Adult: Dosage must be determined by titration of individual components. As substitute for separate dosing of components or as combination when response to single component is suboptimal.
Metoprolol tartrate 50 mg and hydrochlorothiazide 25 mg
Metoprolol tartrate 100 mg and hydrochlorothiazide 25 mg
Metoprolol tartrate 100 mg and hydrochlorothiazide 50 mg
Dose range: 100-200 mg/25-50 mg daily as single or in divided doses. Doses may be adjusted according to patient response. If necessary, another antihypertensive agent may be added gradually, initiating with 50% of the usual starting dose of the other agent.
Metoprolol succinate (extended-release) 25 mg and hydrochlorothiazide 12.5 mg
Metoprolol succinate (extended-release) 50 mg and hydrochlorothiazide 12.5 mg
Metoprolol succinate (extended-release) 100 mg and hydrochlorothiazide 12.5 mg
Initially, 25 mg/12.5 mg once daily, may be titrated at intervals of 2 weeks depending on the blood pressure response. Max: 200 mg/25 mg once daily.
Special Patient Group
Metoprolol is primarily metabolised by the CYP2D6 isoenzyme. It observes stereoselective metabolism that is dependent on oxidation phenotype. CYP2D6 is lacking in approx 8% of Caucasians and approx 2% of other populations.
Poor, intermediate, extensive, and ultrarapid metabolisers of metoprolol have been identified and studies confirmed that plasma concentrations of metoprolol correlate with the metaboliser status. Use of metoprolol with CYP2D6 poor metabolisers exhibit several-fold higher plasma concentrations in comparison to extensive metabolisers. Additionally, drugs that inhibit CYP2D6 are likely to increase metoprolol plasma concentration, thereby causing a decrease in cardioselectivity.
Immediate Release Tab: Should be taken with food. as metoprolol tartrate Extended Release Tab: May be taken with or without food. as metoprolol succinate
Avoid exposure to direct sunlight and UV light, and consider applying sunscreen when going outdoors.
Monitor blood pressure, heart rate and rhythm, renal function, fluid and electrolyte levels (e.g. Na, K). Assess for signs and symptoms of dizziness and light-headedness, photosensitivity reactions, and skin cancer.
Symptoms: Hypotension, bradycardia or tachycardia, shock, cardiac failure, confusion, dizziness, muscle cramps, weakness, paraesthesia, fatigue, nausea, vomiting, thirst, bronchospasm, fluid and electrolyte loss, hypokalaemia, hyponatraemia, hypochloraemia, alkalosis, raised BUN, polyuria, oliguria, or anuria. Management: Symptomatic and supportive treatment. Induce vomiting, perform gastric lavage, or administer activated charcoal to eliminate content. In case of hypotension, raise the patient’s legs, correct fluid and electrolyte loss, and administer vasopressor (e.g. levarterenol, dopamine) as required. Give β2 agonists or theophylline in cases of bronchospasm. Administer atropine to treat bradycardia; may give isoproterenol cautiously if there is no response to vagal blockade. To combat cardiac failure, administer digitalis glycoside and diuretic. In case of shock resulting from inadequate cardiac contractility, may consider giving dobutamine, isoproterenol, or glucagon.
Metoprolol: May increase plasma concentration with strong CYP2D6 inhibitors (e.g. fluoxetine, paroxetine, bupropion, thioridazine, quinidine, propafenone, ritonavir, diphenhydramine, hydroxychloroquine, terbinafine, cimetidine). May cause additive effects with catecholamine-depleting drugs (e.g. reserpine, MAOIs). Increased risk of bradycardia with digitalis glycosides. May increase cardiodepressant effect with general anaesthetics. Metoprolol may reduce the therapeutic effect of epinephrine.
Hydrochlorothiazide: May increase the risk of hypokalaemia with steroids or ACTH. May decrease the arterial response to norepinephrine. May increase effect of tubocurarine. Reduced clearance of lithium thus increases the risk of toxicity. Rarely, concomitant use with methyldopa may increase risk of haemolytic anaemia. Diminished therapeutic effect with NSAIDs. Decreased absorption with colestyramine and colestipol resins.
Alcohol may potentiate the orthostatic hypotensive effect of hydrochlorothiazide.
Hydrochlorothiazide: May affect parathyroid function tests; may reduce serum iodine (protein-bound) without signs of thyroid disturbance. May cause false-negative aldosterone/renin ratio (ARR).
Description: Metoprolol competitively blocks β1- receptors and possesses little to no effect on β2- receptors except at higher doses. It does not exhibit membrane stabilising or intrinsic sympathomimetic activity.
Hydrochlorothiazide, a thiazide diuretic, inhibits Na reabsorption in the distal tubules causing increased Na, water, K and hydrogen ions excretion. Onset: Metoprolol tartrate: Within 1 hour.
Hydrochlorothiazide: Diuresis: Approx 2 hours. Duration: Metoprolol: Variable (as tartrate); Approx 24 hours (as succinate).
Hydrochlorothiazide: 6-12 hours. Pharmacokinetics: Absorption: Metoprolol: Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: Approx 40-50% (as tartrate); 77% (as succinate). Time to peak plasma concentration: 1.5-2 hours; 10-12 hours (as succinate).
Hydrochlorothiazide: Rapidly and well absorbed from the gastrointestinal tract. Enhanced absorption with food. Bioavailability: 65-75%. Time to peak plasma concentration: Approx 1-5 hours. Distribution: Crosses the placenta, enters breast milk.
Metoprolol: Widely distributed. Volume of distribution: 3.2-5.6 L/kg. Plasma protein binding: Approx 10-12%, mainly to albumin.
Hydrochlorothiazide: Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-70%, mainly to albumin. Metabolism: Metoprolol: Extensively metabolised in the liver by CYP2D6, undergoes first-pass metabolism (approx 50%).
Hydrochlorothiazide: Not metabolised. Excretion: Metoprolol: Via urine (95%, <5% as unchanged drug; increased to 30-40% in CYP2D6 poor metabolisers). Elimination half-life: 3-4 hours (7-9 hours in CYP2D6 poor metabolisers).
Hydrochlorothiazide: Via urine (≥61% as unchanged drug). Elimination half-life: Approx 5-15 hours.
C07CB02 - metoprolol and other diuretics ; Belongs to the class of selective beta-blocking agents in combination with other diuretics. Used in the treatment of cardiovascular diseases.
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