Trandolapril

As an angiotensin-converting enzyme inhibitor (ACE inhibitor), Trandolapril is a pharmaceutical prodrug with primary indications for use in the treatment of hypertension and congestive heart failure.

Overview:

Trandolapril, marketed under the brand name Mavik, earned FDA approval in 1996 as a treatment for high blood pressure. It is also used to treat congestive heart failure and in the aftermath of a heart attack or myocardial infarction. Trandolapril works by relaxing the blood vessels, which helps increase circulation, prevent clotting (although it is not an anticoagulant and does not provide antiplatelet protection), and by reducing the amount of oxygen required from the heart.

Trandolapril is an ACE inhibitor (angiotensin-converting enzyme). Trandolapril is a prodrug, meaning that it is converted into a pharmacological agent once it is metabolized in the body. It then becomes a drug called trandolaprilat. This substance binds to the angiotensin-converting enzyme, preventing the enzyme from causing constriction of arteries, veins and capillaries, and results in relaxing of the blood vessels. Because it is inactive upon entering the body, trandolapril improves the bioavailability of the chemical compounds and is more effectively absorbed than a standard medical compound would be.

As a family of medications, ACE inhibitors were first developed in the late 1950s based on research in the medical applications of the venom from the South American pit viper (Bothrops jararaca). From that point, the active substance in the venom, bradykinin potentiating factor, was further studied, isolated and later synthesized to develop what is now a whole class of angiotensin converting enzyme inhibitors, of which trandolapril is one of the newer editions.

In recent years, the standard of practice in treating hypertension has moved to a combination therapy matching ACE inhibitors like trandolapril with an angiotensin II receptor antagonist. These drugs block a different enzyme that can also lead to high blood pressure and cardiac failure. When prescribed together, this double treatment may be more effective at treating these conditions and preventing myocardial infarction, stroke or other potentially fatal outcomes. Recent studies have shown no significant increase in adverse side effects when these medications are taken together and some better outcomes. This also applies to patients with heart failure. The combination of medical agents has shown to reduce morbidity and further damage to the heart.

Conditions treated:

  • hypertension (high blood pressure)
  • post myocardial infarction (after a heart attack)
  • to slow progression of renal failure in patients with hypertension and kidney disease
  • to slow progression of liver failure where hypertension is a contributing factor
  • congestive heart failure
  • left ventricular systolic dysfunction

Type of medication:

  • angiotensin-converting enzyme inhibitor (ACE inhibitor)

Side effects:

The following side effects are not dangerous and occur in less than 1% of patients prescribed Trandolapril (these side effects are common across the family of ACE Inhibitor medications):

  • loss of appetite
  • nausea
  • headache
  • diarrhea
  • abdominal pain
  • vomiting
  • fatigue
  • dry, persistent cough

The following side effects are rare, but are potentially quite serious. If the patient experiences any of the following, he or she should contact a physician or health care provider immediately:

  • skin rash, with or without itching
  • blurred vision
  • low blood pressure
  • numbness or tingling in hands, feet or lips
  • flu-like symptoms (sore throat, cough, fever)
  • depression in the form of poor concentration, loss of interest in activities, insomnia, weight loss or weight gain, suicidal thoughts
  • sudden lack of energy
  • dizziness
  • lightheadedness or fainting
  • kidney problems such as decreased urination, more urination during the night, or blood in the urine
  • confusion and disorientation
  • electrolyte imbalance (including muscle pain or cramps, weakness)
  • irregular heartbeat
  • unusual nosebleeds or cuts that won't stop bleeding
  • blood in the urine
  • coughing blood
  • impaired liver function (e.g. yellowing of skin or whites of the eyes, dark urine)
  • potassium imbalance (e.g. shortness of breath, weakness or heaviness of legs)

The side effects listed below are very rare, but very dangerous. If the patient experiences any of the following, he or she should stop taking Trandolapril immediately and seek medical help right away:

  • abdominal pain, with or without nausea or vomiting
  • angioedema
  • difficulty swallowing
  • difficulty breathing
  • serious allergic reaction
  • swelling of the face and throat
  • blistering, peeling or rash that spreads quickly
  • swelling of the mouth, lips or tongue

Dosage:

Trandolapril comes in tablet form in 3 different strengths - 1 mg, 2 mg and 4 mg. The 1 mg tablet is salmon colored and round shaped. The 2 mg tablet is yellow colored and round shaped. The 4 mg tablet is rose colored and round shaped. All strengths of trandolapril come in units of 100 tablets.

Dosage levels for trandolapril vary according to the condition that it is being used to treat. Trandolapril also has different effects on patients based on their race. Different dosage levels are indicated for African Americans than for non African Americans.

