Dorzolamide Ophthalmic Solution is indicated:
• As adjunctive therapy to beta-blockers,
• As monotherapy in patients unresponsive to beta-blockers or in whom beta-blockers are
contraindicated,
in the treatment of elevated intra-ocular pressure in:
• Ocular hypertension,
• Open-angle glaucoma,
• Pseudo-exfoliative glaucoma.

When used as monotherapy, the dose is one drop of Dorzolamide in the conjunctival sac of the
affected eye(s), three times daily.
When used as adjunctive therapy with an ophthalmic beta-blocker, the dose is one drop of
Dorzolamide in the conjunctival sac of the affected eye(s), two times daily.
When substituting Dorzolamide for another ophthalmic anti-glaucoma agent, discontinue the other
agent after proper dosing on one day, and start Dorzolamide on the next day.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten
minutes apart.
Patients should be instructed to wash their hands before use and avoid allowing the tip of the
container to come into contact with the eye or surrounding structures.
Patients should also be instructed that ocular solutions, if handled improperly, can become
contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and
subsequent loss of vision may result from using contaminated solutions.
Usage instructions
Please follow these instructions carefully when using Dorzolamide eye drops solution. It
is recommended that you wash your hands before putting in your eye drops.
1. You must not use the bottle if the tamper-proof seal on the bottle neck is broken before you
first use it.
2. To open the bottle unscrews the cap by turning it until the tamper-proof seal breaks.
3. Tilt your head back and pull your lower eyelid down slightly to form a pocket between your
eyelid and your eye (Fig. 1).

4. Invert the container, and press gently as shown (Fig. 2) until a single drop as instructed
by your doctor is dispensed into your eye. DO NOT TOUCH YOUR EYE OR EYELID
WITH THE TIP OF THE CONTAINER.

5. Repeat steps 3 and 4 with the other eye if instructed to do so by your doctor.
6. Re-close the bottle by turning the cap firmly immediately after use and return the bottle to the
original outer carton.
7. The dispenser tip is designed to provide a pre-measured drop; therefore, do not enlarge the hole of
the dispenser tip.
Paediatric use:
Limited clinical data in paediatric patients with administration of Dorzolamide three times a day are
available. (For information regarding paediatric dosing see section 5.1).

 

Dorzolamide is contraindicated in patients who are hypersensitive to the active substance or to any of the excipients. Dorzolamide has not been studied in patients with severe renal impairment (CrCl < 30 ml/min) or with hyperchloraemic acidosis. Because Dorzolamide and its metabolites are excreted predominantly by the kidney, Dorzolamide is therefore contra-indicated in such patients.

Dorzolamide has not been studied in patients with hepatic impairment and should therefore be used
with caution in such patients.
The management of patients with acute angle-closure glaucoma requires therapeutic interventions in
addition to ocular hypotensive agents. Dorzolamide has not been studied in patients with acute
angle-closure glaucoma.
Dorzolamide contains a sulphonamido group, which also occurs in sulphonamides and although
administered topically, is absorbed systemically. Therefore the same types of adverse reactions that
are attributable to sulphonamides may occur with topical administration, including severe reactions
such as Stevens-Johnson syndrome and toxic epidermal necrolysis. If signs of serious reactions or
hypersensitivity occur, discontinue the use of this preparation.
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 acidbase
disturbances have been observed with dorzolamide, urolithiasis has been reported infrequently.
Because dorzolamide is 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.
If allergic reactions (e.g. conjunctivitis and eyelid reactions) are observed, discontinuation of
treatment should be considered.
There is a potential for an additive effect on the known systemic effects of carbonic anhydrase
inhibition in patients receiving an oral carbonic anhydrase inhibitor and dorzolamide. The
concomitant administration of dorzolamide and oral carbonic anhydrase inhibitors is not
recommended.

Corneal oedemas and irreversible corneal decompensations have been reported in patients with preexisting
chronic corneal defects and/or a history of intra-ocular surgery while using
DORZOLAMIDE . Topical Dorzolamide should be used with caution in such patients.
Choroidal detachment concomitant with ocular hypotony have been reported after filtration
procedures with administration of aqueous suppressant therapies.
DORZOLAMIDE contains the preservative benzalkonium chloride, which may cause eye
irritation. Contact lenses should be removed prior to application and wait at least 15 minutes before
reinsertion. Benzalkonium chloride is known to discolour soft contact lenses.
Paediatric patients:
Dorzolamide has not been studied in patients less than 36 weeks gestational age and less than 1
week of age. Patients with significant renal tubular immaturity should only receive Dorzolamide
after careful consideration of the risk benefit balance because of the possible risk of metabolic
acidosis.

Specific drug interaction studies have not been performed with Dorzolamide .
In clinical studies, Dorzolamide was used concomitantly with the following medications without
evidence of adverse interactions: timolol ophthalmic solution, betaxolol ophthalmic solution and
systemic medications, including ACE-inhibitors, calcium-channel blockers, diuretics, non-steroidal
anti-inflammatory drugs including aspirin, and hormones (e.g. oestrogen, insulin, thyroxine).
Association between Dorzolamide and miotics and adrenergic agonists has not been fully evaluated
during glaucoma therapy.

