Levobunolol Hydrochloride Ophthalmic Solution 0.5 % - Uses, Mechanism of Action, Precautions, and Side Effects

Introduction:

Levobunolol hydrochloride is a prescription ophthalmic solution that belongs to the class of beta-blockers. The medication regulates intraocular pressure in patients with long-standing open-angle glaucoma or moderate intraocular hypertension. Levobunolol is an enantiomer of bunolol whose pharmacological activity is 60 times more than that of D-bunolol. Levobunolol is used along with hydrochloride, which melts at 209 to 211 degrees Celsius. The drug is soluble in water and methanol and sparingly soluble in ethanol. Levobunolol hydrochloride ophthalmic solution is manufactured by ALLERGAN and was approved by the US (United States) FDA (Food and Drug Administration) on 19th December 1985.

How Does Levobunolol Hydrochloride Solution Work to Treat Ocular Hypertension?

Levobunolol belongs to the category of beta-blockers which implies that the drug blocks beta receptors (beta-1 and beta-2). The drug explicitly antagonizes the effects of catecholamines which play a crucial role in stress response. In addition, Levobunolol blocks the formation of aqueous humor by 24 to 48 %. However, the most significant point to be noted is that topical beta-blockers are usually ineffective during sleep. The most significant advantage of Levobunolol is that it needs to be used only once daily and has a long-lasting effect. Beta-blockers like Levobunolol initially decrease the intraocular pressure (IOP), followed by a transient increase and fall in IOP.

General Information About the Safety and Effectiveness of Levobunolol Hydrochloride Ophthalmic Solution:

A double-masked, multicenter, and parallel study was done for four years to compare the efficacy and safety of Levobunolol hydrochloride and Timolol in 391 patients with open-angle glaucoma. Patients have been randomized to Levobunolol 0.5 percent and Timolol 0.5 percent twice daily. People who took Levobunolol showed improvements in the symptoms of open-angle glaucoma. Hence, the trial results demonstrated that Levobunolol hydrochloride is more effective and safe than Timolol for ocular hypertension.

For Patients:

Ocular Hypertension:

Ocular hypertension is a condition wherein the pressure within the eyes or the intraocular pressure is high. As a result, the eyes fail to drain the fluid properly due to ocular hypertension. People with ocular hypertension tend to experience glaucoma; a condition wherein increased pressure damages the optic nerve. Normally, the patients do not have specific signs and symptoms of ocular hypertension. However, the following factors increase the risk of ocular hypertension:

• Family history of ocular hypertension.

• Diabetes mellitus.

• Hypertension.

• People above 40 are more likely to develop ocular hypertension.

• Myopia or short-sightedness.

• People who are taking steroids for prolonged periods.

• People with eye injuries or those who have undergone eye surgeries.

What Is Levobunolol Hydrochloride Ophthalmic Solution?

Levobunolol hydrochloride is simply an ophthalmic solution or an eye drop that lowers the pressure built up within the eyes due to glaucoma. Normally, a watery gel-like liquid is present near the eyeballs. This liquid is constantly drained out of the eyes and replaced by a new liquid. Hence, the eyes have a mechanism to drain the liquid. However, the problem arises when this mechanism gets disturbed, resulting in a condition called glaucoma. In glaucoma, the liquid persists within the eyes and fails to get drained. As a result, the pressure within the eyes increases resulting in blurred vision and loss of eyesight. Levobunolol hydrochloride reduces the fluid levels within the eyes to reduce pressure.

What Should the Patient Inform the Doctor Before Taking Levobunolol?

Before taking Levobunolol, the patient must inform the doctor if he or she:

• Is allergic to Levobunolol hydrochloride or any of its components.

• Had asthma or other respiratory diseases like COPD (chronic obstructive pulmonary disease) where the patient encounters breathing difficulties, cough, or wheezing.

• Had problems related to the heart, like an irregular heartbeat or heart failure.

• Takes the medications for the following conditions:

  • Hypertension or high blood pressure.

  • Heart problems like an irregular heartbeat.

