Talliton 12.5 mg

Talliton 12.5 mg is a nonselective β-adrenergic blocking agent with α₁-blocking activity. It is -1-(9H-carbazol-4-yloxy)-3-[-2-(2-methoxyphenoxy)ethyl]amino]propan-2-ol. Its molecular formula is C₂₄H₂₆N₂O₄. It is a racemic mixture.

Heart Failure

Talliton 12.5 mg tablets are indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization.

Left Ventricular Dysfunction Following Myocardial Infarction

Talliton 12.5 mg tablets are indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of less than or equal to 40% (with or without symptomatic heart failure).

Hypertension

Talliton 12.5 mg tablets are indicated for the management of essential hypertension. They can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Talliton 12.5 mg is used alone or together with other medicines 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.

Talliton 12.5 mg is also used to prevent further worsening of congestive heart failure. It is also used to treat left ventricular dysfunction after a heart attack. Left ventricular dysfunction occurs when the left ventricle (the main pumping chamber of the heart) stiffens and enlarges and can cause the lungs to fill with blood.

Talliton 12.5 mg belongs to a group of medicines called beta-adrenergic blocking agents, beta-blocking agents, or more commonly, beta-blockers. Beta-blockers work by affecting the response to some nerve impulses in certain parts of the body. As a result, they decrease the heart's need for blood and oxygen by reducing its workload. They also help the heart to beat more regularly.

Talliton 12.5 mg may also be used for other conditions as determined by your doctor.

Talliton 12.5 mg is available only with your doctor's prescription.

Congestive Heart Failure: Dosage must be individualized and closely monitored by a physician during up-titration. Prior to initiation of Talliton 12.5 mg, the dosing of digitalis, diuretics and ACE inhibitors (if used) should be stabilized. The recommended starting dose of Talliton 12.5 mg is 3.125 mg twice daily for 2 weeks. If this dose is tolerated, it can then be increased to 6.25 mg twice daily. Dosing should then be doubled every 2 weeks to the highest level tolerated by the patient. At initiation of each new dose, patients should be observed for signs of dizziness or lightheadedness for 1 hr. The maximum recommended dose is 25 mg twice daily in patients weighing <85 kg (187 lbs) and 50 mg twice daily in patients weighing >85 kg. Before each dose increase, the patient should be evaluated for symptoms of worsening heart failure, vasodilation (dizziness, lightheadedness, symptomatic hypotension) or bradycardia, in order to determine tolerability of Talliton 12.5 mg. Transient worsening of heart failure may be treated with increased doses of diuretics, although occasionally, it is necessary to lower the dose of Talliton 12.5 mg or temporarily discontinue it. Symptoms of vasodilation often respond to a reduction in the dose of diuretics or ACE inhibitor. If these changes do not relieve symptoms, the dose of Talliton 12.5 mg may be decreased. The dose of Talliton 12.5 mg should not be increased until symptoms of worsening heart failure or vasodilation have been stabilized. Initial difficulty with titration should not preclude later attempts to introduce Talliton 12.5 mg. If congestive heart failure patients experience bradycardia (pulse rate <55 bpm), the dose of Talliton 12.5 mg should be reduced.

Hypertension: Dosage must be individualized. The recommended starting dose of Talliton 12.5 mg is 6.25 mg twice daily. If this dose is tolerated, using standing systolic pressure measured about 1 hr after dosing as a guide, the dose should be maintained for 7-14 days, and then increased to 12.5 mg twice daily if needed, based on trough blood pressure, again using standing systolic pressure 1 hr after dosing as a guide for tolerance. This dose should also be maintained for 7-14 days and can then be adjusted upward to 25 mg twice daily if tolerated and needed. The full antihypertensive effect of Talliton 12.5 mg is seen within 7-14 days. Total daily dose should not exceed 50 mg. Talliton 12.5 mg should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects. Addition of a diuretic to Talliton 12.5 mg, or Talliton 12.5 mg to a diuretic can be expected to produce additive effects and exaggerate the orthostatic component of Talliton 12.5 mg's action. Talliton 12.5 mg should not be given to patients with severe hepatic impairment.

See also:
What is the most important information I should know about Talliton 12.5 mg?

