B2 Doc
B2 Doc Uses, Dosage, Side Effects, Food Interaction and all others data.
Brimodin contains the active ingredient brimonidine. It is a relatively selective alpha-2 adrenergic receptor agonist and approximately 1000 times more selective for the alpha-2 adrenoceptor than the alpha-1 adrenoceptor.
Topical administration of brimonidine decreases intraocular pressure (IOP) in humans. When used as directed, brimonidine ophthalmic solution reduces elevated IOP with minimal effect on cardiovascular parameters.
Brimonidine has a rapid onset of action, with the peak ocular hypotensive effect occurring at approximately 2 hours post-dosing. The duration of effect is 12 hours or greater.
Fluorophotometric studies in animals and humans suggest that brimonidine has a dual mechanism of action. Brimonidine lowers IOP by reducing aqueous humor production and increasing uveoscleral outflow.
Brimonidine is a highly selective alpha-2 adrenergic receptor agonist that is 1000-fold more selective for the alpha2-adrenergic receptor than the alpha1-adrenergic receptor. This characteristic gives the drug some therapeutic advantages, since it reduces the risk of systemic side effects, such as systemic hypotension, bradycardia, and sedation. In addition, there is a reduction in the risk for developing alpha-1 mediated ocular unwanted effects, such as conjunctival blanching, mydriasis, and eyelid retraction. However, despite high alpha-2 receptor specificity, brimonidine may still produce alpha-1 adrenoceptor-mediated ocular effects, such as conjunctival vasoconstriction. Brimonidine has a peak ocular hypotensive effect occurring at two hours post-dosing. In a randomized, double-blind clinical study, ocular administration of 0.2% brimonidine in healthy volunteers resulted in a 23% reduction of mean intraocular pressure from baseline at 3 hours following administration. In comparative studies consisting of patients with open-angle glaucoma or ocular hypertension, the ocular hypotensive effect of brimonidine was maintained during treatment periods of up to 1 year.
Brimonidine mediates vasoconstrictive effects and it was shown to exhibit anti-inflammatory properties in ex vivo human skin model and in vivo inflammation models. In a clinial trials consisting of adults with moderate to severe facial erythema of rosacea, brimonidine was shown to improve the extent of redness at 3 hours after application, compared to placebo. It was shown to be a potent vasoconstrictor of human subcutaneous vessels with a diameter of less than 200 µm. In in vivo mouse inflammation models, brimonidine displayed anti-inflammatory properties by inhibiting edema. In a randomized, double-blind study, brimonidine reduced erythema for the 12 hours of the study in a dose-dependent manner.
When adminsitered systemically, brimonidine was shown to cause cardiovascular effects by decreasing blood pressure, decreasing heart and respiratory rate, and prolonging the PR interval in the electrocardiogram. This is due to the targeting of adrenoceptors by the drug. Although the clinical significance has not been established, there is evidence that brimonidine exhibits neuroprotective activity in experimental models of cerebral ischemia and optic nerve injury. In vitro studies show that brimonidine mediated protective effects on neuronal cells from kainate acid insult and on cultured retinal ganglion cells from glutamate-induced cytotoxicity, which is a possible mediator of secondary neuronal degeneration in human glaucoma. Neuroprotective actions of brimonidine were also demonstrated in rat models of acute retinal ischemia and chronic IOP elevation. It has been proposed that brimonidine may exert neuroprotective effects on the retina and optic nerve by enhancing intrinsic retinal ganglion cell survival mechanisms and/or induction of neuronal survival factors, such as bFGF. However, further investigations are needed to conclude on these possible therapeutic benefits of the drug.
Brinzolamide is a carbonic anhydrase II (CA-II) inhibitor that inhibits aqueous humor production to reduce elevated intraocular pressure.
Used in the treatment of glaucoma, brinzolamide inhibits aqueous humor formation and reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Brinzolamide can decrease intraocular pressure by approximately 16-19% in patients with elevated intraocular pressure.
| Trade Name | B2 Doc |
| Generic | Brimonidine + Brinzolamide |
| Weight | 2mg |
| Type | Doc Eye Drops |
| Therapeutic Class | |
| Manufacturer | Lupin |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
It is effective for lowering intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension.
used for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
B2 Doc is also used to associated treatment for these conditions: Increased Intra Ocular Pressure (IOP), Ocular Hypertension, Facial erythemaIncreased Intra Ocular Pressure (IOP), Ocular Hypertension
How B2 Doc 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. Brimonidine 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.
Brinzolamide is a highly specific inhibitor of CA-II, which is the main CA isoenzyme involved in the secretion of aqueous humor. Inhibition of CA in the ciliary process of the eye slows the formation of bicarbonate, and reduces sodium and fluid transport. This results in a reduction in the rate of aqueous humor secretion and the intraocular pressure. Brinzolamide is absorbed systemically following topical ocular administration. Since it has a high affinity for CA-II, brinzolamide binds extensively to red blood cells, where CA-II is primarily found. As sufficient CA-II activity remains, adverse effects resulting from the systemic inhibition of CA by brinzolamide are not observed. The metabolite N-desethyl brinzolamide is also formed. This metabolite binds to CA and accumulates in red blood cells as well. In the presence of brinzolamide, the metabolite binds mainly to carbonic anhydrase I (CA-I).
Dosage
B2 Doc 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.
Instill 1 drop in the affected eye(s) 2-3 times daily. Zolamid may be used concomitantly with other topical ophthalmic drug to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.
Side Effects
Headache; itching of eye; redness of eye or inner lining of eyelid; swelling of eyelid; tearing of eye.
Reported side effects are blurred vision and bitter, sour or unusual taste. Other side effects are blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus and rhinitis.
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
Brimonidine 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.
Brimonidine has not been studied in patients with hepatic or renal impairment; caution should be exercised in treating such patients.
Brimonidine should be used with caution in patients with depression, cerebral or coronary insufficiency.
The concomitant administration of Brinzolamide 1% ophthalmic suspension and oral carbonic anhydrase inhibitor is not recommended due to no additional benefits.If hypersensitivity reaction occurs after instillation patients should be advised to discontinue the use of Brinzolamide and consult with physicians.
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.
In patients treated with oral carbonic anhydrase inhibitors, rare instances to drug interactions have occurred with high-dose salicylate therapy. Therefore, the potential for such drug interactions should be considered in patients receiving Brinzolamide.
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
Brimonidine 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.
Absorbed into systemic circulation following topical ocular application
Half Life
Following ocular administration of 0.2% brimonidine solution, the systemic half-life was approximately 3 hours.
111 days
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
Brimonidine and its metabolites are predominantly eliminated via urinary excretion, with 74% of the total dose being found in the urine.
Pregnancy & Breastfeeding use
Pregnancy:
Brimonidine 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.
Pregnancy Category C.No adequate and well-controlled studies are established in pregnant women. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Brinzolamide is secreted in human milk or not. Caution should be exercised when Brinzolamide is administered to a nursing mother.Pediatric Use:Safety and effectiveness are not established in Pediatric patients.
Contraindication
This eye drops are contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication.Brimonidine Tartrate is also contraindicated in patients receiving monoaminase oxidase inhibitor therapy.
It is contraindicated in patients who are hypersensitive to any component of this product.
Acute Overdose
No data is available on overdosage of brimonidine ophthalmic solution in humans.
Although no human data are available, electrolyte imbalance, development of an acidosis state, and possible nervous system effects may occur following oral administration of an overdose. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
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.
- Store in a cool, dry place and protected from light.- Keep out of the reach of children.- Discard the container 4 weeks after opening.- Shake well before using.
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