Bimatoprost

There is a potential for the IOP-lowering effect of prostaglandin analogues to be reduced in patients with glaucoma or ocular hypertension when used with other prostaglandin analogues.

There is a potential for hair growth to occur in areas where bimatoprost solution comes repeatedly in contact with the skin surface. Thus, it is important to apply bimatoprost as instructed and avoid it running onto the cheek or other skin areas.

Cystoid macular oedema has been uncommonly reported (≥1/1,000 to <1/100) following treatment with bimatoprost 0.3 mg/ml eye drops, solution. Therefore, bimatoprost should be used with caution in patients with known risk factors for macular oedema (e.g. aphakic patients, pseudophakic patients with a torn posterior lens capsule).

Bimatoprost 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.

There are no adequate data from the use of bimatoprost in pregnant women. Animal studies have shown reproductive toxicity at high maternotoxic doses. Bimatoprost should not be used during pregnancy unless clearly necessary.

It is unknown whether bimatoprost is excreted in human breast milk. Animal studies have shown excretion of bimatoprost in breast milk. A decision must be made whether to discontinue breastfeeding or to discontinue from bimatoprost therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

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

Bimatoprost 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.

In a 12-month Phase III clinical study 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 hyperaemia (mostly trace to mild and of a non-inflammatory nature) occurring in 29% of patients. Approximately 4% of patients discontinued due to any 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 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); not known (cannot be estimated from available data) adverse reactions are presented according to System Organ Class in List 1 in order of decreased seriousness within each frequency grouping.

List 1:

Nervous system disorders

Uncommon: headache

Not known: dizziness

Eye disorders

Very common: conjunctival hyperaemia

Common: punctate keratitis, eye irritation, eye pruritus, growth of eyelashes, eye pain, erythema of eyelid, eyelid pruritus

Uncommon: asthenopia, blurred vision, conjunctival disorder, conjunctival oedema, iris hyperpigmentation, madarosis, eyelid oedema

Not known: blepharal pigmentation, macular oedema, periorbital and lid changes including deepening of the eyelid sulcus, dry eye, eye discharge, eye oedema, foreign body sensation in eyes, lacrimation increased, ocular discomfort, photophobia

Respiratory, thoracic and mediastinal disorders

Not known: asthma, asthma exacerbation, COPD exacerbation and dyspnoea

Gastrointestinal disorders

Uncommon: nausea

Skin and subcutaneous tissue disorders

Common: skin hyperpigmentation, hypertrichosis

Uncommon: dry skin, eyelid margin crusting, pruritus

Not known: skin discoloration (periocular)

General disorders and administration site conditions

Common: instillation site irritation

Immune system disorders

Not known: Hypersensitivity reaction including signs and symptoms of eye allergy and allergic dermatitis

Vascular disorders

Not known: hypertension

In clinical studies, over 1800 patients have been treated with bimatoprost 0.3 mg/ml. On combining the data from phase III monotherapy and adjunctive bimatoprost 0.3 mg/ml usage, the most frequently reported adverse reactions were:

• growth of eyelashes in up to 45% 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% 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 0.3 mg/ml are presented in List 2. The list also includes those adverse reactions which occurred with both formulations but at a different frequency. Most were ocular, mild to moderate, and none was serious: With each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

List 2:

Nervous system disorders

Common: headache

Uncommon: dizziness

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

Uncommon: retinal haemorrhage, uveitis, cystoid macular oedema, iritis, blepharospasm, eyelid retraction, periorbital erythema

Vascular disorders

Common: hypertension

Skin and subcutaneous tissue disorders

Uncommon: hirsutism

General disorders and administration site conditions

Uncommon: asthenia

Investigations

Common: liver function test abnormal

Adverse reactions reported in phosphate containing eye drops: Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas.