Buy Combigan eye drops 5 ml
  • Buy Combigan eye drops 5 ml


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Clinical Pharmacology

Combigan - a combination drug that includes 2 active substances: brimonidine - an adrenergic mimetic, which has a stimulating effect on alpha2-adrenoreceptors, and timolol - beta-adrenergic receptor blocker. Both active substances reduce intraocular pressure (IOP) due to the combined interaction, leading to a significantly more pronounced hypotensive effect compared to the effect of each of the components separately.

Brimonidine is an alpha adrenergic receptor agonist, and it has a 1000-fold greater selectivity for alpha2-adrenergic receptors compared to alpha1-adrenoreceptors. Selectivity is expressed in the absence of mydriasis and vasoconstriction of microvasculature vessels. The hypotensive effect of brimonidine is provided by reducing the formation of intraocular fluid and increasing its outflow along the uveoscleral pathway.

Timolol is a non-selective beta-adrenergic blocker; it does not possess internal sympathomimetic and membrane stabilizing activity. Timolol reduces IOP by reducing the formation of intraocular fluid. The exact mechanism of action has not been established, it is possibly associated with inhibition of the synthesis of cyclic adenosine monophosphate (cAMP) and is caused by endogenous stimulation of beta-adrenergic receptors.


  • open-angle glaucoma;
  • ophthalmic hypertension (with insufficient effectiveness of local therapy with beta-blockers).


In 1 ml of eye drops solution contains:

Active ingredients:

  • Brimonidine tartrate - 2.0 mg / ml.
  • Timolol maleate - 6.8 mg / ml.
    • In terms of timolol - 5.0 mg / ml.

Excipients: benzalkonium chloride, sodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate monohydrate, hydrochloric acid, sodium hydroxide, water.

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Dosage and Administration

In adults, including elderly patients:

Locally, instilled in the conjunctival sac of the affected eye 1 drop 2 times / day with an interval of 12 hours.

The combination can be used with other ophthalmologic drugs to reduce intraocular pressure. If you use more than 2 drugs, you need to take a 5 minute break between instillations.

As with other eye drops, in order to reduce possible systemic absorption, a short-term (within 1 minute) pressure on the lacrimal sac in the projection area of ​​the lacrimal sac of the eye near the inner corner of the eye is recommended.

Adverse reactions

The most frequent side effects were conjunctival hyperemia of the eye (about 15% of patients) and a burning sensation of the mucous membrane of the eye (about 11% of patients). In most cases, the severity of these symptoms was weak, and therapy was canceled only in 3.4% and 0.5% of cases, respectively.

During clinical trials of the drug Combigan® The following side effects have been reported, taking into account the frequency of occurrence: very often (> 1/10); often (> 1 / 100,1 / 1000,

On the part of the organ of vision:

very often: conjunctival hyperemia of the eye, burning sensation.

often: acute burning or stabbing pain, allergic conjunctivitis, corneal erosion, superficial keratitis, eyelid itching, conjunctival folliculosis, visual disturbances, blepharitis, epiphora, dryness of the mucous membrane of the eye, discharge from the eye, pain, irritation of the mucous membrane of the eye, feeling of an alien body .

Uncommon: decreased visual acuity, conjunctival edema, follicular conjunctivitis, allergic blepharitis, conjunctivitis, floating precipitates in the vitreous humor, asthenopia, photophobia, papillary hypertrophy of the eye muscles, sore eyelids, pale conjunctiva, corneal edema, corneal infiltrates, vitreous rupture. Mental disorders: often - depression.

From the nervous system:

often - drowsiness, headache;

infrequently, dizziness, syncope.

Since the cardiovascular system:

often - increase in blood pressure;

infrequently: congestive heart failure, palpitations.

On the part of the respiratory system:

infrequently: rhinitis, dry nasal mucosa.

From the digestive system:

often - dryness of the oral mucosa;

Infrequently - the perversion of taste.

On the part of the skin and subcutaneous fat:

often - eyelid edema, eyelid skin itching, redness of the eyelid skin;

infrequently - allergic contact dermatitis.

Other violations:

often asthenic conditions.

Laboratory indicators: often - increased activity of liver enzymes.

The following side effects have been reported additionally since the appearance of the drug Combigan on the market:

Since the cardiovascular system:

The frequency is unknown - arrhythmia, bradycardia, tachycardia, lowering blood pressure.

