Pharmexin

Uses

It is effective for lowering intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension.

Pharmexin is also used to associated treatment for these conditions: Increased Intra Ocular Pressure (IOP), Ocular Hypertension, Facial erythema

How Pharmexin works

In the eye, alpha-1 adrenoceptors play a role in vasoconstriction, mydriasis, eyelid retraction, and elevation of intraocular pressure (IOP) whereas alpha-2 adrenoceptors are responsible for IOP reduction via a complex Gi-coupled signaling cascade pathway. Activation of alpha-2 receptors leads to inhibition of adenylyl cyclase and reduction of cyclic AMP levels. As a result, there is a decrease in norpinephrine (NE) release at the synaptic junction, NE-induced stimulation of beta-2 adrenoceptors, and production of aqueous humor by the ciliary epithelium. An elevated IOP is the most significant risk factor for developing glaucomatous optic neuropathy, which is associated with progressive visual field loss and functional disability if left untreated. Regardless of the etiology of the disease, the aim of current therapies for glaucoma is to reduce IOP, as reduction of IOP significantly reduces the risk of progression of vision loss even when IOP is already within the normal range. When administered ophthalmically, brimonidine is rapidly absorbed into the eye, acts as an agonist at ocular alpha-2 adrenoceptors and lowers IOP via a dual mechanism of action. It is proposed that initial dosing of the drug causes a reduction in aqueous humour production and chronic dosing leads to an increase in uveoscleral outflow. Pharmexin does not affect episcleral venous pressure. By reducing IOP, brimonidine aims to reduce the likelihood of glaucomatous visual field loss in ocular hypertension, and slow the progression of visual field defect in established open-angle glaucoma. When applied topically on skin, brimonidine reduces erythema through direct vasocontriction of small arteries and veins. As brimonidine mediates a potent peripheral vasoconstrictive activity by selectively working on the alpha-2 adrenoceptors, the use of brimonidine is thought to be efficacious for the treatment of facial erythema of rosacea, which is thought to arise from vasomotor instability and abnormal vasodilation of the superficial cutaneous vasculature of the face.

Dosage

Pharmexin dosage

The recommended dose is 1 drop of ophthalmic solution in the affected eye(s) twice daily (doses taken approximately 12 hours apart).

If more than one topical ophthalmic medicine is to be used, other eye drops should not be used within 5 to 10 minutes of using this eye drops.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Side Effects

Headache; itching of eye; redness of eye or inner lining of eyelid; swelling of eyelid; tearing of eye.

Toxicity

LD₅₀ and Overdose

Oral LD₅₀ is 50 mg/kg in mice and 100 mg/kg in rats. While there is limited clinial data on brimonidine overdose in adults, some common symptoms from oral overdoses of alpha-2 adrenergic agonists include hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnoea, hypotonia, hypothermia, respiratory depression and seizure. Treatment of an oral overdose includes supportive and symptomatic therapy. Cases of brimonidine overdose have been reported in neonates, infants, and pediatric patients receiving brimonidine tartrate as part of medical treatment of congenital glaucoma or by accidental oral ingestion. In these cases, children experienced symptoms consistent with previously reported oral overdoses of alpha-2 adrenergic agonists in young children.

Nonclinical Toxicology

At oral doses of up to 2.5 and 5 mg/kg/day in pregnant rats and rabbits, brimonidine was not shown to be teratogenic during gestation days 6 through 18. Findings from various in vitro and in vivo studies, including the Ames bacterial assay, CHO cell chromosomal aberration assay, and CD-1 mice studies, did not demonstrate any mutagenic or clastogenic potential of brimonidine. There were no observable adverse effects on male or female fertility when tested at oral doses of up to 1 mg/kg, which is approximately 200 times the systemic exposure following the maximum recommended ophthalmic dose of 0.5% brimonidine.

