Mavik

trandolapril

Goptin (UK), Mavik

Pharmacologic class: Angiotensin-converting enzyme (ACE) inhibitor

Therapeutic class: Antihypertensive

Pregnancy risk category D

FDA Box Warning

Drugs that act directly on the renin-angiotensin system can cause injury to or death of a developing fetus. Discontinue drug as soon as possible when pregnancy is detected.

Action

Inhibits conversion of angiotensin I to the potent vasoconstrictor angiotensin II, promoting vasodilation. Also increases plasma renin and stimulates aldosterone secretion, inducing diuresis.

Availability

Tablets: 1 mg, 2 mg, 4 mg

Indications and dosages

➣ Hypertension

Adults: For patients not receiving diuretics, 1 mg/day P.O. in nonblack patients or 2 mg/day P.O. in black patients. If response inadequate, may increase at weekly intervals up to 4 mg/day. For patients receiving diuretics, start with 0.5 mg/day P.O.

➣ Heart failure or left ventricular dysfunction after myocardial infarction

Adults: Initially, 1 mg P.O. daily. Titrate up to 4 mg daily, if tolerated.

Dosage adjustment

• Renal impairment (creatinine clearance less than 30 ml/minute)

• Hepatic cirrhosis

Contraindications

• Hypersensitivity to drug or other ACE inhibitors

• Hereditary/idiopathic angioedema and angioedema with previous ACE inhibitor use

• Patients with diabetes mellitus taking insulin or oral hypoglycemics

Precautions

Use cautiously in:

• renal or hepatic impairment, hypovolemia, hyponatremia, aortic stenosis or hypertrophic cardiomyopathy, cerebrovascular or cardiac insufficiency, surgery and anesthesia, risk factors for hyperkalemia (including renal insufficiency, diabetes mellitus, concurrent use of potassium supplements or potassium-containing salt substitutes)

• family history of angioedema

• concurrent diuretic therapy or drugs that cause increased serum potassium level

• black patients with hypertension

• elderly patients

• pregnant patients

• breastfeeding patients (avoid use)

• children (safety not established).

Administration

• Give once or twice daily as prescribed, with or without food.

Adverse reactions

CNS: insomnia, paresthesia, dizziness, drowsiness, asthenia, syncope, cerebrovascular accident

CV: chest pain, palpitations, intermittent claudication, bradycardia, first-degree atrioventricular block, cardiogenic shock

EENT: epistaxis, sinusitis, throat inflammation

GI: vomiting, diarrhea, constipation, abdominal pain or distention, gastritis, dyspepsia, intestinal angioedema, pancreatitis

GU: urinary tract infection, erectile dysfunction, decreased libido

Hematologic: agranulocytosis, neutropenia

Hepatic: syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death (rare)

Metabolic: hypocalcemia, gout, increased creatinine, hyperkalemia

Musculoskeletal: muscle cramps, myalgia, extremity pain

Respiratory: cough, dyspnea, upper respiratory infection

Skin: rash, flushing, pruritus

Other: edema, angioedema (face, extremities, lips, tongue, glottis, and larynx)

Interactions

Drug-drug. Diuretics, general anesthetics, other antihypertensives: increased risk of hypotension

Hypoglycemics (insulin, oral agents): increased risk of blood glucose-lowering effect with greater risk of hypoglycemia

Lithium: increased lithium blood level, greater risk of toxicity

Nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors: increased risk of renal impairment, including acute renal failure in elderly patients, volume-depleted patients, or those with compromised renal function; loss of trandodolapril antihypertensive effect

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium: additive hyperkalemia

Sodium aurothiomalate (gold): increased risk of nitritoid reactions (including facial flushing, nausea, vomiting, and hypotension)

Drug-diagnostic tests. Creatinine, potassium: increased level

Neutrophils, platelets: decreased counts

Drug-food. Salt substitutes containing potassium: hyperkalemia

Patient monitoring

• Monitor vital signs, especially for hypotension and bradycardia when therapy begins.

• Assess CBC with white cell differential. Watch for signs and symptoms of bleeding and infection.