Side effects that were observed when using one of the active ingredients, the possibility of which is not excluded when using the drug Combigan:


On the part of the organ of vision: iridocyclitis, miosis.

Mental disorders: insomnia.

On the part of the respiratory system: inflammatory diseases of the upper respiratory tract, shortness of breath.

From the digestive system: perversion of taste, dyspepsia. Other: systemic allergic reactions.


On the part of the organ of vision: decreased corneal sensitivity, diplopia, ptosis, rupture of the choroid (after filtration surgical treatment), changes in refraction (due to cancellation of miotic therapy in some cases).

Mental disorders: insomnia, nightmares, decreased libido.

The nervous system: memory loss, worsening of symptoms of myasthenia gravis, paresthesia, cerebral ischemia. From the organ of hearing: tinnitus.

Since the cardiovascular system: complete heart block, cardiac arrest.

Vascular disorders: cerebrovascular accident, intermittent claudication, Raynaud's syndrome, cold extremities. On the part of the respiratory system: bronchospasm (mainly in patients with a history of broncho-obstructive diseases), shortness of breath, cough, respiratory failure.

From the digestive system: nausea, diarrhea, dyspepsia.

On the part of the skin and subcutaneous fat: alopecia, psoriasis-like rash or exacerbation of psoriasis.

From the musculoskeletal system, connective tissue and bone tissue: systemic lupus erythematosus

Other: peripheral edema, Peyronie's disease, chest pain.


  • Renal / hepatic impairment (use of the drug is not well understood in this group of patients).
  • Depression
  • Cerebral or coronary insufficiency.
  • Raynaud's syndrome.
  • Orthostatic hypotension
  • Thromboangiitis obliterans.
  • Severe cardiovascular diseases of unstable course.
  • Diabetes.
  • Episodes of hypoglycemia (in the absence of therapy).
  • Pheochromocytoma (without prior treatment).
  • Metabolic acidosis.
  • Simultaneous use of radiopaque drugs.
  • Intravenous administration of lidocaine, blockers of "slow" calcium channels (verapamil, diltiazem) due to the risk of inhibition of atrioventricular conduction, development of bradycardia, heart failure and lowering blood pressure.
  • Simultaneous administration or dose change of drugs taken from adrenomimetic groups (isoprenaline) and adrenergic blockers (prazosin), as well as other agents that affect adrenergic transmission, due to their possible interaction with the active components of the drug or changes in their therapeutic potential.

Drug interactions

Special studies on the drug drug interaction Combigan® has not been conducted. Nevertheless, the possibility of enhancing the effect of drugs that depress the central nervous system (alcohol, barbiturates, opium derivatives, sedatives, general anesthetics) while using the drug Combigan should be considered.

Timolol may exacerbate compensatory tachycardia and increase the risk of marked reduction in blood pressure when used with general anesthetics. It is necessary to warn the anesthesiologist about the use of the drug Combigan before the upcoming operation.

With simultaneous use of timolol and epinephrine may develop mydriasis.

Beta-blockers may enhance the hypoglycemic effect of hypoglycemic drugs. They can also mask hypoglycemia.

The hypertensive reaction to the sudden cancellation of clonidine may be aggravated by the use of a beta-blocker.

Strengthening the hypotensive effect (for example, reducing heart rate) when using timolol together with quinidine is possible, due to the fact that quinidine slows down the metabolism of timolol by isoenzyme cytochrome P450, CYP2D6.

The combined use of beta-blockers with drugs for general anesthesia can hide compensatory tachycardia and increase the risk of marked reduction in blood pressure, so the anesthesiologist should be warned about the patient's use of the drug Combigan.

Cimetidine, hydralazine, ethanol can increase the concentration of timolol in the blood plasma.

It is necessary to use drugs with caution that affect the metabolism and absorption of circulating catecholamines, for example, clopromacin, methylphenidate, reserpine. Concomitant use of MAO inhibitors is contraindicated. Patients receiving MAO inhibitors can be prescribed Combigan treatment 14 days after discontinuation of the MAO inhibitor.

It was reported about the potentiation of the effects of joint use of eye drops containing timolol and ingested blockers of “slow” calcium channels, guanethidine or beta-blockers, antiarrhythmic drugs, cardiac glycosides or parasympathomimetics, which was manifested by a pronounced decrease in blood pressure and / or marked bradycardia. After applying brimonidine in very rare cases (

Pregnancy and Lactation

Controlled studies on the use of the drug Combigan in pregnant women have not been conducted.


