suitable for long-term treatment. 

Method of administration:
For ocular use only 

Use in Elderly:
Dosage recommendations and indications for use in elderly have not been established. 

Use in Patients with Renal Impairment:
Not applicable 

Use in Patients with Hepatic Impairment:
Not applicable 

Use in Children:
Dosage recommendations and indications for use in children have not been established. 

Contraindications:
Hypersensitivity to any of the ingredients. In the event of persisting eye irritation discontinue use and consult your doctor. 

Special Warnings and Special Precautions for Use:
Sodium Hyaluronate Ophthalmic Solution should not be used at the same time as other ophthalmic drugs. If any other eye drops must be used there should be an adequate gap before applying Sodium Hyaluronate Ophthalmic Solution. Eye ointments should always be administered after the application of Sodium Hyaluronate Ophthalmic Solution. 

Interaction with Other Medicinal Products and Other Forms of Interaction:
As Sodium Hyaluronate Ophthalmic Solution reaches its target directly by topical application and has primarily a physical effect (wetting of the surface) and no systemic effect, no drug interactions other than the physical interaction of topically applied eye drops are known. 

Pregnancy and Lactation:
Sodium Hyaluronate Ophthalmic Solution can be applied during pregnancy and lactation as there is no pharmacological effect. 

Effects on Ability to Drive and Use Machines:
Sodium Hyaluronate Ophthalmic Solution may cause blurred vision for a short time after application even at normal dosages and with proper use. This can subsequently impair reaction time while driving or operating machinery. 

Undesirable Effects:
Because it is preservative-free, Sodium Hyaluronate Ophthalmic Solution is well tolerated even when used over a long period of time. Safety data does not provide any evidence that would represent an unacceptable hazard to its use in humans. In rare cases hypersensitive reactions like burning, itching, tearing has been reported which recedes immediately on discontinuation of Sodium Hyaluronate Ophthalmic Solution. 

Overdose:
Overdosage is unlikely to occur with this topical preparation. 

PHARMACOLOGICAL PROPERTIES
Pharmacodynamic Properties:
Dry eye patients present with instability of the precorneal tear film which breaks up much earlier than normal. The instability of the precorneal tear film leads to dry eye symptoms such as the sensation of sand in the eye, recurrent blurred vision, itching, smartness, and the sensation of dryness. 

The main objective of dry eye treatment is to increase the precorneal tear film stability Hyaluronic Acid (HA) as a tear substitute behaves like a pseudoplastic fluid. This means that at very low shear the solution has a very high viscosity and relatively low elasticity, and at higher shear the solution is extremely elastic. These viscoelastic properties are important to lubricate. In addition, the water binding capacity of HA keeps the eye’s surface wet. HA solution forms a lubricating moisture film on the surface of the eye that is not easily rinsed off. The macromolecule sodium hyaluronate has bio-adhesive and mucomimetic properties when applied to the eye because of interactions with the precorneal mucin layer. By this, the solution spreads out very well and forms a regular, stable, and long-lasting tear film. It however does not cause blurred vision and it protects the eyes from dryness and irritation for a long time. 

In Sodium Hyaluronate Ophthalmic Solution, Sodium Hyaluronate acts in a physico-chemical manner without pharmacological action by lubricating the ocular surface HA binds to many extracellular matrix molecules, specifically to cell bodies through cell surface receptors like CD44. Expression of CD44 is increased in patients with moderate dry eye and superficial keratitis. HA might have a direct role in control of ocular surface inflammation in dry eye patients because it is associated with a decreased expression of CD44 in patients with moderate eye and superficial keratitis. 

The duration of contact with the ocular surface (the so-called residence time) is important for the efficacy of artificial tears. Wearing soft or hard contact lenses can be more comfortable by using Sodium Hyaluronate Ophthalmic Solution as it does not form crust or residue. 

It is a phosphate-free, citrate buffered formulation. This can improve the safety as the formulation of insoluble calcium phosphate deposits in the cornea is not formed after instillation of these eye drops. 

Pharmacokinetic Properties:
0.1% sodium hyaluronate, ophthalmic solution reaches their target directly by topical application and have primarily a physical effect (wetting of the surface). The substance does not become systemically available and are not metabolised in the human body. It is washed out of the eye after a while. 

Preclinical Safety Data:
There is no data known about any toxic effect of sodium hyaluronate. Because sodium hyaluronate is a naturally physiologic substance occurring in the eye but also in other parts of the body, the substance is very well tolerated in general. 

Incompatibilities:
None known. 

STORAGE INSTRUCTIONS
Store at a temperature not exceeding 30°C and protect from light. Use the solution within 60 days after opening the container.
For external use only.
Keep out of reach of children. 

PRESENTATION
Tearneal is available in 10mI in Aero Pump 3K® System and exactly delivers a calibrated 28yI drop size. 

Manufactured By:
KH Kilitch Healthcare India Limited 
R-904, 905, T.T.C. Industrial Area 
M.I.D.C., Navi Mumbai, Dist. Thane 
Rabale – 400 701, India 

Marketed By:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015 Gujarat, INDIA 

R0623-00

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY

Active Ingredients: Polyethylene Glycol 400 USP 0.4% w/v, Propylene Glycol I.P. 0.3 % w/v

Inactive Ingredients: Hydroxypropyl Guar, Glycerine, Sorbitol, Sodium Chloride, Potassium Chloride, Calcium Chloride, Magnesium Chloride, Boric Acid, Sodium Hydroxide and Water for Injection.

Composition:
Each ml contains:
Polyethylene Glycol 400 USP-NF ………….. 4 mg
Propylene Glycol I.P. ……………………… 3 mg
Sterile Aqueous Base …………………….. q.s.

ACTIONS & CLINICAL PHARMACOLOGY
The combination of Polyethylene Glycol 400 & Propylene Glycol is clinically proven to reduce both signs and symptoms of dry eye. The mechanism of action is thought to be due to its unique lubricating system formulated to adjust to each user’s individual tear pH. When the ingredients of Polyethylene Glycol and Propylene Glycol Ophthalmic Solution, combine with natural tears, a soft gel forms a network of protection over the eye surface. Since it promotes a healthy environment in eye surface, damaged surface cells of eye can repair more easily.

INDICATIONS
For temporary relief of burning and irritation due to dryness of the eye.

CONTRAINDICATIONS
It is contraindicated if there is hypersensitivity to any ingredients used in the formulation.

WARNINGS
For external use only.
Do not use:

• if this product changes color or becomes cloudy
• if you are sensitive to any ingredient in this product

When using this product:

• do not touch tip of container to any surface to avoid contamination

Stop use and get medical help if:

• you feel eye pain
• changes in vision occur
• redness or irritation of the eye(s) gets worse, persists or lasts more than 72 hours

Keep out of reach of children
If swallowed, get medical help.

PREGNANCY
Pregnancy Category C: Animal reproduction studies have shown an adverse effect on the fetus but there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Nursing Mothers: It is not known whether this formulation is distributed in milk or not. Patient should seek advice of a health care professional before use.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

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

SYMPTOMS AND TREATMENT OF OVERDOSAGE
This medicine may be harmful if swallowed. If swallowing or overdose is suspected, get medical help.

