Usage
Pilocarpine + Timolol ophthalmic solution is prescribed for the reduction of elevated intraocular pressure (IOP) in patients with chronic open-angle glaucoma or ocular hypertension. It combines two different classes of drugs to achieve its therapeutic effect:
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Pilocarpine: A miotic agent, belonging to the class of cholinergic agonists, directly stimulates the muscarinic receptors in the eye, causing contraction of the ciliary muscle. This increases the outflow of aqueous humor through the trabecular meshwork.
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Timolol: A beta-adrenergic blocker that reduces the production of aqueous humor.
Alternate Names
This combination is often referred to as Timolol + Pilocarpine. A common brand name is Timpilo®.
How It Works
Pharmacodynamics: Pilocarpine, a cholinergic agonist, acts directly on muscarinic receptors in the eye, leading to miosis (pupillary constriction), increased trabecular outflow of aqueous humor, and a subsequent decrease in IOP. Timolol, a non-selective beta-blocker, inhibits beta-adrenergic receptors, reducing aqueous humor production and thereby lowering IOP.
Pharmacokinetics: Both drugs are absorbed systemically following topical ophthalmic administration. Timolol reaches peak plasma concentrations within 1 to 2 hours and is metabolized in the liver. It is excreted primarily through the kidneys. Pilocarpine’s systemic absorption is generally low after topical application, with a rapid onset of action (10-30 minutes). Pilocarpine is metabolized in the liver and excreted primarily by the kidneys.
Mode of Action: Pilocarpine directly stimulates muscarinic receptors, specifically M3 subtype, on the ciliary muscle and trabecular meshwork cells. This stimulation leads to contraction of the ciliary muscle, widening the spaces within the trabecular meshwork, facilitating the outflow of aqueous humor. Timolol blocks the action of catecholamines, particularly epinephrine, on beta-adrenergic receptors (primarily beta-2) in the ciliary epithelium, reducing the formation of aqueous humor.
Dosage
Standard Dosage
Adults:
One drop of Timpilo® 2 (0.5% Timolol + 2% Pilocarpine) is instilled into the affected eye(s) twice daily. If IOP control is inadequate, the dosage may be increased to one drop of Timpilo® 4 (0.5% Timolol + 4% Pilocarpine) twice daily.
Children:
The safety and efficacy of Pilocarpine + Timolol have not been established in children.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary based on individual patient responses.
- Patients with Renal Impairment: Dosage modifications are usually not required unless significant renal dysfunction is present.
- Patients with Hepatic Dysfunction: Dosage adjustments may be needed in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with diabetes, cardiovascular disease, and respiratory conditions.
Clinical Use Cases
The combination of Pilocarpine and Timolol is specifically indicated for the long-term management of glaucoma and ocular hypertension. It is not typically used in acute clinical settings like intubation, surgery, mechanical ventilation, ICU, or emergency situations.
Dosage Adjustments
Dose adjustments are based on the patient’s IOP response. If the target IOP is not achieved with Timpilo® 2, the concentration of Pilocarpine can be increased to 4%.
Side Effects
Common Side Effects
Blurred vision, eye irritation, stinging, burning, tearing, headache, brow ache, changes in near vision.
Rare but Serious Side Effects
Bradycardia, hypotension, bronchospasm, retinal detachment, heart failure.
Long-Term Effects
Cataracts, corneal endothelial damage.
Adverse Drug Reactions (ADR)
Significant ADRs are rare but can include severe bradycardia, bronchospasm requiring urgent medical attention, and allergic reactions.
Contraindications
Asthma, bronchitis, severe chronic obstructive pulmonary disease (COPD), sinus bradycardia, second or third-degree atrioventricular block, cardiac failure, hypersensitivity to components.
Drug Interactions
Other beta-blockers (systemic and topical), calcium channel blockers, digitalis glycosides, quinidine, fluoxetine, paroxetine.