  • Eye problems, including ocular hypertension.

  • Pupil dilatation.

  • Diabetes.

• Suffers from the following medical conditions:

  • Coronary heart disease.

  • Delayed heartbeat.

  • Breathlessness.

  • Chest pain.

  • Raynaud’s disease.

  • Diabetes.

  • Overactivity of the thyroid gland.

  • Allergies.

Note -

• Levobunolol hydrochloride ophthalmic solution is not recommended for children.

• Patients must inform the doctor if they are already taking oral beta-blockers.

• Females must inform the doctor if they are pregnant, planning to conceive, or breastfeeding. The drug should be used in pregnancy only after calculating the risk-benefit ratio.

• Levobunolol can make one tired or alter vision, so the patient must avoid driving or operating machinery until the symptoms have subsided.

How Should the Patient Use Levobunolol Hydrochloride Ophthalmic Solution?

The patient must always use the solution as directed by the doctor. In addition, the patient can consult the doctor to know the exact dose of the drug. Normally, the dose is one drop into the affected eye once or twice daily. The doctor will evaluate the pressure within the patient’s eyes four weeks after the treatment. Sometimes the doctor might prescribe additional medications to manage the condition.

Instructions for Use:

1. The patient must avoid using the bottle if the tamper-proof seal on the bottle neck is broken.

2. The person must wash his hands with soap solution before using the ophthalmic solution.

3. Hold the lower eyelid and gently pull it down until there is a formation of a small pocket.

4. Invert the bottle and press it slowly to allow one drop to reach the affected eye.

5. Keep the affected eye closed and press the part where the nose meets the eyes with the index finger for a few minutes.

Note -

• Do not allow the tip of the dropper to touch the eyes to prevent contamination.

• Tighten the cap immediately after using the drug.

• Wipe off the excess liquid from the cheek with the help of a tissue.

• Excess Levobunolol can cause unwanted side effects. Hence, the solution must not be used in excess.

What Are the Side Effects of Levobunolol Hydrochloride Ophthalmic Solution?

• Skin rashes.

• Breathing or swallowing difficulties.

• Swelling of the tongue, lips, throat, and face.

• Asthma.

• Unconsciousness.

• Delayed heartbeat.

• Hypotension or low blood pressure.

• Pain and irritation in the eyes.

• Inflammation of the eyelids.

• Blurred vision.

• Inflammation of the iris, cornea, and other surrounding structures.

• Nasal discomfort.

• Throat irritation.

• Numbness.

• Discoloration of the feet and hands.

• Depression.

• Nervousness.

• Tiredness.

• Nausea.

• Skin hives.

• Hair loss.

Levobunolol gets absorbed into the blood, similar to other eye drops. As a result, the patient might have similar side effects as seen with other beta-blockers. However, the incidences of side effects are lower when medications like beta-blockers are taken orally or injected. Some of the side effects of beta-blockers are listed below:

• Swelling of the face and limbs.

• Obstruction of the airways might result in difficulties in breathing or swallowing.

• Life-threatening adverse reactions.

• Stroke.

• Diminished blood supply to the brain.

• Additional signs and symptoms of myasthenia gravis.

• Tingling sensation in hands and legs.

• Reduced blood glucose levels.

• Nightmares.

• Loss of memory.

• Retinal detachment.

• Loss of vision.

• Corneal erosion.

• Double vision.

• Dropping of the upper eyelid.

• Congestive heart failure.

• Shortness of breath.

• Swelling of the legs and feet due to fluid accumulation.

• Constriction of the air passages.

• Cough.

• Psoriasiform rash (presence of silvery patches on the skin).

• Indigestion.

• Diarrhea.

• Dry mouth.

• Vomiting.

• Abdominal pain.

• Loss of libido.

• Sexual dysfunction.

How Should the Patient Store Levobunolol Hydrochloride Ophthalmic Solution?