DOSAGE AND ADMINISTRATION
Instil 1 or 2 drops in the affected eye(s) as needed.

SPECIAL INSTRUCTIONS
Patients should be advised to avoid contamination of the dispensing tip.

STORAGE
Store in a cool & dark place below 30° C.

PRESENTATION
Aquaneal is available in 10 ml Multi-Dose Preservative Free vials with PureFlow® technology.

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA

R0423-00

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

COMPOSITION  
Each enteric coated soft gelatin capsule contains (Approx.): 
Fish Oil ……………………………….. 1000 mg 
Containing 
Eicosapentaenoic Acid …………… 180 mg 
Docosahexaenoic Acid …………… 120 mg 

NUTRACEUTICAL FORM 
Enteric Coated Soft Gelatin Capsule 

HEALTH CLAIM 
It supports heart, brain, and joint function. It is also recommended for use in Dry Eye (DED) management. 

USAGE AND ADMINISTRATION 
Posology 
The recommended use is to take 1 capsule daily with a meal or as suggested by a Healthcare Professional. 
Method of administration: For oral administration only. 

CONTRAINDICATIONS
Hypersensitivity to the active substance or any of the excipients.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Fatty Acids should be used with caution in persons with known sensitivity or allergy to fish. In the absence of efficacy and safety data, use of this medication in children is not recommended. Clinical data regarding the use of Fatty Acids in elderly patients over 70 years of age are limited. Because of the moderate increase in bleeding time (with the high dosage, i.e. 4 capsules), persons receiving anticoagulant therapy must be monitored and the dosage of anticoagulant adjusted if necessary. Use of this medication does not eliminate the need for the surveillance usually required for persons of this type.
Allergen: Contains Fish
Make allowance for the increased bleeding time in patients at high risk of haemorrhage (because of severe trauma, surgery, etc).
During treatment with Fatty Acids, there is a fall in thromboxane A2 production. No significant effect has been observed on the other coagulation factors. Some studies with omega-3-acids demonstrated a prolongation of bleeding time, but the bleeding time reported in these studies has not exceeded normal limits and did not produce clinically significant bleeding episodes. Only limited information regarding the use in persons with renal impairment is available. In some persons a small but significant increase (within normal values) in ASAT and ALAT was reported, but there are no data indicating an increased risk for persons with hepatic impairment. ALAT and ASAT levels should be monitored in patients with any signs of liver damage (in particular with the high usage, i.e. 4 capsules). Fatty Acid is not indicated in exogenous hypertriglyceridaemia (type 1 hyperchylomicronaemia). 

There is only limited experience in secondary endogenous hypertriglyceridaemia (especially uncontrolled diabetes). There is no experience regarding hypertriglyceridaemia in combination with fibrates.

Do not press the capsule as this may damage the coating of the capsule.

NOT FOR MEDICINAL USE  

DRUG INTERACTION
Fatty Acids has been given in conjunction with warfarin without haemorrhagic complications. However, the prothrombin time must be checked when Fatty Acids is combined with warfarin or when treatment with Fatty Acids is stopped.

USE IN SPECIFIC POPULATION
Pregnancy
There are no adequate data from the use of Fatty Acids in pregnant women. Studies in animals have not shown reproductive toxicity. The potential risk for humans is unknown and therefore Fatty Acids should not be used during pregnancy unless clearly necessary.

Breastfeeding
There are no data on the excretion of Fatty Acids in animal and human milk. Fatty Acids should not be used during lactation.

Fertility
There are no adequate data on the effect of Fatty Acids on fertility.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Effects on ability to drive and use machines have not been studied. Nevertheless, Fatty Acids is expected to have no or negligible influence on the ability to drive and use machines. 

UNDESIRABLE EFFECTS
The frequencies of adverse reactions are ranked according to the following: very common (> 1/10), common (> 1/100 to < 1/10); uncommon (>1/1000 to < 1/100); rare (>1/10,000 to < 1/1000); very rare (< 1/10,000); not known
Immune system disorders:
Rare: hypersensitivity
Metabolism and nutrition disorders:
Uncommon: hyperglycaemia, gout
Nervous system disorders:
Uncommon: dizziness, dysgeusia, headache
Vascular disorders:
Uncommon: hypotension
Respiratory thoracic and mediastinal disorders:
Uncommon: epistaxis
Gastrointestinal disorders:
Common: gastrointestinal disorders (including abdominal distension, abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, eructation, gastro-oesophageal reflux disease, nausea or vomiting)
Uncommon: gastrointestinal haemorrhage
Hepatobiliary disorders:
Rare: liver disorders (including transaminases increased, alanine aminotransferase increased and aspartate aminotransferase increased)
Skin and subcutaneous tissue disorders: Uncommon: rash
Rare: urticarial
Not known: pruritus

OVERUSAGE
There are no special recommendations. Treatment should be symptomatic.

PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
Pharmacotherapeutic group: Omega-3-triglycerides including other esters and acids, ATC code: C10AX06 

The omega-3 series polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential fatty acids. Fatty Acids is active on the plasma lipids by lowering triglyceride levels as a result of a fall in VLDL (very low density lipoprotein), and the substance is also active on haemostasis and blood pressure. Fatty Acids reduces the synthesis of triglycerides in the liver because EPA and DHA are poor substrates for the enzymes responsible for triglyceride synthesis and they inhibit esterification of other fatty acids. The increase in peroxisomes of β-oxidation of fatty acids in the liver also contributes to the fall in triglycerides, by reducing the quantity of free fatty acids available for their synthesis. The inhibition of this synthesis lowers VLDL. Fatty Acids increases LDL-cholesterol in some persons with hypertriglyceridemia. A rise in HDLcholesterol is only small, significantly smaller than seen after administration of fibrates, and not consistent. The long-term lipid-lowering effect (after more than one year) is not known. Otherwise there is no strong evidence that lowering triglycerides reduces the risk of ischaemic heart disease. During treatment with Fatty Acid, there is a fall in thromboxane A2 production and a slight increase in bleeding time. No significant effect has been observed on the other coagulation factors.
Vitamin E deficiency has been linked to disorders such as cystic fibrosis where fat absorption is impaired. It is essential for the normal function of the muscular system and the blood. 

Pharmacokinetic properties
During and after absorption, there are three main pathways for the metabolism of the omega-3 fatty acids: 

• The fatty acids are first transported to the liver where they are incorporated into various categories of lipoproteins and then channeled to the peripheral lipid stores;

• The cell membrane phospholipids are replaced by lipoprotein phospholipids and the fatty acids can then act as precursors for various eicosanoids;

• The majority is oxidised to meet energy requirements.

• The concentration of omega-3 fatty acids, EPA and DHA, in the plasma phospholipids corresponds to the EPA and DHA incorporated into the cell membranes.

• Animal pharmacokinetic studies have shown that there is a complete hydrolysis of the ethyl ester accompanied by satisfactory absorption and incorporation of EPA and DHA into the plasma phospholipids and cholesterol esters.  

Vitamin E is absorbed from the gastro-intestinal tract. Most appears in the lymph and is then widely distributed to all tissues. Most of a usage is slowly excreted in the bile and the remainder is eliminated in the urine as glucuronides of tocopheronic acid or other metabolites.

