AMVASC PLUS Amlodipine Besilate / Hydrochlorothiazide 5mg / 12.5mg Tablet 1's
RXDRUG-DR-XY38045-1pc
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Treatment of hypertension.
Dosage/Direction for Use
Usual Recommended Oral Dose: 1 tablet once daily.
Dose may be increased to 10/12.5 mg once daily depending on the individual patient's response or as prescribed by physician.
Dose may be increased to 10/12.5 mg once daily depending on the individual patient's response or as prescribed by physician.
Overdosage
Amlodipine: Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia.
If massive overdose should occur, active cardiac and respiratory monitoring should be given. Frequent blood pressure measurements are necessary. Cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated should hypotension occur. If hypotension remains unresponsive to these conservative measures, administration of vasopressors eg, phenylephrine should be considered with attention to circulation volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. Hemodialysis is not likely to be of benefit since amlodipine is highly protein bound.
Hydrochlorothiazide: The most common signs and symptoms of HCTZ overdose include electrolyte imbalance (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. Other features of overdose are lethargy, nausea and weakness. Lethargy may progress to coma within a few hours with minimal depression of respiratory and cardiovascular function without evidence of dehydration or serum electrolyte changes. Gastrointestinal irritation and hypermotility may occur, and temporary elevation of blood urea nitrogen has been reported.
In the treatment of thiazide overdosage, gastric contents may be evacuated taking caution to avoid aspiration, particularly in unconscious patients. If the patient is conscious, induction of vomiting with ipecac syrup is effective in removing the drug from the stomach. Do not administer cathartics since they tend to promote loss of fluid and electrolytes. Treatment is generally supportive. Monitor serum electrolyte and renal function. Replacement of fluid and electrolytes may be indicated. Measures may be required to maintain respiratory, cardiovascular and renal function. Gastrointestinal irritation is usually of short duration but may be treated symptomatically. The degree to which HCTZ is removed by hemodialysis has not been established.
If massive overdose should occur, active cardiac and respiratory monitoring should be given. Frequent blood pressure measurements are necessary. Cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated should hypotension occur. If hypotension remains unresponsive to these conservative measures, administration of vasopressors eg, phenylephrine should be considered with attention to circulation volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. Hemodialysis is not likely to be of benefit since amlodipine is highly protein bound.
Hydrochlorothiazide: The most common signs and symptoms of HCTZ overdose include electrolyte imbalance (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. Other features of overdose are lethargy, nausea and weakness. Lethargy may progress to coma within a few hours with minimal depression of respiratory and cardiovascular function without evidence of dehydration or serum electrolyte changes. Gastrointestinal irritation and hypermotility may occur, and temporary elevation of blood urea nitrogen has been reported.
In the treatment of thiazide overdosage, gastric contents may be evacuated taking caution to avoid aspiration, particularly in unconscious patients. If the patient is conscious, induction of vomiting with ipecac syrup is effective in removing the drug from the stomach. Do not administer cathartics since they tend to promote loss of fluid and electrolytes. Treatment is generally supportive. Monitor serum electrolyte and renal function. Replacement of fluid and electrolytes may be indicated. Measures may be required to maintain respiratory, cardiovascular and renal function. Gastrointestinal irritation is usually of short duration but may be treated symptomatically. The degree to which HCTZ is removed by hemodialysis has not been established.
Contraindications
Hypersensitivity to amlodipine besilate, hydrochlorothiazide, other sulfonamide derivatives, or to any of the excipients of Amvasc Plus.
Advanced aortic stenosis because amlodipine can worsen the abnormal valve pressure gradient associated with this condition.
Severe hepatic impairment and/or cholestasis; anuria and renal impairment; gout and/or hyperuricemia.
Known history of cardiogenic shock.
Use in pregnancy: Pregnancy Category C. Amlodipine has been shown to be fetotoxic in laboratory animals. There are no adequate and well-controlled studies in pregnant women.
Thiazides must be avoided during the 1st trimester of pregnancy. Thiazides cross the placental barrier and appear in cord blood.
Amvasc Plus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: Thiazides appear in human breast milk. It is not known whether amlodipine is excreted in breast milk. Clinicians should consider risk/benefit ratio for breastfeeding women.
