Trandate Tablets

/ Perrigo

Populations
Adults: Hypertension – Treatment should start with 100 mg twice daily. If necessary, increases in dosage of 100 mg twice daily should be made at intervals (2 – 14 days). Many patients’ blood pressure is controlled by 200 mg twice daily and up to 800 mg daily may be given as a twice daily regimen. In severe, refractory hypertension daily doses up to 2400 mg (in 3 or 4 divided doses) have been given.
Hospital in-patients with severe hypertension may have daily increases in dosage. Additive hypotensive effects may be expected if labetalol tablets are administered together with other antihypertensives, eg. diuretics, methyldopa etc. When transferring patients from such agents, labetalol tablets should be introduced with a dosage of 100mg twice daily and the previous therapy gradually decreased. Abrupt withdrawal of clonidine or beta-blocking agents is undesirable. For long-term control of hypertension following the use of labetalol Injection, oral therapy with labetalol tablets should start at 100 mg twice daily.
Children: Safety and efficacy in children have not been established.
Elderly: For initiation of anti-hypertensive therapy, the usual starting dose is 100 mg orally twice daily.
Satisfactory blood pressure control may be achieved with lower maintenance doses than those required by younger patients.
Hepatic impairment: In patients with hepatic impairment, lower doses of the oral formulation may be required.

Hypertens.

2nd or 3rd degree AV block, sinus bradycardia, sick sinus syndrome, severe peripheral arterial disease, Printzmetal’s angina, uncompensated cardiac failure (except carvedilol), cardiogenic shock, hypotension, right ventricular failure secondary to pulmonary hypertension, significant cardiomegaly, untreated phaeochromocytoma, metabolic acidosis. Non-cardioselective ?blockers (nadolol, oxprenolol, penbutolol, pindolol, propranolol, timolol) are also generally contraindicated in patients with obstructive airways disease or a history of bronchospasm.

There have been very rare reports of severe hepatocellular injury with labetalol therapy. The hepatic injury is usually reversible and has occurred after both short term and long term treatment. Appropriate laboratory testing should be done at the first sign or symptom of liver dysfunction. If there is laboratory evidence of liver injury or the patient is jaundiced, labetalol should be stopped and not re-started.
Particular care should be taken when labetalol is to be used in patients with hepatic impairment as these patients metabolise labetalol more slowly than patients without hepatic impairment. Lower doses may be required. Labetalol should be used with caution in patients with peripheral vascular disease as their symptoms may be exacerbated. If the patient develops symptomatic bradycardia, then the dosage of labetalol should be reduced. Given the negative effect of beta-adrenoceptor blocking drugs on atrioventricular conduction time, labetalol should be administered with caution to patients with first-degree atrio-ventricular block. As with other beta-adrenoceptor blocking drugs, labetalol may mask the symptoms of hypoglycemia in diabetic patients and thyrotoxicosis. Risk of anaphylactic reaction: While taking  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.
If patients receiving labetalol require adrenaline treatment, a reduced dosage of adrenaline should be used as concomitant administration of labetalol with adrenaline may result in bradycardia and hypertension. There have been reports of skin rashes and/or dry eyes associated with the use of -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 such reaction is not otherwise explicable.
The occurrence of Intraoperative Floppy Iris Syndrome (IFIS, a variation of Small Pupil Syndrome) has been observed during cataract surgery in some patients on, or previously treated with, tamsulosin. Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the cataract operation, current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery. Special care should be taken with patients who suffer from heart failure or poor left ventricular systolic function. Heart failure should be controlled with appropriate therapy before use of labetalol. Labetalol need not be discontinued prior to anaesthesia but patients should receive i.v. atropine prior to induction. Labetalol may enhance the hypotensive effects of halothane. In patients with pheochromocytoma, labetalol may be administered only after adequate alphablockade is achieved. Patients, particularly those with ischaemic heart disease, should not interrupt or discontinue abruptly labetalol therapy. The dosage should be gradually reduced, ie over 1-2 weeks, if necessary at the same time initiating replacement therapy, to prevent exacerbation of angina pectoris. In addition, hypertension and arrhytmias may develop with abrupt discontinuation of labetalol.
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. The elderly should be treated with caution, starting with a lower dosage.

Cold extremities, CNS and sleep disturbances (particularly with the more lipophilic drugs), bradycardia (less with carvedilol, pindolol), exertional tiredness, bronchospasm, heart failure, hypotension, GI upset, alopecia, thrombocytopenia. Withdraw gradually in unexplained dry eyes or skin rash.

The hypotensive effect of labetalol may be reduced when used in combination with prostaglandin synthetase inhibitors (eg. NSAIDs). Dosage adjustments may therefore be necessary. Labetalol fluoresces in alkaline solution at an excitation wavelength of 334nm and a fluorescence wavelength of 412nm and may therefore interfere with the assays of certain fluorescent substances including catecholamines.
The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid (VMA) 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 should be employed in determining levels of catecholamines. Labetalol has been shown to reduce the uptake of radioisotopes of metaiodobenzylguanidine (MIBG). Care should therefore be taken in interpreting results from MIBG scintigraphy. Labetalol may enhance digoxin’s effect of reducing ventricular rate. Concomitant administration of labetalol with adrenaline may result in bradycardia and hypertension. Care should be taken if labetalol is used concomitantly with either Class I antiarrhythmic agents or calcium antagonists of the verapamil type. Concomitant use of tricyclic anti-depressants may increase the incidence of tremor. Cimetidine, may increase the bioavailability of labetalol and care is required in the oral dosing of the latter.

Pregnancy: Although no teratogenic effects have been demonstrated in animals, labetalol should only be used during the first trimester of pregnancy if the potential benefit outweighs the potential risk. In humans labetalol crosses the placental barrier and the possibility of the consequences of - and adrenoceptor blockade in the fetus and neonate 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 preeclampsia, particularly after prolonged intravenous labetalol, recovery may be slower. This may be related to diminished liver metabolism in premature babies. Intra-uterine and neonatal deaths have been reported but other drugs (e.g. vasodilators, respiratory depressants) and the effects of preeclampsia, intra-uterine growth retardation and prematurity were implicated. Such clinical experience warns against unduly prolonging high dose labetalol and delaying delivery and against coadministation of hydralazine.
Lactation: Labetalol is excreted in breast milk in small amounts (approximately 0.004% of the maternal dose). Adverse events of unknown causality (sudden death syndrome, diarrhoea, hypoglycaemia) have been reported very rarely in breast-fed neonates. Caution should be exercised when labetalol is administered to breast feeding women.

Symptoms and Signs: Profound cardiovascular effects are to be expected, eg. excessive, posture-sensitive hypotension and sometimes bradycardia. Oliguric renal failure has been reported after massive overdose of labetalol orally.
Treatment: Patients should be laid supine with the legs raised.
Use a cardiac glycoside and a diuretic in cardiac failure; for bronchospasm, administer a 2-agonist per aerosol. Intravenous atropine 0.25 to 3 mg should be given to relieve bradycardia. Intravenous noradrenaline 5 to 10 g initially, repeated according to response, may be preferable to isoprenaline to improve the circulation. Alternatively, noradrenaline may be infused at a rate of 5 g per minute until the response is satisfactory. In severe overdose, intravenous glucagon may be preferred: an initial bolus dose of 5 to 10 mg in dextrose or saline should be followed by an intravenous infusion of 5 mg/hour or as sufficient to maintain cardiac output. Transvenous pacing may be required.
Oliguric renal failure has been reported after massive overdose of labetalol orally. In one case, the use of dopamine to increase the blood pressure may have aggravated the renal failure. Haemodialysis removes less than 1% labetalol HCl from the circulation. Further management should be as clinically indicated or as recommended by the national poison centre, where available.