You should not take this medication if you are allergic to Talliton 12.5 mg, or if you have asthma, bronchitis, emphysema, severe liver disease, or a serious heart condition such as heart block, sick sinus syndrome, or slow heart rate (unless you have a pacemaker).

If you need surgery, tell the surgeon ahead of time that you are using Talliton 12.5 mg. You may need to stop using the medicine for a short time.

Do not stop taking Talliton 12.5 mg without first talking to your doctor. Stopping suddenly may make your condition worse.

Avoid drinking alcohol within 2 hours before or after taking extended-release Talliton 12.5 mg. Also avoid taking medicines or other products that might contain alcohol. Alcohol may cause the Talliton 12.5 mg in Talliton 12.5 mg to be released too quickly into the body.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Use Talliton 12.5 mg extended-release capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Talliton 12.5 mg extended-release capsules. Talk to your pharmacist if you have questions about this information.
• Take Talliton 12.5 mg extended-release capsules by mouth with food. Take it in the morning unless your doctor tells you otherwise.
• Swallow Talliton 12.5 mg extended-release capsules whole. Do not break, crush, or chew before swallowing. If you cannot swallow the capsule whole, you may open it and sprinkle the contents over a spoonful of cool applesauce. Mix the medicine with the applesauce and swallow the mixture right away, followed by a glass of water. Do not crush or chew the medicine before swallowing. Do not store mixture for future use.
• Do not drink alcohol or take medicines that contain alcohol within 2 hours before or after you take Talliton 12.5 mg extended-release capsules.
• Take Talliton 12.5 mg extended-release capsules on a regular schedule to get the most benefit from it. Taking Talliton 12.5 mg extended-release capsules at the same time each day will help you remember to take it.
• Continue to use Talliton 12.5 mg extended-release capsules even if you feel well. Do not miss any doses.
• Do not suddenly stop taking Talliton 12.5 mg extended-release capsules. You may have an increased risk of side effects. If you need to stop Talliton 12.5 mg extended-release capsules or add a new medicine, your doctor will gradually lower your dose.
• If you miss a dose of Talliton 12.5 mg extended-release capsules, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Talliton 12.5 mg extended-release capsules.

Talliton 12.5 mg is used to treat high blood pressure and heart failure. It is also used after a heart attack to improve the chance of survival if your heart is not pumping well. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

This drug works by blocking the action of certain natural substances in your body, such as epinephrine, on the heart and blood vessels. This effect lowers your heart rate, blood pressure, and strain on your heart. Talliton 12.5 mg belongs to a class of drugs known as alpha and beta blockers.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to treat a certain type of irregular heartbeat (atrial fibrillation).

How to use Talliton 12.5 mg

Read the Patient Information Leaflet if available from your pharmacist before you start taking Talliton 12.5 mg and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with food as directed by your doctor, usually twice daily.

The dosage is based on your medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

For the treatment of high blood pressure, it may take 1 to 2 weeks before you get the full benefit of this drug. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

Tell your doctor if your condition does not improve or if it worsens (for example, your blood pressure readings remain high or increase, or you have worsening symptoms of heart failure like increased shortness of breath).

See also:
What other drugs will affect Talliton 12.5 mg?

Pharmacokinetic Interactions: Effects of Talliton 12.5 mg on the Pharmacokinetics of Other Drugs: Talliton 12.5 mg is a substrate as well as an inhibitor of P-gp. Therefore, the bioavailability of drugs transported by P-gp may be increased with concomitant administration of Talliton 12.5 mg. In addition, the bioavailability of Talliton 12.5 mg can be modified by inducers or inhibitors of P-gp.

Digoxin: An increased exposure to digoxin of up to 20% has been shown in some studies in healthy subjects and patients with heart failure. A significantly larger effect has been seen in male patients compared to female patients. Therefore, monitoring of digoxin levels is recommended when initiating, adjusting or discontinuing Talliton 12.5 mg. Talliton 12.5 mg had no effect on digoxin administered IV.