Advanced aortic stenosis because amlodipine can worsen the abnormal valve pressure gradient associated with this condition.
Severe hepatic impairment and/or cholestasis; anuria and renal impairment; gout and/or hyperuricemia.
Known history of cardiogenic shock.
Use in pregnancy: Pregnancy Category C. Amlodipine has been shown to be fetotoxic in laboratory animals. There are no adequate and well-controlled studies in pregnant women.
Thiazides must be avoided during the 1st trimester of pregnancy. Thiazides cross the placental barrier and appear in cord blood.
Amvasc Plus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: Thiazides appear in human breast milk. It is not known whether amlodipine is excreted in breast milk. Clinicians should consider risk/benefit ratio for breastfeeding women.
Special Precautions
General Precaution: Since the vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral use. However, as with any other peripheral vasodilator, caution should be exercised when administering amlodipine, particularly in patients with severe aortic stenosis.
Increased Angina and/or Myocardial Infarction: Rarely, patients particularly those with severe obstructive coronary disease, have developed documented increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.
Use in Patients with Heart Failure: In general, calcium channel blockers should be used with caution in patients with heart failure. In a controlled trial on amlodipine in patients with New York Heart Association III and IV heart failure of nonischemic etiology, amlodipine was associated with increased reports of pulmonary edema despite no significant difference in the incidence of worsening heart failure.
Beta-Blocker Withdrawal: Amlodipine is not a β-blocker and therefore, gives no protection against the dangers of abrupt β-blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of β-blocker.
Patients with Hepatic Failure: Use with caution in patients with hepatic disease. The amlodipine plasma elimination t½ is prolonged (56 hrs) in patients with hepatic disease and dosage adjustment is recommended.
Hydrochlorothiazide: Hypotension and Fluid/Electrolyte Imbalance: As with all antihypertensive therapy, symptomatic hypotension may occur in some patients. Patients should be observed for clinical signs of fluid or electrolyte imbalance (eg, volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia) which may occur particularly during intercurrent diarrhea or vomiting. Serum electrolytes should be monitored regularly.
Signs and symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances including nausea and vomiting.
Hypokalemia may develop, particularly with brisk diuresis, when liver cirrhosis is present, or after prolonged therapy. Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (eg, increased ventricular irritability).
Although any chloride deficit is generally mild and usually does not require specific treatment, except under extraordinary situations (eg, liver or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Dilutional hyponatremia may be seen in edematous patients in hot weather. Appropriate treatment is water restriction rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. Appropriate replacement therapy is the treatment of choice in actual salt depletion.
Renal Disease: Use with caution in patients with severe renal disease because thiazides may precipitate azotemia.
Hepatic Disease: Use with caution in patients with hepatic disease or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Hypersensitivity Reaction: Hypersensitivity reactions to HCTZ may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history. As a sulfonamide derivative, HCTZ can cause skin rashes and blood dyscrasias.
Systemic Lupus Erythematosus: Exacerbation or activation of systemic lupus erythematosus has been associated with the use of thiazide diuretics.
Metabolic and Endocrine Effects: Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required.
Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Discontinue thiazides before taking parathyroid function test.
Thiazide diuretic therapy may increase cholesterol and triglyceride levels.
Hyperuricemia may occur or acute gout may be precipitated in certain patients taking thiazide therapy.
Thiazides have been reported to increase the urinary excretion of magnesium. This may result in hypomagnesemia.
Use in children: Safety and effectiveness in children have not been established.
Use in the elderly: Amlodipine Besilate: Observe caution in amlodipine dose selection for an elderly. Elderly patients are more likely to experience a delayed clearance of amlodipine and can be at greater risk for toxicity.
Hydrochlorothiazide: Thiazide diuretics are more likely to cause hypovolemia, leading to orthostatic hypotension, and reduced glomerular filtration rate can occur. Elderly patients are also more prone to diuretic-induced hypokalemia due to poor dietary intake of potassium.
Increased Angina and/or Myocardial Infarction: Rarely, patients particularly those with severe obstructive coronary disease, have developed documented increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.
