Timozen Uses

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What is Timozen?

Timozen is used alone or together with other medicines (such as hydrochlorothiazide) to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Timozen is also used after an acute heart attack to decrease its severity and prevent another heart attack. It may also be used to help prevent migraine headaches.

Timozen is a beta-blocker. It works by affecting the response to nerve impulses in certain parts of the body, like the heart. As a result, the heart beats slower and decreases the blood pressure. When the blood pressure is lowered, the amount of blood and oxygen is increased to the heart.

Timozen is available only with your doctor's prescription.

Timozen indications

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Hypertension

Timozen tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Myocardial Infarction

Timozen is indicated in patients who have survived the acute phase of myocardial infarction, and are clinically stable, to reduce cardiovascular mortality and the risk of reinfarction.

Migraine

Timozen is indicated for the prophylaxis of migraine headache.

How should I use Timozen?

Use Timozen as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Ask your health care provider any questions you may have about how to use Timozen.

Uses of Timozen in details

Use: Labeled Indications

Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2017]).

Migraine prophylaxis: Prophylaxis of migraine

Myocardial infarction (secondary prevention): To reduce mortality following MI

Off Label Uses

Atrial fibrillation (rate-control)

Data from a randomized, placebo-controlled trial in patients with atrial fibrillation (AF) associated with a rapid ventricular response while receiving digoxin supports the use of oral Timozen in patients with chronic AF.

Based on the 2014 AHA/ACC/HRS guideline for the management of patients with AF, the use of beta-blockers for ventricular rate control in patients with paroxysmal, persistent, or permanent AF is effective and recommended for this condition.

Timozen description

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A beta-adrenergic antagonist similar in action to propranolol. The levo-isomer is the more active. Timozen has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of migraine disorders and tremor.

Timozen dosage

Patients should be instructed to invert the closed container and shake once before each use. It is not necessary to shake the container more than once. Other topically applied ophthalmic medications should be administered at least 10 minutes before Timozen Ophthalmic Gel Forming Solution.

Timozen Ophthalmic Gel Forming Solution is available in concentrations of 0.25% and 0.5%. The dose is one drop of Timozen Ophthalmic Gel Forming Solution (either 0.25% or 0.5%) in the affected eye(s) once a day.

Because in some patients the pressure-lowering response to Timozen Ophthalmic Gel Forming Solution may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment with Timozen Ophthalmic Gel Forming Solution.

Dosages higher than one drop of 0.5% Timozen Ophthalmic Gel Forming Solution once a day have not been studied. If the patient's intraocular pressure is still not at a satisfactory level on this regimen, concomitant therapy can be considered. The concomitant use of two topical beta-adrenergic blocking agents is not recommended.

When patients have been switched from therapy with Timozen ophthalmic solution administered twice daily to Timozen Ophthalmic Gel Forming Solution administered once daily, the ocular hypotensive effect has remained consistent.

Timozen interactions

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What other drugs will affect Timozen?

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Although TIMOPTIC (Timozen ophthalmic solution) used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with TIMOPTIC (Timozen ophthalmic solution) and epinephrine has been reported occasionally.

Beta-adrenergic blocking agents: Patients who are receiving a beta-adrenergic blocking agent orally and Preservative-free Timozen should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. The concomitant use of two topical beta-adrenergic blocking agents is not recommended.

Calcium antagonists: Caution should be used in the coadministration of beta-adrenergic blocking agents, such as Preservative-free Timozen, and oral or intravenous calcium antagonists, because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, coadministration should be avoided.

Catecholamine-depleting drugs: Close observation of the patient is recommended when a beta blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may result in vertigo, syncope, or postural hypotension.

Digitalis and calcium antagonists: The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.

CYP2D6 inhibitors: Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine, SSRIs) and Timozen.

Clonidine:

Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. There have been no reports of exacerbation of rebound hypertension with ophthalmic Timozen. Injectable epinephrine:

Timozen side effects

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What are the possible side effects of Timozen?

