LOWPROST Eye Drops (Bimatoprost Ophthalmic Solution 0.01%)

Transcription

1 Published on: 14 Apr 2017 LOWPROST Eye Drops (Bimatoprost Ophthalmic Solution 0.01%) For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only Composition Each ml contains: Bimatoprost % w/v Isotonic aqueous vehicle... q.s. (Preserved with an Ionic Buffered System) Dosage Form Ophthalmic solution Pharmacology Pharmacodynamics Bimatoprost, a prostaglandin analogue, is a synthetic structural analogue of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, the prostamides. Bimatoprost is believed to lower the intraocular pressure (IOP) in humans by increasing the outflow of the aqueous humour through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Reduction of the IOP starts approximately 4 hours after the first administration and maximum effect is reached within approximately 8 to 12 hours. The duration of effect is maintained for at least 24 hours. Clinical Trial In a 12-month clinical study of patients with open angle glaucoma or ocular hypertension with an average baseline IOP of 23.5 mmhg, the IOP-lowering effect of Bimatoprost 0.01% ophthalmic solution once daily (in the evening) was up to 7.5 mmhg. The mean diurnal IOP values measured at any visit over the 12-month study period differed by no more than 1.1 mmhg throughout the day and were never greater than 17.7 mmhg. Pharmacokinetics Absorption Bimatoprost penetrates the human cornea and sclera well in vitro. After one drop of bimatoprost ophthalmic solution 0.03% was administered once daily to both eyes of 15 healthy subjects for 2 weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (0.025 ng/ml) in most subjects within 1.5 hours after dosing. Mean C max and AUC 0 24hr values were similar on days 7 and 14 at approximately 0.08 ng/ml and 0.09 ng hr/ml, respectively, indicating that the steady state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation over time.

2 Distribution Bimatoprost is moderately distributed into body tissues, with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma. Metabolism Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites. Elimination Following an intravenous dose of radiolabelled bimatoprost (3.12 mcg/kg) to 6 healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/ml and decreased rapidly, with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Bimatoprost is eliminated primarily by renal excretion. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the faeces. Characteristics in elderly patients After twice daily dosing with bimatoprost 0.3 mg/ml ophthalmic solution, the mean AUC 0-24hr value of ng hr/ml bimatoprost in the elderly (subjects 65 years or older) were significantly higher than ng hr/ml in young healthy adults. However, this finding is not clinically relevant as systemic exposure for both elderly and young subjects remained very low from ocular dosing. There was no accumulation of bimatoprost in the blood over time and the safety profile was similar in elderly and young patients. Indications Bimatoprost 0.01% ophthalmic solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension (as monotherapy or as adjunctive therapy to beta-blockers). Dosage And Administration The recommended dosage is one drop in the affected eye(s) once daily in the evening. Bimatoprost 0.01% ophthalmic solution should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogues may decrease the IOP-lowering effect. Reduction of the IOP starts approximately 4 hours after the first administration, with maximum effect being reached within approximately 8 to 12 hours. Bimatoprost ophthalmic solution 0.01% may be used concomitantly with other topical ophthalmic drug products to lower the IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart. Contraindications Hypersensitivity to the active substance or to any of the excipients. Warnings And Precautions Pigmentation Bimatoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin

3 content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of bimatoprost, the pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long-term effects of increased pigmentation are not known. Iris colour change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with bimatoprost 0.01% ophthalmic solution can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. At 12 months, the incidence of iris hyperpigmentation with bimatoprost 0.1mg/ml ophthalmic solution was 0.5%. At 12 months, the incidence with bimatoprost 0.3 mg/ml ophthalmic solution was 1.5% and did not increase following 3 years treatment. Periorbital tissue pigmentation has been reported to be reversible in some patients. Eyelash Changes Bimatoprost 0.01% ophthalmic solution may gradually change eyelashes and vellus hair in the treated eye(s). These changes include increased length, thickness and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment. Intraocular Inflammation Prostaglandin analogs, including bimatoprost, have been reported to cause intraocular inflammation. In addition, because these products may exacerbate inflammation, caution should be used in patients with active intraocular inflammation (e.g., uveitis). Macular Oedema Macular oedema, including cystoid macular oedema, has been reported during treatment with bimatoprost 0.03% ophthalmic solution. Bimatoprost 0.01% ophthalmic solution should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule or in patients with known risk factors for macular oedema. Angle-closure, Inflammatory or Neovascular Glaucoma Bimatoprost 0.01% ophthalmic solution has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma. 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. There have been rare spontaneous reports of reactivation of previous corneal infiltrates or ocular infections with bimatoprost 0.03% ophthalmic solution. Bimatoprost 0.01% ophthalmic solution should be used with caution in patients with a prior history of significant ocular viral infections (e.g. herpes simplex) or uveitis/iritis. Use with Contact Lenses Contact lenses should be removed prior to instillation of bimatoprost 0.01% ophthalmic solution and may be reinserted 15 minutes following its administration. The tip of the bottle should not be allowed to contact the eye(s), surrounding structures, fingers or any other surface to avoid contamination of the solution.