Cyclosporin: Two (2) studies in renal and cardiac transplant patients receiving oral cyclosporin have shown an increase in cyclosporin plasma concentration following the initiation of Talliton 12.5 mg. It appears that Talliton 12.5 mg increases exposure to oral cyclosporin by around 10-20%. In an attempt to maintain therapeutic cyclosporin levels, an average 10-20% reduction of the cyclosporin dose was necessary. The mechanism for the interaction is not known but inhibition of intestinal P-gp by Talliton 12.5 mg may be involved. Due to wide interindividual variability of cyclosporin levels, it is recommended that cyclosporin concentrations are monitored closely after initiation of Talliton 12.5 mg therapy and that the dose of cyclosporin be adjusted as appropriate. In case of cyclosporin IV administration, no interaction with Talliton 12.5 mg is expected.

Effects of Other Drugs on the Pharmacokinetics of Talliton 12.5 mg: Inhibitors as well as inducers of CYP2D6 and CYP2C9 can modify the systemic and/or presystemic metabolism of Talliton 12.5 mg stereoselectively, leading to increased or decreased plasma concentrations of R- and S-Talliton 12.5 mg. Some examples observed in patients or in healthy subjects are listed as follows but the list is not exhaustive.

Rifampicin: In a study in 12 healthy subjects, exposure to Talliton 12.5 mg decreased by around 60% during concomitant administration with rifampicin and a decreased effect of Talliton 12.5 mg on the systolic blood pressure was observed. The mechanism for the interaction is not known but it may be due to the induction of the intestinal P-gp by rifampicin. A close monitoring of the β-blockade activity in patients receiving concomitant administration of Talliton 12.5 mg and rifampicin is appropriate.

Amiodarone: An in vitro study with human liver microsomes has shown that amiodarone and desethylamiodarone inhibited the oxidation of R- and S-Talliton 12.5 mg. The trough concentration of R- and S-Talliton 12.5 mg was significantly increased by 2.2-fold in heart failure patients receiving Talliton 12.5 mg and amiodarone concomitantly as compared to patients receiving Talliton 12.5 mg monotherapy. The effect on S-Talliton 12.5 mg was attributed to desethylamiodarone, a metabolite of amiodarone, which is a strong inhibitor of CYP2C9. A monitoring of the β-blockade activity in patients treated with the combination Talliton 12.5 mg and amiodarone is advised.

Fluoxetine and Paroxetine: In a randomized, cross-over study in 10 patients with heart failure, co-administration of fluoxetine, a strong inhibitor of CYP2D6, resulted in stereoselective inhibition of Talliton 12.5 mg metabolism with a 77% increase in mean R(+) enantiomer's AUC and a non-statistically 35% increase of the S(-) enantiomer's AUC as compared to the placebo group. However, no differences in adverse events, blood pressure or heart rate were noted between treatment groups. The effect of single-dose paroxetine, a strong CYP2D6 inhibitor, on Talliton 12.5 mg pharmacokinetics was investigated in 12 healthy subjects following single oral administration. Despite significant increase in R- and S-Talliton 12.5 mg exposure, no clinical effects were observed in these healthy subjects.

Pharmacodynamic Interactions: Insulin or

Oral Hypoglycemics:

Catecholamine-Depleting Agents: Patients taking both agents with β-blocking properties and a drug that can deplete catecholamines (eg, reserpine and monoamine oxidase inhibitors) should be observed closely for signs of hypotension and/or severe bradycardia.

Digoxin: The combined use of β-blockers and digoxin may result in additive prolongation of AV conduction time.

Non-Dihydropyridines Calcium-Channel Blockers, Amiodarone or Other Anti-Arrhythmics: In combination with Talliton 12.5 mg can increase the risk of AV conduction disturbances. Isolated cases of conduction disturbance (rarely with hemodynamic compromise) have been observed when Talliton 12.5 mg is co-administered with diltiazem. As with other agents with β-blocking properties, if Talliton 12.5 mg is to be administered orally with non-dihydropyridines calcium-channel blockers of the verapamil or diltiazem type, amiodarone or other anti-arrhythmics, it is recommended that ECG and blood pressure be monitored.

Clonidine: Concomitant administration of clonidine with agents with β-blocking properties may potentiate blood-pressure- and heart-rate-lowering effects. When concomitant treatment with agents with β-blocking properties and clonidine is to be terminated, the β-blocking agent should be discontinued first. Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage.