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Timozen tablets are usually well tolerated in properly selected patients. Most adverse effects have been mild and transient.

In a multi-center (12 week) clinical trial comparing Timozen and placebo in hypertensive patients, the following adverse reactions were reported spontaneously and considered to be causally related to Timozen:

Timozen

(n=176)

%

Placebo

(n=168)

%

BODY AS A WHOLE

fatigue/tiredness

3.4

0.6

headache

1.7

1.8

chest pain

0.6

0

asthenia

0.6

0

CARDIOVASCULAR

bradycardia

9.1

0

arrhythmia

1.1

0.6

syncope

0.6

0

edema

0.6

1.2

DIGESTIVE

dyspepsia

0.6

0.6

nausea

0.6

0

SKIN

pruritus

1.1

0

NERVOUS SYSTEM

dizziness

2.3

1.2

vertigo

0.6

0

paresthesia

0.6

0

PSYCHIATRIC

decreased libido

0.6

0

RESPIRATORY

dyspnea

1.7

0.6

bronchial spasm

0.6

0

rales

0.6

0

SPECIAL SENSES

eye irritation

1.1

0.6

tinnitus

0.6

0

These data are representative of the incidence of adverse effects that may be observed in properly selected patients treated with Timozen, i.e., excluding patients with bronchospastic disease, congestive heart failure or other contraindications to beta-blocker therapy.

In patients with migraine the incidence of bradycardia was 5 percent.

In a coronary artery disease population studied in the Norwegian multi-center trial, the frequency of the principal adverse reactions and the frequency with which these resulted in discontinuation of therapy in the Timozen and placebo groups were:

Adverse Reaction* Withdrawal†
Timozen

(n=945)

%

Placebo

(n=939)

%

Timozen

(n=945)

%

Placebo

(n=939)

%

*
When an adverse reaction recurred in a patient, it is listed only once.
Only principal reason for withdrawal in each patient is listed. These adverse reactions can also occur in patients treated for hypertension.

Asthenia or Fatigue

5

1

<1

<1

Heart Rate < 40 beats/minute

5

<1

4

<1

Cardiac Failure-Nonfatal

8

7

3

2

Hypotension

3

2

3

1

Pulmonary Edema-Nonfatal

2

<1

<1

<1

Claudication

3

3

1

<1

AV Block 2nd or 3rd Degree

<1

<1

<1

<1

Sinoatrial Block

<1

<1

<1

<1

Cold Hands and Feet

8

<1

<1

0

Nausea or Digestive Disorders

8

6

1

<1

Dizziness

6

4

1

0

Bronchial Obstruction

2

<1

1

<1

The following additional adverse effects have been reported in clinical experience with the drug: Body as a Whole: anaphylaxis, extremity pain, decreased exercise tolerance, weight loss, fever; Cardiovascular: cardiac arrest, cardiac failure, cerebral vascular accident, worsening of angina pectoris, worsening of arterial insufficiency, Raynaud's phenomenon, palpitations, vasodilatation; Digestive: gastrointestinal pain, hepatomegaly, vomiting, diarrhea, dyspepsia; Hematologic: nonthrombocytopenic purpura; Endocrine: hyperglycemia, hypoglycemia; Skin: rash, skin irritation, increased pigmentation, sweating, alopecia; Musculoskeletal: arthralgia; Nervous System: local weakness, increase in signs and symptoms of myasthenia gravis; Psychiatric: depression, nightmares, somnolence, insomnia, nervousness, diminished concentration, hallucinations; Respiratory: cough; Special Senses: visual disturbances, diplopia, ptosis, dry eyes; Urogenital: impotence, urination difficulties.

There have been reports of retroperitoneal fibrosis in patients receiving Timozen and in patients receiving other beta-adrenergic blocking agents. A causal relationship between this condition and therapy with beta-adrenergic blocking agents has not been established.

