Each ml of Druphagan® plus Eye Drops contains 2mg of Brimonidine Tartrate and 5mg of Timolol.


Pharmacodynamic Properties

Brimonidine is an alpha-adrenoceptor agonist that is 100 fold more selective for the alpha-2 adrenoceptor than the alpha-1 adrenoceptor.

This selectivity results in no mydriasis and the absence of vasoconstriction in micro vessels associated with human retinal xenografts.

Topical application of Brimonidine Tartrate decreases intraocular pressure (IOP) in humans with minimal effect on cardiovascular or pulmonary parameters.

Brimonidine in Druphagan®plus has a rapid onset of action with peak ocular hypotensive effect seen at two hours post – dosing fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action. It is thought that brimonidine may lower ocular pressure by reducing aqueous humor formation and enhancing uveoscleral outflow.

Timolol is a beta1 and beta2 non-selective adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anaesthetic (membrane-stabilising) activity. Timolol lowers Intraocular Pressure (IOP) by reducing aqueous humour formation. The precise mechanism of action is not clearly established, but inhibition of the increased cyclic Adenosine Monophoshpate( AMP) synthesis caused by endogenous beta-adrenergic stimulation is probable.

Pharmacokinetics Properties

After ocular administration of  0.2% solution twice daily for 10days, plasma concentrations were low (mean Cmax was 0.06ng/ml). There was a slight accumulation in the blood after multiple (2 times daily for 10days) instillations.

The mean apparent half-life in the systemic circulation was approximately 3 hours in humans after topical dosing. The plasma protein binding of brimonidine after topical dosing in humans is approximately 29%.

Brimonidine binds reversibly to melanin in ocular tissues; in vitro and in vivo. Following 2 weeks of ocular instillation, the concentrations of brimonidine in iris, cilliary body and choroid-retina were 3-to 17-fold higher than those after a single dose. Accumulation does not occur in the absence of melanin


After ocular administration of a 0.5% eye drops solution in humans undergoing cataract surgery, peak timolol concentration was 898 ng/ml in the aqueous humour at one hour post-dose. Part of the dose is absorbed systemically where it is extensively metabolised in the liver. The half-life of timolol in plasma is about 7 hours. Timolol is partially metabolised by the liver with timolol and its metabolites excreted by the kidney. Timolol is not extensively bound to plasma protein.


Druphagan®plus is indicated  for the lowering of intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension who are known or thought likely to be intolerant of topical beta-blocker therapy and or in whom topical beta-blocker therapy is contraindicated. Druphagan® plus may be used as adjunctive therapy when intraocular pressure is not adequately controlled by a topical beta-blocking agent.


Druphagan® plus is contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this formulation.

Druphagan®plus is contraindicated in patients receiving Monoamine Oxidase (MAO) inhibitors therapy and patients on anti-depressants which affect nor adrenergic transmission e.g. tricyclic antidepressants and mianserin.


After application of Druphagan® plus, clinically insignificant decreases in blood pressure were noted in some patients.

Caution is advised when using drugs such as anti-hypertensive and or cardiac glycosides concomitantly with Druphagan®plus.


  • Caution should be exercised in treating patients with severe or unstable and uncontrolled cardiovascular disease.
  • Druphagan® plus should be used with caution in patients with depression, cerebral or coronary insufficiency, Reynaud’s phenomenon, orthostatic hypotension or thromboangiitis obliterans.
  • The preservatives in brimonidine tartrate, benzalkonium chloride may be absorbed by soft contact lenses. Patients wearing soft (hydrophilic) contact lenses should be instituted to wait at least 15 minutes before inserting soft contact lenses after instilling Druphagan® plus Eye Drops.






The safety of use during human pregnancy has not been established. In animal studies, brimonidine tartrate did not cause any teratogenic effects. In rabbits, brimonidine tartrate, at plasma levels higher than normal are achieved during therapy. In humans, it has been shown to cause increased preimplatation loss and postnatal growth reduction.

Druphagan® plus should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the foetus.


It is not known if brimonidine is excreted in human milk. The compound is excreted in the milk of the lactating rat. Druphagan® plus should not be used by women nursing infants.


Ocular allergic reactions such as ocular hyperaemia, ocular burning/stinging, blurring, foreign body sensation, conjuctival follicles, ocular allergic reactions and ocular pruritus.

Ocular events occurring occasionally include; corneal erosion/staining, photophobia, eyelid hyperaemia, ocular ache/pain, ocular dryness, tearing eyelid oedema, conjunctiva oedema, conjunctiva discharge and conjunctivitis.


There is no experience in adults with the unlikely case of an overdosage via the ophthalmic route. However symptoms of Druphagan® plus overdose such as hypotension, bradycardia, hypothermia and apnea have been reported in a few neonates receiving Druphagan® plus as part of medical treatment of congenital glaucoma.


One drop of Druphagan® plus Eye Drops in the affected eyes twice daily approximately 12 hours apart. No dosage adjustment is required for the use in elderly patients.

As with any eye drops, to reduce possible systemic absorption, it is recommended that the lachrymal sac be compressed at the media canthus (punctual occlusion) for one minute. This should be performed immediately following the instillation of each drop.

If more than one topical ophthalmic drug is to be used, the different drugs should be instilled 5-15 minutes apart.


Store below 30OC. Protect from light and moisture.


Druphagan® plus Eye Drops is supplied in sterile lupolen bottle containing 5ml of the ophthalmic solution.