INCOMPATIBILITY
Not applicable.

STORAGE INSTRUCTIONS Store protected from light and moisture, at a temperature not exceeding 25°C. Product is required to be stored out of reach of children. Do not use if the seal under the cap is broken or missing. Keep the container tightly closed after every use.

PACKAGING INFORMATION 30 Soft Gelatin Capsules in HDPE Bottle.

MANUFACTURED BY:
Maxcure Nutravedics Limited
13, Sector-6A, I.I.E., SIDCUL
Haridwar-249 403, Uttarakhand, India

MARKETED BY:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA
Contact No.: +91-22-69038182
Customer Care: customercare.india@amneal.com
 
R0523-00 

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY

Drug Substance: Moxifloxacin Hydrochloride

DESCRIPTION
Moxifloxacin eye drops 0.5% w/v is a sterile ophthalmic solution. It is an 8‐ methoxy fluoroquinolone anti‐infective for topical ophthalmic use.  
Moxifloxacin hydrochloride is a slightly yellow to yellow crystalline powder. Its chemical name is 1‐Cyclopropyl‐6‐fluoro‐1,4‐dihydro‐8‐methoxy‐7‐[(4aS,7aS)‐octahydro‐6H‐ pyrrolol[3,4‐b]pyridin‐6‐yl]‐4‐oxo‐3‐quinolinecarboxylic acid, monohydrochloride.  
The chemical structure is presented below: 

Composition:
Each ml contains:
Moxifloxacin Hydrochloride I.P.
equivalent to Moxifloxacin …………… 5 mg
Sterile Aqueous Base ………………….. q.s. 

INDICATIONS
Moxifloxacin eye drops is indicated for the treatment of bacterial conjunctivitis, blepharitis, dacryocystitis, hordeolum, tarsadenitis, keratitis (including corneal ulcer) caused by susceptible strains, as well as in perioperative sterilization (preoperative and postoperative prophylaxis).

MECHANISM OF ACTION (MOA)
Moxifloxacin, a fourth‐generation fluoroquinolone, inhibits the DNA gyrase and topoisomerase IV required for bacterial DNA replication, repair, and recombination. 

MECHANISMS OF RESISTANCE
Resistance to fluoroquinolones, including moxifloxacin, occurs generally by chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV. In Gram‐negative bacteria, moxifloxacin resistance can be due to mutations in mar (the multiple antibiotic resistance) and the qnr (quinolone resistance) gene systems. Cross‐resistance with beta‐lactams, macrolides and aminoglycosides is not expected due to differences in mode of action.  

MICROBIOLOGY
Moxifloxacin is an 8‐methoxy fluoroquinolone with a diazabicyclononyl ring at the C7 position. The antibacterial action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription, and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.  

The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, aminoglycosides, or tetracyclines. Therefore, moxifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to moxifloxacin. There is no cross‐resistance between moxifloxacin and the aforementioned classes of antibiotics. Cross resistance has been observed between systemic moxifloxacin and some other quinolones.  

In vitro resistance to moxifloxacin develops via multiple‐step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between 1.8 x 10^‐9 to < 1 x 10^‐11 for Gram‐positive bacteria.  

Moxifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections: 

Aerobic Gram-positive microorganisms:
Corynebacterium species
Enterococcus faecalis*
Micrococcus luteus
Staphylococcus aureus
Staphylococcus capitis
Staphylococcus epidermidis
Staphylococcus haemolyticus
Staphylococcus hominis
Staphylococcus lugdenesis*
Staphylococcus warneri
Streptococcus pneumoniae
Streptococcus viridans group 

Aerobic Gram-negative microorganisms:
Acinetobacter lwoffii
Burkholderia cepacia
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella planticola
Klebsiella pneumoniae
Moraxella catarrhalis*
Proteus mirabilis*
Proteus vulgaris*
Pseudomonas aeruginosa
Serratia liquefaciens
Serratia marcescens*
Stenotrophomonas (Xanthomonas) maltophilia  

Other microorganisms:
Chlamydia trachomatis
Propionibacterium acnes
*Efficacy for this organism was studied in fewer than 10 infections.  

The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of Moxifloxacin eye drops 0.5% w/v in treating ophthalmological infections 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.  

The list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections. Moxifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2µg/mL or less (systemic susceptible breakpoint) against most (≥90%) of strains of the following ocular pathogens. 

Aerobic Gram-positive microorganisms:
Listeria monocytogenes
Staphylococcus saprophyticus
Streptococcus agalactiae
Streptococcus mitis
Streptococcus pyogenes
Streptococcus Group C, G and F  

Aerobic Gram-negative microorganisms:
Acinetobacter baumannii
Acinetobacter calcoaceticus
Citrobacter freundii
Citrobacter koseri
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Klebsiella oxytoca
Morganella morganii
Neisseria gonorrhoeae
Pseudomonas stutzeri  

Anaerobic microorganisms:
Clostridium perfringens
Fusobacterium species
Prevotella species  

Other microorganisms:
Chlamydia pneumoniae
Legionella pneumophila
Mycobacterium avium
Mycobacterium marinum
Mycoplasma pneumoniae  

PHARMACOKINETICS (PK)
The pharmacokinetics of moxifloxacin in humans has been well characterized following oral, intravenous, and topical ocular administration.  

CONTRAINDICATIONS
Moxifloxacin Eye Drops I.P. is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication.  

WARNINGS
Topical Ophthalmic Use Only: Not for injection. Moxifloxacin Eye Drops I.P. is for topical ophthalmic use only and should not be injected subconjunctivally or introduced directly into the anterior chamber of the eye. 

Avoidance of Contact Lens Wear: Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.  

DRUG INTERACTIONS
Drug-drug interaction studies have not been conducted with Moxifloxacin Eye Drops I.P.  In vitro studies indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, indicating that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these cytochrome P450 isozymes.  

PREGNANCY
Pregnancy Category C: Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis at oral doses as high as 500 mg/kg/day (approximately 21,700 times the highest recommended total daily human ophthalmic dose); however, decreased fetal body weights and slightly delayed fetal skeletal development were observed. There was no evidence of teratogenicity when pregnant Cynomolgus monkeys were given oral doses as high as 100 mg/kg/day (approximately 4,300 times the highest recommended total daily human ophthalmic dose). An increased incidence of smaller fetuses was observed at 100 mg/kg/day. Since there are no adequate and well-controlled studies in pregnant women, Moxifloxacin Eye Drops I.P. should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.  

Nursing Mothers: Moxifloxacin has not been measured in human milk, although it can be presumed to be excreted in human milk. Caution should be exercised when Moxifloxacin ophthalmic solution is administered to a nursing mother.  

Pediatric Use: The safety and effectiveness of Moxifloxacin eye drops 0.5% w/v in bacterial conjunctivitis have been established in all ages including children and neonates. There is no evidence that the ophthalmic administration of Moxifloxacin eye drops 0.5% w/v has any effect on weight bearing joints, even though oral administration of some quinolones has been shown to cause arthropathy in immature animals.  

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients. 

SYMPTOMS AND TREATMENT OF OVERDOSAGE
The limited holding capacity of the conjunctival sac for ophthalmic products practically precludes any overdosing of the medicinal product. The total amount of moxifloxacin in a single container is too small to induce adverse effects after accidental ingestion.  