Pregnancy and Breastfeeding
Timolol has been detected in human milk; use with caution in breastfeeding mothers and only if clinically needed. Pilocarpine + Timolol is generally avoided in pregnancy due to the potential risks of beta-blocker exposure to the fetus.
Drug Profile Summary
- Mechanism of Action: Reduces IOP by increasing aqueous humor outflow (Pilocarpine) and decreasing its production (Timolol).
- Side Effects: Blurred vision, eye irritation, stinging, headache, brow ache, bradycardia, bronchospasm.
- Contraindications: Asthma, COPD, bradycardia, AV block, cardiac failure.
- Drug Interactions: Other beta-blockers, calcium channel blockers.
- Pregnancy & Breastfeeding: Use with caution; potential for adverse effects in infants.
- Dosage: 1 drop Timpilo® 2 twice daily, increased to Timpilo® 4 if needed.
- Monitoring Parameters: IOP, heart rate, respiratory function.
Popular Combinations
Pilocarpine + Timolol itself represents a popular fixed-dose combination. Sometimes, it may be combined with other IOP-lowering medications if necessary, but this requires careful monitoring.
Precautions
- General Precautions: Monitor IOP regularly, assess cardiovascular and respiratory function.
- Specific Populations: Use cautiously in pregnant/breastfeeding women, elderly, and patients with renal/hepatic impairment.
- Lifestyle Considerations: Limit alcohol, avoid driving immediately after application if vision is blurred.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pilocarpine + Timolol?
A: The standard dosage for adults is one drop of Timpilo® 2 (0.5% Timolol + 2% Pilocarpine) instilled in the affected eye(s) twice a day. This can be increased to one drop of Timpilo® 4 (0.5% Timolol + 4% Pilocarpine) twice daily if needed.
Q2: How do I transition a patient from another glaucoma medication to Pilocarpine + Timolol?
A: If switching from another topical beta-blocker, discontinue the previous medication after a full day’s dosage and start Pilocarpine + Timolol the following day. If transitioning from a different class of glaucoma medication, continue the current drug and add Pilocarpine + Timolol. The next day, discontinue the previous drug and continue with Pilocarpine + Timolol.
Q3: What are the common side effects patients should be aware of?
A: Common side effects include blurred vision, eye irritation, stinging, burning, tearing, headache, and brow ache.
Q4: Can Pilocarpine + Timolol be used in patients with asthma?
A: No, Pilocarpine + Timolol is contraindicated in patients with asthma or a history of asthma, as Timolol, a beta-blocker, can trigger bronchospasm.
Q5: How does Pilocarpine + Timolol affect pupil size?
A: Pilocarpine causes miosis (pupillary constriction). While timolol alone doesn’t significantly affect pupil size, it can potentiate the miotic effect of Pilocarpine.
Q6: Are there any specific monitoring parameters for patients using Pilocarpine + Timolol?
A: Monitor intraocular pressure regularly. Also monitor heart rate, respiratory function, and blood glucose levels in susceptible individuals.
Q7: Can Pilocarpine + Timolol be used during pregnancy?
A: Pilocarpine + Timolol should generally be avoided during pregnancy due to the potential risks of beta-blocker exposure to the fetus.
Q8: What should be done in case of an overdose?
A: Overdose can result in systemic beta-blocker effects such as bradycardia, hypotension, and bronchospasm. Supportive care is essential, and in severe cases, atropine may be used to counteract bradycardia.
Q9: How long does it take for Pilocarpine + Timolol to reach its peak effect?
A: Pilocarpine typically reaches its peak effect within 10 to 30 minutes. Timolol achieves peak plasma concentration within 1 to 2 hours, but the full IOP-lowering effect of the combination may take a few weeks to stabilize.
A: Contact lenses should be removed before instilling the eye drops and reinserted at least 15 minutes after application, as the benzalkonium chloride preservative can be absorbed by soft contact lenses.