Antihypertensives: As with other agents with β-blocking activity, Talliton 12.5 mg may potentiate the effect of other concomitantly administered drugs that are anti-hypertensive in action (eg, α₁-receptor antagonists) or have hypotension as part of their adverse effect profile.

Anesthetic Agents: Careful monitoring of vital signs is recommended during anesthesia due to the synergistic negative inotropic and hypotensive effects of Talliton 12.5 mg and anesthetic drugs.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): The concurrent use of NSAIDs and β-adrenergic blockers may result in an increase in blood pressure and impairment of blood pressure control.

β-Agonist Bronchodilators: Non-cardioselective β-blockers oppose the bronchodilator effects of β-agonist bronchodilators. Careful monitoring of patients is recommended.

See also:
What are the possible side effects of Talliton 12.5 mg?

Clinical Trials Experience

Talliton 12.5 mg has been evaluated for safety in subjects with heart failure (mild, moderate, and severe), in subjects with left ventricular dysfunction following myocardial infarction, and in hypertensive subjects. The observed adverse event profile was consistent with the pharmacology of the drug and the health status of the subjects in the clinical trials. Adverse events reported for each of these populations reflecting the use of either Talliton 12.5 mg or immediate-release Talliton 12.5 mg are provided below. Excluded are adverse events considered too general to be informative, and those not reasonably associated with the use of the drug because they were associated with the condition being treated or are very common in the treated population. Rates of adverse events were generally similar across demographic subsets (men and women, elderly and non-elderly, blacks and non-blacks). Talliton 12.5 mg has been evaluated for safety in a 4-week (2 weeks of immediate-release Talliton 12.5 mg and 2 weeks of Talliton 12.5 mg) clinical trial (n = 187) which included 157 subjects with stable mild, moderate, or severe chronic heart failure and 30 subjects with left ventricular dysfunction following acute myocardial infarction. The profile of adverse events observed with Talliton 12.5 mg in this small, short-term trial was generally similar to that observed with immediate-release Talliton 12.5 mg. Differences in safety would not be expected based on the similarity in plasma levels for Talliton 12.5 mg and immediate-release Talliton 12.5 mg.

Heart Failure

The following information describes the safety experience in heart failure with immediate-release Talliton 12.5 mg.

Talliton 12.5 mg has been evaluated for safety in heart failure in more than 4,500 subjects worldwide of whom more than 2,100 participated in placebo-controlled clinical trials. Approximately 60% of the total treated population in placebo-controlled clinical trials received Talliton 12.5 mg for at least 6 months and 30% received Talliton 12.5 mg for at least 12 months. In the COMET trial, 1,511 subjects with mild-to-moderate heart failure were treated with Talliton 12.5 mg for up to 5.9 years (mean: 4.8 years). Both in US clinical trials in mild-to-moderate heart failure that compared Talliton 12.5 mg in daily doses up to 100 mg (n = 765) with placebo (n = 437), and in a multinational clinical trial in severe heart failure (COPERNICUS) that compared Talliton 12.5 mg in daily doses up to 50 mg (n = 1,156) with placebo (n = 1,133), discontinuation rates for adverse experiences were similar in Talliton 12.5 mg and placebo subjects. In placebo-controlled clinical trials, the only cause of discontinuation greater than 1%, and occurring more often on Talliton 12.5 mg was dizziness (1.3% on Talliton 12.5 mg, 0.6% on placebo in the COPERNICUS trial).

Table 2 shows adverse events reported in subjects with mild-to-moderate heart failure enrolled in US placebo-controlled clinical trials, and with severe heart failure enrolled in the COPERNICUS trial. Shown are adverse events that occurred more frequently in drug-treated subjects than placebo-treated subjects with an incidence of greater than 3% in subjects treated with Talliton 12.5 mg regardless of causality. Median trial medication exposure was 6.3 months for both Talliton 12.5 mg and placebo subjects in the trials of mild-to-moderate heart failure, and 10.4 months in the trial of subjects with severe heart failure. The adverse event profile of Talliton 12.5 mg observed in the long-term COMET trial was generally similar to that observed in the US Heart Failure Trials.11

Table 2: Adverse Events (%) Occurring More Frequently with Immediate-Release Talliton 12.5 mg than with Placebo in Subjects with Mild-to-Moderate Heart Failure (HF) Enrolled in US Heart Failure Trials or in Subjects with Severe Heart Failure in the COPERNICUS Trial (Incidence > 3% in Subjects Treated with Talliton 12.5 mg, Regardless of Causality)

Cardiac failure and dyspnea were also reported in these trials, but the rates were equal or greater in subjects who received placebo.