DOSAGE AND ADMINISTRATION
For blepharitis, dacryocystitis, hordeolum, conjunctivitis, tarsadenitis, keratitis (including corneal ulcer): Usually instil one drop in the affected eye 3 times a day. Increase or decrease of frequency of instillation can be adjusted according to the symptoms.  

For preoperative and postoperative prophylaxis: Usually, instil one drop in the affected eye 5 times per day for 2 days before operation, and 3 times a day up to 14 days after operation.  

Patients should be instructed to leave at least 5 minutes between administrations if using moxifloxacin eye drops concurrently with other ophthalmic solutions.  

CLINICAL STUDIES:
Bacterial conjunctivitis (Global studies)  

In three randomized, double‐blind, multicenter, controlled clinical trials, 812 patients (greater than 1 month of age) with bacterial conjunctivitis were dosed 3 times a day for 4 days with moxifloxacin. At Day 9, clinical cure rates ranged from 82% to 94% and microbiological success rates for the eradication of baseline pathogens ranged from 78% to 97%.  

In a randomized, double‐blind, multicenter, parallel‐group clinical trial of pediatric patients with bacterial conjunctivitis between birth and 31 days of age, 107 patients were dosed with moxifloxacin and 102 patients were dosed with ciprofloxacin. At Day 9, clinical cure rate in patients receiving moxifloxacin was 80% and the microbiological eradication success rate was 92%.  

In these studies, strains of the following organisms were susceptible to moxifloxacin: Corynebacterium species* , Micrococcus luteus* , Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri* , Streptococcus pneumoniae, Streptococcus viridans group, Acinetobacter lwoffii* , Haemophilus species including H. influenza, and H. parainfluenzae* and Chlamydia trachomatis.
* Efficacy for this organism was studied in fewer than 10 infections.  

Bacterial conjunctivitis and other ocular conditions (Japan studies)
Clinical effects of moxifloxacin in extraocular infections in 389 cases (Japanese patients) from one double‐blind and two open label trials are shown below according to relevant disorders. The dosage and administration was one drop, 3 times per day, except for keratitis (including corneal ulcer), where administration ranged from 3 to 8 times per day. The rate of effectiveness was determined based on disappearance of the etiologic agent identified in the initial examination, resolution of predominant symptoms and the total score of clinical symptoms (combination therapies with other ophthalmic agents were accepted). In the clinical studies of moxifloxacin in Japan, 38/389 cases were infants or children (41 day‐old to under 12-year‐old), and its rate of effectiveness in this subset was 97.4% (37/38). 

Effects on preoperative and postoperative prophylaxis
In addition, in a preoperative and postoperative sterilization study on Japanese patients, the dosage and administration was one drop 5 times per day before the operation, and one drop 3 times per day after the operation. The bacterial eradication rate before the operation was 85.0% (68/80a). The non‐ bacterial rate on the 15th day after the operation was 98.9% (92/93), with no cases of postoperative infection (endophthalmitis) being reported.  

In these studies, strains sensitive to moxifloxacin included Staphylococcus, Streptococcus (including Streptococcus pneumoniae), Enterococcus, Moraxella, Corynebacterium, Klebsiella, Serratia, Proteus, Pseudomonas, Acinetobacter, Haemophilus influenzae, Burkholderia cepacia, Stenotrophomonas (Xanthomonas) maltophilia and Propionibacterium acnes.  

SPECIAL POPULATIONS
Renal impairment
Dose adjustment of moxifloxacin does not appear to be necessary in patients with renal dysfunction.

Hepatic impairment
Dose adjustment of moxifloxacin does not appear to be necessary in patients with mild to moderate hepatic impairment. The pharmacokinetics of moxifloxacin has not been studied in patients with severe hepatic insufficiency.

Paediatric patients (below 18 years)
Moxifloxacin eye drops 0.5% w/v may be used in paediatric patients at the same dose as in adults.

INFORMATION FOR PATIENTS: 

• To avoid contamination, the dropper tip should not touch any surface. The dropper tip should also not come in contact with the eye as this may cause injury to the eye. 

• After cap is removed, if tamper evident snap collar is loose, it should be removed before using the product. 

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

• Either nasolacrimal occlusion or gently closing the eyelid(s) after administration is recommended. This may reduce the systemic absorption of medicinal products administered via ocular route and result in a decrease in systemic adverse reactions.  

STORAGE
Store in a cool & dark place below 30°C.  

PRESENTATION
Moxneal is available in 5ml RISHPHARM R2 White vials with Tamper Evident ring retention feature, Compliant to US FDA regulatory requirements and exactly delivers a calibrated 30µl drop size, with Outer Packs colour coding adapted from American Academy of Ophthalmology Color Codes guidelines for Topical Ocular Medications.  

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA 

R0423-00

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY  

Drug Substance: Moxifloxacin Hydrochloride & Loteprednol Etabonate  

Composition:
Each ml contains:
Moxifloxacin Hydrochloride I.P.
equivalent to Moxifloxacin ……………. 5 mg
Loteprednol Etabonate ………………… 5 mg
Sterile Aqueous Base ………………….. q.s.

INDICATIONS
It is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists. To treat ocular infection & inflammation.

CONTRAINDICATIONS
Moxifloxacin Hydrochloride & Loteprednol Etabonate combination as with other steroid anti-infective ophthalmic combination drugs is contraindicated in most viral diseases of the cornea and conjunctiva Moxifloxacin Hydrochloride & Loteprednol Etabonate combination is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids.

WARNINGS
As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. To prevent contamination do not touch the tip of the dropper to eye, eyelid or any surface of the affected eye. Keep the bottle tightly closed after use.

PREGNANCY
There are no adequate and well controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Nursing Mothers: It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Systemic steroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when it is administered to a nursing woman. 

Pediatric Use: The efficacy & safety have not been established in children.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.

SYMPTOMS AND TREATMENT OF OVERDOSAGE
This medication may be harmful if swallowed. In case of swallowing or overdose, get medical help.

DOSAGE AND ADMINISTRATION
Shake vigorously before using. Apply one or two drops into the conjunctival sac of the affected eye(s) every four to six hours. During the initial 24 to 48 hours, the dosing may be increased, to every one to two hours. Frequency should be decreased gradually as warranted by improvement in clinical signs.

SPECIAL INSTRUCTIONS
Patients should be advised to avoid contamination of the dispensing tip.

STORAGE
Store in a cool & dark place below 30°C.

PRESENTATION
Moxifloxacin and Loteprednol Etabonate Ophthalmic Suspension are available in 5ml RISHPHARM R2 White vials with Tamper Evident ring retention feature, Compliant to US FDA regulatory requirements and exactly delivers a calibrated 30µl drop size, with Outer Packs colour coding adapted from American Academy of Ophthalmology Color Codes guidelines for Topical Ocular Medications.

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA

R0423-00 

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY  

Drug Substance: Nepafenac  

DESCRIPTION
Nepafenac ophthalmic suspension 0.1% is a sterile, topical, nonsteroidal anti-inflammatory (NSAID) prodrug for ophthalmic use. Each mL of NEPANEAL^TM suspension contains 1 mg of Nepafenac. Nepafenac is designated chemically as 2-amino-3-benzoylbenzeneacetamide with an empirical formula of C₁₅H₁₄N₂O₂.