The patient must keep the solution away from the reach of children. Avoid using the unopened bottle of the drug beyond the expiration date. Store the drug in the original carton to protect it from sun exposure. However, the drug must not be stored at temperatures above 35 degrees Celsius. Avoid using the drug if the tamper-proof seal is broken. Do not allow the solution to become contaminated because it increases the risk of eye infections. Hence, the patient must discard the bottle after four weeks, even if it contains some solution. The patient must not dispose of the drug in household waste. Instead, the drug must be discarded according to the guidelines.

For Doctors:

Description:

Levobunolol hydrochloride ophthalmic solution is a sterile non-cardioselective beta-adrenoceptor blocking agent for ophthalmic purposes. The solution is light yellow or colorless with osmolality in the range of 250 to 360 mOsm/kg. The shelf life pH (potential of hydrogen) range of the drug is 5.5 to 7.5.

Chemical Name - (-)-(S)-5-[3-(tert-Butylamino)-2-hydroxypropoxy]-3,4-dihydro-1(2H)

naphthalenone hydrochloride.

Composition:

Active Ingredient - Levobunolol hydrochloride 0.5 %.

Inactive Ingredients - Edetate disodium, purified water, sodium metabisulfite, potassium phosphate, polyvinyl alcohol 1.4 percent, sodium chloride, sodium phosphate, dibasic, monobasic, and hydrochloric acid or sodium hydroxide to alter the pH.

Indications and Usage:

Levobunolol solution has proven to be effective in reducing intraocular pressure. Hence, the solution can be safely administered to people diagnosed with ocular hypertension or chronic open-angle glaucoma.

Contraindications:

Levobunolol ophthalmic solution is particularly contraindicated in patients with the following conditions or a previous history of the same:

• Bronchial asthma.

• Chronic obstructive pulmonary disease.

• Sinus bradycardia.

• Atrioventricular block.

• Cardiac failure.

• Cardiogenic shock.

• Hypersensitivity to any of the constituents of the drug.

Dosage and Administration:

The recommended starting dose of the drug is one to two drops in the affected eye once daily. However, patients with severe or uncontrolled glaucoma can use the solution twice daily. Such patients must be carefully evaluated for side effects. The patient must not instill more than two drops of the solution in the eyes. Concomitant drugs can be administered if the patient does not show any improvements in his intraocular pressure. However, one must not use two or more topical beta-blocking agents simultaneously.

How Is Levobunolol Hydrochloride Ophthalmic Solution Supplied?

The solution is sterile and supplied in white-colored, low-density polyethylene ophthalmic dispenser bottles with yellow-colored high-intensity polystyrene caps. The drug is supplied as follows:

• 5 mL in a 10 mL bottle.

• 10 mL in a 15 mL bottle.

• 15 mL in a 15 mL bottle.

Storage -

The drug must be stored at 15 to 25 degrees Celsius.

Clinical Pharmacology:

Levobunolol hydrochloride is a beta-adrenoreceptor-blocking agent with equal efficacy against beta-1 and beta-2 receptors. The drug is 60 times more potent than its dextro isomer but is equipotent for direct myocardial depression. Levobunolol does not have any clinically significant membrane-stabilizing effects of sympathomimetic activities. The blockage of beta-adrenoreceptors decreases the cardiac output in healthy patients and ones with heart diseases. In addition, the blockade of these receptors in the bronchi and bronchioles can cause increased airway resistance, which is dangerous for patients with asthma. Levobunolol hydrochloride has proven to be an effective agent in reducing intraocular pressure, which may or may not be accompanied by glaucoma. The higher the pressure, the greater the chances of vision loss and optic nerve damage.

The Onset of Action -

The onset of action of the drug is one hour, and the maximal effects are visible within two to six hours.

Warnings:

Heart Failure:

Patients with diminished myocardial contractility constantly require sympathetic stimulation. Hence, inhibition of the same by beta-blockers might precipitate cardiac failure.

Patients With a History of Cardiac Failure:

Beta-blocking agents can constantly depress the myocardium resulting in cardiac failure. Hence, the patient must discontinue the drug if the signs and symptoms of cardiac failure are visible.