Use During Pregnancy
Dorzolamide should not be used during pregnancy. No adequate clinical data in exposed
pregnancies are available. In rabbits, Dorzolamide produced teratogenic effects at maternotoxic
doses (See Section 5.3)

Use During Lactation
It is not known whether Dorzolamide is excreted in human milk. In lactating rats, decreases in the
body weight gain of offspring were observed. If treatment with Dorzolamide is required, then
lactation is not recommended.

No studies on the effects on the ability to drive and use machines have been performed. Possible
side effects such as dizziness and visual disturbances may affect the ability to drive and use
machines.

Dorzolamide was evaluated in more than 1400 individuals in controlled and uncontrolled clinical
studies. In long-term studies of 1108 patients treated with Dorzolamide as monotherapy or as
adjunctive therapy with an ophthalmic beta-blocker, the most frequent cause of discontinuation
(approximately 3%) from treatment with Dorzolamide was drug-related ocular adverse reactions,
primarily conjunctivitis and lid reactions.
The following adverse reactions have been reported either during clinical trials or during postmarketing
experience:
[Very Common: (≥ 1/10), Common: (≥ 1/100 to <1/10), Uncommon: (≥ 1/1,000 to <1/100), Rare:
(≥ 1/10,000 to <1/1,000)]
Nervous system disorders:
Common: headache
Rare: dizziness, paraesthesia
Eye disorders:
Very Common: burning and stinging,
Common: superficial punctate keratitis, tearing, conjunctivitis, eyelid inflammation, eye itching,
eyelid irritation, blurred vision
Uncommon: iridocyclitis
Rare: irritation including redness, pain, eyelid crusting, transient myopia (which resolved upon
discontinuation of therapy), corneal oedema, ocular hypotony, choroidal detachment following
filtration surgery

Respiratory, thoracic, and mediastinal disorders:
Rare: epistaxis
Gastrointestinal disorders:
Common: nausea, bitter taste
Rare: throat irritation, dry mouth
Skin and subcutaneous tissue disorders:
Rare: contact dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
Renal and urinary disorders:
Rare: urolithiasis
General disorders and administration site conditions:
Common: asthenia/fatigue
Rare: Hypersensitivity: signs and symptoms of local reactions (palpebral reactions) and systemic
allergic reactions including angioedema, urticaria and pruritus, rash, shortness of breath, rarely
bronchospasm
Laboratory findings: Dorzolamide was not associated with clinically meaningful electrolyte
disturbances.
Paediatric patients:
See 5.1.

Only limited information is available with regard to human overdose by accidental or deliberate
ingestion of Dorzolamide hydrochloride.
Symptoms
The following have been reported with oral ingestion: somnolence; topical application: nausea,
dizziness, headache, fatigue, abnormal dreams, and dysphagia.
Treatment
Treatment should be symptomatic and supportive. Electrolyte imbalance, development of an
acidotic state, and possible central nervous system effects may occur. Serum electrolyte levels
(particularly potassium) and blood pH levels should be monitored.

 

Pharmacotherapuetic group: Antiglaucoma preparations and miotics, Carbonic Anhydrase
Inhibitors, Dorzolamide, ATC code: S01EC03
Mechanism of action
Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. In
humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic
anhydrase II (CA-II) found primarily in red blood cells (RBCs) but also in other tissues. Inhibition
of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion. The
result is a reduction in intra-ocular pressure (IOP).
DORZOLAMIDE contains Dorzolamide hydrochloride, a potent inhibitor of human carbonic
anhydrase II. Following topical ocular administration, Dorzolamide reduces elevated intra-ocular
pressure, whether or not associated with glaucoma. Elevated intra-ocular pressure is a major risk
factor in the pathogenesis of optic nerve damage and visual-field loss. Dorzolamide does not cause
pupillary constriction and reduces intra-ocular pressure without side effects such as night blindness,
accommodative spasm. Dorzolamide has minimal or no effect on pulse rate or blood pressure.
Topically applied beta-adrenergic blocking agents also reduce IOP by decreasing aqueous humor
secretion but by a different mechanism of action. Studies have shown that when Dorzolamide is added to a topical beta-blocker, additional reduction in IOP is observed; this finding is consistent with the reported additive effects of beta-blockers and oral carbonic anhydrase inhibitors.

Pharmacodynamic effects
Clinical effects:
Adult Patients
In patients with glaucoma or ocular hypertension, the efficacy of Dorzolamide given t.i.d. as
monotherapy (baseline IOP ≥23 mmHg) or given b.i.d. as adjunctive therapy while receiving
ophthalmic beta-blockers (baseline IOP ≥22 mmHg) was demonstrated in large-scale clinical studies
of up to one-year duration. The IOP-lowering effect of Dorzolamide as monotherapy and as
adjunctive therapy was demonstrated throughout the day and this effect was maintained during longterm
administration. Efficacy during long-term monotherapy was similar to betaxolol and slightly
less than timolol. When used as adjunctive therapy to ophthalmic beta-blockers, Dorzolamide
demonstrated additional IOP lowering similar to pilocarpine 2% q.i.d.