The structural formula of Nepafenac is:

Composition: 
Each ml contains: 
Nepafenac ……………………………………………1 mg 
Stabilized Oxychloro Complex ……….. 0.005% w/v (As Preservative) 
Sterile Aqueous Base ………………………………. q.s. 

INDICATIONS  
Nepafenac Ophthalmic Suspension is indicated for inhibition and treatment of pain and inflammation associated with cataract surgery. Also, to reduce the risk of post-operative macular oedema associated with cataract surgery in diabetic patients. 

MECHANISM OF ACTION 
After topical ocular dosing, nepafenac penetrates the cornea and is converted by ocular tissue hydrolases to amfenac, a nonsteroidal anti-inflammatory drug. Amfenac is thought to inhibit the action of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production.

CONTRAINDICATIONS 
Hypersensitivity to the active substance or to any of the excipients used in the formula. Hypersensitivity to other nonsteroidal anti-inflammatory drugs (NSAIDs). Patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs.

WARNINGS 
The product should not be injected. Patients should be instructed not to swallow Nepafenac. Patients should be instructed to avoid sunlight during treatment with Nepafenac. 

Ocular effects: Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration, or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of Nepafenac Ophthalmic Suspension and should be monitored closely for corneal health. Topical NSAIDs may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. Therefore, it is recommended that caution should be exercised if Nepafenac Ophthalmic Suspension is administered concomitantly with corticosteroids, particularly in patients at high risk for corneal adverse reactions described below. Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g. dry eye syndrome), rheumatoid arthritis or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse reactions which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Prolonged use of topical NSAIDs may increase patient risk for occurrence and severity of corneal adverse reactions. There have been reports that ophthalmic NSAIDs may cause increased bleeding of ocular tissues (including hyphaema) in conjunction with ocular surgery. Nepafenac Ophthalmic Suspension should be used with caution in patients with known bleeding tendencies or who are receiving other medicinal products which may prolong bleeding time. An acute ocular infection may be masked by the topical use of anti-inflammatory medicines. NSAIDs do not have any antimicrobial properties. In case of ocular infection, their use with antiinfectives should be undertaken with care.

Contact lenses: Wearing contact lens is not recommended during the postoperative period following cataract surgery. Therefore, patients should be advised not to wear contact lenses unless clearly indicated by their doctor. 

Cross-sensitivity: There is a potential for cross-sensitivity of Nepafenac Ophthalmic Suspension to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs.

DRUG INTERACTIONS  
In vitro studies have demonstrated a very low potential for interaction with other medicinal products and protein binding interactions. 

Prostaglandin analogues: There are very limited data on the concomitant use of prostaglandin analogues and Nepafenac Ophthalmic Suspension. Considering their mechanism of action, the concomitant use of these medicinal products is not recommended. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. Concomitant use of Nepafenac Ophthalmic Suspension with medications that prolong bleeding time may increase the risk of haemorrhage.

PREGNANCY  
There are no adequate data regarding the use of nepafenac in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Since the systemic exposure in non-pregnant women is negligible after treatment with Nepafenac Ophthalmic Suspension, the risk during pregnancy could be considered low. However, inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonal/foetal development and/or parturition and/or postnatal development. Nepafenac Ophthalmic Suspension is not recommended during pregnancy. 

Nursing Mothers: It is unknown whether nepafenac is excreted in human milk. Animal studies have shown excretion of nepafenac in the milk of rats. However, no effects on the suckling child are anticipated since the systemic exposure of the breastfeeding woman to nepafenac is negligible. Nepafenac Ophthalmic Suspension can be used during breastfeeding. 

Pediatric Use: The safety and effectiveness of Nepafenac Ophthalmic Suspension in pediatric patients below the age of 10 years have not been established. 

Geriatric Use: No overall differences in safety and effectiveness have been observed between elderly and younger patients.

SYMPTOMS AND TREATMENT OF OVERDOSAGE 
No data are available in humans regarding overdosage by accidental or deliberate ingestion. The risk of overdosage by ingestion of the suspension is minimal. No toxic effects are likely to occur in the case of overdose with ocular use, nor in the event of accidental oral ingestion. 

DOSAGE AND ADMINISTRATION 
Adults, including the elderly: For the prevention and treatment of pain and inflammation, the dose is 1 drop in the conjunctival sac of the affected eye(s) 3 times daily beginning 1 day prior to cataract surgery, continued on the day of surgery and for the first 2 weeks of the postoperative period. Treatment can be extended to the first 3 weeks of the postoperative period as directed by the clinician. An additional drop should be administered 30 to 120 minutes prior to surgery. For the reduction in the risk of postoperative macular oedema associated with cataract surgery in diabetic patients, the dose is 1 drop of Nepafenac Ophthalmic Suspension in the conjunctival sac of the affected eye(s) 3 times daily beginning 1 day prior to cataract surgery, continued on the day of surgery and up to 60 days of the postoperative period as directed by the clinician. 

Patients with renal or hepatic impairment: Nepafenac Ophthalmic Suspension has not been studied in patients with hepatic disease or renal impairment. Nepafenac is eliminated primarily through biotransformation and the systemic exposure is very low following topical ocular administration. No dose adjustment is warranted in these patients. 

Paediatric population: The safety and efficacy of Nepafenac Ophthalmic Suspension in children and adolescents have not been established. No data are available. Its use is not recommended in these patients until further data becomes available. 

Geriatric population: No overall differences in safety and effectiveness have been observed between elderly and younger patients.

Method of administration: For ocular use. Patients should be instructed to shake the bottle well before use. After cap is removed, if tamper evident snap collar is loose, remove before using product. If more than one topical ophthalmic medicinal product is being used, the medicinal product must be administered at least 5 minutes apart. Eye ointments should be administered last. To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle. Patients should be instructed to keep the bottle tightly closed when not in use. If a dose is missed, a single drop should be applied as soon as possible before reverting to regular routine. Do not use a double dose to make up for the 1 missed.

SPECIAL INSTRUCTIONS 
Patients should be advised to avoid contamination of the dispensing tip. 

STORAGE  
Store in a cool & dark place below 30°C. Do not allow to freeze. 

PRESENTATION  
Nepaneal is available in 5ml RISHPHARM R2 Teal Green vials with Tamper Evident ring retention feature, Compliant to US FDA regulatory requirements and exactly delivers a calibrated 30µl drop size, with Outer Packs colour coding adapted from American Academy of Ophthalmology Color Codes guidelines for Topical Ocular Medications. 

For further details, please write to:  
Amneal Healthcare Pvt. Ltd. 
9th Floor, 901 to 905, Iscon Elegance 
S. G. Highway, Ahmedabad 380015 
Gujarat, INDIA

R0423-00 

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY  

Drug Substance: Loteprednol Etabonate  

Composition:
Each ml contains:
Loteprednol Etabonate ……………………………. 5 mg
Benzalkonium Chloride Solution I.P. ……. 0.02% v/v (As Preservative)
Sterile Aqueous Base ………………………………… q.s.  

