Drug: Blocadren

BLOCADREN (Timolol Maleate) is a non-selective beta-adrenergic receptor blocking agent. The chemical name for timolol maleate is (S)-1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-2-propanol (Z)-2-butenedioate (1:1) salt. It possesses an asymmetric carbon atom in its structure and is provided as the levo isomer. Its empirical formula is C13H24N4O3S•C4H4O4 and its structural formula is: Timolol maleate has a molecular weight of 432.50. It is a white, odorless, crystalline powder which is soluble in water, methanol, and alcohol. BLOCADREN (timolol) is supplied as tablets in three strengths containing 5 mg, 10 mg or 20 mg timolol maleate for oral administration. Inactive ingredients are cellulose, FD&C Blue 2, magnesium stearate, and starch.

Source: http://www.rxlist.com

BLOCADREN (timolol) is usually well tolerated in properly selected patients. Most adverse effects have been mild and transient. In a multicenter (12-week) clinical trial comparing timolol maleate and placebo in hypertensive patients, the following adverse reactions were reported spontaneously and considered to be causally related to timolol maleate:   Timolol Maleate
(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 BLOCADREN (timolol) , 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 (see CLINICAL PHARMACOLOGY), the frequency of the principal adverse reactions and the frequency with which these resulted in discontinuation of therapy in the timolol and placebo groups were
  Adverse Reaction*** Withdrawal† Timolol
(n=945)
% Placebo
(n=939)
% Timolol
(n=945)
% Placebo
(n=939)
% Asthenia or Fatigue 5 1

Source: http://www.rxlist.com

Hypertension The usual initial dosage of BLOCADREN (timolol) is 10 mg twice a day, whether used alone or added to diuretic therapy. Dosage may be increased or decreased depending on heart rate and blood pressure response. The usual total maintenance dosage is 20-40 mg per day. Increases in dosage to a maximum of 60 mg per day divided into two doses may be necessary. There should be an interval of at least seven days between increases in dosages. BLOCADREN (timolol) may be used with a thiazide diuretic or with other antihypertensive agents. Patients should be observed carefully during initiation of such concomitant therapy. Myocardial Infarction The recommended dosage for long-term prophylactic use in patients who have survived the acute phase of a myocardial infarction is 10 mg given twice daily (see CLINICAL PHARMACOLOGY). Migraine The usual initial dosage of BLOCADREN (timolol) is 10 mg twice a day. During maintenance therapy the 20 mg daily dosage may be administered as a single dose. Total daily dosage may be increased to a maximum of 30 mg, given in divided doses, or decreased to 10 mg once per day, depending on clinical response and tolerability. If a satisfactory response is not obtained after 6-8 weeks use of the maximum daily dosage, therapy with BLOCADREN (timolol) should be discontinued.

Source: http://www.rxlist.com

Catecholamine-depleting drugs: Close observation of the patient is recommended when BLOCADREN (timolol) 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 produce vertigo, syncope, or postural hypotension. Non-steroidal anti-inflammatory drugs: Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by non-steroidal anti-inflammatory drugs has been reported. When using these agents concomitantly, patients should be observed carefully to confirm that the desired therapeutic effect has been obtained. Calcium antagonists: Literature reports suggest that oral calcium antagonists may be used in combination with beta-adrenergic blocking agents when heart function is normal, but should be avoided in patients with impaired cardiac function. Hypotension, AV conduction disturbances, and left ventricular failure have been reported in some patients receiving beta-adrenergic blocking agents when an oral calcium antagonist was added to the treatment regimen. Hypotension was more likely to occur if the calcium antagonist were a dihydropyridine derivative, e.g., nifedipine, while left ventricular failure and AV conduction disturbances were more likely to occur with either verapamil or diltiazem. Intravenous calcium antagonists should be used with caution in patients receiving beta-adrenergic blocking agents. Digitalis and either diltiazem or verapamil: The concomitant use of beta-adrenergic blocking agents with digitalis and either diltiazem or verapamil may have additive effects in prolonging AV conduction time. Quinidine: Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with quinidine and timolol, possibly because quinidine inhibits the metabolism of timolol via the P-450 enzyme, CYP2D6. Clonidine: Beta adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the beta adrenergic blocking agent should be withdrawn several days before the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta adrenergic blocking agents should be delayed for several days after clonidine administration has stopped. Risk from Anaphylactic Reaction: While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions. Read the Blocadren Drug Interactions Center for a complete guide to possible interactions Learn More »

Source: http://www.rxlist.com

Hypertension BLOCADREN (timolol) is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Myocardial Infarction BLOCADREN (timolol) 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 BLOCADREN (timolol) is indicated for the prophylaxis of migraine headache.

Source: http://www.rxlist.com

BLOCADREN (timolol) is contraindicated in patients with bronchial asthma or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease (see WARNINGS); sinus bradycardia; second and third degree atrioventricular block; overt cardiac failure (see WARNINGS); cardiogenic shock; hypersensitivity to this product.Last reviewed on RxList: 12/9/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Overdosage has been reported with Tablets BLOCADREN (timolol) . A 30-year-old female ingested 650 mg of BLOCADREN (timolol) (maximum recommended daily dose — 60 mg) and experienced second and third degree heart block. She recovered without treatment but approximately two months later developed irregular heartbeat, hypertension, dizziness, tinnitus, faintness, increased pulse rate and borderline first degree heart block. The oral LD50 of the drug is 1190 and 900 mg/kg in female mice and female rats, respectively. An in vitro hemodialysis study, using 14C timolol added to human plasma or whole blood, showed that timolol was readily dialyzed from these fluids; however, a study of patients with renal failure showed that timolol did not dialyze readily. The most common signs and symptoms to be expected with overdosage with a beta-adrenergic receptor blocking agent are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. Therapy with BLOCADREN (timolol) should be discontinued and the patient observed closely. The following additional therapeutic measures should be considered:
  1. Gastric lavage.
  2. Symptomatic bradycardia: Use atropine sulfate intravenously in a dosage of 0.25 mg to 2 mg to induce vagal blockade. If bradycardia persists, intravenous isoproterenol hydrochloride should be administered cautiously. In refractory cases the use of a transvenous cardiac pacemaker may be considered.
  3. Hypotension: Use sympathomimetic pressor drug therapy, such as dopamine, dobutamine or levarterenol. In refractory cases the use of glucagon hydrochloride has been reported to be useful.
  4. Bronchospasm: Use isoproterenol hydrochloride. Additional therapy with aminophylline may be considered.
  5. Acute cardiac failure: Conventional therapy with digitalis, diuretics, and oxygen should be instituted immediately. In refractory cases the use of intravenous aminophylline is suggested. This may be followed if necessary by glucagon hydrochloride which has been reported to be useful.
  6. Heart block (second or third degree): Use isoproterenol hydrochloride or a transvenous cardiac pacemaker.

Source: http://www.rxlist.com

No. 3343 — Tablets BLOCADREN (timolol) , 5 mg, are light blue, round, compressed tablets, with code MSD 59 on one side and BLOCADREN (timolol) on the other. They are supplied as follows: NDC 0006-0059-68 bottles of 100. No. 3344 — Tablets BLOCADREN (timolol) , 10 mg, are light blue, round, scored, compressed tablets, with code MSD 136 on one side and BLOCADREN (timolol) on the other. They are supplied as follows: NDC 0006-0136-68 bottles of 100 No. 3371 — Tablets BLOCADREN (timolol) , 20 mg, are light blue, capsule shaped, scored, compressed tablets, with code MSD 437 on one side and BLOCADREN (timolol) on the other. They are supplied as follows: NDC 0006-0437-68 bottles of 100 Storage Store at controlled room temperature, 15-30°C (59-86°F). Keep container tightly closed. Protect from light. MERCK AND CO., INC., Whitehouse Station, NJ 08889, USA. Issued April 2001. FDA Rev date: 2/25/2003 Last reviewed on RxList: 12/9/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