Potential Adverse Effects

In addition, a variety of adverse effects not observed in clinical trials with Timozen, but reported with other beta-adrenergic blocking agents, should be considered potential adverse effects of Timozen. Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics; Cardiovascular: Intensification of AV block; Digestive: Mesenteric arterial thrombosis, ischemic colitis; Hematologic: Agranulocytosis, thrombocytopenic purpura; Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Miscellaneous: Peyronie's disease.

There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis, and sclerosing serositis attributed to the beta-adrenergic receptor blocking agent, practolol. This syndrome has not been reported with Timozen.

Clinical Laboratory Test Findings

Clinically important changes in standard laboratory parameters were rarely associated with the administration of Timozen. Slight increases in blood urea nitrogen, serum potassium, uric acid, and triglycerides, and slight decreases in hemoglobin, hematocrit and HDL cholesterol occurred, but were not progressive or associated with clinical manifestations. Increases in liver function tests have been reported.

Timozen contraindications

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What is the most important information I should know about Timozen?

Hypersensitivity to Timozen or any component of the formulation; sinus bradycardia; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; uncompensated cardiac failure; bronchospastic disease

Documentation of allergenic cross-reactivity for beta-blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Right ventricular failure secondary to pulmonary hypertension; significant cardiomegaly; allergic rhinitis; severe chronic obstructive pulmonary disease; anesthesia with agents that produce myocardial depression (eg, ether hypersensitivity to Timozen)

Active ingredient matches for Timozen:

Timolol Maleate

Timolol


Unit description / dosage (Manufacturer)Price, USD
Timozen Eye 5 ml Drop$ 0.42
TIMOZEN 0.5%W/V EAR DROPS 1 packet / 5 ML ear drop each (Kaizen Pharmaceuticals Pvt Ltd)$ 0.60
Timozen 0.5% w/v Eye Drop (Kaizen Pharmaceuticals Pvt Ltd)$ 0.60

List of Timozen substitutes (brand and generic names):

Timoriv 0.5 % w/v EYE DPS / 5ml (East African (I) Remedies (P) Ltd.)$ 0.48
Timosil 0.5 % x 5 mL (Silom Medical)
Timosil eye drops 0.5 % 5 mL x 1's (Silom Medical)
Timostal ophth soln 0.5% 10 mL x 1's (Stallion Labs)
TIMOSTAR 0.5% EYE DROPS 1 packet / 5 ML eye drop each (Mankind Pharma Ltd)$ 0.69
Timostar 0.5% Eye Drop (Mankind Pharma Ltd)$ 0.69
TIMOWA 0.5% EYE DROPS 1 packet / 5 ML eye drop each (Jawa Pharmaceuticals Pvt Ltd)$ 0.35
Timowa 0.5% Eye Drop (Jawa Pharmaceuticals Pvt Ltd)$ 0.35
Solution; Ophthalmic; Timolol Maleate 0.25% (Pizzard)
Solution; Ophthalmic; Timolol Maleate 0.5% (Pizzard)
0.5 % x 5ml (Talson Pharmaceuticals)$ 0.46
Timtal 0.5 % EYE DPS / 5ml (Talson Pharmaceuticals)$ 0.46
Timtal Eye 5 ml Drop (Talson Pharmaceuticals)$ 0.46
TIMTAL eye drops 0.5 % x 5ml (Talson Pharmaceuticals)$ 0.46
Timtal 0.5 % EYE DPS / 5ml (Talson Pharmaceuticals)$ 0.46
Solution; Ophthalmic; Timolol Maleate 0.25% (Columbia)
Solution; Ophthalmic; Timolol Maleate 0.5% (Columbia)

References

  1. DailyMed. "TIMOLOL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
  2. PubChem. "timolol". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
  3. DrugBank. "timolol". http://www.drugbank.ca/drugs/DB00373 (accessed September 17, 2018).

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Information checked by Dr. Sachin Kumar, MD Pharmacology

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