INDICATIONS
Loteprednol Etabonate Ophthalmic Suspension 0.5% w/v is indicated for the treatment of steroid responsive inflammatory conditions of the eye such as Allergic Conjunctivitis, Giant Papillary Conjunctivitis, Anterior Uveitis, Acne Rosacea, Superficial Punctuate Keratitis, Herpes Zoster Keratitis, Iritis, and In Post-Operative Pain & Inflammation.  

PHARMACOLOGY
Loteprednol Etabonate is a “soft” steroid that belongs to the class of Glucocorticoids. Being structurally like other Glucocorticoids and missing ketone group, prevents formation of proteins, responsible for cataract formation with ketone steroids. Loteprednol Etabonate is highly lipophilic, and its lipophilicity is 10 times greater than that of Dexamethasone, a characteristic that increases its efficacy by enhancing penetration through biological membranes.  

Mode of action: Loteprednol Etabonate is synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. It first binds to the type II Glucocorticoid receptors. Glucocorticoids readily cross cell membranes and bind with high affinity (Affinity is greater when compared with other Glucocorticoids), to specific Cytoplasmic receptors.  

This binding induces a response by modifying transcription and, ultimately protein synthesis to achieve the formation of Anti-Inflammatory Protein that inhibits the enzyme Phospholipase A2 which is needed in supply of Arachidonic acid. The latter is responsible for the formation of the mediators of inflammatory response. Thus inhibits the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation with inflammation. 

DOSAGE & ADMINISTRATION
Steroid Responsive Inflammation: One-Two drops of Loteprednol Etabonate Ophthalmic Suspension 0.5% w/v into the affected eye(s) four times a day.  

Post-Operative Inflammation: One-Two drops of Loteprednol Etabonate Ophthalmic Suspension 0.5% w/v into the operated eye(s) four times a day.  

ADVERSE EFFECTS
Abnormal vision / blurring, burning on instillation, chemosis, discharge, dry eyes, epiphora, foreign body sensation, itching, and photophobia.  

WARNING & PRECAUTION
As per the literary data, Loteprednol Etabonate is contraindicated in patients with ocular infections due to Acanthamoeba, herpes simplex virus, and fungi. Use cautiously for Glaucoma patients. Contraindicated to patients with hypersensitivity towards Loteprednol Etabonate. Prolonged use may increase the risk of corneal fungal infection. If the present symptoms persist consult the Eye Doctor.  

SPECIAL INSTRUCTIONS
Patients should be advised to avoid contamination of the dispensing tip.  

STORAGE
Store in a cool & dark place below 30°C.  

PRESENTATION
Loteneal is presented in 5ml RISHPHARM R2 White vials with Tamper Evident ring retention feature, Compliant to US FDA regulatory requirements and exactly delivers a calibrated 30µl drop size, with Outer Packs colour coding adapted from American Academy of Ophthalmology Color Codes guidelines for Topical Ocular Medications.  

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA  

R0423-00 

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY

Drug Substance: Olopatadine Hydrochloride

DESCRIPTION
Olopatadine ophthalmic solution 0.2% w/v is a sterile ophthalmic solution containing olopatadine for topical administration to the eyes.

Olopatadine hydrochloride is a white, crystalline, water-soluble powder with a molecular weight of 373.88 and a molecular formula of C₂₁H₂₃NO₃ • HCl. Its chemical name is 11-[(Z)-3- (Dimethylamino) propylidene]-6-11- dihydrodibenz[b,e] oxepin-2-acetic acid, hydrochloride

The chemical structure is presented below: 

Composition:
Each ml contains:
Olopatadine Hydrochloride I.P.
equivalent to Olopatadine …………………………. 2 mg
Stabilized Oxychloro Complex ………….. 0.005% w/v (As Preservative)
Sterile Aqueous Base ………………………………….. q.s.

ACTIONS & CLINICAL PHARMACOLOGY
Olopatadine is a mast cell stabilizer and a histamine H1 antagonist. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.

INDICATIONS
Olopatadine Ophthalmic Solution I.P. 0.2% w/v is indicated for the treatment of ocular itching associated with allergic conjunctivitis. 

PHARMACOKINETICS
Systemic bioavailability data upon topical ocular administration of Olopatadine Ophthalmic Solution I.P. 0.2% w/v is not available. Following topical ocular administration of Olopatadine Ophthalmic Solution I.P. 0.2% w/v in man, olopatadine was shown to have a low systemic exposure. Two studies in normal volunteers (totalling 24 subjects) dosed bilaterally with Olopatadine Ophthalmic Solution I.P. 0.2% w/v once every 12 hours for 2 weeks demonstrated plasma concentrations to be generally below the quantisation limit of the assay. Samples in which olopatadine was quantifiable were typically found within 2 hours of dosing and ranged from 0.5 to 1.3 ng/mL. The elimination half-life in plasma following oral dosing was 8 to 12 hours, and elimination was predominantly through renal excretion. Approximately 60 – 70% of the dose was recovered in the urine as parent drug. Two metabolites, the mono-desmethyl and the N-oxide, were detected at low concentrations in the urine.

CONTRAINDICATIONS
Hypersensitivity to the active substance or to any of the excipients used in the formulation. 

WARNINGS
For topical ocular use only. Not for injection or oral use. Contamination of tip and solution as with any eye drop, to prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use.

Contact Lens Use:
Patients should be advised not to wear a contact lens if their eye is red. Olopatadine Ophthalmic Solution should not be used to treat contact lens related irritation. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling Olopatadine Ophthalmic Solution before they insert their contact lenses.

DRUG INTERACTIONS
No interaction studies with other medicinal products have been performed. In vitro studies have shown that Olopatadine did not inhibit metabolic reactions which involve cytochrome P-450 isozymes 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. These results indicate that Olopatadine is unlikely to result in metabolic interactions with other concomitantly administered active substances. 

PREGNANCY
Pregnancy Category C: Olopatadine was found not to be teratogenic in rats and rabbits. There are, however, no adequate and well- controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the embryo or foetus.

Nursing Mothers: Olopatadine has been identified in the milk of nursing rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when Olopatadine Ophthalmic Solution I.P. 0.2% w/v is administered to a nursing mother.

Paediatric Use: Safety and effectiveness in paediatric patients below the age of 2 years have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.

SYMPTOMS AND TREATMENT OF OVERDOSAGE
There have been no reported cases in humans of overdosage of the Olopatadine Ophthalmic Solution I.P. 0.2% w/v. 

DOSAGE AND ADMINISTRATION
Adults and children 2 years of age and older – Put one drop in each affected eye once a day.

SPECIAL INSTRUCTIONS Patients should be advised to avoid contamination of the dispensing tip.

STORAGE
Store in a cool & dark place below 30°C. Do not allow to freeze.

PRESENTATION
Oloneal is available in 5ml RISHPHARM R2 Teal Green vials with Tamper Evident ring retention feature, Compliant to US FDA regulatory requirements and exactly delivers a calibrated 30µl drop size.

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA

R0423-00

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PRESENTATION: Each single use vial with fill volume of 0.23 mL (to deliver a single dose of 0.05 ml) contains: Ranibizumab 2.3 mg.  

