Clovet M

Clovet M Uses, Dosage, Side Effects, Food Interaction and all others data.

Chlortalidone prevents reabsorption of sodium and chloride by inhibiting the Na+/Cl− symporter in the distal convoluted tubule. Thiazides and related compounds also decrease the glomerular filtration rate, which further reduces the drug's efficacy in patients with kidney impairment (e.g. kidney insufficiency). By increasing the delivery of sodium to the distal renal tubule, chlortalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism (i.e. apical ROMK/Na channels coupled with basolateral NKATPases). This can result in hypokalemia and hypochloremia as well as a mild metabolic alkalosis; however, the diuretic efficacy of chlortalidone is not affected by the acid-base balance of the patient being treated.

Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Eventually, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. The reduction in intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy.

Metoprolol is a selective beta1-blocker. Metoprolol reduces or inhibits the agonistic effect on the heart of catecholamines (which are released during physical and mental stress). This means that the usual increase in heart rate, cardiac output, cardiac contractility and blood pressure, produced by the acute increase in catecholamines, is reduced by Metoprolol. Metoprolol interferes less with Insulin release and carbohydrate metabolism than do non-selective beta-blockers. Metoprolol interferes much less with the cardiovascular response to hypoglycaemia than do non-selective beta-blockers.

Administration of metoprolol in normal subjects is widely reported to produce a dose-dependent reduction on heart rate and cardiac output. This effect is generated due to a decreased cardiac excitability, cardiac output, and myocardial oxygen demand. In the case of arrhythmias, metoprolol produces its effect by reducing the slope of the pacemaker potential as well as suppressing the rate of atrioventricular conduction.

The Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial showed a significant improvement in sudden cardiac death and myocardial infarction when patients were given with metoprolol as compared with diuretics. As well, in clinical trials performed in 1990, metoprolol reduces mortality and re-infarction in 17% of the individuals when administered chronically after an episode of myocardial infarction.

Trade Name Clovet M
Generic Chlorthalidone + Metoprolol
Weight 50mg
Type Tablet
Therapeutic Class
Manufacturer Ajanta Pharma Ltd
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Clovet M
Clovet M

Uses

Chlorthalidone is used for the management of hypertension. Chlorthalidone is used for adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis and corticosteroid and estrogen therapy.

ln the management of hypertension and angina pectoris. Cardiac arrhythmias, especially supraventricular tachyarrhythmias. Adjunct to the treatment of hyperthyroidism. Early intervention with Metoprolol in acute myocardial infarction reduces infarct size and the incidence of ventricular fibrillation. Pain relief may also decrease the need for opiate analgesics. Metoprolol has been shown to reduce mortality when administered to patients with acute myocardial infarction.

Clovet M is also used to associated treatment for these conditions: Calcium NephrolithiasisAngina Pectoris, Atrial Fibrillation, High Blood Pressure (Hypertension), Migraine, Myocardial Infarction, Tachycardia, Supraventricular, Thyroid Crisis, Acute hemodynamically stable Myocardial infarction, Chronic heart failure with reduced ejection fraction (NYHA Class II), Chronic heart failure with reduced ejection fraction (NYHA Class III)

How Clovet M works

Chlorthalidone prevents reabsorption of sodium and chloride through inhibition of the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. Reduction of sodium reabsorption subsequently reduces extracellular fluid and plasma volume via an osmotic, sodium-driven diuresis. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism. The exact mechanism of chlorthalidone's anti-hypertensive effect is under debate, however, it is thought that increased diuresis results in decreased plasma and extracellular fluid volume which therefore requires decreased cardiac output and overall lowers blood pressure. Chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects.

Metoprolol is a beta-1-adrenergic receptor inhibitor specific to cardiac cells with negligible effect on beta-2 receptors. This inhibition decreases cardiac output by producing negative chronotropic and inotropic effects without presenting activity towards membrane stabilization nor intrinsic sympathomimetics.

Dosage

Clovet M dosage

Therapy should be initiated with the lowest possible dose and then titrated according to individual patient response. A single dose given in the morning with food is recommended; divided doses are unnecessary.

Edema: Up to 50 mg daily.

Hypertension: 25 mg daily in the morning, increased to 50 mg daily if necessary.

Heart failure: 25-50 mg daily in the morning, increased if necessary to 100-200 mg daily (reduce to lowest effective dose for maintenance).

Maintenance doses may often be lower than initial doses and should be adjusted according to the individual patient.

