Dorzolamide/Timolol 20 Mg/Ml + 5 Mg/Ml Eye Drops Solution
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Dorzolamide/Timolol 20 mg/ml + 5 mg/ml Eye Drops, Solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One millilitre contains 20 mg of dorzolamide as dorzolamide hydrochloride (22.26 mg) and 5 mg of timolol as timolol maleate (6.83 mg).
Excipients
Each ml contains 0.075 mg benzalkonium chloride.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Eye drops, solution.
Colourless, clear, viscous solution, free from visible particles with a pH between 5.25.7, and an osmolality of 242-323 mosmol/kg.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is indicated in th e treatment of elevated intra-o cular pressure (IOP) in p atients with open- angle glaucoma or pseudo- exfoliative glaucoma when topical beta-blocker monotherapy is not sufficient.
4.2 Posology and method of administration
The dose is one drop of Dorzolamide/Timolol in the (conjunctival sac of the) affected eye(s) two times daily.
If another topical ophthalmic agent is being used, Dorzolamide/Timolol and the other agent should be administered at least ten minutes apart.
Patients should be inst ructed to wash their h ands befor e use and a void allowing the tip of the dispensing container to come into contact with the eye or surrounding structures.
Patients should also be i nstructed that ocular solutions, if handled improperl y, can be come contaminated b y common ba cteria known to c ause oc ular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Usage instructions
1. Before using the medication for the first time , be sure the tamper seal is unbroken.
2. To open the bottle, unscrew the cap.
3. Tilt your head back and pull your lower eyelid down slightly to form a pocket between your eyelid and eye.
4. Invert the bottle, and press lightly on the sides of the bottle until a single drop is dispensed into the eye as directed by your doctor. DO NOT TOUCH YOUR EYE OR EYELID WITH THE DROPPER TIP.
5. Repeat steps 3 & 4 with the other eye if instructed to do so by your doctor.
6. Replace the cap by turning until it is firmly touching the bottle.
7. The dispenser tip is designed to provide a pre-measured drop; therefore, do not enlarge the hole of the dispenser tip.
When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity.
Paediatric use
Efficacy in paediatric patients has not been established.
Safety in paediatric patients below the age of two years has not been established. (For information regarding safety in paediatric patients >2 and < 6 years of age, see section 5.1).
4.3 Contraindications
This medicinal product is contra-indicated in patients with:
• hypersensitivity to one or both active substances or to any of the excipients.
• reactive airway disease, including bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease
• sinus bradycardia sick sinus syndrome, sino-atrial block,, second- or third-degree atrioventricular block not controlled with a pace-maker, overt cardiac failure, cardiogenic shock
• severe renal impairment (CrCl < 30 ml/min) or hyperchloraemic acidosis
The above are based on the components and are not unique to the combination.
4.4 Special warnings and precautions for use
Cardiovascular/respiratory reactions
Like other topically-applied ophthalmic agents, the active substances are absorbed systemically. Due to the beta-adrenergic component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur. The incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. To reduce the systemic absorption, see section 4.2.
Cardiac disorders
In patients with cardiovascular diseases (e.g. coronary heart disease, Prinzmetal's angina and cardiac failure) and hypotension therapy with beta-blockers should be critically assessed and therapy with other active substances should be considered. Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and of adverse reactions.
Due to their negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block.
Vascular disorders
Patients with severe peripheral circulatory disturbance/disorders (i.e. severe forms of Raynaud’s disease or Raynaud’s syndrome) should be treated with caution.
Respiratory disorders
Respiratory reactions, including death due to bronchospasm in patients with asthma, have been reported following administration of some ophthalmic beta-blockers.
Dorzolamide/Timolol should be used with caution in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only if the potential benefit outweighs the potential risk.
Hepatic impairment
Dorzolamide/Timolol has not been studied in patients with hepatic impairment and therefore should be used with caution in such patients.