4 Skin There is a potential for hair growth to occur in areas where bimatoprost 0.01% ophthalmic solution comes repeatedly in contact with the skin surface. Thus, it is important to instil bimatoprost 0.01% ophthalmic solution as instructed and avoid it running onto the cheek or other skin areas. Respiratory Bimatoprost 0.01% ophthalmic solution has not been studied in patients with compromised respiratory function. While there is limited information available on patients with a history of asthma or COPD, there have been reports of exacerbation of asthma, dyspnoea and COPD, as well as reports of asthma, in post marketing experience. The frequency of these symptoms is not known. Patients with COPD, asthma or compromised respiratory function due to other conditions should be treated with caution. Cardiovascular Bimatoprost 0.01% ophthalmic solution has not been studied in patients with heart block more severe than first-degree or uncontrolled congestive heart failure. There have been a limited number of spontaneous reports of bradycardia or hypotension with bimatoprost 0.03% ophthalmic solution. Bimatoprost 0.01% ophthalmic solution should be used with caution in patients predisposed to low heart rate or low blood pressure. Bimatoprost 0.01% ophthalmic solution has negligible influence on the ability to drive and use machines. As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machines. Effect on ability to drive and use machines Bimatoprost 0.01% ophthalmic solution has negligible influence on the ability to drive and use machines. As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machines. Drug Interactions No interaction studies have been performed. No interactions are anticipated in humans, since systemic concentrations of bimatoprost are extremely low (less than 0.2 ng/ml) following ocular dosing with bimatoprost 0.3 mg/ml ophthalmic solution. Bimatoprost is biotransformed by any of multiple enzymes and pathways, and no effects on hepatic drug metabolizing enzymes were observed in preclinical studies. In clinical studies, bimatoprost 0.3 mg/ml ophthalmic solution was used concomitantly with several different ophthalmic beta-blocking agents without evidence of interactions. Concomitant use of bimatoprost 0.01% ophthalmic solution and anti-glaucomatous agents other than topical betablockers has not been evaluated during adjunctive glaucoma therapy. There is a potential for the IOP-lowering effect of prostaglandin analogues (e.g. bimatoprost 0.01% ophthalmic solution) to be reduced in patients with glaucoma or ocular hypertension when used with other prostaglandin analogues. Use in Renal and Hepatic Impairment Bimatoprost 0.01% ophthalmic solution has not been studied in patients with renal or moderate-to-severe hepatic impairment and should, therefore, be used with caution in such patients. In patients with a history of liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin at baseline, bimatoprost ophthalmic solution 0.03% had no adverse effect on liver function over 48 months.

5 Pregnancy Category C There are no adequate and well-controlled studies on the administration of bimatoprost ophthalmic solution 0.01% and 0.03% in pregnant women. Bimatoprost 0.01% ophthalmic solution should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. Lactation It is not known whether bimatoprost 0.01% ophthalmic solution is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when bimatoprost 0.01% ophthalmic solution is administered to a nursing woman. Paediatric Use Use in paediatric 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. Undesirable Effects 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. In a 12-month clinical study with bimatoprost 0.01% ophthalmic solution, the most common adverse reaction was conjunctival hyperaemia (31%). Approximately 1.6% of patients discontinued therapy due to conjunctival hyperaemia. Other adverse drug reactions (reported in 1 to 4% of patients) with bimatoprost 0.01% ophthalmic solution in this study included conjunctival oedema, conjunctival haemorrhage, eye irritation, eye pain, eye pruritus, erythema of eyelid, eyelids pruritus, growth of eyelashes, hypertrichosis, instillation site irritation, punctate keratitis, skin hyperpigmentation, vision blurred, and visual acuity reduced. The following adverse reactions were reported during clinical trials with bimatoprost 0.01% ophthalmic solution or in the post-marketing period. Most were ocular, mild and none was serious. Very common ( 1/10); common ( 1/100 to <1/10); uncommon ( 1/1,000 to <1/100); rare ( 1/10,000 to <1/1,000); very rare (<1/10,000); and not known (frequency cannot be estimated from available data) adverse reactions are presented according to System/Organ Class in Table 1 in order of decreased seriousness within each frequency grouping. Table 1: Adverse Reactions System/Organ Class Frequency Adverse Reaction Nervous system disorders Headache Eye disorders Very common Conjunctival hyperaemia

