LUMIGAN

Reduction of elevated intraocular pressure in adult patients with chronic open-angle glaucoma or ocular hypertension (as monotherapy or in association with beta-blockers).

Ocular

Before starting treatment, patients must be informed that BIMATOPROST BIOGARAN is liable to cause prostaglandin-associated periorbitopathy (PAP) and an increase in iris pigmentation, as has been observed in patients treated with BIMATOPROST BIOGARAN. Some of these changes may be permanent and may lead to an alteration of the visual field and differences in appearance between the eyes if only one eye is treated (see section 4.8).

Cases of cystoid macular edema have been reported infrequently ( ≥ 1/1 000 to <1/100) after treatment with the eye drops containing 0,3 mg/ml of bimatoprost. Consequently, BIMATOPROST BIOGARAN must be used with caution in patients with a known risk factor for macular edema (for example: aphakic patients, pseudophakic patients with posterior capsule rupture).

Rare cases of reactivation of old corneal infiltrates or old ocular infections have been spontaneously reported with the eye drops containing 0,3 mg/ml of bimatoprost. BIMATOPROST BIOGARAN must be used with caution by patients with a history of significant viral ocular infections (for example: herpes simplex) or uveitis/iritis.

BIMATOPROST BIOGARAN has not been studied in patients with ocular inflammation, neovascular and inflammatory glaucoma, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.

Dermal

An increase in hair growth may occur at sites of repeated contact of the BIMATOPROST BIOGARAN solution with the skin. It is therefore important to apply BIMATOPROST BIOGARAN according to the instructions and to avoid it running onto the cheek or other areas of the skin.

Respiratory

BIMATOPROST BIOGARAN has not been studied in patients suffering from respiratory insufficiency. Although available data in patients with a history of asthma or COPD are limited, cases of exacerbation of asthma, dyspnea and COPD, as well as the occurrence of asthma attacks, have been reported since marketing. The frequency of these symptoms is undetermined. Patients with COPD, asthmatics or those whose respiratory function is impaired due to other conditions must be treated with caution.

Cardiovascular

BIMATOPROST BIOGARAN has not been studied in patients presenting with a cardiac block more severe than a first-degree block or uncontrolled congestive heart failure. There have been a limited number of spontaneous reports of cases of bradycardia or hypotension during the use of the eye drops containing 0,3 mg/ml of bimatoprost. BIMATOPROST BIOGARAN must be used with caution in patients with predispositions to a slow heart rate or low blood pressure.

Additional information

In studies involving bimatoprost 0,3 mg/ml in patients with glaucoma or ocular hypertension, it has been shown that more frequent exposure of the eye to bimatoprost (i.e., more than one dose per day) may decrease the effect of reducing intraocular pressure (see section 4.5). Patients for whom BIMATOPROST BIOGARAN is combined with other prostaglandin analogues must therefore be monitored to observe the evolution of their intraocular pressure.

BIMATOPROST BIOGARAN contains a preservative, benzalkonium chloride (200 ppm), which can be absorbed by soft contact lenses. Benzalkonium chloride may cause eye irritation and discoloration of contact lenses. Contact lenses must be removed before instillation and may be reinserted 15 minutes after administration.

Benzalkonium chloride, commonly used as a preservative in ophthalmic products, may be the cause of superficial punctate keratitis and/or toxic ulcerative keratopathy. As BIMATOPROST BIOGARAN 0,1 mg/mL contains 200 ppm of benzalkonium chloride (four times the concentration of the eye drops containing 0,3 mg/ml of bimatoprost), it must be used with caution in patients with dry eye, in patients with corneal damage and/or in patients taking multiple eye drops containing benzalkonium chloride. In addition, monitoring is necessary during prolonged use in these patients.

Bacterial keratitis associated with the use of multi-dose containers of topical ophthalmic products has been reported. These containers had been accidentally contaminated by patients, who, in most cases, presented with an underlying ocular pathology.

In patients presenting with an injury to the ocular epithelial surface, the risk of developing bacterial keratitis is higher.

Patients must receive instructions to avoid the tip of the bottle coming into contact with the eye or surrounding structures, to avoid eye injury or contamination of the solution.

No interaction study has been conducted.

No interaction is expected in humans, as systemic concentrations of bimatoprost are extremely low (less than 0,2 ng/ml) after ophthalmic administration of the eye drops containing 0,3 mg/ml of bimatoprost. Bimatoprost is transformed by different metabolic pathways, but no effect on the enzymes involved in hepatic metabolism has been observed in preclinical studies.

In clinical studies, the eye drops in solution containing 0,3 mg/ml of bimatoprost were used simultaneously with several beta-blockers for ophthalmic use without evidence of interactions.