Immunology and hypersensitivity
As with other topically-applied ophthalmic agents, the active substances may be absorbed systemically. Dorzolamide contains a sulphonamido group, which also occurs in sulphonamides. Therefore the same types of adverse reactions found with systemic administration of sulphonamides may occur with topical administration. If signs of serious reactions or hypersensitivity occur, discontinue use of this preparation.
Local ocular adverse effects, similar to those observed with dorzolamide hydrochloride eye drops, have been seen with Dorzolamide/Timolol. If such reactions occur, discontinuation of Dorzolamide/Timolol should be considered.
Anaphylactic reactions
While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge with such allergens and unresponsive to the usual doses of adrenaline (epinephrine) used to treat anaphylactic reactions.
Concomitant therapy
The following concomitant medication is not recommended: dorzolamide and oral carbonic anhydrase inhibitors.
The use of two topical beta-adrenergic blocking agents is not recommended (see section 4.5).
The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when timolol is given to patients already receiving a systemic beta-blocking agent. The response of these patients should be closely observed.
Withdrawal of therapy
As with systemic beta-blockers, if discontinuation of ophthalmic timolol is needed in patients with coronary heart disease, therapy should be withdrawn gradually.
Additional effects of beta-blockade Hypoglycaemia/diabetes
Beta-blockers should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia.
Beta-blockers may also mask the signs of hyperthyroidism. Abrupt withdrawal of beta-blocker therapy may precipitate a worsening of symptoms.
Therapy with beta-blockers may aggravate symptoms of myasthenia gravis.
Surgical anaesthesia
Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of adrenaline (epinephrine). The anaesthesiologist should be informed when the patient is receiving timolol.
Therapy with oral carbonic anhydrase inhibitors has been associated with urolithiasis as a result of acid-base disturbances, especially in patients with a prior history of renal calculi. Although no acid-base disturbances have been observed with Dorzolamide/Timolol, urolithiasis has been reported infrequently. Because Dorzolamide/Timolol contains a topical carbonic anhydrase inhibitor that is absorbed systemically, patients with a prior history of renal calculi may be at increased risk of urolithiasis while using Dorzolamide/Timolol.
Other
The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Dorzolamide/Timolol has not been studied in patients with acute angle-closure glaucoma.
Corneal diseases
Corneal oedema and irreversible corneal decompensation have been reported in patients with pre-existing chronic corneal defects and/or a history of intraocular surgery while using dorzolamide. Topical dorzolamide should be used with caution in such patients.
Ophthalmic beta-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.
Choroidal detachment
Choroidal detachment concomitant with ocular hypotony have been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.
As with the use of other antiglaucoma agents, diminished responsiveness to ophthalmic timolol maleate after prolonged therapy has been reported in some patients. However, in clinical studies in which 164 patients have been followed for at least three years, no significant difference in mean intra-ocular pressure has been observed after initial stabilisation.
Contact lens use
Dorzolamide/Timolol contains the preservative benzalkonium chloride, which may cause eye irritation. Avoid contact with soft contact lenses. Remove contact lenses prior to application and wait at least 15 minutes before reinsertion. Benzalkonium chloride is known to discolour soft contact lenses.
Paediatric use
See section 5.1.
4.5 Interaction with other medicinal products and other forms of interaction
Specific interaction studies have not been performed with Dorzolamide/Timolol.
No specific drug interaction studies have been performed with timolol.
However, there is a potential for additive effects resulting in hypotension and/or marked bradycardia when an ophthalmic beta-blocker solution is administered concomitantly with oral calcium channel blockers, beta-adrenergic blocking agents, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics and guanethidine, narcotics, and monoamine oxidase (MAO) inhibitors.
Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol.
Although dorzolamide/timolol alone has little or no effect on pupil size, mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally.
Beta-blockers may increase the hypoglycaemic effect of antidiabetic agents.
Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.
In clinical studies, dorzolamide/timolol was used concomitantly with the following systemic medications without evidence of adverse interactions: ACE-inhibitors, calcium channel blockers, diuretics, non-steroidal anti-inflammatory drugs including acetylsalicilic acid, and hormones (e.g. oestrogen, insulin, thyroxine).