Oral-

Hypertension: Total daily dosage Metoprolol 100-400 mg to be given as a single or twice daily dose. The starting dose is 100 mg (two Metoprolol-50 tablets) per day. This may be increased by 100 mg per day at weekly intervals. lf full control is not achieved using a single daily dose, a b.i.d. regimen should be initiated. Combination therapy with a diuretic or other anti-hypertensive agent may also be considered.

Angina: Usually Metoprolol 50 mg (one Metoprolol-50 tablet) to 100 mg (two Metoprolol-50 tablets)twice or three times daily.

Cardiac arrhythmias: Metoprolol 50 mg (one Metoprolol-50 tablet) b.i.d or t.i.d should usually control the condition. It necessary the dose can be increased up to 300 mg per day in divided doses. Following the treatment of an acute arrhythmia with Metoprolol injection, continuationtherapy with Metoprolol tablets should be initiated 4-6 hours later. The initial oral dose should not exceed 50 mg t.i.d.

Hyperthyroidism: Metoprolol 50 mg (one Metoprolol-50 tablet) four times a day.The dose should bereduced as the euthyroid state is achieved.

Myocardial infarction: Orally, therapy should commence 15 minutes after the last injection with50 mg every 6 hours for 48 hours. Patients who fail to tolerate the full intravenous dose should begiven half the suggested oral dose. Maintenance – The usual maintenance dose is 200 mg dailygiven in divided doses. Elderly’ There are no special dosage requirements in otherwise healthyelderly patients. Signidcant hepatic dysfunction: A reduction in dosage may be necessary.

Injection-

Arrhythmias: By intravenous injection, up to 5 mg at a rate of 1-2 mg/minute, repeated after 5 minutes if necessary, total dose 10-15 mg.

In surgery: By slow intravenous injection 2-4 mg at induction or to control arrhythmias developing during anaesthesia; 2 mg doses may be repeated to a maximum of 10 mg.

Myocardial Infarction: Early intervention within 12 hours of infarction, by intravenous injection 5 mg every 2 minutes to a maximum of 15 mg, followed after 15 minutes by 50 mg by mouth every 6 hours for 48 hours; maintenance 200 mg daily in divided doses.

Impaired Renal Function: Dose adjustment is not needed in patients with impaired renal function.

Impaired Hepatic Function: Dose adjustment is not normally needed in patients suffering from liver cirrhosis because Metoprolol has low protein binding (5-10%). When there are signs of serious impairment of liver function (e.g. shunt-operated patients), a reduction in dose should be considered.

Elderly: Dose adjustment is not needed.

Side Effects

Dry mouth, thirst, nausea, vomiting, feeling weak, drowsy, restless, or light-headed, fast or uneven heartbeat, muscle pain or weakness, urinating less than usual or not at all, easy bruising or bleeding, unusual weakness, red or purple spots on skin, numbness or tingly feeling, nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools.

Bradycardia, bronchospasm, hypotension, headache, fatigue, sleep & gastro-intestinal disturbances, dizziness, vertigo, visual disturbances etc.

Toxicity

Oral administration of metoprolol to rats presents an LD50 in the range of 3090 to 4670 mg/kg. Cases of overdose have reported bradycardia, hypotension, bronchospasm, and cardiac failure. In the case of an overdose, gastric lavage is recommended followed by specific treatment according to symptoms.

Metoprolol is not reported to be carcinogenic nor mutagenic nor to impair fertility. The only event registered is the increase of macrophages in pulmonary alveoli and slight biliary hyperplasia. When metoprolol was given for long periods of time on the highest dose, there was evidence of small benign lung tumors.

Precaution

Renal impairment: Chlorthalidone dosage should be reduced in moderate renal failure - every 24 or 48 h - and should not be used in advanced renal failure.

Liver disease: There is a risk of precipitating hepatic encephalopathy in patients with liver cirrhosis and ascites.

Use in pregnancy: It is better to avoid Chlorthalidone as it crosses the placenta.

Use in Lactation: In lactating mother, significant amount of Chlorthalidone enter breast milk; like other long-acting thiazides, it can suppress lactation. Chlorthalidone should not be prescribed for lactating mother.

The second or third dose should not be given if the heart rate is <40 beats/minute, the P-R interval is > 0.26 seconds and the systolic blood pressure is <90 mmHg or if there is any aggravation of dyspnoea or cold sweating. Intravenous administration of calcium antagonists of the Verapamil-type should not be given to patients treated with beta-blockers. When treating patients with suspected or definite myocardial infarction, the haemodynamic status of the patient should be carefully monitored after each of the three 5 mg intravenous doses. Use in Pregnancy: As with most medicines, Metoprolol should not be given during pregnancy and lactation unless its use is considered essential. As with all antihypertensive agents, beta-blockers may cause side effects (e.g. bradycardia) in the foetus and in the newborn and breast-fed infant. Use in Lactation: The amount of Metoprolol ingested via breast-milk seems to be negligible as regards beta-blocking effect in the infant if the mother is treated with Metoprolol doses within the normal therapeutic range.

Interaction

Chlorthalidone may add to or potentiate the action of other antihypertensive drugs. Potentiation occurs with ganglionic peripheral adrenergic blocking drugs.

Plasma level of Metoprolol may be raised by co-administration of compounds metabolished by CYP2D6 e.g. Antiarrhythmics, antihistamines, H2 receptor antagonists, antidepressants, antipsychotics and COX-2 inhibitors. The plasma conc. of Metoprolol is lowered by Rifampicin.

Volume of Distribution

Chlorthalidone has been shown to rapidly concentrate within erythrocytes and subsequently equilibrate via a slow diffusion back into the serum compartment, resulting in a large volume of distribution.

The reported volume of distribution of metoprolol is 4.2 L/kg. Due to the characteristics of metoprolol, this molecule is able to cross the blood-brain barrier and even 78% of the administered drug can be found in cerebrospinal fluid.

Elimination Route

When metoprolol is administered orally, it is almost completely absorbed in the gastrointestinal tract. The maximum serum concentration is achieved 20 min after intravenous administration and 1-2 hours after oral administration. The bioavailability of metoprolol is of 100% when administered intravenously and when administered orally it presents about 50% for the tartrate derivative and 40% for the succinate derivative.

The absorption of metoprolol in the form of the tartrate derivative is increased by the concomitant administration of food.

Half Life

40-50 hours

The immediate release formulations of metoprolol present a half-life of about 3-7 hours.

Clearance

The reported clearance rate on patients with normal kidney function is 0.8 L/min. In cirrhotic patients, the clearance rate changes to 0.61 L/min.

Elimination Route

Approximately 50% of the administered dose is excreted unmetabolized through the kidney, and excretion is characterized by biphasic elimination with a rapid phase followed by a slow secretory phase.

Metoprolol is mainly excreted via the kidneys. From the eliminated dose, less than 5% is recovered unchanged.

Pregnancy & Breastfeeding use

Pregnancy category B. Thiazides are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from chlorthalidone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Metoprolol should not be used in pregnancy or lactating mothers unless the physician considers that the benefit outweighs the possible hazard to the fetus or infant.

Contraindication

Patients with anuria and known hypersensitivity to Chlorthalidone or other sulfonamide-derived drugs.

2nd or 3rd degree AV block, sick sinus syndrome, hypotension, decompensated heart failure, sinus bradycardia, severe peripheral arterial circulatory disorders, cardiogenic shock, severe asthma and bronchospasm, untreated phaeochromocytoma, Prinzmetal's angina, metabolic acidosis.

Special Warning

Pediatric Use: Safety and effectiveness of Chlorthalidone tablets in pediatric patients have not been established.

Geriatric Use: Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Renal Impairment: No dosage adjustment needed.

Hepatic Impairment: Reduce dose.

Acute Overdose

Symptoms of acute overdosage include nausea, weakness, dizziness, and disturbances of electrolyte balance. The oral LD50 of the drug in the mouse and the rat is more than 25,000 mg/kg body weight. The minimum lethal dose (MLD) in humans has not been established. There is no specific antidote, but gastric lavage is recommended, followed by supportive treatment. Where necessary, this may include intravenous dextrose-saline with potassium, administered with caution.

Poisoning due to an overdose of metoprolol may lead to severe hypotension, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impairment of consciousness, coma, nausea, vomiting, cyanosis, hypoglycaemia and, occasionally, hyperkalaemia. The first manifestations usually appear 20 minutes to 2 hours after drug ingestion. Treatment: Treatment should include close monitoring of cardiovascular, respiratory and renal function, and blood glucose and electrolytes. Further absorption may be prevented by induction of vomiting, gastric lavage or administration of activated-charcoal if ingestion is recent. Cardiovascular complications should be treated symptomatically, which may require the use of sympathomimetic agents (e.g. noradrenaline, metaramionl), atropine or inotropic agents (e.g. dopamine, dobutamine). Temporary pacing may be required for AV block. Glucagon can reverse the effects of excessive B-blockade, given in a dose of 1-10 mg intravenously. Intravenous B2-stimulants e.g. terbutaline may be required to relieve bronchospasm. Metoprolol cannot be effectively removed by haemodialysis.

Storage Condition

Store in a cool & dry place, away from children

Store in a cool, dry place protected from light. Keep out of reach of children.

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