List of excipients: L-Histidine,L-Histidine Hydrochloride Monohydrate,o,o — trehalose dihydrate, Polysorbate 20, water for injections. 

PHARMACEUTICAL FORM: Solution for Injection, Clear, colorless to pale yellow liquid.  

INDICATIONS: Treatment of Neovascular (wet) Age-related 

Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), Diabetic Retinopathy (DR).  

DOSAGE AND ADMINISTRATION: Administration: 0.5 mg (0.05 ml) by a qualified ophthalmologist. Minimum interval: four weeks; Each vial treats one eye. Use a new vial for the other eye.  

METHOD OF ADMINISTRATION: Administered by a qualified ophthalmologist. Use aseptic technique and ensure proper patient preparation. 

CONTRAINDICATIONS: Hypersensitivity to Ranibizumab or any component of the formulation.  

SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Intraocular Inflammation: Monitor for signs and symptoms.
Increased IOP: Monitor and manage appropriately.
Endophthalmitis: Inform patients of symptoms and monitor post-injection.
Thromboembolic Events: Consider risk factors.
Use in Specific Populations: Pregnancy: Limited data; consider potential risks.
Lactation: Unknown if excreted in human milk; consider benefits versus risks.
Pediatric Use: Safety and efficacy not established.

UNDESIRABLE EFFECTS:
Common: Increased intraocular pressure, Eye pain, Vitreous floaters, Conjunctival haemorrhage, Blurred vision, Headache, Nasopharyngitis, Nausea.
Serious: Endophthalmitis, Retinal detachment, Cataracts, Thromboembolic events, Severe intraocular inflammation. Injection-Related: Bleeding and pain at injection site, Intraocular inflammation.

OVERDOSE: Adverse reactions associated with these reported cases were intraocular pressure increased, transient blindness, reduced visual acuity, coreal oedema, corneal pain, and eye pain. If an overdose occurs, intraocular pressure should be monitored and treated, if deemed necessary by the attending physician. 

PHARMACODYNAMIC PROPERTIES: Inhibits VEGF-A, reducing angiogenesis and vascular permeability in the eye.

PHARMACOKINETIC PROPERTIES:
Absorption: Rapidly absorbed into systemic circulation. Distribution: Limited systemic exposure due to intravitreal administration. Elimination: Half-life in vitreous ~9 days. Storage: Store refrigerated at 2C to 8C (36°F to 46°F). Protect from light. PACK SIZE: 0.23 mL solution in a vial (glass) with rubber stopper and aluminum cap.

Before prescribing, please consult full prescribing information available from:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance,
S. G. Highway, Ahmedabad 380015,
Gujarat, India

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

COMPOSITION
Each film coated tablet contains (Approx.):
Vitamin C…………………………….40mg
Bilberry Extract 25%…………………………….40mg
Pine Bark Extract…………………………….25mg
(Pinus Gerardiana Extract)
Zinc Oxide eq. to Elemental Zinc…………………………….10mg
Lutein 40% (Powder form) …………………………….10mg
Vitamin E…………………………….5mg
Astaxanthin 10%…………………………….4mg
Zeaxanthin 5%…………………………….2mg
Cupric Oxide eq. to
Elemental Copper…………………………….1mg
Vitamin A…………………………….600mcg
Sodium Selenate
eq. to Elemental Selenium…………………………….40mcg 

NUTRACEUTICAL FORM
Film Coated Tablet 

HEALTH CLAIM INDICATION
Supplement for eye health

USAGE AND ADMINISTRATION
Usage and duration should be as advised by a healthcare professional.
Posology
Usual adult usage: 1 tablet a day or as advised by a dietician or healthcare professional. 

Method of administration: For oral use only.
Not to exceed the recommended daily usage unless directed by the dietician or healthcare professional. In case of accidental overdose, contact a Physician. 

CONTRAINDICATIONS
This product should not be used in the event of hypersensitivity to any of the ingredients.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Not to exceed the recommended daily usage.
This product is not intended to diagnose, treat, cure or prevent any disease(s).
Persons receiving. other single vitamins or multivitamin preparations, any other medication or those under medical care should consult a health care professional before taking this product.
Copper should be avoided in persons with biliary tract obstruction or Wilson’s disease. The risks of high dose nutritional supplements are not known. Persons with chronic diseases such as, cancer, heart disease and diabetes should use these preparations with caution. Consult your dietician/healthcare professional before using this product if you are pregnant, lactating, trying to conceive, taking medication or have a medical condition. 

NUTRACEUTICAL, NOT FOR MEDICINAL USE. 

DRUG INTERACTIONS 

No interaction studies have been performed.  

• Products containing copper and zinc may interact with orally administered antacids, gastric acid suppressive medications, antibiotics (tetracyclines, fluoroquinolones), levodopa, bisphosphonates, penicillamine, thyroxine (levothyroxine), trientine, digitalis, antiviral agents and thiazide diuretics, reducing the bioavailability of the medicinal product and/or the minerals in the tablet., If simultaneous use is necessary, administration of the two products should be separated by at least 2 hours. 

• Warfarin: Increased hypoprothrombinemic effect occurs with high doses of vitamin E (>400 IU). Vitamin C can reduce the anticoagulant action of warfarin. 

• Iron: Iron interferes with the absorption of vitamin E. Absorption of iron increases with coadministration of vitamin C. 

• Vitamin C: Acidifies urine resulting in reabsorption of acidic drugs and an increase in the excretion of basic drugs from the renal tubules (unknown clinical relevance). 

• Tetracycline and fluoroquinolones: Zinc decreases the absorption of tetracycline and fluoroquinolones. 

• Copper: Absorption of copper is decreased by concurrent use of high usages of zinc or vitamin C. 

Nevertheless, in case of taking other prescription medicines or OTC drugs, consult with your doctor or a healthcare professional and do not take it without recommendation. 

USE IN SPECIAL POPULATION
The recommended usage should not be exceeded without dietician/healthcare professional. As for every medicinal product, please consult with healthcare professional.

Pregnancy & Lactation
It is advisable to consult your physician or a healthcare professional prior to taking supplements if you are pregnant, lactating, or suspect any medical condition. 

Paediatric population
No studies have been conducted in children. 

UNDESIRABLE EFFECTS
Multivitamins/multiminerals containing products are usually well tolerated; no significant adverse effects observed during long-term administration, unless overdose taken.
Vitamin C & E do not have proven harmful effects that we know of but there has been some data that suggest that they interfere with effectiveness of statin therapy. Elevated levels of zinc have been associated with neurodegeneration in animal models, elevation of glycosylated hemoglobin levels in type 1 diabetics, decreased glucose tolerance in type 2 diabetes and elevated serum zinc levels may be found in patients with Alzheimer’s disease.
If an allergic reaction occurs, treatment must be stopped and a healthcare professional consulted. 

OVERUSAGE
There is no evidence that this product can lead to an overdose when used as recommended. Seek emergency medical treatment or contact the healthcare professional in case of an overdose. In case of occurrence of any fatal adverse drug reaction, discontinue this tablet and consult with the healthcare professional immediately.