4.6 Fertility, pregnancy and lactation
Use during pregnancy
Dorzolamide/timolol should not be used during pregnancy.
Dorzolamide
No adequate clinical data in exposed pregnancies are available. In rabbits, dorzolamide produced teratogenic effects at maternotoxic doses (see section 5.3).
Timolol
There are no adequate data for the use of timolol in pregnant women. Timolol should not be used
during pregnancy unless clearly necessary.
To reduce the systemic absorption, see section 4.2.
Epidemiological studies have not revealed malformative effects but show a risk for intra-uterine growth retardation when beta-blockers are administered by the oral route. In addition, signs and symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If dorzolamide/timolol is administered until delivery, the neonate should be carefully monitored during the first days of life.
It is not known whether dorzolamide is excreted in human milk. In lactating rats receiving dorzolamide, decreases in the body weight gain of offspring were observed. Beta-blockers are excreted in breast milk. However, at therapeutic doses of timolol in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant. To reduce the systemic absorption, see section 4.2.
If treatment with dorzolamide/timolol is required, then breastfeeding is not recommended.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. P ossible si de e ffects such as bl urred vi sion m ay affect s ome patients' ability to drive and/or operate machinery.
4.8 Undesirable effects
In clinical studies no adverse experiences specific to dorzolamide/timolol have been observed; adverse experiences have been limited to those that were reported previously with dorzolamide hydrochloride and/or timolol maleate. Like other topically applied ophthalmic drugs, timolol is absorbed into the systemic circulation. This may cause similar undesirable effects to those seen with systemic beta-blocking agents. The incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. Listed adverse reactions include reactions seen within the class of ophthalmic beta-blockers.
During clinical studies, 1,035 patients were treated with Dorzolamide/Timolol. Approximately 2.4% of all patients discontinued therapy with Dorzolamide/Timolol because of local ocular adverse reactions, approximately 1.2% of all patients discontinued because of local adverse reactions suggestive of allergy or hypersensitivity (such as lid inflammation and conjunctivitis).
The following adverse reactions have been reported with Dorzolamide/Timolol or one of its components either during clinical trials or during post-marketing experience: [Very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100) and rare (>1/10,000 to <1/1000); not known (cannot be estimated from the available data)]
Immune system disorders Dorzolamide/Timolol
Rare: signs and symptoms of systemic allergic reactions, including
angioedema, urticaria, pruritus, rash, anaphylaxis
Timolol maleate ophthalmic solution
Rare: signs and symptoms of allergic reactions including angioedema,
urticaria, localised and generalised rash, anaphylaxis Not known: pruritus
Metabolism and nutrition disorders
Timolol maleate ophthalmic solution Not known: Hypoglycaemia
Psychiatric disorders
Timolol maleate eye drops, solution Uncommon: depre ssion*
Rare: insomnia*, nightmares*, memory loss
Nervous system disorders
Dorzolamide hydrochloride eye drops, solution Common: heada che*
Rare: diz ziness*, paraesthesia*
Timolol maleate eye drops, solution Common: heada che*
Uncommon: diz ziness*, syncope*
Rare: paraesthesia*, increase in signs and symptoms of myasthenia
gravis, decreased libido*, cerebrovascular accident*, cerebral ischaemia
Eye disorders
Dorzolamide/Timolol
Very Common: burning and stinging