No data on the use of brimonidine in pregnant women. Animal studies have demonstrated reproductive toxicity at high doses of the drug, with toxic effects on the mother. The degree of risk for the person is not installed.


In animal studies, reproductive toxicity has been established with the use of doses of the drug far exceeding those recommended for use in clinical practice. Epidemiological studies have not revealed congenital malformations of the fetus, but there is a known risk of intrauterine growth of the fetus when orally taking drugs of the beta-blockers group. In addition, symptoms typical for the group of beta-adrenergic blockers (bradycardia, lowering blood pressure, respiratory dyspnea and hypoglycemia) were observed in newborns in cases where beta-adrenergic blockers were used by the mother until delivery.

In this regard, if the Combigan is prescribed during pregnancy up to the moment of delivery, medical monitoring of the condition of the newborn during the first days of life is necessary.

The combination can be used during pregnancy only in case of special need.

During lactation

In preclinical studies, it has been established that brimonidine and timolol are excreted in breast milk. Breastfeeding for the period of treatment should be discontinued.

Special instructions

It is unacceptable to touch the tip of the bottle to any surfaces in order to avoid infection of the eye and the contents of the bottle. Like all ophthalmic drugs used topically, the Combigan can be absorbed systemically.

If allergic reactions occur, Combigan treatment should be discontinued.

In patients with severely impaired renal function on hemodialysis, treatment with timolol is accompanied by a pronounced decrease in blood pressure.

While taking the drug of the beta-adrenergic blocking group in patients with agonistic manifestations and severe anaphylactic reactions to various allergens in history, it is possible to reduce or lack efficacy from the administration of epinephrine in commonly used doses. Beta-blockers can also hide the symptoms of hyperthyroidism and worsen Prinzmetal's angina, vascular diseases, both peripheral and central, as well as arterial hypotension.

Signs that indicate acute hypoglycemia, in particular, tachycardia, palpitations and sweating, may be masked during therapy with beta-blockers.

If it is necessary to discontinue therapy with Combigan, as well as when treating cardiovascular diseases with beta-blockers of systemic action, therapy is gradually canceled, in order to avoid the development of heart rhythm disturbances, myocardial infarction and / or sudden death, the risk of which increases with abrupt cancellation of drugs given groups.

Auxiliary substance benzalkoniya chloride contained in the preparation Combigan®may irritate the mucous membrane of the eyes. Before installing the drug Combigan, you must remove contact lenses, they can be put on again after 15 minutes. The shelf life of the drug after the first opening of the dropper bottle is 28 days.After the specified time has elapsed, it is recommended to discard the dropper bottle, even if it still contains a residual amount of the drug. This is necessary in order to avoid the danger of infection. Patients are advised to write the date of opening the bottle on the carton.

Impact on the ability to drive vehicles and mechanisms

The combination has a negligible effect on the ability to drive vehicles and machinery. In the context of drug treatment Combigan, a possibly transient visual disturbance (indistinctness), development of episodes of weakness and drowsiness, which can have an adverse effect if the patient’s work is associated with potentially dangerous activities. If this symptom occurs, you should refrain from performing hazardous activities.



Overdose with topical administration: loss of consciousness, lowering blood pressure, bradycardia, hypothermia, cyanosis and apnea.

Overdose by accidental ingestion: in case of accidental ingestion of brimonidine, clinical manifestations included: CNS depression, short-term confusion, loss of consciousness or coma, low blood pressure, bradycardia, hypothermia, and apnea; which led to the need for urgent hospitalization in the emergency room, in some cases, tracheal intubation was performed. Reported full restoration of functions in all reported cases in the period from 6 to 24 hours. In case of an overdose caused by drugs of the alpha2-adrenergic group, the following symptoms were reported: reduction in blood pressure, asthenia, vomiting, drowsiness, sedation, bradycardia, arrhythmia, miosis, apnea, hypothermia, respiratory depression, seizures.


Symptoms of a total overdose of timolol: bradycardia, lowering blood pressure, bronchospasm, headache, dizziness, cardiac arrest. A clinical study shows that timolol is not completely eliminated by hemodialysis.

If overdose is diagnosed, symptomatic therapy is carried out.

Studies and clinical trials of Combigan (Click to expand)

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