Vascular Insufficiency:

Levobunolol hydrochloride solution can potentiate the symptoms of vascular insufficiency. Hence, the drug must be used cautiously in such patients.

Chronic Obstructive Pulmonary Disease:

Levobunolol hydrochloride is contraindicated in patients with COPD, chronic bronchitis, emphysema, and mild or moderate bronchospastic disease. However, if the drug is necessary for such patients, the doctor must calculate the risk-benefit ratio.

Major Surgeries:

Not much information is available regarding the withdrawal of beta-adrenergic blockers before major surgeries. However, as the beat receptors get blocked, the patient might develop severe hypotension when the anesthesia is administered during the procedure. Some patients have also reported difficulties in maintaining their heartbeat. Hence, it is recommended to discontinue the drug during elective surgery.

Diabetes Mellitus:

The drug must be administered cautiously in patients at risk of hypoglycemia or hyperglycemia. In addition, it must be given carefully to the ones taking insulin.

Thyrotoxicosis:

Beta-adrenergic blocking agents might conceal the clinical signs of hyperthyroidism. Hence, abrupt drug withdrawal must be considered in patients with a risk of developing thyrotoxicosis.

Choroidal Detachment:

Choroidal detachment has been reported after the administration of aqueous suppressant therapy. In addition, it contains metabisulphite, which can induce allergic reactions or symptoms of anaphylaxis. However, nothing has been known about the prevalence of sulfite sensitivity.

Muscle Weakness:

Levobunolol can potentiate muscle weakness along with certain myasthenic symptoms.

Drug Interactions:

• Avanafil.

• Escitalopram.

• Fluoxetine.

• Haloperidol.

• Tadalafil.

• Ranolazine.

• Methimazole.

• Sildenafil.

• Viloxazine.

• Verapamil.

• Vardenafil.

• Calcium antagonists.

• Phenothiazines.

Adverse Reactions:

• Headache.

• Asthenia (lack of energy).

• Transient ataxia (difficulty in muscle coordination).

• Diminished corneal sensitivity.

• Dizziness.

• Urticaria (skin rashes).

• Lethargy.

• Pruritus (itching or irritation in the skin).

• Bradycardia (decreased heart rate).

• Arrhythmia (irregular heart rate).

• Heart block.

• Cerebral vascular accident,

• Congestive heart failure.

• Palpitations.

• Cardiac arrest.

• Depression.

• Confusion.

• Paresthesia (tingling sensation in the hands or legs).

• Stevens-Johnson syndrome (a serious disorder of the skin and mucous membrane).

• Bronchospasm (tightening of the airway muscles).

• Impotence.

• Blepharoptosis (drooping of upper eyelids).

• Diplopia (double vision).

Overdose:

Nothing has been known about the overdosage of Levobunolol hydrochloride ophthalmic solution in humans. However, the patient can flush his eyes with warm water or saline in case of an accidental overdose. Gastric lavage can be done if the drug has been ingested. In addition, the patient can consider the following supportive measures for different signs and symptoms of drug overdose:

• Bradycardia - Atropine sulfate 0.25 to 2 mg can be infused intravenously to stimulate vagal blockade. Patients with persistent bradycardia can be given Isoproterenol hydrochloride intravenously.

• Hypotension - Sympathomimetic pressor drugs like Dopamine or Dobutamine can be used. In addition, Aminophylline therapy can be considered.

• Bronchospasm - Isoproterenol hydrochloride and Aminophylline can be considered.

• Heart Failure - Digitalis, oxygen therapy, or diuretics can be safely given to the patient.

• Second or Third-Degree Heart Blockade - Isoproterenol hydrochloride or transvenous pacemakers can be used.

Use in Specific Populations:

Pregnancy:

No adequate or well-controlled studies have been performed on pregnant females. However, fetotoxicity and teratogenicity have been observed in animals when the drug was given at 200 to 700 times the human dose.

Lactating Females:

Nothing has been known about the presence of Levobunolol hydrochloride in human milk. However, systemic beta-blockers have been found in human milk.