PHARMACOLOGICAL PROPERTIES
This product (film coated tablets) is a multivitamin/multimineral formula, contains clinically validated ingredients like lutein, zeaxanthin and astaxanthin along with bilberry and Pinus extract with essential vitamins (vitamin C & E), minerals and trace elements (like Zinc, Copper & Selenium) to ensure an adequate micronutrient supply, in case of unbalanced dietary intake.
Vitamins are essential nutrients. They are indispensable for the normal development and growth, for the metabolism and formation of carbohydrates, energy, lipids, nucleic acids and proteins, as well as for the synthesis of amino acids, collagen and neurotransmitters. Recent literature indicates that nutrients important in vision health include vitamins and minerals with antioxidant functions (e.g., vitamins C and E, carotenoids [lutein, zeaxanthin, zinc], and compounds with anti-inflammatory properties may ameliorate the risk for age-related eye disease.
The active ingredients of this preparation, vitamins, minerals and trace elements, are essential micronutrients, which are widely distributed in the human body. The plasma and tissue levels of micronutrients are homeostatically regulated and affected by various factors such as diurnal fluctuations, nutritional status, growth, and pregnancy and lactation. 

DESCRIPTION
This product contains clinically validated ingredients like lutein, zeaxanthin and astaxanthin along with bilberry and Pinus extract with essential vitamins and minerals, which are known to relieve eye strain, help moisturizes dry eyes and reduce eye fatigue while enhancing visual acuity and night vision. Lutein and zeaxanthin are concentrated in the macula or central region of the retina, and are referred to as macular pigment. In addition to their role as antioxidants, lutein and zeaxanthin are believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching reactive oxygen species. In general, this formulation helps in preventing or correcting disorders due to a vitamin or mineral imbalance or deficiency diet. It is also helpful to reduce the risk of age-related macular degeneration and improves overall vision and eye health. This formulation is designed to provide nutritional supplementation for the health of the eyes. It should be used as directed by the Physician or a healthcare professional. 

BENEFITS
Lutein and zeaxanthin are known as “eye vitamins” are a category of carotenoids that have specific beneficial effects for vision – like protection of your eyes against harmful UV rays or blue rays we are frequently exposed to from computers, mobile phones, etc. Additionally, it also gives protection against retinal macular degeneration, blurry visions or cataracts. In published clinical studies, Lutein and zeaxanthin has been proven to promote healthy eye function by an increase in macular pigment density and improvements in Photostress recovery and Glare which are direct indicators of improvements in visual performance and reduced visual fatigue. Supplementation with Bilberry has shown improvements in subjective symptoms of eye fatigue, ocular fatigue sensation, ocular pain, eye heaviness, uncomfortable sensation, and foreign body sensation. Zinc was added due to high concentration of it in the retinal pigment epithelium (RPE). Age-related macular degeneration (AMD) may be linked to its deficiency and the loss of zinc dependent coenzymes. Copper was added to prevent zinc induced copper deficiency. As this formulation is close to AREDS II, it is beneficial in ARMD cases. Scientific evidence suggests vitamin C lowers the risk of developing cataracts and when taken in combination with other essential nutrients, it can slow the progression of age-related macular degeneration and visual acuity loss. Vitamin E protects cells in the eyes from unstable molecules called free radicals, which break down healthy tissue.

INCOMPATIBILITY
None stated.

PACKAGING INFORMATION
10 Tablets pack in Alu-Alu Blister & such 1 Blister in a mono carton & such 10 mono cartons in a outer carton.

STORAGE INSTRUCTIONS
Store protected from light & moisture, at a temperature not exceeding 25°C.
Product is required to be stored out of reach of children.

MANUFACTURED BY:
Maxcure Nutravedics Limited
13, Sector-6A, I.I.E., SIDCUL
Haridwar-249 403, Uttarakhand, India 

MARKETED BY:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA
Contact No.: +91-22-69038182
Customer Care: customercare.india@amneal.com 

R0623-00 

For the use of an Ophthalmologist or a Hospital or a Laboratory only.

PHARMACEUTICAL INFORMATION CHEMISTRY  

Drug Substance: Ganciclovir  

Composition:
Each gram contains:
Ganciclovir I.P. ……………………………. 1.5 mg
Benzalkonium Chloride I.P. …… 0.01% w/w
(As Preservative)
Sterile Aqueous Gel Base ………………….. q.s.  

INDICATIONS
Ganciclovir Ophthalmic Gel 0.15% is indicated for the treatment of acute herpetic keratitis (dendritic and geographic ulcers).  

CONTRAINDICATIONS
Ganciclovir Ophthalmic Gel 0.15% is contraindicated in patients with a history of hypersensitivity to the active substance or to any of the excipients used in the formulation.  

WARNINGS
Ganciclovir Ophthalmic Gel 0.15% is not indicated in the treatment of cytomegalovirus (CMV) retina infections. Efficacy in other viral types of keratoconjunctivitis has not been demonstrated. No specific clinical studies were performed in immunodepressed subjects. This medicine contains Benzalkonium Chloride which may also cause eye irritation, especially in dry eyes or disorders of the cornea. Benzalkonium chloride may be absorbed by soft contact lenses and may change the colour of the contact lenses. Remove contact lenses prior to application and wait at least 15 min before reinsertion. 

DRUG INTERACTIONS
If more than one topical ophthalmic drug is being used, the drugs should be administered at least fifteen minutes apart. Ganciclovir Ophthalmic Gel 0.15% should be instilled last. Although the quantities of ganciclovir passing into the general circulation after ophthalmic use are small, the risk of drug interactions cannot be ruled out. Interactions with ganciclovir administered systemically have been observed. Binding of ganciclovir to plasma proteins is only about 1-2% and drug interactions involving binding site displacement are not anticipated. 

PREGNANCY
There are no adequate and well-controlled studies in pregnant women, Ganciclovir Ophthalmic Gel 0.15% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether topical administration of Ganciclovir Ophthalmic Gel 0.15% could result in sufficient systemic absorption to produce detectable quantities in breast milk. Therefore, use is not recommended in women breast-feeding infants. 

Paediatric Use: Safety and effectiveness in infants below the age of one year have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.  

SYMPTOMS AND TREATMENT OF OVERDOSAGE
No information is available on overdosage in humans.  

DOSAGE AND ADMINISTRATION
Instil one drop of gel in the inferior conjunctival sac of the eye to be treated, 5 times a day until complete corneal re-epithelialisation. Then 3 instillations a day for 7 days after healing. The treatment does not usually exceed 21 days.  

Use in the elderly: The dosage in the elderly is the same as in adults. There is no need to adjust the dosage in the elderly as in clinical trials patients up to the age of 85 years have been treated and no specific health concerns were observed.

Use in children: Use of the medicinal product in children under 18 years is not recommended since no specific studies have been conducted.  

SPECIAL INSTRUCTIONS
Patients should be advised to avoid contamination of the dispensing tip. No special requirements for disposal.  

STORAGE
Store in a cool & dark place below 30°C.  

PRESENTATION
Ganciclovir Ophthalmic Gel 0.15% is available in 5 g laminated tube.  

For further details, please write to:
Amneal Healthcare Pvt. Ltd.
9th Floor, 901 to 905, Iscon Elegance
S. G. Highway, Ahmedabad 380015
Gujarat, INDIA  

R0423-00 

For the use of an Ophthalmologist or a Hospital or a Laboratory only.