The following adverse events were reported with a frequency of greater than 1% but less than or equal to 3% and more frequently with Talliton 12.5 mg in either the US placebo-controlled trials in subjects with mild-to-moderate heart failure, or in subjects with severe heart failure in the COPERNICUS trial.

Incidence Greater Than 1% To Less Than Or Equal To 3%

Body as a Whole: Allergy, malaise, hypovolemia, fever, leg edema.

Cardiovascular: Fluid overload, postural hypotension, aggravated angina pectoris, AV block, palpitation, hypertension.

Central and Peripheral Nervous System: Hypesthesia, vertigo, paresthesia.

Gastrointestinal: Melena, periodontitis.

Liver and Biliary System: SGPT increased, SGOT increased.

Metabolic and Nutritional: Hyperuricemia, hypoglycemia, hyponatremia, increased alkaline phosphatase, glycosuria, hypervolemia, diabetes mellitus, GGT increased, weight loss, hyperkalemia, creatinine increased.

Musculoskeletal: Muscle cramps.

Platelet, Bleeding, and Clotting: Prothrombin decreased, purpura, thrombocytopenia.

Psychiatric: Somnolence.

Reproductive, male: Impotence.

Special Senses: Blurred vision.

Urinary System: Renal insufficiency, albuminuria, hematuria.

Left Ventricular Dysfunction following Myocardial Infarction

The following information describes the safety experience in left ventricular dysfunction following acute myocardial infarction with immediate-release Talliton 12.5 mg.

Talliton 12.5 mg has been evaluated for safety in survivors of an acute myocardial infarction with left ventricular dysfunction in the CAPRICORN trial which involved 969 subjects who received Talliton 12.5 mg and 980 who received placebo. Approximately 75% of the subjects received Talliton 12.5 mg for at least 6 months and 53% received Talliton 12.5 mg for at least 12 months. Subjects were treated for an average of 12.9 months and 12.8 months with Talliton 12.5 mg and placebo, respectively.

The most common adverse events reported with Talliton 12.5 mg in the CAPRICORN trial were consistent with the profile of the drug in the US heart failure trials and the COPERNICUS trial. The only additional adverse events reported in CAPRICORN in greater than 3% of the subjects and more commonly on Talliton 12.5 mg were dyspnea, anemia, and lung edema. The following adverse events were reported with a frequency of greater than 1% but less than or equal to 3% and more frequently with Talliton 12.5 mg: flu syndrome, cerebrovascular accident, peripheral vascular disorder, hypotonia, depression, gastrointestinal pain, arthritis, and gout. The overall rates of discontinuations due to adverse events were similar in both groups of subjects. In this database, the only cause of discontinuation greater than 1%, and occurring more often on Talliton 12.5 mg was hypotension (1.5% on Talliton 12.5 mg, 0.2% on placebo).

Hypertension

Talliton 12.5 mg was evaluated for safety in an 8-week double-blind trial in 337 subjects with essential hypertension. The profile of adverse events observed with Talliton 12.5 mg was generally similar to that observed with immediate-release Talliton 12.5 mg. The overall rates of discontinuations due to adverse events were similar between Talliton 12.5 mg and placebo.

Table 3: Adverse Events (%) Occurring More Frequently with Talliton 12.5 mg than with Placebo in Subjects with Hypertension (Incidence ≥ 1% in Subjects Treated with Talliton 12.5 mg, Regardless of Causality)

The following information describes the safety experience in hypertension with immediate-release Talliton 12.5 mg.