General Impaired Hepatic or Renal Function: Since BLOCADREN (timolol) is partially metabolized in the liver and excreted mainly by the kidneys, dosage reductions may be necessary when hepatic and/or renal insufficiency is present. Dosing in the Presence of Marked Renal Failure: Although the pharmacokinetics of BLOCADREN (timolol) are not greatly altered by renal impairment, marked hypotensive responses have been seen in patients with marked renal impairment undergoing dialysis after 20 mg doses. Dosing in such patients should therefore be especially cautious. Muscle Weakness: Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms. Cerebrovascular Insufficiency: Because of potential effects of beta-adrenergic blocking agents relative to blood pressure and pulse, these agents should be used with caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow are observed, consideration should be given to discontinuing these agents. Carcinogenesis, Mutagenesis, Impairment of Fertility In a two-year study of timolol maleate in rats, there was a statistically significant increase in the incidence of adrenal pheochromocytomas in male rats administered 300 mg/kg/day (250 times** the maximum recommended human dose). Similar differences were not observed in rats administered doses equivalent to approximately 20 or 80 times** the maximum recommended human dose. In a lifetime study in mice, there were statistically significant increases in the incidence of benign and malignant pulmonary tumors, benign uterine polyps and mammary adenocarcinoma in female mice at 500 mg/kg/day (approximately 400 times** the maximum recommended human dose), but not at 5 or 50 mg/kg/day. In a subsequent study in female mice, in which post-mortem examinations were limited to uterus and lungs, a statistically significant increase in the incidence of pulmonary tumors was again observed at 500 mg/kg/day. The increased occurrence of mammary adenocarcinoma was associated with elevations in serum prolactin that occurred in female mice administered timolol at 500 mg/kg/day, but not at doses of 5 or 50 mg/kg/day. An increased incidence of mammary adenocarcinomas in rodents has been associated with administration of several other therapeutic agents which elevate serum prolactin, but no correlation between serum prolactin levels and mammary tumors has been established in man. Furthermore, in adult human female subjects who received oral dosages of up to 60 mg of timolol maleate, the maximum recommended daily human oral dosage, there were no clinically meaningful changes in serum prolactin. Timolol maleate was devoid of mutagenic potential when evaluated in vivo (mouse) in the micronucleus test and cytogenetic assay (doses up to 800 mg/kg) and in vitro in a neoplastic cell transformation assay (up to 100 µg/mL). In Ames tests the highest concentrations of timolol employed, 5000 or 10,000 µg/plate, were associated with statistically significant elevations of revertants observed with tester strain TA100 (in seven replicate assays), but not in three additional strains. In the assays with tester strain TA100, no consistent dose response relationship was observed, nor did the ratio of test to control revertants reach 2. A ratio of 2 is usually considered the criterion for a positive Ames test. Reproduction and fertility studies in rats showed no adverse effect on male or female fertility at doses up to 125 times** the maximum recommended human dose. Pregnancy Pregnancy Category C. Teratogenicity studies with timolol in mice, rats and rabbits at doses up to 50 mg/kg/day (approximately 40 times** the maximum recommended daily human dose) showed no evidence of fetal malformations. Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1000 mg/kg/day (approximately 830 times** the maximum recommended daily human dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of approximately 40 times** the maximum recommended daily human dose, in this case without apparent maternotoxicity. There are no adequate and well-controlled studies in pregnant women. BLOCADREN (timolol) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Timolol maleate has been detected in human milk. Because of the potential for serious adverse reactions from timolol in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. ** Based on patient weight of 50 kg Last reviewed on RxList: 12/9/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Health Services in

Drug Database Online

Welcome to Senior Healthcare Matters an online drug guide and dictionary, here you can get drug information and definitaions for most popular pharmaceutical and medicinal drugs, and specifically Blocadren. Find what medications you are taking today.