For the use of a Registered Medical Practitioner, a health care provider or a Laboratory only
BIMATOPROST OPHTHALMIC SOLUTION 0.03% w/v
COMPOSITION
Each ml contains:
Bimatoprost 0.3 mg
Benzalkonium Chloride Solution BP 0.01% w/v (as preservative)
Water for Injections BP q.s.
DESCRIPTION
A clear, colorless to almost colorless solution.
PHARMACODYNAMIC
Pharmacotherapeutic group: Ophthalmologicals, prostaglandin analogues
ATC Code: S01EE03
Mechanism of action
The mechanism of action by which bimatoprost reduces intraocular pressure in humans is by increasing aqueous humour outflow through the trabecular meshwork and enhancing uveoscleral outflow. Reduction of the intraocular pressure 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.
Bimatoprost is a potent ocular hypotensive agent. It is a synthetic prostamide, structurally related to prostaglandin F2α (PGF2α), that does not act through any known prostaglandin receptors. Bimatoprost selectively mimics the effects of newly discovered biosynthesised substances called prostamides. The prostamide receptor, however, has not yet been structurally identified.
PHARMACOKINETICS
Absorption
Bimatoprost penetrates the human cornea and sclera well in vitro. After ocular administration in adults, the systemic exposure of bimatoprost is very low with no accumulation over time. After once daily ocular administration of one drop of bimatoprost 0.3 mg/ml to both eyes for two weeks, blood concentrations peaked within 10 minutes after dosing and declined to below the lower limit of detection (0.025 ng/ml) within 1.5 hours after dosing. Mean Cmax and AUC 0-24 hours values were similar on days 7 and 14 at approximately 0.08 ng/ml and 0.09 ng/ml respectively, indicating that a steady bimatoprost concentration was reached during the first week of ocular dosing.
Distribution
Bimatoprost is moderately distributed into body tissues and the systemic volume of distribution in humans at steady-state was 0.67 l/kg. In human blood, bimatoprost resides mainly in the plasma. The plasma protein binding of bimatoprost is approximately 88%.
Biotransformation
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
Bimatoprost is eliminated primarily by renal excretion, up to 67% of an intravenous dose administered to healthy adult volunteers was excreted in the urine, 25% of the dose was excreted via the faeces. The elimination half-life, determined after intravenous administration, was approximately 45 minutes; the total blood clearance was 1.5 l/hr/kg.
THERAPEUTIC INDICATION
Reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension in adults (as monotherapy or as adjunctive therapy to beta-blockers)
DOSAGE AND ADMINISTRATION
The recommended dose is one drop in the affected eye(s) once daily, administered in the evening. The dose should not exceed once daily as more frequent administration may lessen the intraocular pressure lowering effect.
Paediatric population:
The safety and efficacy of bimatoprost in children aged 0 to 18 years has not yet been established.
Patients with hepatic and renal impairment:
Bimatoprost 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 mild liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin at baseline, Bimatoprost 0.3 mg/ml eye drops, solution had no adverse effect on liver function over 24 months.
Method of administration
If more than one topical ophthalmic medicinal product is being used, each one should be administered at least 5 minutes apart.
INSTRUCTION FOR USE
Apply BIMWELL Eye Drops in the following way:
- Wash your hands. Tilt your head back and look at the ceiling.
- Gently pull the lower eyelid down until there is a small pocket.
- Turn the bottle upside down and gently press the bottle to release drops into eyes that needs treatment.
- Let go of the lower lid, and close your eye for 30 seconds.
- To avoid contamination, do not let the tip of dropper touch your eye or anything else.
- Replace and tighten the cap straight after use.
OVERDOSE
No case of overdose has been reported, and is unlikely to occur after ocular administration.
CONTRAINDICATION
- Hypersensitivity to the active substance or to any of the excipients.
WARNING AND PRECAUTIONS
- It is not for injection.
- Do not use the eye drop with contact lenses.
- Talk to your doctor if you have any breathing problem, liver or kidney problems, cataract surgery in past, dry eye, have had problem with your cornea, have had low blood pressure or low heart rate, viral infection or inflammation of the eye before you use Bimatoprost.
- During treatment, Bimatoprost may cause a loss of fat around the eye, which may cause your eyelid crease to deepen, your eye to appear sunken (enophthalmos), your upper eyelid to droop (ptosis), the skin around your eye to tighten (involution of dermatochalasis) and the lower white part of your eye to become more visible (inferior scleral show). The changes are typically mild, but if pronounced, they can affect your field of vision. The changes may disappear if you stop taking Bimatoprost.
- Bimatoprost may cause your eyelashes to darken and grow, and cause the skin around the eyelid to darken too. The colour of your iris may also go darker over time. These changes may be permanent. The change may be more noticeable if you are only treating one eye.
- Bimatoprost has not been tested in children under the age of 18 and therefore Bimatoprost should not be used by patients under 18 years.
- Tell your doctor or pharmacist if you are taking, or have recently taken, or might take any other medicines.
PREGNANCY, LACTATION AND FERTILITY
Pregnancy
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.
Lactation
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 breastfeeding for the child and the benefit of therapy for the woman.
Fertility
There are no data on the effects of bimatoprost on human fertility.
DRUG INTERACTION
No interaction studies have been performed.
ADVERSE EFFECTS
Very common (Affecting the eye):
Longer eyelashes, Slight redness, Itchiness, loss of fat in the eye region which can lead to deepening of your eyelid crease, sunken eye (enophthalmos), drooping eyelid (ptosis), tightening of the skin around your eye (involution of dermatochalasis), and the lower white part of your eye to become more visible (inferior scleral show).
Common (Affecting the eye):
An allergic reaction in the eye, Tired eyes, Sensitivity to light, Darker skin colour around the eye, Darker eyelashes, Pain, A feeling that something is in your eye, Sticky eyes, Darker iris colour, Difficulty in seeing clearly, Irritation, Burning, Inflamed, red and itchy eyelids, Tears, Dryness, Worsening of vision, Blurred vision, Swelling of the see-through layer which covers the surface of the eye, Small breaks in the surface of the eye, with or without inflammation
Common (Affecting the body):
Headaches, an increase in blood-test results that show how your liver is working, Increased blood pressure.
Uncommon (Affecting the eye):
Cystoid macular oedema (swelling of the retina within the eye leading to worsening vision), Inflammation within the eye, Retinal bleeding, Swollen eyelids, Eyelid twitching, Eyelid shrinking, moving away from surface of the eye, Skin redness around the eye.
Uncommon (Affecting the body):
Nausea, Dizziness, Weakness, Hair growth around the eye
Not known (Affecting the eye):
Ocular discomfort
Not known (Affecting the body):
Asthma, worsening of asthma, worsening of the lung disease called chronic obstructive pulmonary disease (COPD), Shortness of breath, Symptoms of allergic reaction (swelling, redness of the eye and rash of the skin), Skin discoloration (periocular).
PRESENTATION
BIMWELL Eye Drops are supplied in 5 ml sterilized opaque plastic container with nozzle and cap.
STORAGE AND OTHER INFORMATION
Store at temperature below 30 °C. Keep this medicine out of the sight and reach of children. Do not touch the dropper tip or dispensing tip to any surface since this may contaminate the solution. Use the solution within one month after opening the container.