Bimatoprost + Timolol (Bimatoprostum + Tymololum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Beta-blockers

Prostaglandins, thromboxanes, leukotrienes and their antagonists

Included in the formulation
  • Ganfort®
    drops d / eye 
    Allergen Pharmaceuticals Airland     Ireland
    • АТХ:

    S.01.E.D.51   Timolol in combination with other drugs

    Pharmacodynamics:

    Combined medicinal product, included in its composition bimatoprost and timolol reduce intraocular pressure due to the combined interaction, leading to a much more pronounced hypotensive effect compared to the effect of each of the components alone.

    Bimatoprost refers to synthetic proteams, by chemical structure is similar to prostaglandin F2a (PGF2a). Bimatoprost does not affect any of the known types of prostaglandin receptors. The hypotensive effect of bimatoprost is due to increased outflow of intraocular fluid through the trabeculae and the uveoscleral pathway of the eye.

    Timolol is a non-selective beta-blocker, it does not possess internal sympathomimetic and membrane-stabilizing activity.

    Timolol reduces intraocular pressure by reducing the formation of aqueous humor. The exact mechanism of action is not established, it may be associated with inhibition of the synthesis of cyclic adenosine monophosphate and is caused by endogenous stimulation of beta-adrenergic receptors.

    Pharmacokinetics:

    Systemic absorption of the drug is minimal, it does not differ either with combined treatment or with instillation of each component of the drug alone.

    In two studies of 12 months duration, no systemic cumulation of any of the active substances was noted.

    Bimatoprost

    In studies in vitro shown, that bimatoprost penetrates the iris and sclera. When instillation 0.03% solution of bimatoprost by 1 drop in both eyes once a day for 2 weeks Cmax Bimatoprost in blood plasma is reached within 10 minutes after application, and within 1.5 hours its concentration in blood plasma is reduced to the lower limit of detection (0.025 ng / ml). Average values ​​of Cmax and the area under the concentration-time curve (AUC0-24 h) of bimatoprost were close on the 7th and 14th day of administration, and were 0.08 ng / ml and 0.09 ng × h / ml, respectively, indicating that the equilibrium concentration of bimatoprost was reached during the first week of use.

    Bimatoprost is moderately distributed in tissues, and the systemic volume of distribution when the equilibrium concentration of the drug is reached is 0.67 l / kg. Bimatoprost is mainly in the blood plasma. The association of bimatoprost with plasma proteins is approximately 88%. Bimatoprost is subjected to oxidation, N-deethylation and glucuronation with the formation of various metabolites.

    Bimatoprost is excreted mainly by the kidneys. About 67% of the drug, injected intravenously to healthy volunteers, was excreted in the urine, and 25% - through the gastrointestinal tract. The half-life of bimatoprost, determined after its intravenous administration, was approximately 45 minutes; and the total ground clearance is 1.5 l / h / kg.

    In elderly patients

    When bimatoprost is applied 2 times a day, the mean AUC0-24 h in elderly patients is 0.0634 ng · h / ml, which significantly exceeds the value of this parameter in healthy young people - 0.0218 ng · h / ml.

    Nevertheless, this difference is not of clinical importance, since the systemic exposure of bimatoprost in its local application in elderly patients and healthy young people remains very low. Cumulation of bimatoprost in the systemic circulation is not observed, the safety profile is not different in elderly patients and young people.

    Timolol

    In patients who underwent surgical cataract treatment, after instillation of eye drops in the form of a 0.5% solution, Cmax Timolol in the intraocular fluid after 1 h was 898 ng / ml. Some of the drug enters the systemic circulation, and is metabolized in the liver. The half-life of timolol is about 4-6 hours. A part of timolol, subjected to metabolism in the liver, is excreted through the gastrointestinal tract, and the other part and metabolites are excreted by the kidneys. Timolol to a small extent binds to blood plasma proteins.

    Indications:

    Decrease in intraocular pressure in patients with open-angle glaucoma and intraocular hypertension with insufficient effectiveness of topical application of beta-adrenoblockers and prostaglandin analogues.

    ICD-10

    VII.H40-H42.H40.0   Suspicion of glaucoma

    VII.H40-H42.H40.1   Primary open angle glaucoma

    Contraindications:

    Hypersensitivity to the components of the drug; a syndrome of increased reactivity of the respiratory tract, including bronchial asthma in the acute stage and previous episodes in history, severe chronic obstructive pulmonary disease; sinus bradycardia, atrioventricular blockade of II and III degrees,clinically significant heart failure, cardiogenic shock; age to 18 years; pregnancy, the period of breastfeeding.

    Carefully:

    Dysfunction of the liver and kidneys (the drug is not sufficiently studied in this category of patients).

    In patients with risk factors for edema of the macula (for example, with aphakia, pseudophakia, lens rupture).

    In patients with diabetes mellitus (unstable flow) and impaired glucose tolerance, as the beta-blocker included in the drug timolol can mask signs of hypoglycemia.

    In patients with inflammatory changes in the eyes, neovascular, inflammatory, occlusive glaucoma, congenital glaucoma or narrow-angle glaucoma (no data on efficacy and safety).

    Pregnancy and lactation:

    Contraindicated in pregnancy and lactation.

    Dosing and Administration:

    Recommended doses in adults (including elderly patients): 1 drop is instilled in the conjunctival sac of the affected eye 1 time per day in the morning.

