Sandoz Canada Inc. Date of Preparation: 145 Jules-Leger February 07, 2008 Boucherville, QC, Canada J4B 7K8
Table of Contents
SUMMARY PRODUCT INFORMATION 3
INDICATIONS AND CLINICAL USE 3
CONTRAINDICATIONS 3
WARNINGS AND PRECAUTIONS 3
ADVERSE REACTIONS 5
DRUG INTERACTIONS 7
DOSAGE AND ADMINISTRATION 7
OVERDOSAGE 8
ACTION AND CLINICAL PHARMACOLOGY 8
STORAGE AND STABILITY 9
SPECIAL HANDLING INSTRUCTIONS 9
DOSAGE FORMS, COMPOSITION AND PACKAGING 9
PHARMACEUTICAL INFORMATION 11
CLINICAL TRIALS 12
DETAILED PHARMACOLOGY 11
MICROBIOLOGY 12
TOXICOLOGY 14
REFERENCES 18
PrSandoz(r) Brimonidine Professed Standard (Brimonidine Tartrate Ophthalmic Solution 0.2%) | ||
|---|---|---|
| Route of Administration | Dosage Form/ Strength | Clinically Relevant Nonmedicinal Ingredients |
| Topical | Ophthalmic Solution/ 0.2% | 0.005% benzalkonium chloride as preservative. For a complete listing see DOSAGE FORMS, COMPOSITION AND PACKAGING section . |
Sandoz Brimonidine (Brimonidine Tartrate Ophthalmic Solution 0.2%) is indicated for the control of IOP (Intraocular Pressure) in patients with chronic open-angle glaucoma or ocular hypertension.
Geriatrics (>65 years of age):
No data is available
Pediatrics (0-18 years of age):
The use of Sandoz Brimonidine in pediatric patients is currently not recommended.
Sandoz Brimonidine is contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication. It is also contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy.
Sandoz Brimonidine should be used with caution in patients with known hypersensitivity to other alpha-adrenoceptor agonists. Sandoz Brimonidine as with other similar medications can potentially cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential for a decrease in mental alertness. The preservative in Sandoz Brimonidine, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after instilling Sandoz Brimonidine to insert soft contact lenses.
No compound-related carcinogenic effects were observed in 21 months and 2 year studies in mice and rats given oral doses of 2.5 mg base/kg/day and 1.0 mg base/kg/day, respectively. These oral doses are approximately 830 and 330 times greater, respectively, than the maximum recommended human daily ophthalmic dosage for Brimonidine Tartrate Ophthalmic Solution % (0.003 mg base/kg/day) based on a 60 kg human. Brimonidine was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, host-mediated assay, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, cytogenic studies in mice and dominant lethal assay.
Although Brimonidine Tartrate Ophthalmic Solution 0.2% 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 Tartrate Ophthalmic Solution 0.2% has not been studied in patients with hepatic or renal impairment; caution should be exercised in treating such patients.
Brimonidine Tartrate Ophthalmic Solution 0.2% should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangiitis obliterans.
Teratogenicity studies showed no adverse effects in rats and rabbits when oral doses (1.65 mg base/kg/day and 3.33 mg base/kg/day) were administered at approximately 550 and 1 110 times, respectively, the maximum recommended human daily ophthalmic dosage for Brimonidine Tartrate Ophthalmic Solution 0.2% (based on a 60 kg human).
There are no studies of Brimonidine Tartrate Ophthalmic Solution 0.2% in pregnant women. However, in animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent (ratio of drug-related material in fetal: maternal blood = 0.1-0.3). Drug-derived material was eliminated from fetal tissues by 24 hours post-dose. Sandoz Brimonidine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
It is not known whether brimonidine is excreted in human milk, although in animal studies, brimonidine has been shown to be excreted in breast milk. During treatment with Sandoz Brimonidine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
. Several serious adverse reactions have been reported in association with the administration of Brimonidine Tartrate Ophthalmic Solution 0.2% to infants in the age range of 28 days to 3 months. These reactions included: bradycardia, hypotension, hypothermia, hypotonia, apnea, dyspnea, hypoventilation, cyanosis and lethargy resulting in hospitalization. Upon discontinuation of Brimonidine Tartrate Ophthalmic Solution 0.2% the infants recovered without sequelae (see
).
No data is available
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Adverse Drug Reaction Overview Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
Table 1 - Most Frequent Adverse Drug Reactions
| Brimonidine Tartrate Ophthalmic Solution 0.2% N=717 (%) | |
| Ears/Nose/Throat | 25.8% |
| Oral Dryness | |
| Ocular Hyperemia | 24.8% |
| Burning and Stinging | 22.5% |
| Blurring | 17.3% |
| Corneal Straining/Erosion | 10.0% |
| Ocular Allergic Reactions | 9.9% |
| Ocular Pruritus | 9.8% |
| Conjuctival Follicles | 9.6% |
| Neurologic | |
| Headache | 16.3% |
| Foreign Body Sensation | 15.5% |
| Fatigue/Drowsiness | 15.2% |
Events occurring less frequently included photophobia [7.4%], ocular dryness [7.0%], eyelid erythema [6.1%], ocular ache/pain [6.0%], upper respiratory symptom [6.0%], tearing [5.6%], conjunctival edema [5.3%], eyelid edema [4.9%], dizziness [4.2%], conjunctival blanching [3.8%], blepharitis [3.6%], ocular irritation [3.1%], gastrointestinal symptoms [3.1%], asthenia [2.8%], abnormal vision [2.6%], abnormal taste [1.4%], conjunctival discharge [1.4%], conjunctival papillae [1.0%] and nasal dryness [1.0%].
