Drug Interaction Report

The chlorthalidone in chlorthalidone / clonidine has a moderate potential interaction with Abnormal Glucose Tolerance.

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.

Zonisamide has a moderate potential interaction with Acidosis.

Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Alcoholism.

Patients may experience a sedative effect, dizziness, or accommodation disorder with the use of clonidine. Patients should be cautioned about engaging in activities such as driving a vehicle or operating machinery. The sedative effect may be increased with the concomitant use of alcohol or other sedating drugs.

Zonisamide has a major potential interaction with Allergies.

The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Anuria.

The use of thiazide diuretics is contraindicated in patients with anuria.

Zonisamide has a major potential interaction with Asthma.

The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.

The chlorthalidone in chlorthalidone / clonidine has a moderate potential interaction with Asthma.

Thiazide diuretics should be used with caution in patients with history of bronchial asthma as sensitivity reactions may occur.

Zonisamide has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

The use of carbonic anhydrase inhibitors may rarely cause bone marrow suppression and blood dyscrasias at recommended dosages. Aplastic anemia, thrombocytopenia or thrombocytopenia purpura, leukopenia, agranulocytosis, and hemolytic anemia have been reported. Extreme caution should be exercised if carbonic anhydrase inhibitors are administered to patients with these preexisting conditions. A baseline CBC and platelet count is recommended, as well as monitoring at regular intervals during therapy.

Zonisamide has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

The use of sulfonamides has been associated with hematologic toxicity, including methemoglobinemia, sulfhemoglobinemia, leukopenia, granulocytopenia, eosinophilia, hemolytic anemia, aplastic anemia, purpura, clotting disorder, thrombocytopenia, hypofibrinogenemia, and hypoprothrombinemia. Acute dose-related hemolytic anemia may occur during the first week of therapy due to sensitization, while chronic hemolytic anemia may occur with prolonged use. Patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency should be observed closely for signs of hemolytic anemia. Therapy with sulfonamides should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Complete blood counts should be obtained regularly, especially during prolonged therapy (>2 weeks), and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Cerebrovascular Insufficiency.

Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.

Zonisamide has a moderate potential interaction with COPD.

Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Dehydration.

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.

Zonisamide has a moderate potential interaction with Dehydration.

The use of zonisamide may infrequently be associated with the development of nephrolithiasis. The reported incidence for clinically possible or confirmed kidney stones was 4.0% (40 of 991 patients) during premarketing use, representing a rate of 34 per 1000 patient-years of exposure (40 patients with 1168 years of exposure). Therapy with zonisamide should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during zonisamide therapy.

Zonisamide has a major potential interaction with Depression.

Antiepileptic drugs including zonisamide can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Depression.

Central alpha-2 adrenoreceptor agonists may occasionally cause mental depression and should be used cautiously in patients with a history of depression.

Zonisamide has a moderate potential interaction with Depression.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

The chlorthalidone in chlorthalidone / clonidine has a moderate potential interaction with Diabetes Mellitus.

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.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Diarrhea.

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.

Zonisamide has a moderate potential interaction with Diarrhea.

Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Electrolyte Abnormalities.

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.

Zonisamide has a major potential interaction with Fever.

Oligohidrosis (decreased sweating) and hyperthermia have been reported in association with the use of some carbonic anhydrase inhibitor anticonvulsants such as topiramate and zonisamide. Most of the reports have been in children. Caution and close monitoring of body temperature is advised when prescribing these drugs, especially in patients with a fever, in hot weather, or if combined with other drugs that predispose to heat related disorders. Zonisamide is not approved for use in pediatric patients in the U.S.

The chlorthalidone in chlorthalidone / clonidine has a moderate potential interaction with Gout.

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.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Heart Block.

Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system. Heart rate is decreased, which may lead to or exacerbate sinus bradycardia and atrioventricular block. Therapy with central alpha-2 adrenoreceptor agonists should be administered cautiously in patients with conduction disturbances such as sinus node dysfunction or AV nodal disease.

The chlorthalidone in chlorthalidone / clonidine has a moderate potential interaction with High Cholesterol.