Use in Patients with Heart Failure: In general, calcium channel blockers should be used with caution in patients with heart failure. In a controlled trial on amlodipine in patients with New York Heart Association III and IV heart failure of nonischemic etiology, amlodipine was associated with increased reports of pulmonary edema despite no significant difference in the incidence of worsening heart failure.
Beta-Blocker Withdrawal: Amlodipine is not a β-blocker and therefore, gives no protection against the dangers of abrupt β-blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of β-blocker.
Patients with Hepatic Failure: Use with caution in patients with hepatic disease. The amlodipine plasma elimination t½ is prolonged (56 hrs) in patients with hepatic disease and dosage adjustment is recommended.
Hydrochlorothiazide: Hypotension and Fluid/Electrolyte Imbalance: As with all antihypertensive therapy, symptomatic hypotension may occur in some patients. Patients should be observed for clinical signs of fluid or electrolyte imbalance (eg, volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia) which may occur particularly during intercurrent diarrhea or vomiting. Serum electrolytes should be monitored regularly.
Signs and symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances including nausea and vomiting.
Hypokalemia may develop, particularly with brisk diuresis, when liver cirrhosis is present, or after prolonged therapy. Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (eg, increased ventricular irritability).
Although any chloride deficit is generally mild and usually does not require specific treatment, except under extraordinary situations (eg, liver or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Dilutional hyponatremia may be seen in edematous patients in hot weather. Appropriate treatment is water restriction rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. Appropriate replacement therapy is the treatment of choice in actual salt depletion.
Renal Disease: Use with caution in patients with severe renal disease because thiazides may precipitate azotemia.
Hepatic Disease: Use with caution in patients with hepatic disease or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Hypersensitivity Reaction: Hypersensitivity reactions to HCTZ may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history. As a sulfonamide derivative, HCTZ can cause skin rashes and blood dyscrasias.
Systemic Lupus Erythematosus: Exacerbation or activation of systemic lupus erythematosus has been associated with the use of thiazide diuretics.
Metabolic and Endocrine Effects: Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required.
Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Discontinue thiazides before taking parathyroid function test.
Thiazide diuretic therapy may increase cholesterol and triglyceride levels.
Hyperuricemia may occur or acute gout may be precipitated in certain patients taking thiazide therapy.
Thiazides have been reported to increase the urinary excretion of magnesium. This may result in hypomagnesemia.
Use in children: Safety and effectiveness in children have not been established.
Use in the elderly: Amlodipine Besilate: Observe caution in amlodipine dose selection for an elderly. Elderly patients are more likely to experience a delayed clearance of amlodipine and can be at greater risk for toxicity.
Hydrochlorothiazide: Thiazide diuretics are more likely to cause hypovolemia, leading to orthostatic hypotension, and reduced glomerular filtration rate can occur. Elderly patients are also more prone to diuretic-induced hypokalemia due to poor dietary intake of potassium.
Use In Pregnancy & Lactation
Use in pregnancy: Pregnancy Category C. Amlodipine has been shown to be fetotoxic in laboratory animals.
There are no adequate and well-controlled studies in pregnant women.
Thiazides must be avoided during the 1st trimester of pregnancy. Thiazides cross the placental barrier and appear in cord blood.
Amvasc Plus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: Thiazides appear in human breast milk. It is not known whether amlodipine is excreted in breast milk. Clinicians should consider risk/benefit ratio for breastfeeding women.
There are no adequate and well-controlled studies in pregnant women.
Thiazides must be avoided during the 1st trimester of pregnancy. Thiazides cross the placental barrier and appear in cord blood.
Amvasc Plus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: Thiazides appear in human breast milk. It is not known whether amlodipine is excreted in breast milk. Clinicians should consider risk/benefit ratio for breastfeeding women.
