Auget contains Bimatoprost, a powerful ocular hypotensive agent, analogous to prostaglandins. Bimatoprost is a synthetic prostamide, structurally related to prostaglandin F2a (PGF2a), which does not act through any known prostaglandin receptor; rather, it selectively exerts the effects of prostamides, recently discovered biosynthesized substances. However, the prostamide receptor has not yet been structurally identified.
Mechanism of action
Bimatoprost decreases intraocular pressure in humans because it increases the drainage of the aqueous humor through the trabecular body and intensifies the uveo-scleral drainage. The decrease in intraocular pressure begins approximately 4 hours after the first administration and reaches its maximum intensity approximately within the following 8-12 hours. The duration of its effect lasts for at least 24 hours.
Bimatoprost penetrates well into the human cornea and sclera in vitro. After ocular administration in adults, systemic exposure to Bimatoprost is very low, with no accumulation over time. Following once-daily administration of one drop of Bimatoprost eye drops 0.3 mg / ml in both eyes for two weeks, blood concentrations peaked within 10 minutes of dosing and decreased to the lower limit of detection ( 0.025 mg / ml) in 1.5 hours after application. The mean values of Cmax and AUCO-24 hours were similar on days 7 and 14, reaching 0.08 ng / ml and 0.09 ng.h / ml respectively, indicating that a stationary concentration of Bimatoprost was reached during the first administration week.
Bimatoprost is moderately distributed in the tissues of the body and in humans, its volume of systemic distribution is 0.67 l / kg in the stationary phrase. In human blood, Bimatoprost remains mainly in plasma. Its binding to plasma proteins is approximately 88.9%. After ocular administration, it is found mostly in the blood as unmodified Bimatoprost. It then undergoes oxidation, N-deethylation and glucuronidation processes, generating a variety of metabolites. Bimatoprost is eliminated mainly by renal excretion; up to 67% of a dose is excreted in the urine and 25% is excreted in the faeces. The elimination half-life, determined after intravenous administration, is approximately 45 minutes. The total blood clearance is 1.5 l / h / kg.
Auget is indicated to reduce elevated intraocular pressure in chronic open angle glaucoma and in ocular hypertension in adults (as monotherapy or as combination therapy with beta-blockers).
Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed. No drug interactions can be expected in humans, as the systemic concentrations of Bimatoprost observed after ocular dosing are extremely low (less than 0.2 ng / ml) with Bimatoprost 0.3 mg / ml eye drops, solution. Bimatoprost is biotransformed by multiple different pathways and enzymes, and no effects on hepatic drug-metabolizing enzymes have been observed in preclinical studies.
Bimatoprost 0.3 mg / ml eye drops, solution, has been applied concomitantly with various ophthalmic beta-blocking agents in clinical studies without drug interactions being observed.
The concomitant use of Bimatoprost with other antiglaucomatous agents other than beta-blockers has not been evaluated in combination therapy for glaucoma. It may decrease the IOP lowering effect of prostaglandin analogs (eg, Bimatoprost) in patients with glaucoma or ocular hypertension when used with other prostaglandin analogs.
Fertility, pregnancy and lactation
There are insufficient data on the use of Bimatoprost in pregnant women. Animal studies have shown reproductive toxicity at high maternotoxic doses. Bimatoprost should not be applied during pregnancy unless clearly necessary.
It is not known whether Bimatoprost is excreted in human milk. Animal studies have shown its excretion in breast milk. A decision should be made whether to discontinue breast-feeding or treatment, taking into account the benefit of breast-feeding for the child and the benefit of treatment for the mother.
Each ml contains:
Bimatoprost 0.10 mg
C.S.P. Excipients 1 ml
Posology and method of administration
Administration route: Ophthalmic.
The recommended dose of Auget is one drop in the affected eye (s), administered once daily in the evening. The dose should not exceed once a day because a higher frequency of administration, may decrease its reducing effect on intraocular pressure.
Bimatoprost has not been studied in patients with heart block severity greater than grade one or with uncontrolled congestive heart failure. There are a limited number of spontaneous reports of bradycardia or hypotension with Bimatoprost 0.3 mg / ml eye drops, solution. It should be used with caution in patients predisposed to have a low heart rate or low blood pressure.
In studies of bimatoprost 3.0 mg / ml in patients with glaucoma or ocular hypertension, it has been shown that frequent exposure of the eye to more than one daily dose of bimatoprost can 4 decrease the reducing effect of IOP. Patients using Bimatoprost with other prostaglandin analogues should be monitored for changes in their intraocular pressure. Bimatoprost 0.1 mg / ml contains benzalkonium chloride (200 ppm) as a preservative, which can be absorbed by soft contact lenses. Irritation and discoloration of soft contact lenses may also occur due to the presence of benzalkonium chloride. Contact lenses should be removed before each instillation, and can be put back 15 minutes after administration. Benzalkonium chloride, normally used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and / or toxic ulcerative keratopathy. Since Bimatoprost 0.1 mg / ml contains benzalkonium chloride at 200 ppm (four times the concentration of Bimatoprost 0.3 mg / ml eye drops), it should be used with caution in patients with dry eye, in patients whose cornea may be compromised and in patients using multiple eye drops containing BAK. In addition, monitoring is necessary in patients who use it for prolonged periods. Bacterial keratitis cases associated with the use of multidose containers of topical ophthalmic products have been rarely reported. These packages had been unintentionally contaminated by patients who, in most cases, suffered from concurrent eye disease. Patients with altered ocular epithelial surface are at increased risk of developing bacterial keratitis. Patients will be instructed to prevent the tip of the dropper from contacting the eye or surrounding structures to avoid eye injury and contamination of the solution.