    If the administration of the drug is missed once, the drug is administered the next day.Do not exceed the dose - 1 injection once a day. If you use more than 2 drugs, you need to make a five-minute break between each instillation.

    Side effects:

    From the side of the organ of vision: allergic conjunctivitis, cataract, darkening of the eyelashes, increased pigmentation of the iris, blepharospasm, retraction of the eyelids, bleeding in the retina of the eye, uveitis, decreased sensitivity of the cornea, diplopia, ptosis, retinal detachment (after surgical treatment), refraction change (due to abolition of miotic agents in some cases), keratitis.

    Mental disorders: Insomnia, nightmarish dreams, decreased libido.

    From the central nervous system: myasthenia gravis, paresthesia, ischemia of the brain.

    From the organ of hearing and the vestibular apparatus: noise in ears.

    From the cardiovascular system: heart block, cardiac arrest, heart rhythm disturbances, loss of consciousness, bradycardia, heart failure, congestive heart failure; reduction in blood pressure, chest pain, cerebral blood flow disorder, intermittent claudication, Raynaud's syndrome, cold extremities, palpitations.

    From the respiratory system: bronchospasm (mainly in individuals with episodes of bronchospasm in the anamnesis), dyspnea, cough.

    From the gastrointestinal tract: nausea, diarrhea, dyspepsia, dryness of the oral mucosa.

    From the skin and subcutaneous fat: alopecia, psoriasis-like rashes, exacerbation of psoriasis.

    From the side of the musculoskeletal system and connective tissue: systemic lupus erythematosus.

    From the urinary system: Peyronie's disease.

    Others: edema, pain in the chest, fatigue.

    Overdose:

    No cases of drug overdose have been reported; When administered in the form of eye drops, an overdose is unlikely.

    Bimatoprost

    If the product is inadvertently ingested orally, the following information may be useful: no symptoms of toxic effects of bimatoprost in doses up to 100 mg / kg per day during a two-week oral administration in an experiment in rats and mice. The dose applied in the study, expressed in mg / m, exceeds by 70 times the possible dose of bimatoprost in case of accidental ingestion of the contents of the preparation's bottle with a child weighing 10 kg.

    Timolol

    When an overdose of timolol, the following symptoms can occur: bradycardia, lowering of blood pressure, bronchospasm, headache, dizziness, dyspnea, cardiac arrest. In studies it is shown that timolol is not completely excreted by hemodialysis. If an overdose occurs, symptomatic therapy is necessary.

    Interaction:

    Do not use simultaneously with other eye drops.

    Special instructions:

    Like other ophthalmic drugs, this drug can enter the systemic circulation.

    Symptoms of heart failure should be compensated before starting the drug. It is necessary to regularly monitor the condition of patients with severe heart failure, determine the heart rate. When using timolol, there were reports of side effects from the cardiovascular system and respiratory organs, including deaths due to bronchospasm in patients with bronchial asthma, and also less often from heart failure.

    Beta-adrenoblockers can mask symptoms of hypoglycemia, hyperthyroidism and cause a worsening of Prinzmetal's angina,severe peripheral and central vascular disorders, as well as arterial hypotension.
    In patients with atopic manifestations in the anamnesis and severe anaphylactic reactions to various allergens, the doses of epinephrine (adrenaline), which are usually used to arrest anaphylactic reactions, against the background of the use of beta-blockers may be ineffective. In patients with liver disease of the lung, or initially increased activity of liver enzymes alanine aminotransferase, aspartate aminotransferase and / or total bilirubin, bimatoprost had no effect on liver function during the study period lasting more than 24 months.

    Before starting treatment, patients should be informed of possible eyelash growth, increased eyelid skin pigmentation and iris pigmentation, since these side effects are established during bimatoprost and drug studies. Some changes may be permanent, and may be accompanied by the appearance of differences between the eyes, if the instillations of the drug were carried out only in one eye. After the drug is discontinued, the pigmentation of the iris may remain constant.After 12 months of treatment, the incidence of iris pigmentation was noted in 0.2% of patients. And after 12 months of treatment, only bimatoprostom in the form of eye drops 1.5%, further increase in the frequency of this effect was not observed during therapy duration of 3 years. The increase in pigmentation of the iris is due to the increased production of melanocytes, and not simply by the increase in their number.

    Excipient benzalkonium chloride, which is part of the preparation, can cause irritation of the mucous membrane of the eyes and change the color of soft contact lenses. Contact lenses should be removed prior to the administration of the drug, they can be worn 15 minutes after instillation. Benzalkonium chloride can cause acute keratitis and / or toxic corneal ulcer. In this regard, it is necessary to monitor the patient's condition with frequent or prolonged treatment with a drug in individuals with dry eye syndrome and with corneal changes.

    After opening the vial, it is impossible to exclude the possibility of microbial contamination of its contents, which can lead to inflammatory lesions of the eyes. The shelf life of the drug after the first opening of the bottle is 28 days.After the expiration of the specified time, the vial should be discarded, even if the solution is not completely used.

    It is recommended to record on the cardboard pack of the drug the date of opening the vial.

    Impact on the ability to manage vehicles and mechanisms

    There may be a transient visual impairment after the administration of the drug, so the patient must wait until the vision is fully restored before proceeding to driving the car or controlling the mechanisms.

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