• Monitor electrolyte levels, especially potassium. Stay alert for hyperkalemia.

• Assess renal function tests and fluid intake and output.

Stay alert for signs and symptoms of hypersensitivity reactions (including angioedema). Discontinue drug immediately if laryngeal stridor or angioedema of face, tongue, or glottis occurs, treat appropriately, and closely observe patient until swelling disappears.

Be aware that rarely ACE inhibitors have been associated with a syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death. If patient develops jaundice, discontinue drug and provide appropriate followup care.

Patient teaching

• Tell patient drug may cause bleeding tendency or increase his infection risk. Teach him which warning signs to report.

Teach patient to recognize and report signs or symptoms of hyperkalemia, infection, angioedema (including intestinal angioedema that may present as abdominal pain with or without nausea), and syndrome of cholestatic jaundice.

• Instruct patient to move slowly when sitting up or standing, to avoid dizziness from sudden blood pressure drop.

• Caution patient not to exercise vigorously in hot environments.

• Advise patient not to use salt substitutes containing potassium. Tell him to avoid high-potassium foods.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.

trandolapril

(tran-doe-la-pril) ,

Mavik

(trade name)

Classification

Therapeutic: antihypertensives
Pharmacologic: ace inhibitors

Pregnancy Category: D

Indications

Alone or with other agents in the management of hypertension.Reduction of risk of death and heart-failure-related hospitalizations in patients with left ventricular systolic dysfunction or heart failure symptoms following myocardial infarction.

Action

Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to the vasoconstrictor angiotensin II. ACE inhibitors also prevent the degradation of bradykinin and other vasodilatory prostaglandins. ACE inhibitors also ↑ plasma renin levels and ↓ aldosterone levels. Net result is systemic vasodilation.

Therapeutic effects

Lowering of BP in hypertensive patients.

Increased survival after myocardial infarction.

Pharmacokinetics

Absorption: 70% bioavailability as trandolaprilat following oral administration.

Distribution: Crosses the placenta; enters breast milk.

Protein Binding: 80%.

Metabolism and Excretion: Converted by the liver to trandolaprilat, the active metabolite; 33% excreted in urine, 66% in feces.

Half-life: Trandolapril: 6 hr; Trandolaprilat: 22.5 hr (↑ in renal impairment).

Time/action profile (antihypertensive effect)

ROUTE	ONSET	PEAK	DURATION
PO	within 1–2 hr*	within 1 wk†	up to 24 hr†

*After single dose†Chronic dosing

Contraindications/Precautions

Contraindicated in: Hypersensitivity; History of angioedema with previous use of ACE inhibitors; Concurrent use with aliskiren in patients with diabetes or moderate-to-severe renal impairment (CCr <60 mL/min) Obstetric: Can cause injury or death of fetus – if pregnancy occurs, discontinue immediately. Lactation: Discontinue drug or use formula.

Use Cautiously in: genetic implication Black patients (monotherapy for hypertension less effective, may require additional therapy; higher risk of angioedema); Surgery/anesthesia (hypotension may be exaggerated); Women of childbearing potential; Renal impairment, hypovolemia, hyponatremia, concurrent diuretic therapy, and Geriatric: Initial dose ↓ recommended; Pediatric: Safety not established.

Exercise Extreme Caution in: Family history of angioedema.

Adverse Reactions/Side Effects

Central nervous system

• weakness

Respiratory

• cough (most frequent)

Cardiovascular

• hypotension (most frequent)

Endocrinologic

• hyperuricemia

Gastrointestinal

• diarrhea
• dyspepsia

Genitourinary

• impaired renal function

Dermatologic

• rashes

Fluid and Electrolyte

• hyperkalemia
• hypocalcemia

Musculoskeletal

• myalgia

Miscellaneous

• angioedema (life-threatening)

Interactions

Drug-Drug interaction

Excessive hypotension may occur with concurrent use of diuretics.Additive hypotension with other antihypertensive agents.↑ risk of hyperkalemia with concurrent use ofpotassium supplements,potassium-containing salt substitutes, and potassium-sparing diuretics.↑ risk of hyperkalemia, renal dysfunction, hypotension, and syncope with concurrent use of angiotensin II receptor antagonists or aliskiren ; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/minNSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal dysfunction.↑ levels and may ↑ the risk oflithium toxicity.