Paediatric Patients
A 3-month, double-masked, active-treatment controlled, multicentre study was undertaken in 184
(122 for Dorzolamide ) paediatric patients from 1 week of age to <6 years of age with glaucoma or
elevated intraocular pressure (baseline IOP ≥ 22 mmHg) to assess the safety of DORZOLAMIDE
when administered topically t.i.d. (three times a day). Approximately half the patients in both
treatment groups were diagnosed with congenital glaucoma; other common aetiologies were Sturge
Weber syndrome, iridocorneal mesenchymal dysgenesis, aphakic patients. The distribution by age
and treatments in the monotherapy phase was as follows:

Age cohort < 2 years : 

1) Dorzolamide 2% - N=56 Age range: 1 to 23 months

2) Timolol - Timolol GS 0.25% N=27 Age range: 0.25 to 22 months

Age cohort ≥ 2 - < 6 years:

1) N=66 Age range: 2 to 6 years

2)Timolol 0.50% N=35 Age range: 2 to 6 years

Across both age cohorts approximately 70 patients received treatment for at least 61 days and
approximately 50 patients received 81-100 days of treatment.
If IOP was inadequately controlled on Dorzolamide or timolol gel-forming solution monotherapy, a
change was made to open-label therapy according to the following: 30 patients <2 years were
switched to concomitant therapy with timolol gel-forming solution 0.25% daily and Dorzolamide
2% t.i.d.; 30 patients ≥ 2 years were switched to 2% Dorzolamide /0.5% timolol fixed combination
b.i.d (twice a day).
Overall, this study did not reveal additional safety concerns in paediatric patients: approximately
26% (20% in Dorzolamide monotherapy) of paediatric patients were observed to experience drug
related adverse affects, the majority of which were local, non-serious ocular effects such as ocular
burning and stinging, injection and eye pain. A small percentage <4% was observed to have corneal
oedema or haze. Local reactions appeared similar in frequency to comparator. In post marketing
data, metabolic acidosis in the very young particularly with renal immaturity/impairment has been
reported.

Efficacy results in paediatric patients suggest that the mean IOP decrease observed in the
Dorzolamide group was comparable to the mean IOP decrease observed in the Timolol group even
if a slight numeric advantage was observed for Timolol.
Longer-term efficacy studies (>12 weeks) are not available.

 

 

Unlike oral carbonic anhydrase inhibitors, topical administration of Dorzolamide hydrochloride
allows for the active substance to exert its effects 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 disturbances or alterations in electrolytes characteristic of oral carbonic anhydrase
inhibitors.
When topically applied, Dorzolamide reaches the systemic circulation. To assess the potential for
systemic carbonic anhydrase inhibition following topical administration, active substance and
metabolite concentrations in red blood cells (RBCs) and plasma and carbonic anhydrase inhibition
in RBCs 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 substance but also inhibits a less active isoenzyme (CA-I). The
metabolite also accumulates in RBCs where it binds primarily to CA-I. Dorzolamide binds
moderately to plasma proteins (approximately 33%). Dorzolamide is primarily excreted unchanged
in the urine; the metabolite is also excreted in urine. After dosing ends, Dorzolamide washes out of
RBCs non linearly, resulting in a rapid decline of active substance concentration initially, followed
by a slower elimination phase with a half-life of about four months.
When Dorzolamide was given orally to simulate the maximum systemic exposure after long-term
topical ocular administration, steady state was reached within 13 weeks. At steady state, there was
virtually no free active substance or metabolite in plasma; CA inhibition in RBCs was less than that
anticipated to be necessary for a pharmacological effect on renal function or respiration. Similar
pharmacokinetic results were observed after chronic, topical administration of Dorzolamide.
However, some elderly patients with renal impairment (estimated CrCl 30-60 ml/min) had higher
metabolite concentrations in RBCs, but no meaningful differences in carbonic anhydrase inhibition
and no clinically significant systemic side effects were directly attributable to this finding.

The main findings in animal studies with Dorzolamide hydrochloride administered orally were
related to the pharmacological effects of systemic carbonic anhydrase inhibition. Some of these
findings were species-specific and/or were a result of metabolic acidosis. In rabbits given
maternotoxic doses of Dorzolamide associated with metabolic acidosis, malformations of the
vertebral bodies were observed.
In clinical studies, patients did not develop signs of metabolic acidosis or serum electrolyte changes
that are indicative of systemic CA inhibition. Therefore, it is not expected that the effects noted in
animal studies would be observed in patients receiving therapeutic doses of Dorzolamide.

1. Benzalkonium Chloride
2. Sodium Citrate
3. Mannitol
4. Hydroxyethyl Cellulose
5. Sodium Hydroxide 1 N and/or Hydrochloric Acid 1N to adjust pH
6. Water for Injection

Not Applicable.

2 years (Unopening) After First opining: Discard after 30 days of opening the bottle.

Do not store above 30°C
Keep out of the reach and sight of children.

5ml of Xola Ophthalmic Solution filled in 10ml of HDPE (High Density Polyethylene) opaque
bottles with LDPE nozzle and HDPE cap.

No special requirements.