Less Common Clinical Trial Adverse Drug Reactions (<1%)
The following adverse reactions were reported infrequently (<1%): depression [0.8%], systemic allergic reactions [0.8%] and palpitations [0.4%].
Abnormal Hematologic and Clinical Chemistry Findings
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Postmarket Adverse Drug Reactions
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Although specific drug interaction studies have not been conducted with Brimonidine Tartrate Ophthalmic Solution 0.2%, the possibility of an additive or potential effect with CNS depressants (alcohol, barbiturates, opiates, sedatives or anesthetics) should be considered. Brimonidine Tartrate Ophthalmic Solution 0.2% did not have clinically significant effects on pulse and blood pressure in chronic clinical studies. However, since alpha-agonists, as a class, may reduce pulse and blood pressure, caution in the concomitant use of drugs such as beta- blockers (ophthalmic and/or systemic), antihypertensives and/or cardiac glycosides is advised. Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with Brimonidine Tartrate Ophthalmic Solution 0.2% can lead to an interference in IOP-lowering effect. No data are available on the level of circulating catecholamines after Brimonidine Tartrate Ophthalmic Solution 0.2% is instilled. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.
Interactions with food have not been established.
Interactions with herbal products have not been established.
Interactions with laboratory tests have not been established.
The preservative in Sandoz Brimonidine, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should remove their contact lenses prior to using Sandoz Brimonidine and wait at least 15 minutes after instilling Sandoz Brimonidine to insert soft contact lenses.
The recommended dose is one drop of Sandoz Brimonidine in the affected eye(s) twice daily (doses instilled approximately 12 hours apart).
If you forget to apply your eye drops at your regular time, simply apply them as soon as you remember. Then go back to the original schedule as directed by your doctor. Don't try to catch up on missed drops by applying more than one dose at a time.
The recommended dose is one drop of Sandoz Brimonidine in the affected eye(s) twice daily (doses instilled approximately 12 hours apart).
No data are available on overdosage of Brimonidine Tartrate Ophthalmic Solution 0.2% in humans. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained. Evacuation of the stomach should be considered during the first few hours after an overdosage. For management of a suspected drug overdose, contact your regional Poison Control Centre.
Brimonidine tartrate is a relatively selective alpha-adrenergic receptor agonist that in radioligand binding assays and in functional assays is approximately 1 000 times more selective for the alpha-2 adrenoceptor than the alpha-l adrenoceptor. This selectivity results in the absence of vasoconstriction in micro vessels associated with human retinal xenografts. Topical administration of brimonidine decreases intraocular pressure (IOP) in humans. When used as directed, Brimonidine Tartrate Ophthalmic Solution 0.2% reduces elevated IOP with minimal effect on cardiovascular parameters. Brimonidine Tartrate Ophthalmic Solution 0.2% has a rapid onset of action with the peak ocular hypotensive effect occurring at approximately two hours post-dosing. The duration of effect is 12 hours or greater. Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action. Brimonidine Tartrate Ophthalmic Solution 0.2% lowers IOP by reducing aqueous humour production and increasing uveoscleral outflow.
Brimonidine Tartrate Ophthalmic Solution 0.2% has no effect on pulmonary function or exercise- induced tachycardia. The cardiovascular effects of Brimonidine Tartrate Ophthalmic Solution 0.2% during exercise in normal volunteers were found to be limited to a slight suppression of systolic blood pressure, which was clinically insignificant, during the recovery period following a treadmill test.
After ocular administration of Brimonidine Tartrate Ophthalmic Solution 0.2% twice daily (both eyes) in humans for 10 days, plasma concentrations were low (mean Cmax = 0.06 ng/mL). With the Brimonidine Tartrate Ophthalmic Solution concentrations, plasma brimonidine levels peaked within 1 to 4 hours and declined with a systemic half-life of approximately 3 hours. In humans, brimonidine is eliminated rapidly via extensive systemic metabolism: there is no marked systemic accumulation after multiple dosing. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites. Approximately 87% of an orally-administered radioactive dose was eliminated within 120 hours with 74% found in the urine in the first 96 hours.
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Sandoz Brimonidine (Brimonidine Tartrate Ophthalmic Solution 0.2%) should be stored between 15 and 30oC. Keep out of reach of children.
Sandoz Brimonidine (Brimonidine Tartrate Ophthalmic Solution 0.2%). Each mL of Sandoz Brimonidine contains brimonidine tartrate 2.0 mg with the following nonmedicinal ingredients: benzalkonium chloride 0.0050% (as preservative), dihydrate sodium citrate, monohydrate citric acid, polyvinyl alcohol, purified water, hydrochloric acid and/or sodium hydroxide to adjust pH. Sandoz Brimonidine is supplied in white, opaque, sterile, plastic dropper bottles. Sandoz Brimonidine (Brimonidine Tartrate Ophthalmic Solution 0.2%) is supplied in boxes of 1 x 5 mL (in a 10 mL bottle) and 1 x 10 mL (in a 15 mL bottle).