Monoprost: composition and presentation
Monoprost is an eye drop solution in which one millilitre contains 50 µg of latanoprost. Its defining feature is what the product leaves out: the solution is made without a preservative. In drops that are instilled for years on end this matters, since preservatives are the commonest cause of chronic irritation of the eye surface during long-term glaucoma treatment.
The packaging carries the one ambiguity in the description: in one place it refers to a single-dose container holding enough solution for both eyes and discarded straight after use, in another to a multi-dose bottle with a pump, likewise preservative-free, intended for one or for three months of treatment. Both presentations exist, so before the first use it is worth looking at your own pack: it decides whether the container is thrown away after a single application or the bottle kept until the course ends.
How Monoprost works
Latanoprost is an analogue of prostaglandin F2α and a selective agonist of the prostanoid FP receptor. It lowers intraocular pressure not by reducing the production of aqueous humour but by improving its outflow. Studies in animals and in humans indicate that the main mechanism is increased uveoscleral outflow, that is, drainage through the choroid and the sclera; in addition, some easing of outflow through reduced resistance is seen in people.
A practical conclusion about the dosing schedule follows from this. The drug acts on the structures responsible for drainage rather than damping down secretion, so the effect builds smoothly and holds for a full day, which is why one instillation a day is enough. For the same reason, instilling more often does not lower pressure further but weakens the effect: the receptor ends up saturated rather than further stimulated.
Indications
Monoprost has a single indication, narrowly worded: reduction of raised intraocular pressure in adult patients with open-angle glaucoma and with ocular hypertension. The list ends with those two conditions, and it must not be widened on your own initiative — in the closed-angle form, in inflammatory or neovascular glaucoma the drainage conditions differ, and experience with latanoprost there is either limited or absent.
Ocular hypertension means persistently raised pressure with no demonstrated damage to the optic nerve or the visual field; open-angle glaucoma is the state in which such damage is already progressing. The difference is fundamental for the prognosis but not for the dosing schedule: in both cases the aim is the same, to keep pressure at a level that is safe for the optic nerve. On use in children and adolescents there are no data for this presentation.
Method of use and dosage
Adults, including elderly patients, instil one drop into the affected eye or into both eyes once a day. The best result comes from instilling in the evening. The medicine is not used more than once a day: more frequent administration has been shown to weaken the reduction in intraocular pressure. If a dose is missed, treatment continues with the next scheduled dose, without doubling it.
The technique of instillation affects tolerability as much as the dose does. As soon as the drop reaches the eye, the inner corner of the eyelid opening is pressed with a finger for one minute, which reduces passage of the active substance into the bloodstream. Contact lenses are removed before instillation and put back no sooner than 15 minutes later. If other ophthalmic preparations have been prescribed, a gap of at least five minutes is left between them. The tip must not touch the eye or the eyelids, and solution from a single-dose container is used immediately after opening with the remainder discarded at once: sterility cannot be maintained once the container is open, and there is no preservative to maintain it. The effect on the ability to drive has not been studied, but vision may blur briefly straight after instillation, and until it clears it is better not to get behind the wheel.
Contraindications
The description gives a single outright contraindication: hypersensitivity to latanoprost or to any of the excipients of the drops. Among the excipients, macrogolglycerol hydroxystearate — hydrogenated polyoxyethylated castor oil — is singled out as capable of causing skin reactions; data on the safety of its long-term use are not yet available.
So short a list does not mean the medicine suits everyone. With latanoprost the limitations are gathered not in the section of prohibitions but in the section of warnings, and there are many of them there: some conditions call for caution, and for others there is simply no experience. In practice this means the decision rests with the ophthalmologist, who takes in the type of glaucoma, the state of the cornea, the presence of an artificial lens and the accompanying illnesses, not merely the number on the tonometer.
Special warnings and precautions
The main thing patients are warned about before treatment starts is that latanoprost can gradually change the colour of the eye by increasing the amount of brown pigment in the iris. In a five-year open safety study that change occurred in 33% of patients. It concerns almost exclusively people with a mixed iris colour — blue-brown, grey-brown, yellow-brown, green-brown — and within that group the frequency ranges from 7 to 85%, being highest with a yellow-brown iris. In uniformly blue eyes no changes were seen, and in grey, green and brown ones they were exceptionally rare. The change usually begins within the first eight months, rarely in the second or third year and never after the fourth; by five years the process stabilises. It rests on melanin accumulating in the melanocytes of the stroma rather than on their number increasing: the brown colour spreads in a ring from the pupil towards the periphery. After the drug is stopped no further darkening occurs, and five years of observation have revealed no harmful consequences of this pigmentation — when it appears, treatment is continued and the patient examined regularly. Treatment of one eye alone deserves separate attention, because the difference in colour may remain for good.
