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Trandate

Trandate


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Trandate Drug Description


TRANDATE®
(labetalol hydrochloride) Tablets

DRUG DESCRIPTION

Trandate (labetalol) Tablets are adrenergic receptor blocking agents that have both selective alpha1-adrenergic and nonselective beta-adrenergic receptor blocking actions in a single substance.

Labetalol hydrochloride (HCl) is a racemate chemically designated as 2-hydroxy-5-[1-hydroxy-2-[(1methyl-3-phenylpropyl)amino]ethyl]benzamide monohydrochloride, and it has the following structure:

 

TRANDATE® (labetalol hydrochloride) Structural Formula Illustration

Labetalol HCl has the empirical formula C19H24N2O3•HCl and a molecular weight of 364.9. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs. Dilevalol, the R,R' stereoisomer, makes up 25% of racemic labetalol.

Labetalol HCl is a white or off-white crystalline powder, soluble in water.

Trandate Tablets contain 100, 200, or 300 mg of labetalol HCl and are taken orally. The tablets also contain the inactive ingredients corn starch, FD&C Yellow No. 6 (100- and 300-mg tablets only), hydroxypropyl methylcellulose, lactose, magnesium stearate, pregelatinized corn starch, sodium benzoate (200-mg tablet only), talc (100-mg tablet only), and titanium dioxide.

 

What are the possible side effects of labetalol (Normodyne, Trandate)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • slow or uneven heartbeats;
  • feeling light-headed, fainting;
  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice...

Read All Potential Side Effects and See Pictures of Trandate »

 

What are the precautions when taking labetalol (Trandate)?

Before taking labetalol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain types of heart rhythm problems (such as a slow heartbeat, second- or third-degree atrioventricular block), severe heart failure, breathing problems (such as asthma, chronic bronchitis, emphysema).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: treated stable heart failure, kidney disease, liver disease,...

 

Trandate


Trandate Indications & Dosage


INDICATIONS

Trandate (labetalol) Tablets are indicated in the management of hypertension. Trandate (labetalol) Tablets may be used alone or in combination with other antihypertensive agents, especially thiazide and loop diuretics.

DOSAGE AND ADMINISTRATION

DOSAGE MUST BE INDIVIDUALIZED. The recommended initial dosage is 100 mg twice daily whether used alone or added to a diuretic regimen. After 2 or 3 days, using standing blood pressure as an indicator, dosage may be titrated in increments of 100 mg b.i.d. every 2 or 3 days. The usual maintenance dosage of labetalol HCl is between 200 and 400 mg twice daily.

Since the full antihypertensive effect of labetalol HCl is usually seen within the first 1 to 3 hours of the initial dose or dose increment, the assurance of a lack of an exaggerated hypotensive response can be clinically established in the office setting. The antihypertensive effects of continued dosing can be measured at subsequent visits, approximately 12 hours after a dose, to determine whether further titration is necessary.

Patients with severe hypertension may require from 1,200 to 2,400 mg per day, with or without thiazide diuretics. Should side effects (principally nausea or dizziness) occur with these doses administered twice daily, the same total daily dose administered three times daily may improve tolerability and facilitate further titration. Titration increments should not exceed 200 mg twice daily.

When a diuretic is added, an additive antihypertensive effect can be expected. In some cases this may necessitate a labetalol HCl dosage adjustment. As with most antihypertensive drugs, optimal dosages of Trandate (labetalol) Tablets are usually lower in patients also receiving a diuretic.

When transferring patients from other antihypertensive drugs, Trandate (labetalol) Tablets should be introduced as recommended and the dosage of the existing therapy progressively decreased.

Elderly Patients

As in the general patient population, labetalol therapy may be initiated at 100 mg twice daily and titrated upwards in increments of 100 mg b.i.d. as required for control of blood pressure. Since some elderly patients eliminate labetalol more slowly, however, adequate control of blood pressure may be achieved at a lower maintenance dosage compared to the general population. The majority of elderly patients will require between 100 and 200 mg b.i.d.

HOW SUPPLIED

Trandate (labetalol) Tablets, 100 mg, light orange, round, scored, film-coated tablets engraved on one side with “TRANDATE (labetalol) 100,” bottles of 100 (NDC 65483-391-10) and 500 (NDC 65483-391-50) and unit dose packs of 100 tablets (NDC 65483-391-11).

Trandate (labetalol) Tablets, 200 mg, white, round, scored, film-coated tablets engraved on one side with “TRANDATE (labetalol) 200,” bottles of 100 (NDC 65483-392-10) and 500 (NDC 65483-392-50) and unit dose packs of 100 tablets (NDC 65483-392-22).

