- Approval Id
- 918c0b0ad01ff528
- Drug Approval Emc Name
- Brinzolamide/Timolol 10 mg/ml + 5 mg/ml eye drops, suspension
- Drug Name
- Brinzolamide/Timolol 10 mg/ml + 5 mg/ml eye drops, suspension
- Company Address
- First Floor, Andrews House, College Road, Guildford, Surrey, GU1 4QB, UK
- Company Website
- https://www.zentiva.co.uk/contact/mi-form
- Company Medical Info Direct Line
- +44 (0)800 090 2408
- Company Medical Info Email
- [email protected]
- Company Customer Care Direct Line
- +44 (0)844 8793 188
- Atc Code
- S01ED51
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Zentiva Pharma UK Limited 12 New Fetter Lane London EC4A 1JP United Kingdom
- Authorisation Number
- 8. Marketing authorisation number(s) PL 17780/1148
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 05/07/2024
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Zentiva Pharma UK Limited 12 New Fetter Lane London EC4A 1JP United Kingdom
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) PL 17780/1148
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 05/07/2024
- Instruction Composition
- 2. Qualitative and quantitative composition One ml of suspension contains 10 mg brinzolamide and 5 mg timolol (as timolol maleate). Excipient(s) with known effect: One ml of suspension contains 0.0975 mg benzalkonium chloride. For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Eye drops, suspension (eye drops) White homogenous suspension, pH 7.2 (approximately).
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications Decrease of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction (see section
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Ophthalmologicals, Antiglaucoma preparation and miotics ATC code: S01ED51 Mechanism of action Brinzolamide/Timolol contains two active substances: brinzolamide and timolol maleate. These two components decrease elevated IOP primarily by reducing aqueous humour secretion, but do so by different mechanisms of action. The combined effect of these two active substances results in additional IOP reduction compared to either compound alone. Brinzolamide is a potent inhibitor of human carbonic anhydrase II (CA-II), the predominant isoenzyme in the eye. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humour secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Timolol is a non-selective adrenergic-blocking agent that has no intrinsic sympathomimetic, direct myocardial depressant or membrane-stabilising activity. Tonography and fluorophotometry studies in man suggest that its predominant action is related to reduced aqueous humour formation and a slight increase in outflow facility. Pharmacodynamic effects Clinical effects: In a twelve month, controlled clinical trial in patients with open-angle glaucoma or ocular hypertension who, in the investigator's opinion could benefit from a combination therapy, and who had baseline mean IOP of 25 to 27 mmHg, the mean IOP-lowering effect of Brinzolamide/Timolol dosed twice daily was 7 to 9 mmHg. The non-inferiority of Brinzolamide/Timolol as compared to dorzolamide 20 mg/mL + timolol 5 mg/ml in the mean IOP reduction was demonstrated across all time-points at all visits. In a six-month, controlled clinical study in patients with open-angle glaucoma or ocular hypertension and baseline mean IOP of 25 to 27 mmHg, the mean IOP-lowering effect of Brinzolamide/Timolol dosed twice daily was 8 to 9 mmHg, and was up to 3 mmHg greater than that of brinzolamide 10 mg/ml dosed twice daily and up to 2 mmHg greater than that of timolol 5 mg/mL dosed twice daily. A statistically superior reduction in mean IOP was observed compared to both brinzolamide and timolol at all time-points and visits throughout the study. In three controlled clinical trials, the ocular discomfort upon instillation of Brinzolamide/Timolol was significantly lower than that of dorzolamide 20 mg/ml + timolol 5 mg/ml. 5.2 Pharmacokinetic properties Absorption Following topical ocular administration, brinzolamide and timolol are absorbed through the cornea and into the systemic circulation. In a pharmacokinetic study, healthy subjects received oral brinzolamide (1 mg) twice daily for 2 weeks to shorten the time to reach steady-state prior to starting Brinzolamide/Timolol administration. Following twice daily dosing of Brinzolamide/Timolol for 13 weeks, red blood cell (RBC) concentrations of brinzolamide averaged 18.8 ± 3.29 μM, 18.1 ± 2.68 μM and 18.4 ± 3.01 μM at weeks 4, 10 and 15, respectively, indicating that steady-state RBC concentrations of brinzolamide were maintained. At steady state, following administration of Brinzolamide/Timolol, the mean plasma Cmax and AUC0-12h of timolol were 27 % and 28 % lower (Cmax: 0.824 ± 0.453 ng/ml; AUC0-12h: 4.71 ± 4.29 ng·h/ml), respectively, in comparison to the administration of timolol 5 mg/mL (Cmax: 1.13 ± 0.494 ng/ml; AUC0-12h:
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients Benzalkonium chloride Mannitol (E421) Carbopol 974P Poloxamer 407 Disodium edetate Sodium chloride Hydrochloric acid and/or sodium hydroxide (for pH adjustment) Water for Injection 6.2 Incompatibilities Not applicable. 6.3 Shelf life 2 years 4 weeks after first opening. 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container 10 ml white opaque low density polyethylene ophthalmic bottles with a white low density polyethylene sealed dropper tip and a white high/low density polyethylene cap with tamper proof seal, containing 5 ml white homogenous suspension. Cartons containing 1 or 3 bottles. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling No special requirements.
