Trandat (Labetalol) tablets 100 mg No. 30 - Instructions

Pharmacological properties of the drug Labetalol

Non-selective blocker of β-adrenergic receptors with a selective blocking effect on postsynaptic α1-adrenergic receptors. Due to the presence of two optical centers in the molecule, there are four diastereoisomers of labetalol, which differ in the degree of pharmacological activity. The ratio of β- and α-adrenergic blocking activity of racemic labetalol is 3–7:1. As a result of interaction with α- and β-adrenergic receptors, labetalol causes vasodilation and a decrease in peripheral vascular resistance, leading to a decrease in systemic blood pressure without a significant decrease in cardiac output and the development of reflex tachycardia. The adverse effect of labetalol on the lipid spectrum of blood plasma is minimal. With systematic use, labetalol reduces the severity of left ventricular myocardial hypertrophy in patients with hypertension (arterial hypertension). Labetalol has a quinidine-like membrane-stabilizing effect, which, however, only occurs when labetalol is administered in very high doses. Compared with other beta-adrenergic blockers (eg propranolol), labetalol does not reduce glomerular filtration and renal blood flow. After oral administration, labetalol is rapidly and almost completely absorbed. Concomitant use with food slows down the absorption of labetalol in the intestine, but increases absolute bioavailability. It undergoes significant first-pass metabolism in the mucous membrane of the digestive tract and during the initial passage through the liver, due to which only about 25% of the administered dose of labetalol enters the systemic circulation unchanged. The hypotensive effect develops within 20 minutes - 2 hours after oral administration, the maximum effect occurs after 1-4 hours. The duration of the hypotensive effect is dose-dependent and ranges from 8 to 24 hours. The hypotensive effect after IV administration develops after 2-5 minutes and reaches its maximum expression in 5–15 minutes; its duration is 2–4 hours. The half-life in patients with normal renal function ranges from 2.5–8 hours. With severe renal failure, accumulation of labetalol is possible. Widely distributed in all tissues of the body, penetrates the placenta, and is excreted in breast milk. In small quantities it penetrates the BBB. Extensively metabolized in the liver by glucuronidation. About 30% is excreted in bile and excreted in feces, the rest is excreted in urine (55–60% as metabolites and 5% unchanged).

Trandat (Labetalol) tablets 100 mg No. 30 - Instructions

Dosage form

Tablets, 30 pieces per pack.

Compound

1 tablet contains 100 mg of the active substance Labetalol.

Excipients: microcrystalline cellulose, lactose, magnesium stearate, E 110, titanium dioxide, sodium stearate, colloidal silicon dioxide, povidone, talc, eudragit, propylene glycol, polysorbate 80, macrogol 6000, sodium citrate, kaolin.

pharmachologic effect

Pharmacodynamics

Labetalol lowers blood pressure by blocking peripheral arteriolar alpha-adrenergic receptors, thereby reducing peripheral resistance, and simultaneously with beta blockade protects the heart from reflex sympathetic drive that would otherwise occur. Cardiac output does not decrease significantly at rest or after moderate exercise. The increase in systolic blood pressure during exercise is reduced, but the corresponding changes in diastolic pressure are largely normal.

In patients with angina pectoris and hypertension, a decrease in peripheral resistance reduces myocardial afterload and oxygen demand. All of these effects are expected to benefit hypertensive and angina patients.

Pharmacokinetics

The plasma half-life of labetalol is approximately 4 hours. About 50% of labetalol in the blood is bound to proteins. Labetalol is metabolized primarily by conjugation with inactive glucuronide metabolites. They are excreted both in urine and bile in feces.

Only a small amount of the drug crosses the blood-brain barrier in animal studies.

Indications for use

Trandate tablets are indicated for the treatment of:

1. Mild, moderate or severe hypertension

2. Hypertension during pregnancy

3. Angina with existing hypertension

Directions for use and doses

Trandat tablets should be taken orally with meals.

Adults:

High blood pressure

Treatment should begin with 100 mg twice daily. In patients already receiving antihypertensive drugs and in patients with low body weight, this may be sufficient to control blood pressure. In others, increasing the dose of 100 mg twice daily should be done every two weeks. Many patients have their blood pressure controlled with 200 mg twice daily, and up to 800 mg daily can be given twice daily. For severe refractory hypertension, the daily dose is up to 2400 mg. Such doses should be divided into a regimen of three or four times a day.

Elderly

In elderly patients, an initial dose of 50 mg twice daily is recommended. This provided satisfactory control in some cases.

For hypertension during pregnancy

The starting dose of 100 mg twice daily can be increased, if necessary, at weekly intervals by 100 mg twice daily. During the second and third trimester, the severity of hypertension may require further dosage titration up to three times daily, ranging from 100 mg to 400 mg daily. The total daily dose should not exceed 2400 mg. Inpatients with severe arterial hypertension, especially during pregnancy, can increase the dosage daily.

Angina pectoris coexisting with hypertension

In patients with angina pectoris coexisting with hypertension, the dose of Trandate will be that required to control hypertension.

Children

Safety and effectiveness in children have not been established.

Contraindications

• Cardiogenic shock.
• Uncontrolled, incipient or refractory heart failure.
• Sick sinus syndrome (including sinoatrial block).
• Heart block of the second or third degree.
• Prinzmetal's angina.
• History of wheezing or asthma.
• Untreated pheochromocytoma.
• Metabolic acidosis.
• Bradycardia (<45-50 beats per minute).
• Hypotension.
• Hypersensitivity to labetalol.
• Severe peripheral circulatory disorders.

Special warnings and precautions for use

There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is low, and in most cases symptoms resolved after discontinuation of treatment. Gradual discontinuation of the drug should be considered unless any such reaction is otherwise explained.

The occurrence of intraoperative flexible iris syndrome (IFIS, a variant of Horner's syndrome) has been observed during cataract surgery in some patients treated with tamsulosin or treated with tamsulosin in the past. IFIS has also been reported when other alpha-1 blockers have been used, and the possibility of a class effect cannot be excluded. Because IFIS may lead to a higher likelihood of complications during cataract surgery, the ophthalmologist should be informed whether alpha-1 blockers are currently being used or have been used in the past.

There have been rare reports of severe hepatocellular injury with labetalol therapy. Liver injury is usually reversible and occurs after short- and long-term treatment. Appropriate laboratory testing should be done at the first sign or indication of liver dysfunction. If there are laboratory signs of liver damage or the patient is jaundiced, labetalol therapy should be discontinued and not restarted.

Due to negative inotropic effects, special caution should be exercised in patients who have low cardiac reserve and heart failure should be monitored before initiating therapy with Trandate.

Patients, especially those with coronary artery disease, should not suddenly interrupt/discontinue Trandat therapy. The dosage should be reduced gradually, i.e. over 1-2 weeks if necessary, at the same time as replacement therapy is started, to prevent exacerbation of angina. In addition, hypertension and arrhythmia may develop.

There is no need to discontinue Trandat therapy in patients requiring anesthesia, but the anesthesiologist should be informed and the patient should receive intravenous atropine prior to induction. During anesthesia, Trandate may mask compensatory physiological responses to breakthrough bleeding (tachycardia and vasoconstriction). Therefore, close attention must be paid to blood loss and blood volume maintenance. If beta blockade is interrupted in preparation for surgery, therapy should be discontinued for at least 24 hours. Anesthetic agents that cause myocardial depression (eg, cyclopropane, trichlorethylene) should be avoided. Trandate may enhance the hypotensive effects of halothane.

In patients with peripheral circulatory disorders (Raynaud's disease or syndrome, intermittent claudication), beta-blockers should be used with great caution, as exacerbation of these disorders may occur.

Beta blockers may cause bradycardia. If the heart rate decreases to less than 50-55 beats per minute at rest and the patient develops symptoms associated with bradycardia, the dosage should be reduced.

Beta blockers, even those with apparent cardioselectivity, should not be used in patients with asthma or a history of obstructive airway disease unless alternative treatment is available. In such cases, the risk of bronchospasm should be assessed and appropriate precautions taken. If bronchospasm occurs after using Trandate, it can be treated with an inhaled beta2-agonist such as salbutamol (the dose of which may be higher than usual for asthma) and, if necessary, 1 mg intravenous atropine.

Because of their negative effect on conduction time, beta blockers should be used only with caution in patients with first-degree heart block. Patients with hepatic or renal impairment may require lower dosage, depending on the pharmacokinetic profile of the compound. Caution should be used in the elderly, starting with a lower dose, but is generally well tolerated in the elderly.

Patients with a history of psoriasis should only take beta blockers after careful consideration.

Risk of Anaphylactic Reaction: While taking beta blockers, patients with a history of severe anaphylactic reactions to various allergens may be more susceptible to reinfection, whether incidental, diagnostic, or therapeutic. Such patients may not respond to the usual doses of epinephrine used to treat an allergic reaction.

The label will say: "Do not take Trandate if you have wheezing or asthma because it may make your breathing worse."

Trandate tablets contain sodium benzoate, which is a mild irritant to the eyes, nose and mucous membranes. This may increase the risk of jaundice in newborns.

Patients with rare hereditary problems of galactose intolerance, Lappase deficiency or glucose-galactose malabsorption should not take this medicine.

Interaction with other drugs and other forms of interaction

Use not recommended:

• Calcium antagonists, such as verapamil and to a lesser extent diltiazem, have a negative effect on contractility and atrioventricular conduction.
• Glycosides used in combination with beta blockers may increase atrioventricular conduction time.
• Clonidine: Beta blockers increase the risk of hypertension. When clonidine is used in combination with non-selective beta blockers such as propranolol, treatment with clonidine should be continued for some time after discontinuation of beta blocker treatment.
• Monoamine oxidase inhibitors (except MOA-B inhibitors).

Use with caution:

• Class I antiarrhythmic agents (eg, disopyramide, quinidine) and amiodarone may have a potentiating effect on atrial conduction time and cause a negative inotropic effect.
• Insulin and oral antidiabetic drugs may enhance the blood sugar-lowering effects, especially of non-selective beta blockers. Beta blockade may prevent signs of hypoglycemia (tachycardia).
• Anesthetic drugs may weaken reflex tachycardia and increase the risk of hypotension. Continued beta blockade reduces the risk of arrhythmia during induction and intubation. The anesthesiologist should be informed when a patient is receiving a beta blocking agent.
• It is best to avoid the use of anesthetics that cause myocardial depression, such as cyclopropane and trichlorethylene.
• Cimetidine, hydralazine and alcohol may increase the bioavailability of labetalol.
• Several different drugs or classes of drugs can enhance the hypotensive effect of labetalol: ACE inhibitors; angiotensin II antagonists; aldesleukin, alprostadil; tranquilizers; sleeping pills; diuretics; alpha blockers.
• Several different drugs or classes of drugs can antagonize the hypotensive effects of labetalol: NSAIDs, corticosteroids; estrogens; progesterones.

Take into account:

• Calcium antagonists: dihydropyridine derivatives such as nifedipine. The risk of hypotension may be increased. In patients with latent heart failure, treatment with beta blockers may lead to heart failure.
• Drugs that inhibit prostaglandin synthetase may reduce the hypotensive effect of beta blockers.
• Sympathomimetic agents may antagonize the effects of beta-adrenergic blocking agents.
• Concomitant use of tricyclic antidepressants, barbiturates, phenothiazines or other antihypertensive drugs may enhance the blood pressure-lowering effect of labetalol. Concomitant use of tricyclic antidepressants may increase the incidence of tremor.
• Labetalol has been shown to reduce the uptake of metaiodobenzylguanidine (MIBG) radioisotopes and may increase the likelihood of a false-negative test. Therefore, caution should be exercised when interpreting MIBG scintigraphy results. Consideration should be given to stopping labetalol for several days, at least before MIBG scintigraphy, and replacing it with other beta- or alpha-blocking drugs.
• Antimalarial drugs such as mefloquine or quinine may increase the risk of bradycardia.
• Ergot derivatives may increase the risk of peripheral vasoconstriction.

Pregnancy and breastfeeding

Although teratogenic effects have not been demonstrated in animals, Trandate should only be used during the first trimester of pregnancy if the potential benefit outweighs the potential risk. Trandate crosses the placental barrier, and the possible effects of alpha- and beta-adrenergic receptor blockade in the fetus and newborn should be considered. Perinatal and neonatal distress (bradycardia, hypotension, respiratory depression, hypoglycemia, hypothermia) are rarely reported. Sometimes these symptoms developed a day or two after birth. Response to supportive measures (eg, intravenous fluids and glucose) is usually rapid, but with severe preeclampsia, especially after long-term intravenous labetalol injection, recovery may be slower. This may be due to decreased liver metabolism in premature infants.

Beta blockers reduce placental perfusion, which can lead to intrauterine fetal death and premature birth. There is an increased risk of cardiac and pulmonary complications in newborns during the postpartum period.

Fetal and neonatal deaths have been reported with the use of Trandate, but other drugs (eg, vasodilators, respiratory depressants) have been implicated, as have the effects of preeclampsia, intrauterine growth restriction, and prematurity.

This clinical experience cautions against excessive prolonged use of high doses of labetalol, as well as concomitant administration of hydralazine.

Trandate is excreted in breast milk. Therefore, breastfeeding is not recommended.

Effect on the ability to drive and use machines

There are no studies on the effect of this medicine on the ability to drive.

When driving vehicles or operating machines, it should be taken into account that dizziness or fatigue may sometimes occur.

Adverse reactions

Blood and lymphatic system disorders:

Blood cell changes, hyperkalemia, especially in patients who may have impaired renal potassium excretion, thrombocytopenia.

Mental disorders:

Depressed mood and lethargy, hallucinations, psychosis, confusion, sleep disturbances, nightmares.

Nervous system disorders:

Headache, fatigue, dizziness, and tremor are noted in the treatment of hypertension during pregnancy.

Eye disorders:

Visual impairment, dry eyes.

Heart disorders:

Bradycardia, heart block, heart failure, hypotension.

Vascular disorders:

Ankle swelling, increased claudication, postural hypotension, cold or cyanotic extremities, Raynaud's phenomenon, limb paresthesia.

Respiratory, thoracic and mediastinal disorders:

Bronchospasm (in patients with asthma or a history of asthma), nasal congestion, interstitial lung disease.

Gastrointestinal disorders:

Epigastric pain, nausea, vomiting, diarrhea.

Hepato-biliary disorders:

Elevated liver tests, jaundice (both hepatocellular and cholestatic), hepatitis and liver necrosis.

Diseases of the skin and subcutaneous tissue:

Sweating, tingling sensation in the scalp, usually transient, may be observed in a few patients at the beginning of treatment, reversible lichenoid rash, systemic lupus erythematosus, exacerbation of psoriasis.

Disorders of the musculoskeletal system, connective tissue and bones:

Spasms, toxic myopathy.

Kidney and urinary disorders:

Acute urinary retention, difficulty urinating.

Reproductive system and breast diseases:

Ejaculatory failure.

Common disorders:

Hypersensitivity (rash, itching, angioedema and shortness of breath), drug fever, masking symptoms of thyrotoxicosis or hypoglycemia, reversible alopecia.

Overdose

Symptoms of overdose are: bradycardia, hypotension, bronchospasm and acute heart failure.

After overdose or in case of hypersensitivity, the patient should be closely monitored and treated in an intensive care unit.

Absorption of any drug material still present in the gastrointestinal tract can be prevented by gastric lavage, administration of activated charcoal and a laxative. Artificial respiration may be required. Bradycardia or extensive vagal reactions should be treated with atropine or methylatropine.

Hypotension and shock should be treated with plasma expanders and, if necessary, catecholamines. The beta-blocking effect can be counteracted by slow intravenous administration of isoprenaline hydrochloride, starting at a dose of approximately 5 mcg/min, or dobutamine, starting at a dose of approximately 2.5 mcg/min, until the desired effect is achieved. If this does not produce the desired effect, intravenous administration of 8-10 mg of glucagon may be considered. If necessary, the injection should be repeated within one hour, and then, if necessary, an intravenous infusion of glucagon at a dose of 1-3 mg/hour.

Labetalol has membrane-stabilizing activity, which may be clinically significant in overdose.

Hemodialysis removes less than 1% of labetalol hydrochloride from the circulation.

Storage conditions

At room temperature, out of the reach of children.

Best before date

5 years.

Vacation category

On prescription.

Use of the drug Labetalol

In case of hypertensive crisis, it is administered intravenously slowly (over 2 minutes) at a dose of 20 mg (2 ml of 1 % solution). If necessary, the administration is repeated at intervals of 10 minutes. It is preferable to administer labetalol as an infusion in an isotonic solution of sodium chloride or glucose (the concentration of the solution for infusion is 1 mg/ml) at a rate of 2 mg/min. Typically the effective dose is 50–200 mg. The total dose for adults when administered intravenously should not exceed 300 mg. Information on use in children is limited. It is recommended to administer orally at a rate of 4 mg/kg/day in 2 divided doses with constant monitoring of blood pressure levels. When administered intravenously, the bolus dose (administered slowly) is 0.2–1 mg/kg. The initial infusion rate is 0.4–1 mg/kg/h, the maximum is no more than 3 mg/kg/h.

Norepinephrine Velpharm

General recommendations

Administered only intravenously.

The individual dose of the drug is set by the doctor depending on the clinical condition of the patient.

Norepinephrine should be administered via central venous access devices to reduce the risk of extravasation and subsequent tissue necrosis (see section "Special Instructions").

Before starting or during therapy, correction of hypovolemia, hypoxia, acidosis, and hypercapnia is necessary.

Administration of the drug

The recommended initial dose and rate of administration of the drug is from 0.1 to 0.3 mcg/kg/min of norepinephrine bitartrate. The infusion rate is progressively increased by titration in steps of 0.05-0.1 mcg/kg/min, in accordance with the observed pressor effect, until the desired normotension is achieved.

There are individual differences in the dose required to achieve and maintain normotension. The goal is to achieve the lower limit of normal systolic pressure (100-120 mm Hg) or achieve a sufficient level of the average value (above 65 - 80 mm Hg, depending on the patient’s condition). The individual dose, due to the high variability of the clinical response when administering the drug, is set depending on the patient's condition.

Norepinephrine should be used simultaneously with adequate replenishment of circulating blood volume.

It is necessary to be careful when injecting norepinephrine solution under the skin and into muscles due to the risk of developing necrosis.

Concentrate dilution

The concentrate should be diluted in a 5% glucose solution (dextrose). Do not administer undiluted! Do not mix with other drugs!

For administration using a syringe infusion pump: add 48 ml of a 5% glucose solution (dextrose) to 2 ml of concentrate to prepare a solution for intravenous administration of the drug.

For administration via a dropper: add 480 ml of a 5% glucose solution (dextrose) to 20 ml of concentrate to prepare a solution for intravenous administration of the drug. With both dilution options, the final concentration of the resulting intravenous solution is 0.08 mg/ml norepinephrine bitartrate, which corresponds to 0.04 mg/ml norepinephrine base.

Volume of fluid administered: the dilution level depends on the patient's condition. If the administration of a large volume of liquid is required, the drug should be diluted with a large amount of glucose (dextrose) and, thus, a drug with a lower concentration should be used for administration. If it is undesirable to introduce a large volume of liquid, the concentrate is diluted with a smaller volume of glucose (dextrose), obtaining a more concentrated solution.

To determine the infusion rate of a drug solution with a concentration of 0.08 mg/ml and the corresponding amount of norepinephrine bitartrate, you can use the data from the table:

Table. Calculation of the infusion rate (ml/h) of a drug solution with a concentration of 0.08 mg/ml*

*When using a different dilution of the concentrate, you should replace the value of the solution concentration in the formula used:

Infusion rate (ml/h) = dosage (µg/kg/min x patient weight (kg) x 60 (min) x 0.001 / 0.08 mg/ml

Arterial pressure

The duration, rate of administration and dosage of the norepinephrine solution are determined by cardiac monitoring data with mandatory medical monitoring of blood pressure (BP) (every 2 minutes until normotension is achieved, then every 5 minutes throughout the infusion) to avoid the occurrence of arterial hypertension. Concomitant use of MAO inhibitors of the imipramine and triptyline series increases the risk of developing a pronounced and prolonged increase in blood pressure.

Discontinuation of therapy

Drug therapy should be reduced gradually, since abrupt withdrawal can lead to acute arterial hypotension.

The course of treatment can last from several hours to 6 days.

Features of the drug's effect upon first use or upon withdrawal

When starting the infusion, it is necessary to titrate the dose of the drug until the target blood pressure is achieved. With long-term use, a decrease in plasma volume is possible with the necessary correction to avoid recurrent hypotension when the drug is discontinued.

Side effects of the drug Labetalol

dizziness, hypertension (arterial hypertension), syncope, orthostatic hypotension (mainly with intravenous administration), sinus bradycardia, AV block, increased symptoms of heart failure, headache, fatigue, depression, nightmares, paresthesia, nausea, vomiting, hepatotoxic effect, shortness of breath, sexual dysfunction (impotence, ejaculation disorders, decreased libido, priapism), urinary retention, hypoglycemia, itching, xerosis and hyperpigmentation of the skin, reversible alopecia, exfoliative dermatitis.

Drug interactions Labetalol

With simultaneous use of labetalol with other antihypertensive drugs, an additive effect is observed. When prescribed with verapamil or diltiazem, the risk of developing AV block increases. Undesirable pharmacodynamic interactions are possible when combined with the simultaneous use of labetalol and antidiabetic agents. Anesthetics can potentiate and prolong the hypotensive effect of labetalol. The combination of halothane and labetalol may produce a synergistic hypotensive effect, reducing cardiac output and lowering central venous pressure. Labetalol should be used with caution in patients taking MAO inhibitors due to the possibility of developing sinus bradycardia. Cimetidine increases the bioavailability of labetalol when administered concomitantly, probably by increasing absorption or decreasing first pass metabolism. Concomitant use of sympathomimetics may reduce the hypotensive effect of labetalol. Labetalol reduces nitroglycerin-induced reflex tachycardia and has additive hypotensive effects. With simultaneous use of labetalol with tricyclic antidepressants, tremor may develop. When used simultaneously with mefloquine, the risk of developing ECG changes and cardiac arrest increases.

List of pharmacies where you can buy Labetalol:

• Moscow
• Saint Petersburg

Publications in the media

(Labetalolum) INN

Synonyms. Trandat.

Composition and release form. Tablets of 0.1 and 0.2 g labetalol; 1% solution of labetalol for injection in ampoules of 5 ml.

Indications. Hypertension of varying degrees.

Pharmachologic effect. An antiadrenergic agent that blocks beta and alpha 1-adrenergic receptors, leading to vasodilation, a decrease in peripheral vascular resistance and virtually no postural hypotension. The drug does not significantly affect cardiac output and heart rate. The maximum effect of the drug is observed 1 hour - 4 hours after administration and lasts up to 8-12 hours or up to 24 hours when using high doses.

Pharmacokinetics. Labetalol is almost completely absorbed from the gastrointestinal tract into the blood, but undergoes active “presystemic metabolism”, and its bioavailability is 25%. The maximum concentration in the blood is achieved 2-4 hours after a single oral dose. The drug is 50% bound to blood proteins. T 1/2 is 6-8 hours. Labetalol is metabolized in the liver and excreted from the body through the gastrointestinal tract, 55-60% in the urine.

Side effects. Heart failure, bronchospasm, hypoglycemia, dizziness, headache, nausea, vomiting, diarrhea or constipation, feeling tired.

Contraindications. Severe heart failure, AV block.

Adverse reactions when interacting with other drugs. Hypotension may develop when used in combination with other antihypertensive drugs or diuretics. When labetalol is used concomitantly with halogenated general anesthetics, excessive hypotension, a significant decrease in cardiac output and an increase in central venous pressure may occur. Cimetidine increases plasma concentrations of labetalol when used together. Estrogens reduce the hypotensive effect of labetalol. Labetalol reduces reflex tachycardia caused by nitroglycerin and increases the hypotensive effect. When using phenothiazines with labetalol, the plasma concentration of these drugs increases. Propafenone increases the plasma concentration and half-life of labetalol.

Information for the patient. Labetalol is taken 0.1 g 2-3 times a day after meals, mixed with liquid (water, juices), non-solid food (applesauce, pudding). If necessary, the dose can be increased. For hypertensive crises, the drug is used intravenously. Caution should be exercised when using the drug for bronchial asthma. The drug is discontinued gradually. Take the missed dose as soon as possible and do not take it at all if the next dose is less than 4 hours away; do not take double doses.