Trandate (labetalol) Tablets, 300 mg, mid-orange, round, scored, film-coated tablets engraved on one side with “TRANDATE (labetalol) 300,” bottles of 100 (NDC 65483-393-10) and 500 (NDC 65483-393-50) and unit dose packs of 100 tablets (NDC 65483-393-33).

Trandate (labetalol) Tablets should be stored between 2° and 30°C (36° and 86°F). Trandate (labetalol) Tablets in the unit dose boxes should be protected from excessive moisture.

Prometheus Laboratories Inc. Manufactured in Canada by WellSpring Pharmaceutical Canada Corp. Oakville, ON L6H 1M5 for Prometheus Laboratories Inc. San Diego, CA 92121. Revised: November 2010

 

Trandate


Trandate Side Effects & Drug Interactions


SIDE EFFECTS

Most adverse effects are mild and transient and occur early in the course of treatment. In controlled clinical trials of 3 to 4 months' duration, discontinuation of Trandate (labetalol) Tablets due to one or more adverse effects was required in 7% of all patients. In these same trials, other agents with solely beta-blocking activity used in the control groups led to discontinuation in 8% to 10% of patients, and a centrally acting alpha-agonist led to discontinuation in 30% of patients.

The incidence rates of adverse reactions listed in the following table were derived from multicenter, controlled clinical trials comparing labetalol HCl, placebo, metoprolol, and propranolol over treatment periods of 3 and 4 months. Where the frequency of adverse effects for labetalol HCl and placebo is similar, causal relationship is uncertain. The rates are based on adverse reactions considered probably drug related by the investigator. If all reports are considered, the rates are somewhat higher (e.g., dizziness, 20%; nausea, 14%; fatigue, 11%), but the overall conclusions are unchanged.

 

Labetalol HCI
(n = 227)
%
Placebo
(n = 98)
%
Propranolol
(n = 84)
%
Metoprolol
(n = 49)
%
Body as a whole
Fatigue 5 0 12 12
Asthenia 1 1 1 0
Headache 2 1 1 2
Gastrointestinal
Nausea 6 1 1 2
Vomiting <1 0 0 0
Dyspepsia 3 1 1 0
Abdominal pain 0 0 1 2
Diarrhea <1 0 2 0
Taste distortion 1 0 0 0
Central and peripheral nervous systems
Dizziness 11 3 4 4
Paresthesia <1 0 0 0
Drowsiness <1 2 2 2
Autonomic nervous system
Nasal stuffiness 3 0 0 0
Ejaculation failure 2 0 0 0
Impotence 1 0 1 3
Increased sweating <1 0 0 0
Cardiovascular
Edema 1 0 0 0
Postural hypotension 1 0 0 0
Bradycardia 0 0 5 12
Respiratory
Dyspnea 2 0 1 2
Skin
Rash 1 0 0 0
Special senses
Vision abnormality 1 0 0 0
Vertigo 2 1 0 0

The adverse effects were reported spontaneously and are representative of the incidence of adverse effects that may be observed in a properly selected hypertensive patient population, i.e., a group excluding patients with bronchospastic disease, overt congestive heart failure, or other contraindications to beta-blocker therapy.

Clinical trials also included studies utilizing daily doses up to 2,400 mg in more severely hypertensive patients. Certain of the side effects increased with increasing dose, as shown in the following table that depicts the entire US therapeutic trials data base for adverse reactions that are clearly or possibly dose related.

 

Labetalol HCl Daily Dose (mg) 200 300 400 600 800 900 1,200 1,600 2,400
Number of patients 522 181 606 608 503 117 411 242 175
Dizziness (%) 2 3 3 3 5 1 9 13 16
Fatigue 2 1 4 4 5 3 7 6 10
Nausea < 1 0 1 2 4 0 7 11 19
Vomiting 0 0 < 1 < 1 < 1 0 1 2 3
Dyspepsia 1 0 2 1 1 0 2 2 4
Paresthesia 2 0 2 2 1 1 2 5 5
Nasal stuffiness 1 1 2 2 2 2 4 5 6
Ejaculation failure 0 2 1 2 3 0 4 3 5
Impotence 1 1 1 1 2 4 3 4 3
Edema 1 0 1 1 1 0 1 2 2

In addition, a number of other less common adverse events have been reported:

Body as a Whole: Fever.

Cardiovascular: Hypotension, and rarely, syncope, bradycardia, heart block.

Central and Peripheral Nervous Systems: Paresthesia, most frequently described as scalp tingling. In most cases, it was mild and transient and usually occurred at the beginning of treatment.

Collagen Disorders: Systemic lupus erythematosus, positive antinuclear factor.

Eyes: Dry eyes.

Immunological System: Antimitochondrial antibodies.

Liver and Biliary System: Hepatic necrosis, hepatitis, cholestatic jaundice, elevated liver function tests.

Musculoskeletal System: Muscle cramps, toxic myopathy.

Respiratory System: Bronchospasm.

Skin and Appendages: Rashes of various types, such as generalized maculopapular, lichenoid, urticarial, bullous lichen planus, psoriaform, and facial erythema; Peyronie's disease; reversible alopecia.

Urinary System: Difficulty in micturition, including acute urinary bladder retention.

Hypersensitivity: Rare reports of hypersensitivity (e.g., rash, urticaria, pruritus, angioedema, dyspnea) and anaphylactoid reactions.

Following approval for marketing in the United Kingdom, a monitored release survey involving approximately 6,800 patients was conducted for further safety and efficacy evaluation of this product. Results of this survey indicate that the type, severity, and incidence of adverse effects were comparable to those cited above.

Potential Adverse Effects

In addition, other adverse effects not listed above have been reported with other beta-adrenergic blocking agents.

Central 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 psychometrics.

Cardiovascular

Intensification of A-V block (see CONTRAINDICATIONS).

Allergic

Fever combined with aching and sore throat, laryngospasm, respiratory distress.

Hematologic

Agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura.

Gastrointestinal

Mesenteric artery thrombosis, ischemic colitis.

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with labetalol HCl.

Clinical Laboratory Tests

There have been reversible increases of serum transaminases in 4% of patients treated with labetalol HCl and tested and, more rarely, reversible increases in blood urea.

DRUG INTERACTIONS

In one survey, 2.3% of patients taking labetalol HCl in combination with tricyclic antidepressants experienced tremor, as compared to 0.7% reported to occur with labetalol HCl alone. The contribution of each of the treatments to this adverse reaction is unknown, but the possibility of a drug interaction cannot be excluded.

Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal antiasthmatic dose of beta-agonist bronchodilator drugs may be required.

Cimetidine has been shown to increase the bioavailability of labetalol HCl. Since this could be explained either by enhanced absorption or by an alteration of hepatic metabolism of labetalol HCl, special care should be used in establishing the dose required for blood pressure control in such patients.

Synergism has been shown between halothane anesthesia and intravenously administered labetalol HCl. During controlled hypotensive anesthesia using labetalol HCl in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure. The anesthesiologist should be informed when a patient is receiving labetalol HCl.

Labetalol HCl blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If labetalol HCl is used with nitroglycerin in patients with angina pectoris, additional antihypertensive effects may occur.

Care should be taken if labetalol is used concomitantly with calcium antagonists of the verapamil type.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Risk of Anaphylactic Reaction

While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Drug/Laboratory Test Interactions

The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with labetalol HCl, a specific method, such as a high performance liquid chromatographic assay with solid phase extraction (e.g., J Chromatogr 385:241,1987) should be employed in determining levels of catecholamines.

Labetalol HCl has also been reported to produce a false-positive test for amphetamine when screening urine for the presence of drugs using the commercially available assay methods TOXI-LAB® A (thinlayer chromatographic assay) and EMIT-d.a.u.® (radioenzymatic assay). When patients being treated with labetalol have a positive urine test for amphetamine using these techniques, confirmation should be made by using more specific methods, such as a gas chromatographic-mass spectrometer technique.

 

Trandate


 

Trandate Warnings & Precautions


WARNINGS

Hepatic Injury

Severe hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology. Similar hepatic events have been reported with a related research compound, dilevalol HCl, including two deaths. Dilevalol HCl is one of the four isomers of labetalol HCl. Thus, for patients taking labetalol, periodic determination of suitable hepatic laboratory tests would be appropriate. Appropriate laboratory testing should be done at the first symptom/sign of liver dysfunction (e.g., pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, or unexplained “flu-like” symptoms). If the patient has laboratory evidence of liver injury or jaundice, labetalol should be stopped and not restarted.

Cardiac Failure

Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta-blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, labetalol HCl can be used with caution in patients with a history of heart failure who are well compensated. Congestive heart failure has been observed in patients receiving labetalol HCl. Labetalol HCl does not abolish the inotropic action of digitalis on heart muscle.

In Patients Without a History of Cardiac Failure

In patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or be given a diuretic, and the response should be observed closely. If cardiac failure continues despite adequate digitalization and diuretic, therapy with Trandate (labetalol) Tablets should be withdrawn (gradually, if possible).

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal

Angina pectoris has not been reported upon labetalol HCl discontinuation. However, hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered Trandate (labetalol) Tablets, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1 to 2 weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, therapy with Trandate (labetalol) Tablets should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue therapy with Trandate (labetalol) Tablets abruptly in patients being treated for hypertension.

Nonallergic Bronchospasm (e.g., Chronic Bronchitis and Emphysema): Patients with bronchospastic disease should, in general, not receive beta-blockers. Trandate (labetalol) Tablets may be used with caution, however, in patients who do not respond to, or cannot tolerate, other antihypertensive agents. It is prudent, if Trandate (labetalol) Tablets are used, to use the smallest effective dose, so that inhibition of endogenous or exogenous beta-agonists is minimized.

Pheochromocytoma

Labetalol HCl has been shown to be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, use caution when administering labetalol HCl to patients with pheochromocytoma.

Diabetes Mellitus and Hypoglycemia

Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; it may therefore be necessary to adjust the dose of antidiabetic drugs.

Major Surgery

Do not routinely withdraw chronic beta blocker therapy prior to surgery. The effect of labetalol's alpha adrenergic activity has not been evaluated in this setting.

A synergism between labetalol HCl and halothane anesthesia has been shown (see PRECAUTIONS: DRUG INTERACTIONS).

PRECAUTIONS

General

Impaired Hepatic Function

Trandate (labetalol) Tablets should be used with caution in patients with impaired hepatic function since metabolism of the drug may be diminished.

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients treated with alpha-1 blockers (labetalol is an alpha/beta blocker). This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery.

Jaundice or Hepatic Dysfunction

(see WARNINGS).

Laboratory Tests

As with any new drug given over prolonged periods, laboratory parameters should be observed over regular intervals. In patients with concomitant illnesses, such as impaired renal function, appropriate tests should be done to monitor these conditions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term oral dosing studies with labetalol HCl for 18 months in mice and for 2 years in rats showed no evidence of carcinogenesis. Studies with labetalol HCl using dominant lethal assays in rats and mice and exposing microorganisms according to modified Ames tests showed no evidence of mutagenesis.

Pregnancy

Teratogenic Effects

Pregnancy Category C: Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD. A teratology study performed with labetalol in rabbits at IV doses up to 1.7 times the MRHD revealed no evidence of drug-related harm to the fetus. There are no adequate and well-controlled studies in pregnant women. Labetalol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Hypotension, bradycardia, hypoglycemia, and respiratory depression have been reported in infants of mothers who were treated with labetalol HCl for hypertension during pregnancy. Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.

Labor and Delivery

Labetalol HCl given to pregnant women with hypertension did not appear to affect the usual course of labor and delivery.

Nursing Mothers

Small amounts of labetalol (approximately 0.004% of the maternal dose) are excreted in human milk. Caution should be exercised when Trandate (labetalol) Tablets are administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Elderly Patients

As in the general population, some elderly patients (60 years of age and older) have experienced orthostatic hypotension, dizziness, or lightheadedness during treatment with labetalol. Because elderly patients are generally more likely than younger patients to experience orthostatic symptoms, they should be cautioned about the possibility of such side effects during treatment with labetalol.

 

Trandate


Trandate Overdosage & Contraindications


OVERDOSE

Overdosage with labetalol HCl causes excessive hypotension that is posture sensitive and, sometimes, excessive bradycardia. Patients should be placed supine and their legs raised if necessary to improve the blood supply to the brain. If overdosage with labetalol HCl follows oral ingestion, gastric lavage or pharmacologically induced emesis (using syrup of ipecac) may be useful for removal of the drug shortly after ingestion. The following additional measures should be employed if necessary:

Excessive bradycardia-administer atropine or epinephrine.

Cardiac failure-administer a digitalis glycoside and a diuretic. Dopamine or dobutamine may also be useful.

Hypotension-administer vasopressors, e.g., norepinephrine. There is pharmacologic evidence that norepinephrine may be the drug of choice.

Bronchospasm-administer epinephrine and/or an aerosolized beta2-agonist.

Seizures-administer diazepam.

In severe beta-blocker overdose resulting in hypotension and/or bradycardia, glucagon has been shown to be effective when administered in large doses (5 to 10 mg rapidly over 30 seconds, followed by continuous infusion of 5 mg per hour that can be reduced as the patient improves).

Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol HCl from the general circulation ( < 1%).

The oral LD50 value of labetalol HCl in the mouse is approximately 600 mg/kg and in the rat is > 2 g/kg. The IV LD50 in these species is 50 to 60 mg/kg.

CONTRAINDICATIONS

Trandate (labetalol) Tablets are contraindicated in bronchial asthma, overt cardiac failure, greater-than-first-degree heart block, cardiogenic shock, severe bradycardia, other conditions associated with severe and prolonged hypotension, and in patients with a history of hypersensitivity to any component of the product (see WARNINGS).

Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with a history of obstructive airway disease, including asthma.

 

Trandate

Trandate Clinical Pharmacology


CLINICAL PHARMACOLOGY

Labetalol HCl combines both selective, competitive, alpha1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta-blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. Beta2-agonist activity has been demonstrated in animals with minimal beta1-agonist (ISA) activity detected. In animals, at doses greater than those required for alpha- or beta-adrenergic blockade, a membrane stabilizing effect has been demonstrated.

Pharmacodynamics

The capacity of labetalol HCl to block alpha receptors in man has been demonstrated by attenuation of the pressor effect of phenylephrine and by a significant reduction of the pressor response caused by immersing the hand in ice-cold water (“cold-pressor test”). Labetalol HCl's beta1-receptor blockade in man was demonstrated by a small decrease in the resting heart rate, attenuation of tachycardia produced by isoproterenol or exercise, and by attenuation of the reflex tachycardia to the hypotension produced by amyl nitrite. Beta2-receptor blockade was demonstrated by inhibition of the isoproterenol-induced fall in diastolic blood pressure. Both the alpha- and beta-blocking actions of orally administered labetalol HCl contribute to a decrease in blood pressure in hypertensive patients. Labetalol HCl consistently, in dose-related fashion, blunted increases in exercise-induced blood pressure and heart rate, and in their double product. The pulmonary circulation during exercise was not affected by labetalol HCl dosing.

Single oral doses of labetalol HCl administered to patients with coronary artery disease had no significant effect on sinus rate, intraventricular conduction, or QRS duration. The atrioventricular (A-V) conduction time was modestly prolonged in two of seven patients. In another study, IV labetalol HCl slightly prolonged A-V nodal conduction time and atrial effective refractory period with only small changes in heart rate. The effects on A-V nodal refractoriness were inconsistent.

Labetalol HCl produces dose-related falls in blood pressure without reflex tachycardia and without significant reduction in heart rate, presumably through a mixture of its alpha- and beta-blocking effects. Hemodynamic effects are variable, with small, nonsignificant changes in cardiac output seen in some studies but not others, and small decreases in total peripheral resistance. Elevated plasma renins are reduced.

Doses of labetalol HCl that controlled hypertension did not affect renal function in mildly to severely hypertensive patients with normal renal function.

Due to the alpha1-receptor blocking activity of labetalol HCl, blood pressure is lowered more in the standing than in the supine position, and symptoms of postural hypotension (2%), including rare instances of syncope, can occur. Following oral administration, when postural hypotension has occurred, it has been transient and is uncommon when the recommended starting dose and titration increments are closely followed (see DOSAGE AND ADMINISTRATION). Symptomatic postural hypotension is most likely to occur 2 to 4 hours after a dose, especially following the use of large initial doses or upon large changes in dose.

The peak effects of single oral doses of labetalol HCl occur within 2 to 4 hours. The duration of effect depends upon dose, lasting at least 8 hours following single oral doses of 100 mg and more than 12 hours following single oral doses of 300 mg. The maximum, steady-state blood pressure response upon oral, twice-a-day dosing occurs within 24 to 72 hours.

The antihypertensive effect of labetalol has a linear correlation with the logarithm of labetalol plasma concentration, and there is also a linear correlation between the reduction in exercise-induced tachycardia occurring at 2 hours after oral administration of labetalol HCl and the logarithm of the plasma concentration.

About 70% of the maximum beta-blocking effect is present for 5 hours after the administration of a single oral dose of 400 mg with suggestion that about 40% remains at 8 hours.

The antianginal efficacy of labetalol HCl has not been studied. In 37 patients with hypertension and coronary artery disease, labetalol HCl did not increase the incidence or severity of angina attacks.

Exacerbation of angina and, in some cases, myocardial infarction and ventricular dysrhythmias have been reported after abrupt discontinuation of therapy with beta-adrenergic blocking agents in patients with coronary artery disease. Abrupt withdrawal of these agents in patients without coronary artery disease has resulted in transient symptoms, including tremulousness, sweating, palpitation, headache, and malaise. Several mechanisms have been proposed to explain these phenomena, among them increased sensitivity to catecholamines because of increased numbers of beta receptors.

Although beta-adrenergic receptor blockade is useful in the treatment of angina and hypertension, there are also situations in which sympathetic stimulation is vital. For example, in patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. Beta-adrenergic blockade may worsen A-V block by preventing the necessary facilitating effects of sympathetic activity on conduction. Beta2-adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm, and it may also interfere with exogenous bronchodilators in such patients.

Pharmacokinetics and Metabolism

Labetalol HCl is completely absorbed from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The relative bioavailability of labetalol HCl tablets compared to an oral solution is 100%. The absolute bioavailability (fraction of drug reaching systemic circulation) of labetalol when compared to an IV infusion is 25%; this is due to extensive “first-pass” metabolism. Despite “first-pass” metabolism, there is a linear relationship between oral doses of 100 to 3,000 mg and peak plasma levels. The absolute bioavailability of labetalol is increased when administered with food.

The plasma half-life of labetalol following oral administration is about 6 to 8 hours. Steady-state plasma levels of labetalol during repetitive dosing are reached by about the third day of dosing. In patients with decreased hepatic or renal function, the elimination half-life of labetalol is not altered; however, the relative bioavailability in hepatically impaired patients is increased due to decreased “first-pass” metabolism.

The metabolism of labetalol is mainly through conjugation to glucuronide metabolites. These metabolites are present in plasma and are excreted in the urine and, via the bile, into the feces. Approximately 55% to 60% of a dose appears in the urine as conjugates or unchanged labetalol within the first 24 hours of dosing.

Labetalol has been shown to cross the placental barrier in humans. Only negligible amounts of the drug crossed the blood-brain barrier in animal studies. Labetalol is approximately 50% protein bound. Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol HCl from the general circulation ( < 1%).

Elderly Patients

Some pharmacokinetic studies indicate that the elimination of labetalol is reduced in elderly patients. Therefore, although elderly patients may initiate therapy at the currently recommended dosage of 100 mg b.i.d., elderly patients will generally require lower maintenance dosages than nonelderly patients.

 

Trandate


Trandate Medication Guide


PATIENT INFORMATION

As with all drugs with beta-blocking activity, certain advice to patients being treated with labetalol HCl is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects. While no incident of the abrupt withdrawal phenomenon (exacerbation of angina pectoris) has been reported with labetalol HCl, dosing with Trandate (labetalol) Tablets should not be interrupted or discontinued without a physician's advice. Patients being treated with Trandate (labetalol) Tablets should consult a physician at any signs or symptoms of impending cardiac failure or hepatic dysfunction (see WARNINGS). Also, transient scalp tingling may occur, usually when treatment with Trandate Tablets is initiated (see ADVERSE REACTIONS).

 

Trandate


Trandate Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

LABETALOL - ORAL

 

(luh-BET-uh-lol)

 

COMMON BRAND NAME(S): Normodyne, Trandate

 

WARNING: Do not stop taking this medication without consulting your doctor. Some conditions may become worse when you suddenly stop this drug. Some people who have suddenly stopped taking similar drugs have had chest pain, heart attack, and irregular heartbeat. If your doctor decides you should no longer use this drug, he or she may direct you to gradually decrease your dose over 1 to 2 weeks.

When gradually stopping this medication, it is recommended that you temporarily limit physical activity to decrease strain on the heart. Seek immediate medical attention if you develop chest pain/tightness/pressure, chest pain spreading to the jaw/neck/arm, unusual sweating, trouble breathing, or fast/irregular heartbeat.

 

USES: Labetalol is used with or without other medications to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

This medication is both an alpha blocker and beta blocker. It works by blocking the action of certain natural chemicals in your body such as epinephrine on the heart and blood vessels. This effect lowers the heart rate, blood pressure, and strain on the heart.

 

HOW TO USE: See also Warning section.

Take this medication by mouth, usually twice a day or as directed by your doctor. You may take this medication with or without food, but it is important to choose one way and take this medication the same way with every dose.

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.

Use 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 several 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).

 

Trandate


Trandate Consumer (continued)

SIDE EFFECTS: See also Warning and Precautions sections.

Dizziness and tiredness may occur. Scalp tingling may also occur as your body adjusts to the medication. Decreased sexual ability has been reported infrequently. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This drug may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: very slow heartbeat, severe dizziness, fainting, blue fingers/toes, trouble breathing, new or worsening symptoms of heart failure (such as swelling ankles/feet, severe tiredness, shortness of breath, unexplained/sudden weight gain), mental/mood changes (such as confusion, mood swings, depression).

This drug may rarely cause serious (rarely fatal) liver disease. If you notice any of the following rare but serious side effects, seek immediate medical attention: persistent nausea/vomiting, severe stomach/abdominal pain, yellowing eyes/skin, dark urine.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

PRECAUTIONS: Before taking labetalol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain types of heart rhythm problems (such as a slow heartbeat, second- or third-degree atrioventricular block), severe heart failure, breathing problems (such as asthma, chronic bronchitis, emphysema).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: treated stable heart failure, kidney disease, liver disease, overactive thyroid disease (hyperthyroidism), serious allergic reactions including those needing treatment with epinephrine, blood circulation problems (such as Raynaud's disease, peripheral vascular disease), mental/mood disorders (such as depression), a certain muscle disease (myasthenia gravis).

If you have diabetes, this product may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness and sweating, are unaffected by this drug. This product may also make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst/urination. Your diabetes medication or diet may need to be adjusted.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, older adults may be more sensitive to the side effects of this drug, including dizziness and lightheadedness.

Labetalol has been used to treat high blood pressure in pregnant women. It is important to control high blood pressure for the health of the mother and unborn baby. If you are planning pregnancy, become pregnant, or think you may be pregnant, discuss with your doctor the benefits and risks of using this medication during pregnancy. Rarely, babies born to mothers who took labetalol during pregnancy may have symptoms of low blood pressure, slow heartbeat, slow breathing, and low blood sugar (such as shaking, unusual sweating) for a few days after delivery. Tell the doctor immediately if you notice any of these symptoms in your newborn.

This medication passes into breast milk, and the effect on a nursing infant is unknown. Consult your doctor before breast-feeding.

 

Trandate

Trandate Consumer (continued)

DRUG INTERACTIONS: See also Precautions section.

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: cimetidine.

Check the labels on all your medicines (such as cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs such as ibuprofen for pain/fever reduction) because they may contain ingredients that could increase your blood pressure or heart rate. Ask your pharmacist about using those products safely.

If your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually at dosages of 81-325 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

This medication may interfere with certain medical/laboratory tests, possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: very slow heartbeat, severe dizziness, severe weakness, fainting, trouble breathing.

 

NOTES: Do not share this medication with others.

Talk with your doctor about making changes to your lifestyle that may help this medication work better (such as stress reduction programs, exercise, and dietary changes).

Have your blood pressure and pulse (heart rate) checked regularly while taking this medication. Learn how to check your own blood pressure and pulse at home, and share the results with your doctor.

Laboratory and/or medical tests (such as liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store between 36-86 degrees F (2-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Trandate

Trandate Patient Information Including Side Effects

Brand Names: Normodyne, Trandate

Generic Name: labetalol (Pronunciation: la BAY ta lol)

 

  • What is labetalol (Trandate)?
  • What are the possible side effects of labetalol (Trandate)?
  • What is the most important information I should know about labetalol (Trandate)?
  • What should I discuss with my healthcare provider before taking labetalol (Trandate)?
  • How should I take labetalol (Trandate)?
  • What happens if I miss a dose (Trandate)?
  • What happens if I overdose (Trandate)?
  • What should I avoid while taking labetalol (Trandate)?
  • What other drugs will affect labetalol (Trandate)?
  • Where can I get more information?

 

What is labetalol (Trandate)?

Labetalol is in a group of drugs called beta-blockers. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).

Labetalol is used to treat hypertension (high blood pressure).

Labetalol may also be used for purposes other than those listed in this medication guide.

Labetalol 100 mg-EON

round, white, imprinted with E 10

What are the possible side effects of labetalol (Trandate)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • slow or uneven heartbeats;
  • feeling light-headed, fainting;
  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • depression; or
  • cold feeling in your hands and feet.

Other less serious side effects are more likely to occur, such as:

  • decreased sex drive, impotence, or difficulty having an orgasm;
  • sleep problems (insomnia);
  • tired feeling; or
  • anxiety, nervousness.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What is the most important information I should know about labetalol (Trandate)?

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

If you need to have any type of surgery, you may need to temporarily stop using labetalol. Be sure the surgeon knows ahead of time that you are using labetalol.

Labetalol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking labetalol.

Labetalol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

Hypertension often has no symptoms, so you may not even feel that you have high blood pressure. Continue using this medicine as directed, even if you feel well. You may need to use blood pressure medication for the rest of your life.

Related Drug Centers
  • Trandate

 

 

Trandate


Trandate Patient Information including How Should I Take

In this Article

  • What is labetalol (Trandate)?
  • What are the possible side effects of labetalol (Trandate)?
  • What is the most important information I should know about labetalol (Trandate)?
  • What should I discuss with my healthcare provider before taking labetalol (Trandate)?
  • How should I take labetalol (Trandate)?
  • What happens if I miss a dose (Trandate)?
  • What happens if I overdose (Trandate)?
  • What should I avoid while taking labetalol (Trandate)?
  • What other drugs will affect labetalol (Trandate)?
  • Where can I get more information?

What should I discuss with my healthcare provider before taking labetalol (Trandate)?

Before taking labetalol, tell your doctor if you have:

  • asthma, bronchitis, emphysema;
  • diabetes;
  • low blood pressure;
  • a heart problem such as heart block, sick sinus syndrome, slow heart rate, or congestive heart failure;
  • depression;
  • liver or kidney disease;
  • a thyroid disorder;
  • myasthenia gravis;
  • pheochromocytoma; or
  • problems with circulation (such as Raynaud's syndrome).

If you have any of these conditions, you may not be able to use labetalol, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Labetalol can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using labetalol.

How should I take labetalol (Trandate)?

Take labetalol exactly as it was prescribed for you. Do not take the medication in larger amounts or for longer than recommended by your doctor.

Take this medication with a full glass of water.

Take labetalol at the same time every day.

Do not skip doses or stop taking labetalol without first talking to your doctor. Stopping suddenly may make your condition worse.

To be sure this medication is helping your condition, your blood pressure will need to be tested on a regular basis. It is important that you not miss any scheduled visits to your doctor.

If you need to have any type of surgery, tell the surgeon that you are using labetalol. You may need to briefly stop using labetalol before having surgery.

Labetalol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

Hypertension often has no symptoms, so you may not even feel that you have high blood pressure. Continue using this medicine as directed, even if you feel well. You may need to use blood pressure medication for the rest of your life.

Store labetalol at room temperature away from moisture and heat.

Related Drug Centers
  • Trandate

 

 

Trandate

Trandate Patient Information including If I Miss a Dose

In this Article

  • What is labetalol (Trandate)?
  • What are the possible side effects of labetalol (Trandate)?
  • What is the most important information I should know about labetalol (Trandate)?
  • What should I discuss with my healthcare provider before taking labetalol (Trandate)?
  • How should I take labetalol (Trandate)?
  • What happens if I miss a dose (Trandate)?
  • What happens if I overdose (Trandate)?
  • What should I avoid while taking labetalol (Trandate)?
  • What other drugs will affect labetalol (Trandate)?
  • Where can I get more information?

What happens if I miss a dose (Trandate)?

Take the missed dose as soon as you remember. If your next dose is less than 8 hours away, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Trandate)?

Seek emergency medical attention if you think you have used too much of this medicine.

Symptoms of a labetalol overdose may include uneven heartbeats, shortness of breath, bluish-colored fingernails, dizziness, weakness, fainting, or seizure (convulsions).

What should I avoid while taking labetalol (Trandate)?

Labetalol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking labetalol.

What other drugs will affect labetalol (Trandate)?

Before taking labetalol, tell your doctor if you are using:

  • allergy treatments (or if you are undergoing allergy skin-testing);
  • clonidine (Catapres);
  • guanabenz (Wytensin);
  • an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), or selegiline (Eldepryl, Emsam);
  • a diabetes medication such as insulin, glyburide (Diabeta, Micronase, Glynase), glipizide (Glucotrol), chlorpropamide (Diabinese), or metformin (Glucophage);
  • a heart medication such as nifedipine (Procardia, Adalat), reserpine (Serpasil), verapamil (Calan, Verelan, Isoptin), diltiazem (Cartia, Cardizem);
  • medicine for asthma or other breathing disorders, such as albuterol (Ventolin, Proventil), bitolterol (Tornalate), metaproterenol (Alupent), pirbuterol (Maxair), terbutaline (Brethaire, Brethine, Bricanyl), and theophylline (Theo-Dur, Theolair); or
  • cold medicines, stimulant medicines, or diet pills.

If you are using any of these drugs, you may not be able to take labetalol, or you may need dosage adjustments or special tests during treatment.

There may be other drugs not listed that can affect labetalol. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist has additional information about labetalol written for health professionals that you may read.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2010 Cerner Multum, Inc. Version: 7.03. Revision date: 4/12/2009.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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