Common: con junctival injection, blurred vision, corneal erosion, ocular
itching, tearing
Dorzolamide hydrochloride eye drops, solution Common: eyelid inflammation*, eyelid irritation*
Uncommon: ir idocyclitis*
Rare: irritation including redness*, pain*, eyelid crusting*, transient
myopia (which resolved upon discontinuation of therapy), corneal oedema*, ocular hypotony*, choroidal detachment (following filtration surgery)*
Timolol maleate eye drops, solution
Common: signs and symptoms of ocular irritation including blepharitis*,
keratitis*, decreased corneal sensitivity, and dry eyes* Uncommon: visual disturbances including refractive changes (due to
withdrawal of miotic therapy in some cases)*
Rare: ptosis, diplopia, choroidal detachment following filtration
surgery(see section 4.4)*
Not known: itching, tearing, redness, blurred vision, corneal erosion
Ear and labyrinth disorders
Timolol maleate eye drops, solution Rare: t innitus*
Cardiac disorders
Timolol maleate eye drops, solution Uncommon: brady cardia*
Rare: chest pain*, palpitations*, oedema*, arrhythmia*, congestive heart
failure*, cardiac arrest*, heart block Not known: cardiac failure, atrioventricular block
Vascular disorders
Timolol maleate eye drops, solution
Rare: hypotension*, claudication, Raynaud’s phenomenon*, cold hands
and feet
Respiratory, thoracic, and mediastinal disorders
Dorzolamide/Timolol
Common: sinu sitis
Rare: shortness of breath, respiratory failure, rhinitis, rarely
bronchospasm
Dorzolamide hydrochloride eye drops, solution
Rare: epis taxis*
Timolol maleate eye drops, solution
Uncommon: dy spnoea*
Rare: bronchospasm (predominantly in patients with pre-existing
bronchospastic disease)*, respiratory failure, cough*
Gastro-intestinal disorders
Dorzolamide/Timolol Very Common: dysgeusia
Dorzolamide hydrochloride eye drops, solution Common: nause a*
Rare: throat irritation, dry mouth*
Timolol maleate eye drops, solution Uncommon: nause a*, dyspepsia*
Rare: diarrhoea, dry mouth*
Not known: dysgeusia, abdominal pain, vomiting
Skin and subcutaneous tissue disorders
Dorzolamide/Timolol
Rare: contact dermatitis, Stevens-Johnson syndrome, toxic epidermal
necrolysis
Dorzolamide hydrochloride eye drops, solution Rare: rash*
Timolol maleate eye drops, solution
Rare: alopecia*, psoriasiform rash or exacerbation of psoriasis*
Not known: skin rash
Musculoskeletal and connective tissue disorders
Timolol maleate eye drops, solution
Rare: systemic lupus erythematosus
Not known: myalgia
Renal and urinary disorders
Dorzolamide/Timolol Uncommon: urol ithiasis
Reproductive system and breast disorders
Timolol maleate eye drops, solution
Rare: Peyronie's disease*, decreased libido
Not known: sexual dysfunction,
General disorders and administration site disorders
Dorzolamide hydrochloride eye drops, solution Common: asth enia/fatigue*
Timolol maleate ophthalmic solution Uncommon: asth enia/fatigue*
*These adverse reactions were also observed with Dorzolamide/Timolol during postmarketing experience.
Laboratory findings
Dorzolamide/Timolol was not associated with clinically meaningful electrolyte disturbances in clinical studies.
4.9 Overdose
No dat a ar e avai lable i n hum ans i n re gard to overdose by a ccidental or deliberate ingestion of Dorzolamide/Timolol.
There h ave b een reports of ina dvertent ove rdoses with timolol ma leate ophthalmic solution resulting in s ystemic effect s simila r to those seen with systemic beta- adrenergic blocking a gents suc h as di zziness, heada che, shortness of breath, bradycardia, bronchospasm, and cardiac arrest. The most common signs and s ymptoms to be ex pected with overdoses of dorz olamide are el ectrolyte i mbalance, devel opment of an aci dotic st ate, and possi bly central nervous system effects.