Use in special populations

Due to limited clinical data on the use of brimonidine pregnant or breastfeeding female patients, the use of brimonidine in these patients is generally not recommended and the use should be only considered after taking into account the benefit-to-risk ratio of continuing the drug therapy in these patients. In nursing mothers, the decision should be made whether to discontinue the drug or discontinue breastfeeding. As the systemic absorption and elimination of brimonidine are not significantly affected by age, the use of brimonidine is considered safe in geriatric patients. In contrast, the use of brimonidine in infants under the age of 2 and pediatric patients under the age of 18 is strongly not recommended due to the reports of serious adverse events following ophthalmic administration of brimonidine in infants between the age of 28 days and 3 months.

Precaution

General

Pharmexin ophthalmic solution 0.2% should be used with caution in patients with known hypersensitivity to other alpha-adrenoceptor agonists.

Although brimonidine had minimal effect on blood pressure and heart rate of patients in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease.

Pharmexin has not been studied in patients with hepatic or renal impairment; caution should be exercised in treating such patients.

Pharmexin should be used with caution in patients with depression, cerebral or coronary insufficiency.

Interaction

Although specific drug interaction studies have not been conducted with brimonidine, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered.

Food Interaction

• Avoid alcohol. Alcohol intake may potentially lead to additive CNS depressant effects.

Pharmexin Alcohol interaction

[Moderate]

Topically administered alpha-2 adrenergic receptor agonists such as apraclonidine and brimonidine are systemically absorbed, with the potential for producing rare but clinically significant systemic effects.

Although the interaction has not been specifically studied, the possibility of an additive or potentiating effect with central nervous system (CNS) depressants such as alcohol, barbiturates, opiates, anxiolytics, sedatives, and anesthetics should be considered.

Additive hypotensive effects and orthostasis may also occur with some CNS depressants and other agents that have these effects, particularly during initial dosing and/or parenteral administration.

Patients receiving topical alpha-2 adrenergic receptor agonists in combination with agents that can cause CNS depression should be made aware of the potential for increased adverse effects such as drowsiness, dizziness, lightheadedness and confusion, and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

Patients should also avoid rising abruptly from a sitting or recumbent position and notify their physician if they experience orthostasis or tachycardia.

Pharmexin Disease Interaction

Moderate: cardiovascular, depression, renal/liver

Volume of Distribution

The volume of distribution of brimonidine has not been established. In animal studies, brimonidine was shown to cross the placenta and enter into the fetal circulation to a limited extent. As its lipophilicity is relatively low, brimonidine is not reported to easily cross the blood-brain barrier.

Elimination Route

Pharmexin readily penetrates the cornea following ocular administration to reach pharmacologically active concentrations in the aqueous humor and ciliary body, the putative sites of its IOP-lowering activity. Following ocular administration of 0.2% brimonidine solution, the peak plasma concentrations were achieved within 1 to 4 hours.

In a clinical study of adult subjects with facial erythema of rosacea, brimonidine was cutaneously applied on facial skin in a repeated manner. While there was no drug accumulation in plasma, the highest peak plasma concentrations (Cmax) and AUC were 46 ± 62 pg/mL and 417 ± 264 pgxhr/mL, respectively.

Half Life

Following ocular administration of 0.2% brimonidine solution, the systemic half-life was approximately 3 hours.

Clearance

The apparent clearance has not been studied. However, the systemic clearance of brimonidine is reported to be rapid. Approximately 87% of the total radioactive dose of brimonidine was shown to be eliminated within 120 hours following oral administration.

Elimination Route

Pharmexin and its metabolites are predominantly eliminated via urinary excretion, with 74% of the total dose being found in the urine.

Pregnancy & Breastfeeding use

Pregnancy:

Pharmexin has not been studied in pregnant women. Studies in animals have shown that brimonidine crosses the placenta, but very high doses have not been shown to cause harmful effects in the fetus.

Lactation:

It is not known whether brimonidine passes into human breast milk. However, it has been shown to pass into the milk of nursing animals.

Contraindication

This eye drops are contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication.Pharmexin Tartrate is also contraindicated in patients receiving monoaminase oxidase inhibitor therapy.

Acute Overdose

No data is available on overdosage of brimonidine ophthalmic solution in humans.

Storage Condition

Store in a cool, dry place & protected from light.

Keep out of reach of children.

Do not use more than 4 weeks after opening.

Innovators Monograph

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