In the treatment of hypertension, the recommended dosage is 1 mg a day delivered orally for non African American populations. This is the initial dosage. Once it has been established that the medication can be well tolerated, the maintenance regimen is 2 mg - 4 mg daily. For African American patients, the initial dosage is 2 mg with a daily maintenance of 2 mg - 4 mg. If patients are also taking prescribed diuretics, careful medical supervision is necessary. Patients should come off the diuretic 3 days prior to beginning the trandolapril treatment. If the patient cannot safely discontinue use of diuretics, then the recommended initial dose is 0.5 mg. Generally, dosage levels are adjusted after one week until blood pressure is stabilized and target rates are reached. If the 4 mg dosage level does not reduce blood pressure levels enough, patients can take the dose twice daily. Trandolapril has not been studied at dosages of more than 8 mg a day. It can be taken in combination with other antihypertensive medications.

It can also be taken in conjunction with a diuretic if blood pressure levels are not satisfactorily lowered with taking trandolapril alone. Again, this needs to be monitored closely to avoid hypotensive situations.

Potassium salt substitutes, potassium sparing diuretics and potassium supplements should generally be avoided in combination with trandolapril as they can lead to dangerously high potassium levels in the body.

When used in the treatment of congestive heart failure, the recommended dosage of trandolapril is 4 mg per day, with an initial dosage of 1 mg. If the drug is not well tolerated, the daily dosage can be less than 4 mg.

The same dosage levels are indicated in the treatment of left ventricular systolic dysfunction with the same precautions and medical supervision.

Trandolapril can also be prescribed in the immediate aftermath of an acute myocardial infarction in an effort to quickly lower blood pressure and prevent subsequent damage to the heart.

When it is used as part of a treatment plan for severe renal dysfunction, the recommended initial dose is 0.5 mg.

When trandolapril is prescribed as part of a protocol for treating hepatic cirrhosis, the recommended initial dose is 0.5 mg. In these cases, trandolapril is part of a combination of medications treating complicated conditions. It is not used alone to treat these conditions.

Trandolapril may be taken with or without food.

Interactions:

Given the mechanism of action and how trandolapril is metabolized in the body, it does negatively interact with many other medications. The most serious of those interactions include the following:

  • sacubitril ( this drug in combination with trandolapril can cause a very severe reaction, particularly angioedema, and so they are not prescribed together)
  • lithium
  • trimethoprim
  • MTOR inhibitors (used in the treatment of renal cancer)
  • aliskeren
  • sodium bowel phosphate cleansers

Trandolapril has moderate interactions with the following medications, and should be carefully monitored by a physician if a patient is taking both:

  • NSAIDs (naproxen, celecoxib, ibuprofen etc.)
  • ARBS
  • ┬ápotassium sparing diuretics
  • potassium preparations
  • loop diuretics
  • high dose aspirin
  • tizanidine
  • some antihypertensives
  • selected monoamine oxidase inhibitors (MAOIs such as selegiline, isocarboxazid, tranylcypromine, phenelzine)
  • other ACE inhibitors such as drospirienone, canaglifoxin, dapagliflozin and asathioprine

It is recommended that patients taking trandolapril should be advised to avoid moderately high or high potassium dietary intake. This can cause high levels of potassium in your blood. Do not use salt substitutes or potassium supplements while taking trandolapril, unless a doctor has recommended that regimen.

Warnings:

Trandolapril should never be prescribed in combination with the drug sacubitril (brand name Entresto). It was approved for treatment of heart failure in 2015. It also functions as a hypertensive, but has a different mechanism of action. It works primarily by reducing blood volume. It has been found that when trandolapril and sacubitril are taken together, the patient is at great risk for angioedema in the face and throat, which can cause difficulty in breathing.

For patients taking trandolapril, it is recommended that they avoid diets with high potassium. The combination of dietary potassium and trandolapril can cause elevated levels of potassium in the blood stream. Elevated potassium can result in the following symptoms:

  • trouble breathing
  • chest pain
  • nausea and vomiting
  • tiredness and fatigue
  • muscle weakness
  • numbness or tingling
  • heart palpitations and/or irregular heartbeat

Trandolapril, as with any ACE inhibitor, increases patient risk of angioedema, particularly if he or she already has had some history with swelling of extremities or facial features. This can lead to difficulty breathing and swallowing and may require emergency treatment. For patients with hereditary predisposition for angioedema, trandolapril is contraindicated.

Another danger is bone marrow suppression. This happens rarely in most patients who are only suffering from high blood pressure, but is much more common in patients who are also treating renal impairment. Conditions such as neutropenia (reduced white blood cells), aplastic anemia or hemolytic anemia are possible complications. Thrombocytopenia, erythematosus, scleroderma and eosinophilia have also been reported as a result of suppression in conjunction with ACE Inhibitor use. Frequent blood work, and monitoring of red and white blood cell counts are very important.

For patients whose renal function is impaired, close supervision in the initial stages of trandolapril use is indicated. In some cases, treatment may result in further renal failure or excessive hypotension. When used to treat congestive heart failure, careful monitoring is critical, as trandolapril has rarely been reported to cause oliguria (dangerous decreases in urinary output) and progressive azotemia (excessive nitrogen levels in the blood). This has led to renal failure, myocardial ischemia and death.