Only limite d informa tion is a vailable with rega rd to huma n overdose b y accidental or d eliberate i ngestion o f dorz olamide h ydrochloride. W ith oral ingestion, somnolenc e has be en r eported. W ith topical applic ation the following have been reported: nausea, dizziness, headache, fatigue, abnormal
dreams, and dysphagia. Treatment
Treatment should be s ymptomatic and supporti ve. Se rum electrol yte levels (particularly pot assium) and blood pH levels s hould be monitored. Studies have shown that timolol does not dialyse readily.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group:
(Antiglaucoma preparations and miotics - Beta-Blocking Agents)
ATC code: S01E D51
Mechanism of action
Dorzolamide/Timolol i s comprised of two components: dorz olamide
hydrochloride and timol ol maleate. Each of thes e two components decreases elevated intra-ocular pressure by reducing aqueous humor secretion, but does so by a different mechanism of action.
Dorzolamide hydrochloride is a potent inhibitor of human carbonic anhydrase II. Inhibition of c arbonic a nhydrase in the c iliary pro cesses of the ey e decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with s ubsequent reduction in sodium and fluid transport. Timolol m aleate i s a no n-selective bet a-adrenergic r eceptor bl ocking a gent. The precise mechanism of action of timolol ma leate in low ering intra-ocular pressure is not clearly established at this time, although a fluorescein study and tonography studies indicate that the pr edominant action ma y b e rel ated to reduced aqu eous fo rmation. Howeve r, in som e studies a sli ght incr ease in outflow facility was also observed. The combined effect of these two age nts results in a dditional intra -ocular pre ssure reduc tion c ompared to either component administered alone.
Following topical administration, Dorzolamide/Timolol reduces elevated intraocular pressu re, whet her or not associ ated wi th g laucoma. El evated i ntra-ocular pressure is a m ajor risk fa ctor in the pathogenesis of optic n erve damage and glaucomatous visual fiel d loss. Dorzolamide/Timolol re duces intra-ocular pressure without the common side effects of miotics such as night blindness, accommodative spasm and pupillary constriction.
Pharmacodynamic effects Clinical effects:
Clinical studies of up to 15 months duration were conducted to comp are the IOP-lowering e ffect of Dorz olamide/Timolol b.i.d. (dosed morning and bedtime) to individuall y- and concomitantly-administered 0.5% timolol and 2.0% dorzolamide in patients with glaucoma or ocular hypertension for whom concomitant the rapy w as c onsidered a ppropriate in the trials. This inc luded both untre ated pa tients a nd pa tients ina dequately c ontrolled with timolol monotherapy. The majorit y of patients we re treated with topical beta-blocker monotherapy prior to study enrollment. In an analysis of the combined studies, the IOP-lowering effect of Dorzolamide/Timolol b.i.d. was greater than that of monotherapy with either 2% dorzolamide t.i.d. or 0.5% timolol b.i.d. The IOP-lowering effect of Dor zolamide/Timolol b.i.d. was equivalent to that of concomitant ther apy wi th dorzola mide b.i.d. and timolol b.i.d. The IOP-lowering effect of Do rzolamide/Timolol b. i.d. wa s de monstrated w hen measured at various time points thr oughout t he da y and this ef fect was maintained during long-term administration.
Paediatric use
A three month controlled study, with the primary objective of documenting the safety of 2% dorzolamide hydrochloride ophthalmic solution in children under the age of 6 years has been conducted. In this study, 30 patients under six and greater tha n or equal to two years of a ge who se I OP was not adequately controlled with mon otherapy b y dorz olamide or timolo l received Dorzolamide/Timolol in an open label phase. Efficacy in those patients has not been established. In this small group of patients, twice daily administration of Dorzolamide/Timolol was generally well tolerated with 19 patients completing the treatment period and 11 patients disc ontinuing fo r sur gery, a change i n medication, or other reasons.
5.2 Pharmacokinetic properties
Dorzolamide hydrochloride:
Unlike oral carbonic anh ydrase inhib itors, topical administratio n of dorzolamide hydrochloride allows for th e active substance to e xert its e ffects directly in the eye at substantially lower doses and therefore with less systemic exposure. In clinical trials, this resulted in a reduction in IOP without the acid-base di sturbances or al terations i n el ectrolytes ch aracteristic of oral carbonic anhydrase inhibitors.