Talliton 12.5 mg has been evaluated for safety in hypertension in more than 2,193 subjects in US clinical trials and in 2,976 subjects in international clinical trials. Approximately 36% of the total treated population received Talliton 12.5 mg for at least 6 months. In general, Talliton 12.5 mg was well tolerated at doses up to 50 mg daily. Most adverse events reported during Talliton 12.5 mg therapy were of mild to moderate severity. In US controlled clinical trials directly comparing Talliton 12.5 mg monotherapy in doses up to 50 mg (n = 1,142) with placebo (n = 462), 4.9% of Talliton 12.5 mg subjects discontinued for adverse events versus 5.2% of placebo subjects. Although there was no overall difference in discontinuation rates, discontinuations were more common in the Talliton 12.5 mg group for postural hypotension (1% versus 0). The overall incidence of adverse events in US placebo-controlled trials was found to increase with increasing dose of Talliton 12.5 mg. For individual adverse events this could only be distinguished for dizziness, which increased in frequency from 2% to 5% as total daily dose increased from 6.25 mg to 50 mg as single or divided doses.

Table 4 shows adverse events in US placebo-controlled clinical trials for hypertension that occurred with an incidence of greater than or equal to 1% regardless of causality, and that were more frequent in drug-treated subjects than placebo-treated subjects.

Table 4: Adverse Events (% Occurrence) in US Placebo-Controlled Hypertension Trials with Immediate-Release Talliton 12.5 mg (Incidence ≥ 1% in Subjects Treated with Talliton 12.5 mg, Regardless of Causality)*

Dyspnea and fatigue were also reported in these trials, but the rates were equal or greater in subjects who received placebo.

The following adverse events not described above were reported as possibly or probably related to Talliton 12.5 mg in worldwide open or controlled trials with Talliton 12.5 mg in subjects with hypertension or heart failure.

Incidence Greater Than 0.1% To Less Than Or Equal To 1%

Cardiovascular: Peripheral ischemia, tachycardia.

Central and Peripheral Nervous System: Hypokinesia.

Gastrointestinal: Bilirubinemia, increased hepatic enzymes (0.2% of hypertension patients and 0.4% of heart failure patients were discontinued from therapy because of increases in hepatic enzymes).

Psychiatric: Nervousness, sleep disorder, aggravated depression, impaired concentration, abnormal thinking, paroniria, emotional lability.

Respiratory System: Asthma.

Reproductive, male: Decreased libido.

Skin and Appendages: Pruritus, rash erythematous, rash maculopapular, rash psoriaform, photosensitivity reaction.

Special Senses: Tinnitus.

Urinary System: Micturition frequency increased.

Autonomic Nervous System: Dry mouth, sweating increased.

Metabolic and Nutritional: Hypokalemia, hypertriglyceridemia.

Hematologic: Anemia, leukopenia.

The following events were reported in less than or equal to 0.1% of subjects and are potentially important: complete AV block, bundle branch block, myocardial ischemia, cerebrovascular disorder, convulsions, migraine, neuralgia, paresis, anaphylactoid reaction, alopecia, exfoliative dermatitis, amnesia, GI hemorrhage, bronchospasm, pulmonary edema, decreased hearing, respiratory alkalosis, increased BUN, decreased HDL, pancytopenia, and atypical lymphocytes.

Laboratory Abnormalities

Reversible elevations in serum transaminases (ALT or AST) have been observed during treatment with Talliton 12.5 mg. Rates of transaminase elevations (2 to 3 times the upper limit of normal) observed during controlled clinical trials have generally been similar between subjects treated with Talliton 12.5 mg and those treated with placebo. However, transaminase elevations, confirmed by rechallenge, have been observed with Talliton 12.5 mg. In a long-term, placebo-controlled trial in severe heart failure, subjects treated with Talliton 12.5 mg had lower values for hepatic transaminases than subjects treated with placebo, possibly because Talliton 12.5 mg-induced improvements in cardiac function led to less hepatic congestion and/or improved hepatic blood flow.

Talliton 12.5 mg therapy has not been associated with clinically significant changes in serum potassium, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine. No clinically relevant changes were noted in fasting serum glucose in hypertensive subjects; fasting serum glucose was not evaluated in the heart failure clinical trials.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of COREG® or Talliton 12.5 mg. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders

Aplastic anemia.

Immune System Disorders

Hypersensitivity (e.g., anaphylactic reactions, angioedema, urticaria).

Renal and Urinary Disorders

Urinary incontinence.

Respiratory, Thoracic and Mediastinal Disorders

Interstitial pneumonitis.

Skin and Subcutaneous Tissue Disorders

Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.