Exforge HCT (amlodipine / hydrochlorothiazide / valsartan) Disease Interactions
There are 18 disease interactions with Exforge HCT (amlodipine / hydrochlorothiazide / valsartan):
- Cardiogenic Shock/Hypotension
- Coronary Artery Disease
- Liver Disease
- Electrolyte Losses
- Liver Disease
- Lupus Erythematosus
- Renal Function Disorders
- Renal Artery Stenosis
- Thyroid Function Tests
- Renal/Liver Disease
Angiotensin II receptor (AR) antagonists can cause symptomatic hypotension in patients with an activated renin-angiotensin system, such as volume- and/or sodium-depleted patients. Therapy with AR antagonists should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if high doses were used or if recently instituted; those on dietary salt restriction; renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with AR antagonists, and the patient should be hemodynamically stable. Ideally, patients at risk for excessive hypotension should initiate AR antagonist therapy under close medical supervision, preferably with a lower dose, and followed closely for the first 2 weeks of treatment and whenever the dosage of AR antagonist or diuretic is increased.
In general, calcium channel blockers (CCBs) should not be used in patients with hypotension (systolic pressure < 90 mm Hg) or cardiogenic shock. Due to potential negative inotropic and peripheral vasodilating effects, the use of CCBs may further depress cardiac output and blood pressure, which can be detrimental in these patients. The use of verapamil and diltiazem is specifically contraindicated under these circumstances.
Increased frequency, duration, and/or severity of angina, as well as acute myocardial infarction, have rarely developed during initiation or dosage increase of calcium channel blockers (CCBs), particularly in patients with severe obstructive coronary artery disease and those treated with immediate-release formulations. The mechanism of this effect is not established. Therapy with CCBs should be administered cautiously in patients with significant coronary artery disease.
Calcium channel blockers (CCBs) are extensively metabolized by the liver. The half-lives of CCBs may be prolonged substantially in patients with severe hepatic impairment, with the potential for significant drug accumulation. In addition, the use of some CCBs has been associated with elevations in serum transaminases, both with and without concomitant elevations in alkaline phosphatase and bilirubin. While these effects may be transient and reversible, several patients have developed cholestasis or hepatocellular injury that was proven by rechallenge. Therapy with CCBs should be administered cautiously and often at reduced dosages in patients with significantly impaired hepatic function. Periodic monitoring of liver function and for excessive pharmacologic effects (e.g., abnormal prolongation of PR interval) is advised, and the dosage adjusted if necessary.
The use of thiazide diuretics is contraindicated in patients with anuria.
The use of thiazide diuretics is commonly associated with loss of electrolytes, most significantly potassium but also sodium, chloride, bicarbonate, and magnesium. The loss of other electrolytes such as phosphate, bromide and iodide is usually slight. Potassium and magnesium depletion may lead to cardiac arrhythmias and cardiac arrest. Other electrolyte-related complications include metabolic alkalosis and hyponatremia, which are rarely life-threatening. Therapy with thiazide diuretics should be administered cautiously in patients with or predisposed to fluid and electrolyte depletion, including patients with primary or secondary aldosteronism (may have low potassium levels); those with severe or prolonged diarrhea or vomiting; and those with poor nutritional status. Fluid and electrolyte abnormalities should be corrected prior to initiating therapy, and blood pressure as well as serum electrolyte concentrations monitored periodically and maintained at normal ranges during therapy. Patients should be advised to immediately report signs and symptoms of fluid or electrolyte imbalance, including dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting. Digitalized patients and patients with a history of ventricular arrhythmias should be monitored carefully, since development of hypokalemia may be particularly dangerous in these patients. The risk of hypokalemia may be minimized by slow diuresis, a lower thiazide dosage, potassium supplementation, or combined use with a potassium-sparing diuretic.
Patients with severe liver disease or cirrhosis are very susceptible to thiazide-induced hypokalemic hypochloremic alkalosis. Blood ammonia concentrations may be further increased in patients with previously elevated concentrations. Hepatic encephalopathy and death have occurred secondary to the electrolyte alterations accompanying diuretic use. Therapy with thiazide diuretics should be administered cautiously in patients with impaired hepatic function or progressive liver disease, and discontinued promptly if signs of impending hepatic coma appear (e.g., tremors, confusion, and increased jaundice).
The use of thiazide diuretics has been reported to possibly exacerbate or activate systemic lupus erythematosus. Reported cases have generally been associated with chlorothiazide and hydrochlorothiazide. Therapy with thiazide diuretics should be administered cautiously in patients with a history or risk of SLE.
