timolol maleate
Blocadren, Timoptic, Timoptic-XE

Available forms
Available by prescription only
Ophthalmic gel: 0.25%, 0.5%
Ophthalmic solution: 0.25%, 0.5%
Tablets: 5 mg, 10 mg, 20 mg

Indications and dosages
 Hypertension. Adults: Initially, 10 mg P.O. b.i.d. Usual maintenance dose is 20 to 40 mg daily. Maximum dose is 60 mg daily. There should be an interval of at least 7 days between dose increases.
 Reduction of risk of CV mortality and reinfarction after MI. Adults: 10 mg P.O. b.i.d. started within 1 to 4 weeks after infarction.
 Migraine headache. Adults: 10 mg P.O. b.i.d.; then increase up to 20 mg. Or, 30-mg dose (10 mg P.O. in the morning and 20 mg P.O. in the evening).
 Glaucoma. Adults: 1 drop of 0.25% or 0.5% solution to the conjunctiva once or twice daily. Or, 1 drop of 0.25% or 0.5% gel to the conjunctiva once daily.
 Angina ◇. Adults: 15 to 45 mg P.O. daily given in three divided doses.

Pharmacodynamics
Antihypertensive action: Exact mechanism of antihypertensive effect of timolol is unknown. Timolol may reduce blood pressure by blocking adrenergic receptors (decreasing cardiac output), by decreasing sympathetic outflow from the CNS, and by suppressing renin release.
MI prophylactic action: Exact mechanism by which timolol decreases risk of mortality after MI is unknown. Timolol produces a negative chronotropic and inotropic activity. This decrease in heart rate and myocardial contractility results in reduced myocardial oxygen consumption.
Antiglaucoma action: Beta-blocking action of timolol decreases the production of aqueous humor, decreasing intraocular pressure.

Pharmacokinetics
Absorption: About 90% of an oral dose is absorbed from the GI tract.
Distribution: After oral administration, timolol is distributed throughout the body; depending on assay method, drug is 10% to 60% protein-bound.
Metabolism: About 80% of a given dose is metabolized in the liver to inactive metabolites.
Excretion: Drug and its metabolites are excreted primarily in urine; half-life is about 4 hours.

Contraindications and precautions
Contraindicated in patients with bronchial asthma, severe COPD, sinus bradycardia and heart block greater than first degree, cardiogenic shock, heart failure, overt cardiac failure, or hypersensitivity to drug.
  Use cautiously in patients with diabetes, hyperthyroidism, or respiratory disease (especially nonallergic bronchospasm or emphysema). Use oral form cautiously in patients with compensated heart failure and hepatic or renal disease. Use ophthalmic form cautiously in patients with cerebrovascular insufficiency.

Interactions
Drug-drug. Antihypertensives, general anesthetics, fentanyl, NSAIDs: Causes hypotension. Monitor patient closely.
Cardiac glycosides, diltiazem, verapamil: Causes excessive bradycardia and increased depressant effect on myocardium. Use together cautiously.
Indomethacin: Decreases antihypertensive effect. Monitor patient closely; dose may need adjustment.
Insulin, oral antidiabetics: Alters requirements for these drugs. Monitor glucose levels; dose may need adjustment.

Adverse reactions
CNS: CVA, fatigue, lethargy, dizziness; depression, hallucinations, confusion (with ophthalmic form).
CV: arrhythmias, bradycardia, hypotension, heart failure, peripheral vascular disease (with oral administration); cardiac arrest, heart block, palpitations (with ophthalmic form).
EENT: minor eye irritation, decreased corneal sensitivity with long-term use, conjunctivitis, blepharitis, keratitis, visual disturbances, diplopia, ptosis (with ophthalmic form).
GI: nausea, vomiting, diarrhea (with oral administration), constipation.
Metabolic: hyperkalemia, hyperuricemia, hyperglycemia.
Respiratory: dyspnea, bronchospasm, increased airway resistance, pulmonary edema (with oral administration); asthmatic attacks in patients with history of asthma (with ophthalmic form).
Skin: pruritus (with oral administration).

Effects on lab test results
• May increase BUN, potassium, glucose, and uric acid levels.
• May decrease hemoglobin and hematocrit.

Overdose and treatment
Effects of overdose include severe hypotension, bradycardia, heart failure, and bronchospasm.
 After acute ingestion, empty stomach by induced emesis or gastric lavage and give activated charcoal to reduce absorption. Subsequent treatment is usually symptomatic and supportive.

Special considerations
• Dosage adjustment may be needed for patient with renal or hepatic impairment.
• Although controversial, drug may need to be discontinued 48 hours before surgery in patients receiving ophthalmic timolol because systemic absorption occurs.
• Monitor patient for cardiac and respiratory symptoms.
Pregnant patients
• Use drug during pregnancy only when potential benefits justify possible risk to fetus.
Breast-feeding patients
• Timolol appears in breast milk. Because of the potential for serious adverse reactions in breast-fed infants, an alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Safety and efficacy in children haven’t been established. Use only if potential benefit outweighs risk.
Geriatric patients
• These patients may need lower oral maintenance dosages because of increased bioavailability or delayed metabolism; they also may experience enhanced adverse effects. Use cautiously because half-life may be prolonged in elderly patients.

Patient education
• For ophthalmic form of timolol, teach patient proper method of eyedrop administration. Warn patient not to touch dropper to eye or surrounding tissue. Tell him to lightly press lacrimal sac with finger after administration to decrease systemic absorption.
• Instruct patient to invert ophthalmic gel container once before each use.
• Instruct patient to administer other ophthalmic drugs at least 10 minutes before the ophthalmic gel.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use