Apart from beta-blockers for local use, the combination of BIMATOPROST BIOGARAN with other antiglaucoma agents has not been studied in the treatment of glaucoma.

The intraocular pressure-lowering effect exerted by prostaglandin analogues (for example BIMATOPROST BIOGARAN) may be less if they are used with other prostaglandin analogues in patients with glaucoma or ocular hypertension (see section 4.4).

Pregnancy

There are no relevant data on the use of bimatoprost in pregnant women. Studies conducted in animals have shown reproductive toxicity at high maternotoxic doses (see section 5.3).

BIMATOPROST BIOGARAN must not be used during pregnancy, except in cases of absolute necessity.

Breastfeeding

It is unknown if bimatoprost is excreted in breast milk. Animal studies have shown passage of bimatoprost into milk. The decision to discontinue breastfeeding or to stop treatment with BIMATOPROST BIOGARAN should be made taking into account the benefit of breastfeeding for the child and the benefit of treatment for the mother.

Fertility

There are no data on the effects of bimatoprost on human fertility.

BIMATOPROST BIOGARAN has a negligible effect on the ability to drive and use machines.

As with any ophthalmic treatment, if transient blurred vision occurs after instillation, the patient must wait until their vision returns to normal before driving or using machines.

In the phase III clinical study conducted over twelve months, approximately 38 % of patients treated with BIMATOPROST BIOGARAN 0.1 mg/ml experienced adverse reactions. The most common adverse reaction was conjunctival hyperaemia occurring in 29 % of patients; most of the time, the hyperaemia was minimal to mild and non-inflammatory in nature. Approximately 4 % of patients discontinued treatment due to adverse reactions.

The adverse reactions described below were reported during clinical trials with BIMATOPROST BIOGARAN 0.1 mg/ml, eye drops, solution or post-marketing. Most were ocular, mild in intensity and none were 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); not known (cannot be estimated from the available data) are classified in Table 1 according to system organ classes. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1

In clinical studies, more than 1 800 patients were treated with bimatoprost 0,3 mg/ml. Pooling data from phase III clinical studies with bimatoprost 0,3 mg/ml as monotherapy or as an adjunct, the most frequent treatment-related adverse events were:

· eyelash growth in up to 45 % in the first year with an incidence of new cases reduced

· to 7 % at 2 years and 2 % at 3 years,

· conjunctival hyperaemia (mostly trace to mild and considered to be of

· non-inflammatory nature) in up to 44 % of patients in the first year with an incidence of

· new cases reduced to 13 % at 2 years and 12 % at 3 years,

· eye pruritus in up to 14 % of patients in the first year with an incidence of new

· cases reduced to 3 % at 2 years and 0 % at 3 years. Less than 9 % of patients had to discontinue treatment

· due to an adverse event in the first year, with an incidence of

· additional discontinuations of 3 % in the second and third year.

Other adverse effects reported with bimatoprost 0.3 mg/ml are presented in Table 2. This table also includes adverse effects that occurred with both formulations, but with different frequencies. Most of these effects are ocular, mild to moderate, and none were serious: for each frequency, the adverse effects are presented in decreasing order of severity.

Table 2.

Description of selected adverse reactions

Prostaglandin analog periorbitopathy (PAP)

Prostaglandin analogs, including BIMATOPROST BIOGARAN, may cause periorbital lipodystrophic changes that can cause deepening of the eyelid sulcus, ptosis, enophthalmos, eyelid retraction, involution of dermatochalasis and inferior scleral show. The changes are typically mild, can occur as early as one month after starting treatment with BIMATOPROST BIOGARAN and can result in visual field alteration even without patient recognition. PAP is also associated with periorbital skin hyperpigmentation or discoloration and hypertrichosis. These changes have been found to be partially or completely reversible upon discontinuation or switching to another treatment.

Iris hyperpigmentation

The increase in iris pigmentation will likely be permanent. The change in pigmentation is due to an increase in melanin content in the melanocytes rather than an increased number of melanocytes. The long-term effects of increased iris pigmentation are unknown. Iris color changes observed with ophthalmic administration of bimatoprost may not be visible for several months or years. Typically, the brown pigmentation around the pupils spreads concentrically towards the periphery of the iris, and all or part of the iris becomes brownish. The treatment appears not to affect iris nevi and freckles. The incidence of iris hyperpigmentation after 12 months of treatment with an eye drop containing 0,1 mg/mL of bimatoprost was 0,5 %. With the eye drop containing 0,3 mg/mL of bimatoprost, the incidence which was 1,5 % at 12 months (see section 4.8, Table 2), did not increase during the 3 years of treatment.

Adverse effects reported with eye drops containing phosphate:

A few rare cases of corneal calcification have been reported in association with the use of phosphate-containing drops in some patients with significantly damaged corneas. Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse reaction via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr.