Mavik - General Information
Mavik is an ACE inhibitor used to treat high blood pressure, it may also be used to treat other conditions. It is marketed by Abbott Laboratories with the brand name Mavik®.
Mavik is a prodrug that is deesterified to trandolaprilat. It is believed to exert its antihypertenive effect through the renin-angiotensin-aldosterone system.
Pharmacology of Mavik
Mavik is the ethyl ester prodrug of a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, trandolaprilat. Mavik is deesterified to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE activity. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates secretion of aldosterone by the adrenal cortex and provides negative feedback for renin secretion.
Mavik for patients
Angioedema, including laryngeal edema, may occur at any time during treatment with ACE inhibitors, including MAVIK. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to stop taking the drug until they have consulted with their physician.
Patients should be cautioned that light-headedness can occur, especially during the first days of MAVIK therapy, and should be reported to a physician. If actual syncope occurs, patients should be told to stop taking the drug until they have consulted with their physician All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting, resulting in reduced fluid volume, may precipitate an excessive fall in blood pressure with the same consequences of light-headedness and possible syncope.
Patients planning to undergo any surgery and/or anesthesia should be told to inform their physician that they are taking an ACE inhibitor that has a long duration of action.
Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting their physician.
Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which could be a sign of neutropenia.
Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible. NOTE: As with many other drugs, certain advice to patients being treated with MAVIK is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.
Concomitant diuretic therapy:
As with other ACE inhibitors, patients on diuretics, especially those on recently instituted diuretic therapy, may experience an excessive reduction of blood pressure after initiation of therapy with MAVIK. The possibility of exacerbation of hypoten-sive effects with MAVIK may be minimized by either discontinuing the diuretic or cautiously increasing salt intake prior to initiation of treatment with MAVIK. If it is not possible to discontinue the diuretic, the starting dose of trandolapril should be reduced.
Agents increasing serum potassium:
Trandolapril can attenuate potassium loss caused by thiazide diuretics and increase serum potassium when used alone. Use of potassium-sparing diuretics (spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes concomitantly with ACE inhibitors can increase the risk of hyperkalemia. If concomitant use of such agents is indicated, they should be used with caution and with appropriate monitoring of serum potassium.
Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.
No clinically significant interaction has been found between trandolaprilat and food, cimetidine, digoxin, or furosemide. The anticoagulant effect of warfarin was not significantly changed by trandolapril.
MAVIK is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an ACE inhibitor.
Additional information about Mavik
Mavik Indication: For the treatment of hypertension.
Mechanism Of Action: The effect of trandolapril in hypertension appears to result primarily from the inhibition of circulating and tissue ACE activity thereby reducing angiotensin II formation, decreasing vasoconstriction, decreasing aldosterone secretion, and increasing plasma renin. Decreased aldosterone secretion leads to diuresis, natriuresis, and a small increase of serum potassium.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Trandolapril
Synonyms: Not Available
Drug Category: Angiotensin-converting Enzyme Inhibitors; Antihypertensive Agents
Drug Type: Small Molecule; Approved
Absorption: Absolute bioavailability after oral administration of trandolapril is about 10% as trandolapril and 70% as trandolaprilat. Food slows absorption of trandolapril, but does not affect the area under the plasma concentration–time curve (AUC) or peak plasma concentration (Cmax) of trandolaprilat or Cmax of trandolapril.
Toxicity (Overdose): No data are available with respect to overdosage in humans. The oral LD50 of trandolapril in mice was 4875 mg/Kg in males and 3990 mg/Kg in females. In rats, an oral dose of 5000 mg/Kg caused low mortality (1 male out of 5; 0 females). In dogs, an oral dose of 1000 mg/Kg did not cause mortality and abnormal clinical signs were not observed. In humans the most likely clinical manifestation would be symptoms attributable to severe hypotension.
Protein Binding: Serum protein binding of trandolapril is about 80% (independent of concentration) while that of trandolaprilat is 65 to 94% (concentration-dependent).
Biotransformation: Cleavage of the ester group of trandolapril, primarily in the liver, is responsible for conversion to trandolaprilat, the active metabolite. Seven other metabolites, resulting primarily from glucuronidation or de-esterification, have been identified.
Half Life: The elimination half lives of trandolapril and trandolaprilat are about 6 and 10 hours, respectively, but, like all ACE inhibitors, trandolaprilat also has a prolonged terminal elimination phase, involving a small fraction of administered drug, probably representing binding to plasma and tissue ACE.
Dosage Forms of Mavik: Capsule Oral
Chemical IUPAC Name: (2S,3aR,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid
Chemical Formula: C24H34N2O5
Trandolapril on Wikipedia: https://en.wikipedia.org/wiki/Trandolapril
Organisms Affected: Humans and other mammals