Thiazide diuretics may be ineffective when the glomerular filtration rate is low (GFR < 25 mL/min) because they are not expected to be filtered into the renal tubule, their site of action. In addition, thiazide diuretics decrease the GFR and may precipitate azotemia in renal disease. Cumulative effects may also develop because most of these drugs are excreted unchanged in the urine by glomerular filtration and active tubular secretion. Therapy with thiazide diuretics should be administered cautiously at reduced dosages in patients with renal impairment. If renal function becomes progressively worse, as indicated by rising BUN or serum creatinine levels, an interruption or discontinuation of thiazide therapy should be considered.
Angiotensin II receptor (AR) antagonists can cause renal impairment in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system. In addition, symptomatic hypotension can occur in susceptible individuals, which may compromise renal and myocardial perfusion. In patients with severe congestive heart failure (CHF), treatment with AR antagonists has been associated with oliguria and/or progressive azotemia and, rarely, renal failure, myocardial ischemia, and death. Therapy with AR antagonists should be initiated cautiously in patients with severe CHF, especially when accompanied by volume and/or sodium depletion. In patients who experience a decline in renal function, discontinuation of AR antagonist therapy is usually not required provided there is symptomatic improvement of the heart failure and renal deterioration is well-tolerated. Transient hypotension is also not a contraindication to further treatment with AR antagonists, since therapy can usually be reinstated without difficulty after blood pressure stabilizes.
In patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney, angiotensin II receptor (AR) antagonists may reduce renal perfusion to a critically low level. Increases in serum creatinine or blood urea nitrogen have been reported with ACE inhibitors, a class of drugs that also block the renin-angiotensin-aldosterone system. Although there are no long-term data on the use of AR antagonists in patients with renal artery stenosis, a similar effect should be anticipated. Renal function should be monitored closely for the first few weeks of therapy.
Calcium channel blockers (CCBs) may have varying degrees of negative inotropic effect. Congestive heart failure (CHF), worsening of CHF, and pulmonary edema have occurred in some patients treated with a CCB, primarily verapamil. Some CCBs have also caused mild to moderate peripheral edema due to localized vasodilation of dependent arterioles and small blood vessels, which can be confused with the effects of increasing left ventricular dysfunction. Although some CCBs have been used in the treatment of CHF, therapy with CCBs should be administered cautiously in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. Likewise, caution is advised in patients with acute myocardial infarction and pulmonary congestion documented by X-ray on admission, since associated heart failure may be acutely worsened by administration of a CCB.
Thiazide diuretics may cause hyperglycemia and glycosuria in patients with diabetes. They may also precipitate diabetes in prediabetic patients. These effects are usually reversible following discontinuation of the drugs. Therapy with thiazide diuretics should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during thiazide therapy, and their antidiabetic regimen adjusted accordingly.
Thiazide diuretics may increase serum triglyceride and cholesterol levels, primarily LDL and VLDL. Whether these effects are dose-related and sustained during chronic therapy are unknown. Patients with preexisting hyperlipidemia may require closer monitoring during thiazide therapy, and adjustments made accordingly in their lipid-lowering regimen
Urinary calcium excretion is decreased by thiazide diuretics during chronic administration. Pathologic changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been reported during prolonged therapy. However, the common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen. Clinicians should be cognizant of these effects when prescribing or administering thiazide therapy to patients with hyperparathyroidism. These drugs should be discontinued before carrying out tests for parathyroid function.
Thiazide diuretics decrease the rate of uric acid excretion. Hyperuricemia occurs frequently but is usually asymptomatic and rarely leads to clinical gout except in patients with a history of gout or chronic renal failure. Therapy with thiazide diuretics should be administered cautiously in such patients.
Thiazide diuretics may decrease serum PBI (protein-bound iodine) levels without associated thyroid disturbance. Clinicians should be cognizant of this effect when prescribing or administering thiazide therapy to patients with thyroid disorders.
Valsartan is primarily eliminated by biliary excretion, and a minority is excreted in the urine. Dosage adjustments are not necessary in patients with renal impairment unless they are also volume-depleted, in which case therapy should be initiated under medical supervision. Likewise, patients with mild to moderate hepatic impairment or biliary obstruction generally do not require a dosage adjustment. The manufacturer recommends administering valsartan therapy with caution in patients with impaired renal and/or liver function, particularly if these conditions are severe.
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Drug Interaction Classification
The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
|Major||Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.|
|Moderate||Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.|
|Minor||Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.|
Do not stop taking any medications without consulting your healthcare provider.
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