When topicall y applied, dorz olamide r eaches t he s ystemic circul ation. To assess the potential fo r s ystemic carbonic anh ydrase inhibition following topical administration, active substance and metabolite concentrations in red blood cells (R BCs) and plasma and carbonic anh ydrase inhibition in R BCs were measured. Dorzolamide accumulates in RBCs during chronic dosing as a result of selective binding to CA-II while extremely low concentrations of free active substance in plasma are maintained. The parent active substance forms a single N-desethyl metabolite that inhibits CA-II less potently than the parent active subst ance but al so i nhibits a l ess act ive i soenzyme (C A-I). The metabolite also accumu lates in RB Cs where it binds primaril y to CA- I. Dorzolamide binds moderatel y to pl asma p roteins (approx imately 33%). Dorzolamide is prima rily excreted unchanged in the urine; the metabolite is also ex creted i n uri ne. After dosi ng ends, dorz olamide washes out of RBCs non-linearly, r esulting i n a rapid d ecline of active substanceconcent ration
initially, followed by a slower elimination phase with a half-life of about four months.
When dorzola mide was g iven ora lly to simul ate the ma ximum s ystemic exposure after lon g-term topical ocul ar administration, stead y state was reached wi thin 13 weeks. At st eady st ate, t here was vi rtually no fr ee a ctive substance or metabolite in plasma; CA inhibition in RB Cs was less than that anticipated to be n ecessary for a pha rmacological effect on r enal function or respiration. Similar pharmac okinetic results w ere obs erved after chronic, topical administration of dorzola mide hydrochloride. However, some eld erly patients with re nal impa irment (e stimated CrCl 30-60 ml/min) ha d hi gher metabolite concentrations in RBCs, but no meaningful differences in carbonic anhydrase inhibition a nd no c linically significant systemic side effects were directly attributable to this finding.
Timolol maleate:
In a stud y of plasma active substan ce conc entration in si x subjects, the systemic exposure to timolol wa s de termined following twic e da ily to pical administration of timolo l maleate opht halmic solution 0.5%. The mean peak plasma concentration following morning dosing was 0.46 ng/ml and following afternoon dosing was 0.35 ng/ml.
5.3 Preclinical safety data
The ocular and s ystemic safety profile of the in dividual components is well established.
Dorzolamide
In rabbits given maternotoxic doses of dorzolamide associated with metabolic acidosis, malformations of the vertebral bodies were observed.
Timolol
Animal studies have not shown teratogenic effect.
Furthermore, no adverse ocular effects were seen in animals treated topically with dorzolamide h ydrochloride and timolol maleate ophthalmic solution or with c oncomitantly-administered dorzola mide h ydrochloride a nd timolol maleate. In vitro and in vivo studies with e ach of the components did not reveal a mutagenic potential. Therefore, no significant risk for human safety is expected with therapeutic doses of Dorzolamide/Timolol.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Hydroxyethyl cellulose, Mannitol
Sodium citrate dihydrate Sodium hydroxide (to adjust pH) Benzalkonium chloride Water for injections
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
After first opening: 28 days maximum
6.4 Special precautions for storage
Store below 30°C.
Do not refrigerate or freeze.
6.5 Nature and contents of container
<Dorzolamide/Timolol 20 mg /ml + 5 mg /ml E ye drops, solution a nd associated names> is filled into a 5 ml fill volume capacity white LDPE bottle equipped with a white L DPE droppe r app licator and closed with a yellow HDPE tamper proof cap.
Pack sizes:
1 x 5 ml (a single 5 ml bottle)
2 x 5 ml (two 5 ml bottles)
3 x 5 ml (three 5 ml bottles)
6 x 5 ml (six 5 ml bottles)
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
TEVA UK Limited
Brampton Road, Hampden Park, Eastbourne, East Sussex, BN22 9AG
8 MARKETING AUTHORISATION NUMBER(S)
PL 00289/1130
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22/04/2010
10 DATE OF REVISION OF THE TEXT
21/06/2013