Route/Dosage

Oral (Adults) Hypertension—1 mg once dailygenetic implication (2 mg in Black patients). May be ↑ weekly up to 4 mg once daily; twice-daily dosing may be necessary in some patients (initiate therapy with 0.5 mg/day in patients receiving diuretics). Heart failure post-MI or left ventricular dysfunction post-MI—Initiate therapy at 1 mg once daily, titrate up to 4 mg once daily if possible.

Renal Impairment

Oral (Adults) CCr <30 mL/min—Initiate therapy at 0.5 mg once daily, may be slowly titrated upward (max dose = 4 mg/day).

Hepatic Impairment

Oral (Adults) Initiate therapy at 0.5 mg once daily, may be slowly titrated upward (max dose = 4 mg/day).

Availability (generic available)

Tablets: 1 mg, 2 mg, 4 mg

In combination with: verapamil (Tarka). See combination drugs.

Nursing implications

Nursing assessment

• Hypertension: Monitor BP and pulse frequently during initial dose adjustment and periodically during therapy. Notify health care professional of significant changes.
  • Monitor frequency of prescription refills to determine compliance.
• Assess patient for signs of angioedema (dyspnea, facial swelling).
• Heart Failure: Monitor weight and assess patient routinely for resolution of fluid overload (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).
• Lab Test Considerations: Monitor renal function. May cause ↑ BUN and serum creatinine.
  • May cause hyperkalemia.
  • Monitor CBC periodically during therapy in patients with collagen vascular disease and/or renal disease. May rarely cause agranulocytosis.
  • May cause ↑ AST, ALT, alkaline phosphatase, serum bilirubin, and uric acid.

Potential Nursing Diagnoses

Decreased cardiac output (Indications,  Side Effects)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)
Noncompliance (Patient/Family Teaching)

Implementation

• Due to risk for precipitous drop in BP at initiation of therapy, correct pre-existing volume depletion, if possible. Discontinuing diuretic therapy or cautiously increasing salt intake 2–3 days prior to initiation may decrease this risk. Monitor closely for at least 1 hr after BP has stabilize.
• Oral: May be taken with or without food.

Patient/Family Teaching

• Emphasize importance of continuing to take medication as directed at the same time each day, even if feeling well. Take missed doses as soon as remembered but not if almost time for next dose. Do not double doses. Warn patient not to discontinue ACE inhibitor therapy unless directed by health care professional.
  • Caution patient to avoid salt substitutes containing potassium or foods containing high levels of potassium or sodium unless directed by health care professional. See.
  • Caution patient to change positions slowly to minimize orthostatic hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may increase orthostatic hypotension.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially cough, cold, or allergy remedies.
  • May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
  • Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
  • Instruct patient to notify health care professional if rash; mouth sores; sore throat; fever; swelling of hands or feet; irregular heartbeat; chest pain; dry cough; hoarseness; swelling of face, eyes, lips, or tongue; or if difficulty swallowing or breathing occurs. Persistent dry cough may occur and may not subside until medication is discontinued. Consult health care professional if cough becomes bothersome. Also notify health care professional if nausea, vomiting, or diarrhea occurs and continues.
  • Advise women of childbearing age to use contraception and notify health care professional if pregnancy is planned or suspected. If pregnancy is detected, discontinue medication as soon as possible.
  • Emphasize the importance of follow-up examinations to monitor effectiveness of medication.
• Hypertension: Encourage patient to comply with additional interventions for hypertension (weight reduction, low sodium diet, discontinuation of smoking, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.
  • Instruct patient and family on correct technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes to health care professional.

Evaluation/Desired Outcomes

• Decrease in BP without appearance of side effects.
• Reduction of risk of death or heart-failure-related hospitalizations following myocardial infarction.

Mavik®

Trandolapril, see there.