Patients in dialysis have reported anaphylactoid reactions. Trandolapril has also been associated with elevated serum potassium levels. For patients also suffering with some hepatic impairment, initial dosages of trandolapril may need to be reduced as the drug is not metabolized as efficiently and remains at much higher levels in the body for a longer period of time.

Trandolapril is contraindicated for women who are pregnant or likely to become pregnant. It has been linked to the formation of congenital birth defects. It has also been linked directly to fetal toxicity and its use should be discontinued immediately if a woman discovers she is pregnant while taking trandolapril. It is also not recommended for mothers who are nursing, as trandolapril may be passed from mother to child in breast milk.

It is also contraindicated for patients who suffer from the following conditions:

  • Hypersensitivity to ACE inhibitors, including trandolapril
  • Hypovolemia or dehydration
  • Hemodialysis with high-flux polyacrylonitrile membranes
  • Aortic valve stenosis or cardiac outflow obstruction
  • Impaired renal function not linked to hypertension

In post marketing studies, patients who were prescribed trandolapril reported the following side effects and conditions, but all of these have not been clinically studied or verified. This is only voluntary information provided by those taking the medication.

In terms of general function, patients reported increased levels of malaise and fever. Some reported cardiovascular events including myocardial infarction, angina pectoris, ventricular tachycardia, arrhythmia, transient ischemic attack and cardiac failure. Trandolapril was also potentially linked to cerebral hemorrhage.

Some people indicated a dermatologic response such as alopecia, Stevens-Johnson syndrome or increased sweating. Patients have also reported increased rates of upper respiratory tract infection, perhaps tied to persistent cough, as well as throat inflammation and epistaxis. People also indicated increased incidence of bronchitis. They also indicated decreased libido, impotence and increased anxiety. Reports of abdominal cramping, constipation, diarrhea, vomiting and nausea were also linked to taking trandolapril. In terms of blood testing and red and white blood cell counts, patients self-reported decreased leukocytes and neutrophils. There were also reported issues with pancreatitis, jaundice and hepatitis, as well as chronic dry mouth.

In later clinical tests, ACE inhibitors have been potentially linked to eosinophilic pneumonitis. This form of pneumonia occurs when white blood cells accumulate in the alveoli of the lungs, preventing normal extraction of oxygen. While easily treatable once it is detected, this condition can be potentially very dangerous, particularly to patients who are suffering from other serious conditions such as heart disease.

There have been no clinical studies regarding overdosing and its effects on humans. There have been some studies of the effects of overdosing levels of trandolapril in mice and in dogs, which have led to the hypothesis that an overdose would take the form of extreme hypotension (very low blood pressure). More research and study is recommended on the effects of overdose, and how it might best be counteracted in humans in the event of a serious overdose. In general, treatment presently is the delivery of normal saline solution to dilute the effects of the medication and speed its elimination from the body.

Storage:

Trandolapril should be stored at room temperature and away from direct light. It should be stored in the original container with the label until it is used. It should also be stored in a dry place. The bathroom is not recommended for storage. As with any medication, Trandolapril should be stored safely and securely away from the reach of children and pets. Consult a pharmacist to dispose of unused Trandolapril. Do not take the medication if the packaging or seal is broken.

Summary:

Trandolapril represents one of the newest drugs in a cluster of medications known as ACE inhibitors. These medications are prescribed to patients suffering from a variety of cardiovascular conditions and impairments including high blood pressure, left ventricular systolic dysfunction, post myocardial infarction and in the treatment of certain liver and kidney impairments that are linked to complications in high blood pressure. It has been found in clinical studies that trandolapril can be more efficacious when used in combination with a member of the family of drugs called angiotensin II receptor antagonists. It may also be more effective in lowering blood pressure when prescribed in conjunction with a diuretic.

Generally speaking, trandolapril is a safe medication for the treatment of various cardiovascular diseases, however it interacts with a whole range of other medications, most seriously with a medicine called sacubitril. It can also interact with anticoagulants, antiplatelet medications, antibiotics, antacids, diuretics, other ACE inhibitors and some cancer medications.

Because trandolapril can have a negative effect on bone marrow production, liver function and kidney function, careful monitoring of these functions is indicated with frequent blood tests and medical supervision. It has also been linked to some dangerous side effects including angioedema and eosinophilic pneumonitis that would require immediate discontinuation of use and medical treatment. Other side effects such as tiredness, a persistent dry cough or frequent headaches are worth mentioning, but can generally be tolerated by patients. Often these more minor side effects dissipate with continued use.

The usual dosage of trandolapril for most conditions is between 2-4 mg daily. Dosages in excess of 8 mg have not been studied and there has really been no substantial research into overdosing of trandolapril and counter treatments for that outcome.

As part of the arsenal of treatments for heart disease, most particularly hypertension, trandolapril has proven, since its approval in 1996, to be a reliable weapon. While all drugs in this class of medications can come with significant side effects and interactions, it remains a viable part of the standard of care.

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Last Reviewed:
December 24, 2017
Last Updated:
December 22, 2017