6 Common Punctate keratitis, eye irritation, eye pruritus, growth of eyelashes, eye pain, erythema of eyelid, eyelid pruritus Respiratory, thoracic and mediastinal disorders Not known Not known Asthenopia, blurred vision, conjunctival disorder, conjunctival oedema, iris hyperpigmentation, madarosis, eyelid oedema Blepharal pigmentation, macular oedema, periorbital and lid changes including deepening of the eyelid sulcus, dry eye Asthma, asthma exacerbation, COPD exacerbation & dyspnoea Gastrointestinal disorders Nausea Skin and subcutaneous tissue disorders General disorders and administration site conditions Common Common skin hyperpigmentation, hypertrichosis Dry skin, eyelid margin crusting, pruritus Instillation site irritation Immune system disorders Not known Hypersensitivity reaction including signs and symptoms of eye allergy and allergic dermatitis In clinical studies, over 1,800 patients have been treated with bimatoprost 0.01% ophthalmic solution. On combining the data from Phase III monotherapy and adjunctive usage of bimatoprost 0.03% ophthalmic solution, the most frequently reported adverse reactions were as below: Growth of eyelashes in up to 45% of patients in the first year, with the incidence of new reports decreasing to 7% at 2 years and 2% at 3 years. Conjunctival hyperaemia (mostly trace to mild and thought to be of a non-inflammatory nature) in up to 44% of patients in the first year, with the incidence of new reports decreasing to 13% at 2 years and 12% at 3 years. Ocular pruritus in up to 14% of patients in the first year, with the incidence of new reports decreasing to 3% at 2 years and 0% at 3 years. Less than 9% of patients discontinued due to any adverse event in the first year, with the incidence of additional patient discontinuations being 3% at both 2 and 3 years. Additional adverse reactions reported with bimatoprost 0.03% ophthalmic solution are presented in Table 2. The table also includes those adverse reactions that occurred with both formulations but at a different frequency. Most were ocular, mild to moderate, and none were serious. With each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 2: Adverse Reactions System Organ Class Frequency Adverse Reaction Nervous system disorders Common Headache Dizziness

7 Eye disorders Very common Ocular pruritus, growth of eyelashes Common Corneal erosion, ocular burning, allergic conjunctivitis, blepharitis, worsening of visual acuity, asthenopia, conjunctival oedema, foreign body sensation, ocular dryness, eye pain, photophobia, tearing, eye discharge, visual disturbance/ blurred vision, increased iris pigmentation, eyelash darkening Retinal haemorrhage, uveitis, cystoid macular oedema, iritis, blepharospasm, eyelid retraction, periorbital erythema Vascular disorders Common Hypertension Skin and subcutaneous tissue disorders General disorders and administration site conditions Hirsutism Asthenia Investigations Common Liver function test abnormal Post-marketing Experience The following reactions have been identified during the post-marketing use of bimatoprost 0.01% ophthalmic solution in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to bimatoprost 0.01% ophthalmic solution, or a combination of these factors, includes headache. In post-marketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed. Overdosage No case of overdose has been reported, and is unlikely to occur after ocular administration. If overdose occurs, treatment should be symptomatic and supportive. If bimatoprost 0.01% ophthalmic solution is accidentally ingested, the following information may be useful: in 2-week oral rat and mouse studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m 2 is at least 210 times higher than the accidental dose of one bottle of bimatoprost 0.01% ophthalmic solution in a 10kg child. Incompatibility Not applicable. Storage And Handling Instructions Store below 25 C.

8 Packaging Information LOWPROST Eye Drops: 3ml in Vial of 5 ml Last updated: April 2017 Last reviewed: April 2017 Information For Patients There is a potential for increased brown pigmentation of the iris, which may be permanent. Also, there is a possibility of eyelid skin darkening, which may be reversible after discontinuation of bimatoprost ophthalmic solution 0.01%. In bimatoprost ophthalmic solution 0.01% treated eyes, there is a possibility of eyelash and vellus hair changes. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment. Avoid allowing the tip of the dispensing container to contact the eye(s), surrounding structures, fingers or any other surface to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye(s) and subsequent loss of vision may result from using contaminated solutions. In case of development of an intercurrent ocular condition (e.g. trauma or infection), or ocular surgery or development of any ocular reactions, particularly conjunctivitis and eyelid reactions, immediately seek physician's advice concerning the continued use of bimatoprost 0.01% ophthalmic solution. Contact lenses should be removed prior to instillation of bimatoprost 0.01% ophthalmic solution and may be reinserted 15 minutes following its administration. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between instillations. LOWPROST Eye Drops Source URL: