Labetalol Tablets Bp 100 Mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Labetalol Tablets BP 100 mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Labetalol Hydrochloride BP 100 mg
3. PHARMACEUTICAL FORM
Tablets
4. CLINICAL PARTICULARS
4.1 Therapeutic Indications
Hypertension; mild, moderate and severe Hypertension in pregnancy Hypertension with angina
4.2 Posology and Method of Administration ADULTS
Hypertension:
Initially 100 mg twice a day, which may be enough to control some patients, e.g. those already being treated with other antihypertensive drugs and those of low bodyweight.
Where hypertension is not controlled by the starting dose, increases of 100 mg twice a day may be made at intervals of about 14 days.
Many patients are controlled on 200 mg twice a day; 400 mg twice a day may be given, thereafter the total daily dose should be given as three or four divided doses. Daily doses of up to 2,400 mg have been given for severe, refractory hypertension.
Hypertension with angina:
The doses needed are those required to control the hypertension.
Hypertension in pregnancy:
Initially, 100 mg twice a day, which may be increased at weekly intervals by 100 mg twice a day to a maximum of 2,400 mg daily in the second or third trimesters if the severity of the hypertension dictates. Higher doses should be divided into a three times daily dosage regimen, the usual range being 100 mg - 400 mg three times a day.
Where rapid reduction of blood pressure is a necessity, labetalol injection should be used. Following the use of labetalol injection, and where long term control is required, initial therapy with oral labetalol should start with 100 mg twice a day.
Those patients admitted to hospital may have their dosage increased at daily intervals if needed.
Tablets should be taken with food.
Elderly
Initially, 50 mg twice a day, which may be sufficient for some.
Children
Not recommended.
Labetalol may be administered with other antihypertensive agents, e.g. methyldopa and diuretics, where the effects will be additive. When transferring a patient from one form of antihypertensive therapy to labetalol, introduce labetalol at 100 mg twice a day and then withdraw the previous therapy gradually.
In hepatic disease, oral dose reduction may be advised.
4.3 Contra-Indications
Hypersensitivity to labelatol.
Any condition associated with severe or prolonged hypotension Cardiogenic shock.
Bradycardia of less than 45-50 beats per minute.
Second or third degree heart block.
Uncontrolled, incipient or digitalis-refractory heart failure.
History of wheezing,bronchospasm or bronchial asthma.
Prinzmetals angina, severe peripheral circulatory disturbances, sick sinus syndrome (including sino-atrial block), untreated phaechromocytoma and metabolic acidosis.
4.4 Special Warnings and Special Precautions for Use
Due to negative inotropic effects, special care should be taken with patients whose cardiac reserve is poor and heart failure should be controlled with a cardiac glycoside and diuretic therapy before treatment is initiated.
Labetalol hydrochloride must not be used to treat asthmatic patients or individuals prone to bronchospasm or a history of obstructive airways disease unless there are no alternatives. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken. If bronchospasm should occur after the use of labetalol, it may be controlled by an inhaled selectively-acting bronchodilator such as salbutamol; the required dose may be greater than the normal anti-asthmatic dose. If further treatment is required, intravenous atropine 1 mg should be given.
It is not necessary to discontinue labetalol tablets in patients requiring anaesthesia but they should be given intravenous atropine prior to induction. If beta-blockers are to be withdrawn prior to surgery they should be discontinued for at least 24 hours preop. Anaesthetic agents causing myocardial depression (eg. cyclopropane, trichloroethylene) should be avoided. Labetalol 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 aggravation of these disorders may occur.
Beta blockers may induce bradycardia. If the pulse rate decrease to less than 50-55 beats per minute at rest and the patients experience symptoms related to bradycardia, the dosage should be reduced.
Due to a negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block. Patients with liver or kidney insufficiency may need a lower dosage, depending on the pharmacokinetic profile of the compound. The elderly should be treated with caution, starting with a lower dosage but tolerance is usually good in the elderly.
There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenoceptor blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when the treatment was withdrawn. Gradual discontinuance of the drug should be considered if any reaction is not otherwise explicable.
There have been rare reports of severe hepatocellular injury with labetalol therapy, which has occurred after both short-term and long-term therapy and is usually reversible. Appropriate testing should be performed at the first indication of liver dysfunction. If there is laboratory evidence of liver injury or jaundice, labetalol should be stopped and not restarted.
Patients, particularly those with ischaemic heart disease, should not interrupt/discontinue abruptly labetalol therapy. The dosage should be gradually reduced, i.e. over 1-2 weeks, if necessary at the same time initiating replacement therapy, to prevent exacerbation of angina pectoris. In addition, hypertension and arrhythmias may develop.
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 adrenaline used to treat allergic reaction. (see interactions section).
Labetalol interferes with laboratory tests for catecholamines.
Patients with psoriasis should take beta-blockers only after careful consideration.
Special care should be taken when treating the elderly and in renal insufficiency a lower dose may be required.
Beta-blockers may mask the signs of thyrotoxicosis.
Warnings
The leaflet will include the following statement: ‘Do not take this medicine if you have a history of wheezing or asthma. Consult your doctor or pharmacist first’.
The label will carry the following warning: ‘Important warning: Do not take this medicine if you have a history of wheezing or asthma as it can make your breathing worse’.
Patients with rare hereditary problems of galactose intolerance, the
Lapp lactase deficiency or glucose-galactose malabsorption should not take this
medicine.
4.5 Interaction with other Medicinal Products and other Forms of Interaction
Concomitant use not recommended:
B-blockers may enhance the negative inotropic and chronotropic effects of calcium channel blockers such as verapamil and to a lesser extent diltiazem Concurrent use should be avoided.
Cardiac glycosides in association with B-blockers, may increase AV block and precipitate bradycardia.
B-blockers can exacerbate the rebound hypertension associated with sudden withdrawal of clonidine. If combined treatment has to be interrupted, the B-blocker should be withdrawn several days before clonidine.
Monoamineoxidase Inhibitors (except MOA-B inhibitors)
Use with caution:
The negative inotropic effects of Class 1 antidysrythmic agents such as disopyramide and amiodarone may also be enhanced by B-blockers.
Certain anaesthetic drugs may cause attenuation of reflex tachycardia and increase the risk of hypotension. Continuation of beta-blockers reduce the risk of arrhythmia during induction and intubation. The anaesthesiologist should be informed when the patient is receiving a beta-blocking agent. Anaesthetic agents causing myocardial depression, such as cyclopropane and trichlorethylene are best avoided. The hypotensive effect of halothane may be enhanced by labetalol hydrochloride.
B-blockers may enhance the hypoglycaemic effects of oral antidiabetic agents and insulin and mask the warning signs of hypoglycaemia such as tremor and tachycardia.
Cimetidine, hydralazine and alcohol may increase the plasma concentration of labetalol.
Take into account:
Calcium antagonists, dihydropyridine derivates such as nifedipine. The risk of hypotension may be increased. In patients with latent cardiac insufficiency, treatment with beta-blockers may lead to cardiac failure.
Prostaglandin synthetase inhibiting drugs may decrease the hypotensive effects of beta-blockers.
Sympathomimetic agents may counteract the effect of beta-adrenergic blocking agents. Parenteral administration of preparations containing adrenaline to patients who are taking B-blockers may, rarely, result in vasoconstriction, hypertension and bradycardia.
Other antihypertensive agents will have an additive antihypertensive action when used concomitantly with labetalol.
Concomitant use of tricyclic antidepressants, barbiturates and phenothiazines may increase the incidence of tremor and blood pressure lowering effect of Labetalol.
Labetalol has been shown to reduce the uptake of radioisotopes of metaiodobenzylguanidine (MIBG), and may increase the likelihood of a false negative study. Care should therefore be taken in interpreting results from MIBG scintigraphy. Consideration should be given to withdrawing labetalol for several days at least before MIBG scintigraphy, and substituting other beta or alpha-blocking drugs.
4.6 Pregnancy and Lactation
Although there are no reported teratogenic effects in animals, labetalol should only be given in the first trimester if the expected benefits to the mother outweigh the risks to the foetus.
Labetalol crosses the placental barrier; the consequences of re- and B- adrenoceptor blockade in the foetus should be borne in mind.
Perinatal and neonatal distress (bradycardia, hypotension, respiratory depression, hypoglycaemia, hypothermia) has been rarely reported. Sometimes these symptoms developed a day or two after birth. Response to supportive measures (e.g. intravenous fluids and glucose) is usually prompt but with severe pre-eclampsia, particularly after prolonged intravenous labetalol, recovery may be slower. This may be related to diminished liver metabolism in premature babies. Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveries. There is an increased risk of cardiac and pulmonary complications in the neonate in the post-natal period. Intra-uterine and neonatal deaths have been reported but other drugs (e.g. vasodilators, respiratory depressants) and the effects of pre-eclampsia, intra-uterine growth retardation and prematurity were implicated. Such clinical experience warns against unduly prolonging high dose labetalol and delaying delivery and against co-administration of hydralazine.
Labetalol is excreted in breast milk. Breast feeding is not recommended.
4.7 Effects on Ability to Drive and Use Machines
In view of possible side effects of tiredness and dizziness, patients should be warned to take care when driving or operating machinery.
4.8 Undesirable effects
Most side-effects are transient and resolve within the first few weeks of therapy.
They include: headache, lethargy, tiredness, depressed mood, dizziness, nasal stuffiness, sweating and scalp tingling.
Postural hypertension generally occurs where initial dosing has been too high, increases in doses have been too rapid, or the doses being used are very high. It is otherwise uncommon.
Tremor has been reported in the treatment of hypertension during pregnancy. Acute urinary retention, difficulty in micturation, ejaculatory failure, epigastric pain, nausea and vomiting have been reported.
The following have been reported rarely: positive anti-nuclear factor test unassociated with disease, ankle oedema, raised liver function tests, jaundice (both hepatocellular and cholestatic), hepatitis, hepatic necrosis, bradycardia, heart block, systematic lupus erythematosus, hypersensitivity (rash, pruritis, angioedema, dyspnoea), reversible lichenoid rash. Signs and symptoms of hepatic damage usually reversible on withdrawal of labetalol.
Very rarely reports have been received of the following: drug fever, toxic myopathy.
Blurred/impaired vision, dry eyes, eye irritation and cramps have been reported in association with labetalol but a causal link has not been confirmed.
Other possible side effects of beta-blockers are: heart failure, cold or cyanotic extremeties, Raynaud’s phenomenon, paraesthesia of the extremities, increase of an existing intermittent claudication, hallucinations, psychoses, confusion, sleep disturbances, nightmares, diarrhoea, bronchospasm (in patients with asthma or a history of asthma), masking of the symptoms of thyrotoxicosis or hypoglycaemia.
4.9 Overdose
Overdosage with labetalol hydrochloride causes excessive hypotension, which is posture sensitive and sometimes, excessive bradycardia, bronchopasm and acute cardiac insufficency. After ingestion of an overdose or in case of hypersensitivity, the patient should be kept under close supervision and be treated in an intensive-care ward.
Absorption of any drug material still present in the gastro-intestinal tract can be prevented by gastric lavage, administration of activated charcoal and a laxative. Artificial respiration may be required.
Patients should be laid supine and their legs raised if necessary to improve blood supply to the brain. Atropine 3 mg or methylatropine should be given intravenously to relieve bradycardia or extensive vagal reactions. Massive overdosage with labetalol hydrochloride in man has not been reported but profound cardiovascular effects are to be expected. Atropine, at least 3 mg intravenously, should always be given. Gastric lavage or induced emesis is warranted for a few hours after oral ingestion of the drug. Hypotension and shock should be treated with plasma/plasma substitutes and, if necessary, catecholamines. The beta-blocking effect can be counteracted by slow intravenous administration of isoprenaline hydrochloride, starting with a dose of approximately 5mcg/min, or dobutamine, starting with a dose of approximately 2.5mcg/min, until the required effect has been obtained.
If this does not produce the desired effect, intravenous administration of 8-10 mg glucagon may be considered. If required the injection should be repeated within one hour, to be followed if required by an i.v. infusion of glucagon at an administration rate of 1-3 mg/hour. Administration of calcium ions, or the use of a cardiac pacemaker may also be considered.
Oliguric renal failure has been reported after massive overdosage of labetalol orally. In one case, the use of dopamine to increase the blood pressure may have aggravated the renal failure.
Labetalol does have membrane stabilising activity which may have clinical significance in overdosage.
Labetalol does have membrane stabilising activity which may have clinical significance in overdosage.
Haemodialysis removes less than 1% labetalol hydrochloride from the circulation.
PHARMACOLOGICAL PROPERTIES
5.
5.1 Pharmacodynamic Properties
Labetalol hydrochloride lowers the blood pressure primarily by blocking alpha-adrenoceptors in peripheral arterioles and thereby reducing the peripheral resistance. Concurrent beta-blockade protects the heart from the reflex sympathetic drive normally induced by peripheral vasodilatation. Cardiac output is not significantly reduced at rest or after moderate exercise. Increases in systolic pressure during exercise are, however, reduced after labetalol hydrochloride; corresponding changes in the diastolic pressure are essentially normal. In patients with co-existing angina the reduced peripheral resistance leads to a decreased left ventricular afterload and, hence, reduced myocardial oxygen demand. All these effects would be expected to benefit hypertensive patients and those with co-existing angina.
5.2 Pharmacokinetic Properties
Labetalol hydrochloride is readily absorbed from the gastro-intestinal tract but is subject to first pass metabolism. Bioavailability varies widely between patients and may be increased in the presence of food. Peak levels occur at about 1-2 hours after an oral dose. It is metabolised predominantly in the liver, the metabolites being excreted in the urine together with only small amounts of unchanged labetalol; its major metabolite has not been found to have significant alpha-or beta-adrenoceptor blocking effects. Excretion also occurs in the
faeces via the bile. The elimination half life at steady state is reported to be 8 hours. Labetalol crosses the placenta and is excreted in breast milk. Only very small amounts appear to cross the blood-brain barrier in animals. It is about 50% protein bound. Labetalol is not removed by dialysis.
5.3 Pre-clinical Safety Data
None presented
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose BP
Starch BP
Povidone BP
Isopropanol BP
Sodium Starch Glycollate BP
Magnesium Stearate BP
Coating
Hydroxy Propyl Methyl Cellulose BP Mastercote FA 1293 (E110)
Triacetin USP Water BP IMS BP
6.2 Incompatibilities
None known other than those stated in above.
6.3 Shelf-Life
3 years from date of manufacture
6.4 Special Precautions for Storage
Store in a cool dry place.
6.5 Nature and Content of Container
Polypropylene container with a low density polyethylene lid incorporating a tear-off sealing band containing 7, 14, 21, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 250, 500 and 1000 tablets and PVdC coated PVC/Aluminium blister packs (60g/m2 PVdC on 250pm PVC/20pm Al) containing 7, 14, 21, 28, 30, 50, 56, 60, 84, 90, 100, 112 and 120 tablets.
6.6 Instructions for Use, Handling and Disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Ltd. 3 Howard Road Eaton Socon
St Neots Cambridgeshire PE198ET United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
PL 11311/0375
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29/07/2009
10 DATE OF REVISION OF THE TEXT
01/07/2010