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition One ml of suspension contains 10 mg brinzolamide and 5 mg timolol (as timolol maleate). Excipient(s) with known effect: One ml of suspension contains 0.0975 mg benzalkonium chloride. For the full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Eye drops, suspension (eye drops) White homogenous suspension, pH 7.2 (approximately).
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications Decrease of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction (see section
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Ophthalmologicals, Antiglaucoma preparation and miotics ATC code: S01ED51 Mechanism of action Brinzolamide/Timolol contains two active substances: brinzolamide and timolol maleate. These two components decrease elevated IOP primarily by reducing aqueous humour secretion, but do so by different mechanisms of action. The combined effect of these two active substances results in additional IOP reduction compared to either compound alone. Brinzolamide is a potent inhibitor of human carbonic anhydrase II (CA-II), the predominant isoenzyme in the eye. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humour secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Timolol is a non-selective adrenergic-blocking agent that has no intrinsic sympathomimetic, direct myocardial depressant or membrane-stabilising activity. Tonography and fluorophotometry studies in man suggest that its predominant action is related to reduced aqueous humour formation and a slight increase in outflow facility. Pharmacodynamic effects Clinical effects: In a twelve month, controlled clinical trial in patients with open-angle glaucoma or ocular hypertension who, in the investigator's opinion could benefit from a combination therapy, and who had baseline mean IOP of 25 to 27 mmHg, the mean IOP-lowering effect of Brinzolamide/Timolol dosed twice daily was 7 to 9 mmHg. The non-inferiority of Brinzolamide/Timolol as compared to dorzolamide 20 mg/mL + timolol 5 mg/ml in the mean IOP reduction was demonstrated across all time-points at all visits. In a six-month, controlled clinical study in patients with open-angle glaucoma or ocular hypertension and baseline mean IOP of 25 to 27 mmHg, the mean IOP-lowering effect of Brinzolamide/Timolol dosed twice daily was 8 to 9 mmHg, and was up to 3 mmHg greater than that of brinzolamide 10 mg/ml dosed twice daily and up to 2 mmHg greater than that of timolol 5 mg/mL dosed twice daily. A statistically superior reduction in mean IOP was observed compared to both brinzolamide and timolol at all time-points and visits throughout the study. In three controlled clinical trials, the ocular discomfort upon instillation of Brinzolamide/Timolol was significantly lower than that of dorzolamide 20 mg/ml + timolol 5 mg/ml. 5.2 Pharmacokinetic properties Absorption Following topical ocular administration, brinzolamide and timolol are absorbed through the cornea and into the systemic circulation. In a pharmacokinetic study, healthy subjects received oral brinzolamide (1 mg) twice daily for 2 weeks to shorten the time to reach steady-state prior to starting Brinzolamide/Timolol administration. Following twice daily dosing of Brinzolamide/Timolol for 13 weeks, red blood cell (RBC) concentrations of brinzolamide averaged 18.8 ± 3.29 μM, 18.1 ± 2.68 μM and 18.4 ± 3.01 μM at weeks 4, 10 and 15, respectively, indicating that steady-state RBC concentrations of brinzolamide were maintained. At steady state, following administration of Brinzolamide/Timolol, the mean plasma Cmax and AUC0-12h of timolol were 27 % and 28 % lower (Cmax: 0.824 ± 0.453 ng/ml; AUC0-12h: 4.71 ± 4.29 ng·h/ml), respectively, in comparison to the administration of timolol 5 mg/mL (Cmax: 1.13 ± 0.494 ng/ml; AUC0-12h:
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients Benzalkonium chloride Mannitol (E421) Carbopol 974P Poloxamer 407 Disodium edetate Sodium chloride Hydrochloric acid and/or sodium hydroxide (for pH adjustment) Water for Injection 6.2 Incompatibilities Not applicable. 6.3 Shelf life 2 years 4 weeks after first opening. 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container 10 ml white opaque low density polyethylene ophthalmic bottles with a white low density polyethylene sealed dropper tip and a white high/low density polyethylene cap with tamper proof seal, containing 5 ml white homogenous suspension. Cartons containing 1 or 3 bottles. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling No special requirements.
- Company Detail Path
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