Dorzolamide + Timolol

Usage

• Dorzolamide + Timolol is prescribed for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers alone. It is also used for pseudoexfoliative glaucoma.
• Pharmacological Classification: Ophthalmic carbonic anhydrase inhibitor and beta-blocker combination.
• Mechanism of Action: Dorzolamide inhibits carbonic anhydrase in the ciliary processes of the eye, reducing aqueous humor formation. Timolol is a non-selective beta-adrenergic receptor blocking agent that decreases aqueous humor production. The combined effect leads to a greater reduction in IOP than either drug alone.

Alternate Names

• Dorzolamide hydrochloride/timolol maleate
• Brand Names: Cosopt, Cosopt PF

How It Works

• Pharmacodynamics: Reduces intraocular pressure by decreasing the production of aqueous humor.
• Pharmacokinetics:
  • Absorption: Dorzolamide is absorbed systemically following topical ocular administration. Timolol is also absorbed systemically, although to a lesser extent than dorzolamide.
  • Metabolism: Dorzolamide is metabolized to a single N-desethyl metabolite that has less carbonic anhydrase inhibitory activity than the parent compound. Timolol is metabolized in the liver.
  • Elimination: Dorzolamide and its metabolite are primarily excreted unchanged in the urine. Timolol is excreted primarily by the kidneys.
• Mode of Action:
  • Dorzolamide inhibits carbonic anhydrase II in the ciliary processes, reducing bicarbonate ion formation, which subsequently decreases sodium and fluid transport, and thus aqueous humor production.
  • Timolol blocks beta-adrenergic receptors in the ciliary epithelium, leading to reduced aqueous humor production.
• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Dorzolamide inhibits carbonic anhydrase II. Timolol blocks beta-adrenergic receptors (non-selective).
• Elimination pathways: Primarily renal excretion for both dorzolamide and timolol.

Dosage

Standard Dosage

Adults:

• One drop in the affected eye(s) twice daily (morning and evening).

Children:

• 2 years and older: One drop in the affected eye(s) twice daily.
• Younger than 2 years: Safety and efficacy have not been established.

Special Cases:

• Elderly Patients: No specific dosage adjustments are typically required.
• Patients with Renal Impairment: Not recommended in severe renal impairment (CrCl < 30 mL/min). Use with caution in mild to moderate impairment.
• Patients with Hepatic Dysfunction: Use with caution.
• Patients with Comorbid Conditions: Caution in patients with asthma, COPD, cardiovascular disease, diabetes, hyperthyroidism, myasthenia gravis.

Clinical Use Cases

Dorzolamide/Timolol is not typically used in these clinical settings:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations

Dosage Adjustments:

• Adjustments based on renal function are described above. Dosage may need to be individualized based on the patient’s response and tolerability.

Side Effects

Common Side Effects:

• Blurred vision, burning/stinging, itching, redness, tearing, dry eyes, altered taste (bitter, sour, metallic), headache.

Rare but Serious Side Effects:

• Bronchospasm, bradycardia, hypotension, heart failure, syncope, severe allergic reactions (angioedema, urticaria). Corneal endothelial damage.

Long-Term Effects:

• Potential for worsening of pre-existing respiratory or cardiovascular conditions with chronic use.

Adverse Drug Reactions (ADR):

• As above, including Stevens-Johnson syndrome, toxic epidermal necrolysis.

Contraindications

• Bronchial asthma, history of bronchial asthma, severe COPD.
• Sinus bradycardia, second- or third-degree atrioventricular block, overt cardiac failure, cardiogenic shock.
• Hypersensitivity to any component of the product.
• Severe renal impairment.

Drug Interactions

• Other beta-blockers (systemic and ophthalmic): Increased risk of bradycardia, hypotension.
• CYP2D6 inhibitors: May increase timolol levels.
• Oral carbonic anhydrase inhibitors: Additive systemic effects.
• Calcium channel blockers: Additive effects on heart rate and blood pressure.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (Timolol). Dorzolamide: data limited.
• Fetal risks: Potential for bradycardia, hypotension, and respiratory depression in the neonate.
• Breastfeeding: Timolol is present in breast milk. Dorzolamide’s presence is unknown. Not recommended during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Decreases aqueous humor production.
• Side Effects: Ocular irritation, altered taste, bradycardia, hypotension, bronchospasm.
• Contraindications: Asthma/COPD, bradycardia/heart block, heart failure.
• Drug Interactions: Other beta-blockers, oral carbonic anhydrase inhibitors.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: One drop twice daily.
• Monitoring Parameters: IOP, heart rate, blood pressure, respiratory function.

Popular Combinations

• Often used as a standalone therapy, but may be combined with other IOP-lowering medications like prostaglandin analogs or alpha-agonists if additional IOP reduction is needed.

Precautions

• Monitor for respiratory and cardiovascular side effects.
• Caution in patients with diabetes, hyperthyroidism, myasthenia gravis.
• Assess renal and hepatic function before initiating therapy.
• Educate patients on proper administration technique.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Dorzolamide + Timolol?

A: One drop in the affected eye(s) twice a day.

Q2: Can Dorzolamide + Timolol be used in children?

A: Yes, in children 2 years and older.

Q3: What are the common side effects of Dorzolamide + Timolol?

A: Burning/stinging, blurred vision, altered taste, dry eyes.

Q4: Is Dorzolamide + Timolol safe during pregnancy?

A: Not recommended.

Q5: Can Dorzolamide + Timolol be used with contact lenses?

A: Remove contact lenses before instillation and wait 15 minutes before reinserting.

Q6: What should I do if I miss a dose?

A: Instill the missed dose as soon as remembered, unless it is almost time for the next dose. Do not double the dose.

Q7: How does Dorzolamide + Timolol interact with other medications?

A: Can interact with other beta-blockers, oral carbonic anhydrase inhibitors. Inform your doctor about all medications you are taking.

Q8: What are the contraindications for Dorzolamide + Timolol?

A: Asthma/COPD, severe heart conditions, hypersensitivity to the drug.

Q9: How should Dorzolamide + Timolol be stored?

A: Store at room temperature and protect from light.

Q10: Can I use Dorzolamide + Timolol if I have renal impairment?

A: Not recommended in patients with severe renal impairment. Use with caution in those with mild to moderate impairment.