Store at a temperature between 15 °C and 25 °C. Protect from freezing.
Box containing a 3 ml dropper bottle.
Medical sample with 1 ml dropper bottle.
Pediatric population: The safety and efficacy of Bimatoprost in children aged 0-18 years have not yet been established.
Patients with decreased liver or kidney function: Bimatoprost has not been studied in patients with decreased kidney function or with moderate to severe decrease in liver function; therefore, it should be used with caution in these cases. In patients with a history of mild liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and / or baseline bilirubin, administration of Bimatoprost 0.3 mg / ml eye drops, solution did not cause any adverse effect on function liver during a 24-month period.
Method of administration: When more than one topical ophthalmic drug is used, each should be administered with an interval of at least 5 minutes.
Auget is contraindicated in patients suspected of having a prior adverse reaction to benzalkonium chloride that has forced them to discontinue its administration.
Special warnings and precautions for use
Patients should be informed of possible eyelash growth, darkening of the skin of the eyelids, and increased pigmentation of the iris, as these changes have been observed during treatment with Bimatoprost. Some of these changes may be permanent and may lead to differences in appearance between the eyes when the treatment is applied to only one of them. Iris pigmentation is likely to be permanent. The change in pigmentation is due to the increased melanin content in the melanocytes, rather than an increase in the number of these. The long-term effects of increased iris pigmentation are unknown. The changes in the color of the iris observed with the ophthalmic administration of Bimatoprost can go unnoticed for several months or years. Normally, the brown pigmentation around the pupil extends concentrically towards the periphery of the iris, and all or parts of the iris take on a more brownish color. Nevus and freckles do not appear to be affected by the treatment. At 12 months, the incidence of iris hyperpigmentation with Bimatoprost 0.1 mg / ml eye drops, solution was 0.5%. At 12 months, the incidence with bimatoprost 0.3 mg / ml eye drops, solution was 1.5% and did not increase in the following three years of treatment. Periorbital tissue pigmentation has been shown to be reversible in some patients. Rarely (> 1/1000 to Rarely (> 1/1000 to Rarely (> 1/1000 to <1/1000)) cases of cystoid macular edema have been reported after treatment with Bimatoprost 0.3 mg / ml eye drops, solution For this reason, it should be used with caution in patients with known risk factors for macular edema (for example, aphakic patients, pseudophakic patients with a tear of the posterior lens capsule.) Cases of reactivation of corneal infiltrates or previous eye infections, with Bimatoprost 0.3 mg / ml eye drops, solution Bimatoprost should be used with caution in patients with a history of significant viral eye infections (eg herpes simplex) or uveitis / iritis.
Bimatoprost has not been studied in patients with inflammatory eye conditions, neovascular glaucoma, inflammatory glaucoma, angle-closure glaucoma, congenital glaucoma, or narrow-angle glaucoma.
It can cause hair growth on areas of the skin repeatedly exposed to Bimatoprost, so it is important to apply it as indicated and avoid contact with the cheek and other areas of the skin.
Bimatoprost has not been studied in patients with compromised respiratory function. Although limited information is available in patients with a history of asthma or COPD, cases of exacerbation of asthma, dyspnea, and COPD, as well as cases of asthma, have been reported after marketing. The frequency of these symptoms is not known. It should be administered with caution in patients with COPD, asthma, or compromised respiratory function due to other conditions.
There are no data on the effects of Bimatoprost on human fertility.
Effects on ability to drive and use machines
The influence of Bimatoprost on the ability to drive and use machines is negligible. As with all ocular medications, if the patient has transient blurred vision immediately after eye drops application, he should wait until his vision clears before driving or operating machinery.
In a 12-month phase III clinical trial, approximately 38% of patients treated with Bimatoprost 0.1 mg / ml eye drops, solution experienced adverse reactions. The most frequently reported adverse reaction was conjunctival hyperemia, (mostly insignificant to mild and non-inflammatory type) that was observed in 29% of patients. Approximately 4% of patients discontinued administration due to some adverse event in the 12-month study. The following adverse reactions were reported during clinical trials with Bimatoprost 0.1 mg / ml eye drops, solution, or in the post-marketing period. Most were ocular, mild, and none were serious. Very frequent adverse reactions (> 1/10); frequent (> 1/100 to <1/10); uncommon (> 1/1000 to <1/100); rare (from> 1/10000 to <1/1000); very rare (<1/10000); and frequency not known (cannot be estimated from the possible data) are presented in Table 1 according to the organ classification system in decreasing order of severity within each frequency group.