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

Zonisamide has a moderate potential interaction with History, Nephrolithiasis.

The use of zonisamide may infrequently be associated with the development of nephrolithiasis. The reported incidence for clinically possible or confirmed kidney stones was 4.0% (40 of 991 patients) during premarketing use, representing a rate of 34 per 1000 patient-years of exposure (40 patients with 1168 years of exposure). Therapy with zonisamide should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during zonisamide therapy.

Zonisamide has a major potential interaction with History of Blood Dyscrasias.

The use of carbonic anhydrase inhibitors may rarely cause bone marrow suppression and blood dyscrasias at recommended dosages. Aplastic anemia, thrombocytopenia or thrombocytopenia purpura, leukopenia, agranulocytosis, and hemolytic anemia have been reported. Extreme caution should be exercised if carbonic anhydrase inhibitors are administered to patients with these preexisting conditions. A baseline CBC and platelet count is recommended, as well as monitoring at regular intervals during therapy.

Zonisamide has a major potential interaction with HIV-1 Infection.

The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Hyperaldosteronism.

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.

The chlorthalidone in chlorthalidone / clonidine has a moderate potential interaction with Hyperparathyroidism.

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.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Hypokalemia.

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.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Hyponatremia.

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.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Hypotension.

Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Ischemic Heart Disease.

Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Liver Disease.

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).

Zonisamide has a major potential interaction with Liver Disease.

The use of carbonic anhydrase inhibitors is contraindicated in patients with marked liver disease or cirrhosis. Carbonic anhydrase inhibitors increase the risk of developing hepatic encephalopathy in these patients. Extreme caution should be exercised if carbonic anhydrase inhibitors are administered in patients with mild to moderate liver disease as the clearance of the drug can be decreased. A dose reduction might be needed and monitoring of the liver function is recommended.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Lupus Erythematosus.

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.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Magnesium Imbalance.

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.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Malnourishment.

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.

Zonisamide has a moderate potential interaction with Nephrolithiasis.

The use of zonisamide may infrequently be associated with the development of nephrolithiasis. The reported incidence for clinically possible or confirmed kidney stones was 4.0% (40 of 991 patients) during premarketing use, representing a rate of 34 per 1000 patient-years of exposure (40 patients with 1168 years of exposure). Therapy with zonisamide should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during zonisamide therapy.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Peripheral Arterial Disease.

Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.

Zonisamide has a moderate potential interaction with Psychosis.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Renal Dysfunction.

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.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Renal Dysfunction.

Clonidine is primarily eliminated unchanged by the kidney. The serum concentrations and half-life of clonidine may be increased in patients with impaired renal function, so patients may benefit from a lower initial dose. Dosage adjustments may be necessary and modifications should be based on the degree of renal impairment. Only a minimal amount of clonidine is removed during routine hemodialysis, and there is no need to give supplemental clonidine following dialysis.

Zonisamide has a moderate potential interaction with Renal Dysfunction.

Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.

Zonisamide has a moderate potential interaction with Renal Dysfunction.

The major route of elimination of carbonic anhydrase inhibitors is through the kidney. These drugs should be administered cautiously in patients with reduced renal function and a dose adjustment might be required depending on the level of impairment.

Zonisamide has a moderate potential interaction with Seizures.

The abrupt withdrawal of zonisamide capsules in patients with epilepsy may precipitate the increase of seizure frequency or status epilepticus. Caution is advised when using this drug in patients with seizures. Dose reduction or discontinuation should be done gradually.

The cloNIDine in chlorthalidone / clonidine has a moderate potential interaction with Sinus Node Dysfunction.

Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system. Heart rate is decreased, which may lead to or exacerbate sinus bradycardia and atrioventricular block. Therapy with central alpha-2 adrenoreceptor agonists should be administered cautiously in patients with conduction disturbances such as sinus node dysfunction or AV nodal disease.

The chlorthalidone in chlorthalidone / clonidine has a moderate potential interaction with Thyroid Disease.

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.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Ventricular Arrhythmia.

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.

The chlorthalidone in chlorthalidone / clonidine has a major potential interaction with Vomiting.

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.