| Situation | What the doctor weighs up |
| Mixed iris colour | the highest risk of irreversible darkening; warn before the first drop |
| Treatment of one eye only | a lasting difference in eye colour is possible |
| Past herpetic keratitis | use with caution |
| Active or recurrent herpetic keratitis | use is avoided, especially where relapses are linked to prostaglandin analogues |
| Aphakia, pseudophakia with a torn posterior capsule, a lens in the anterior chamber | caution because of the risk of macular oedema |
| Diabetic retinopathy, retinal vein occlusion | the same concerns about cystoid macular oedema |
| Tendency to iritis and uveitis | use is possible but calls for caution |
| Bronchial asthma | experience is limited; there are post-marketing reports of worsening and breathlessness |
| Chronic closed-angle glaucoma, open-angle glaucoma in pseudophakic eyes, pigmentary glaucoma | clinical experience is limited |
| Inflammatory, neovascular or congenital glaucoma, an acute closed-angle attack, the period around cataract surgery | no experience or few data; caution required |
The second visible change in appearance affects the eyelashes and the vellus hair of the eyelid on the treated side: they lengthen, thicken, darken, grow more numerous and sometimes grow in the wrong direction; according to the description these changes subside during continued treatment. Darkening of the skin of the orbital area has also been recorded, chiefly in patients from Japan; it was not permanent and in some cases disappeared despite the therapy continuing. None of these phenomena threatens sight, but it is better to know about them in advance, because the cosmetic effect is often noticed by those around the patient sooner than by the patient.
Interactions with other medicines
There are no conclusive data on interactions between latanoprost and other medicines, and this is one of the rare cases where the emptiness of the section stems not from a gap in research but from the route of administration: the drop goes into the eye, and only a negligible fraction of the substance reaches the general circulation, so classic hepatic interactions are foreign to it.
One important exception is nevertheless described, and it happens inside the eye. When two medicines from the prostaglandin analogue group were instilled together, a paradoxical rise in intraocular pressure was recorded — the exact opposite of the aim of treatment. Combining two or more prostaglandins, their analogues or derivatives is therefore not recommended. If monotherapy fails to hold the pressure, the doctor adds an agent with a different mechanism rather than a second product of the same class.
Pregnancy and breastfeeding
The safety of Monoprost in pregnancy has not been established, and the wording of the description is sterner here than usual: the medicine has a potentially dangerous effect on the course of pregnancy, on the foetus and on the newborn, so it should not be used while pregnant. This is not a situation of weighing benefit against risk but a direct refusal to prescribe for the duration of the pregnancy.
Latanoprost and its metabolites may pass into breast milk, so breastfeeding women are either not given the medicine or stop feeding. Animal studies found no effect of latanoprost on the fertility of males or females. A woman planning a pregnancy while being treated for glaucoma should discuss a change of medicine with the ophthalmologist in advance, not once the pregnancy has already begun.
Adverse reactions
The overwhelming majority of adverse reactions fall on the organ of vision itself and arise at the moment of instillation, passing off afterwards. Very often there is increased pigmentation of the iris, mild or moderate reddening of the conjunctiva, irritation of the eye — burning, itching, stinging or the sensation of a foreign body — and the changes to lashes and vellus hair described above, the great majority of such reports coming from patients in Japan. Often recorded are transient punctate defects of the corneal epithelium, mostly symptomless, inflammation of the eyelid margins, eye pain and photophobia.
Uncommonly there is swelling of the eyelids, dry eye, keratitis, blurred vision, conjunctivitis and skin rash. Rarely described are inflammation of the iris or the uvea — as a rule in people with predisposing factors — macular oedema, symptomatic corneal oedema and corneal defects, periorbital oedema, a change in the direction of lash growth that irritates the eye, and the appearance of a second row of lashes at the openings of the meibomian glands; among rare reactions outside the eye are asthma, its worsening and breathlessness, along with a local skin reaction on the eyelids and darkening of their skin. Very rarely, deepening of the eyelid sulcus from changes around the orbit, unstable angina and chest pain were observed. With unknown frequency, herpetic keratitis, headache and dizziness, palpitations, muscle and joint pain and iris cyst have been reported. There are no data on the use of this presentation in children and adolescents.
Overdose
Overdosing eye drops is difficult, and the consequences of a local excess are limited to irritation of the eye and reddening of the conjunctiva: no other ocular reactions linked to overdose are known. The scenario with real practical meaning is a different one, accidental swallowing of the contents. A bottle intended for one month of treatment contains 125 µg of latanoprost and a three-month bottle 300 µg, and more than 90% of the substance is inactivated on its very first pass through the liver.
Experiments show the order of magnitude. An intravenous infusion of 3 µg per kilogram of body weight in healthy volunteers produced mean plasma concentrations 200 times higher than during ordinary treatment and caused no symptoms at all; a dose of 5.5 to 10 µg per kilogram led to nausea, abdominal pain, dizziness, fatigue, hot flushes and sweating. In monkeys, intravenous administration of up to 500 µg per kilogram had no material effect on the cardiovascular system but was accompanied by transient bronchospasm; in patients with moderate bronchial asthma, instilling into the eye a dose seven times the therapeutic one did not provoke bronchospasm. There is no specific antidote: an overdose is treated symptomatically.
How to get a Monoprost prescription online
Monoprost is dispensed on prescription, and at e-zdrowie.com the prescription can be obtained remotely. You fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the drops against it. The format is most useful for continuing treatment that was settled long ago: glaucoma requires constant instillation, and a supply of drops runs out predictably.
Choosing the treatment in the first place is another matter: glaucoma is diagnosed by measuring intraocular pressure, examining the optic disc and testing the visual field, and a questionnaire cannot replace those examinations. So state in it who prescribed Monoprost and when, what pressure readings were recorded at the last appointment and when the visual field was last checked. Be sure to mention eye operations, cataract surgery among them, herpetic damage to the cornea, diabetes with retinopathy, bronchial asthma, pregnancy or breastfeeding, and also every other eye drop you use — particularly if another prostaglandin analogue is among them.