Adverse Reactions
Fatigue, insomnia, dizziness, vertigo, headache, paresthesia, hypotension, hyperglycemia, impotence, thrombocytopenia, leukopenia, purpura, alopecia, urticaria, rash, erythema multiforme, muscle cramps, anorexia, pancreatitis, nausea, vomiting, constipation, diarrhea. Amlodipine: Asthenia, malaise, pain; hypertonia, hypoesthesia, peripheral neuropathy, tremor, mood changes, somnolence, nervousness, depression, abnormal dreams, anxiety, depersonalization; syncope, vasculitis, palpitations, MI, arrhythmia, tachycardia, flushing, edema, chest pain, peripheral ischemia, postural dizziness & hypotension; dry mouth, thirst, altered bowel habits, dyspepsia, gastritis, gingival hyperplasia, abdominal pain, dysphagia, flatulence; gynecomastia, increased/decreased wt, skin discoloration, pruritus, angioedema; micturition disorder, nocturia; hepatitis, jaundice, hepatic enzyme elevations; arthralgia, arthrosis, myalgia, back pain; cough, dyspnea, rhinitis, epistaxis; taste perversion, tinnitus, visual disturbances, abnormal vision, conjunctivitis, diplopia, eye pain. Hydrochlorothiazide: Fever, weakness; cephalalgia, restlessness; transient cerebral ischemic attacks; sialadenitis, spasms, stomach irritation, cramping, gastric irritation; hyperuricemia, hypokalemia, hyponatremia, hypochloremic alkalosis, hypophosphatemia, hypomagnesemia, hypercalcemia, glucose tolerance impairment, glycosuria, increases in total cholesterol, LDL & VLDL cholesterol & triglycerides; agranulocytosis, aplastic & hemolytic anemia; exfoliative dermatitis, anaphylactic reaction, necrotizing angiitis, photosensitivity, polyarteritis nodosa; glycosuria, interstitial nephritis, renal dysfunction, failure & impairment; icterus; muscle spasm; resp distress; transient blurred vision, xanthopsia.
Drug Interactions
Hydrochlorothiazide: Potentiation of orthostatic hypotension w/ alcohol, barbiturates or narcotics. Increased risk of adverse effects w/ amantadine. Potentiate aminoglycoside nephrotoxicity w/ aminoglycoside antibiotics. Increase availability of thiazide diuretics by decreasing GI motility & stomach emptying rate w/ anticholinergic agents (eg, atropine, biperidine). Oral antidiabetics & insulin. Impaired HCTZ absorption w/ cholestyramine & colestipol resins. Intensified hypokalemia w/ corticosteroids, ACTH. Possible decreased renal excretion & increased myelosuppressive effects w/ cytotoxic agents. Decreased response to pressor amines (eg, adrenaline). Possible increased responsiveness to muscle relaxant w/ nondepolarizing skeletal muscle relaxants (eg, tubocurarine). Increases lithium absorption & may cause lithium toxicity. Reduce diuretic, natriuretic & antihypertensive effects of diuretics w/ NSAIDs including COX-2 inhibitors. Additive effect w/ other antihypertensive drugs.
Storage
Store at temperature not exceeding 30°C.
Shelf-Life: 24 months.
Shelf-Life: 24 months.
Action
Pharmacodynamics: Mechanism of Action: Amlodipine: Amlodipine is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac and vascular smooth muscles are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels.
Amlodipine inhibits calcium ion influx across cell membrane selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of dissolution with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and a decrease in blood pressure.
Hydrochlorothiazide: Hydrochlorothiazide (HCTZ), a thiazide diuretic, increases the excretion of water by inhibiting the reabsorption of sodium and chloride ions at the distal renal tubule. The excretion of potassium and magnesium is also increased while the elimination of calcium and uric acid is decreased. Thiazide diuretics usually do not affect the normal blood pressure. When chronically administered, thiazide diuretics decrease peripheral vascular resistance. The exact mechanism responsible for lowered peripheral resistance is not known, however, excretion of urinary sodium by the kidneys is required to achieve blood pressure reduction.
Indirectly, the diuretic action of HCTZ reduces plasma volume, with consequent increases in plasma renin activity, aldosterone secretion, urinary potassium loss, and decrease in serum potassium.
Diuresis begins with 2 hrs, peaks in about 4 hrs and lasts about 6-12 hrs after oral administration of HCTZ.
Pharmacokinetics: Amlodipine: After oral administration of therapeutic doses of amlodipine, peak plasma concentrations are reached between 6 and 12 hrs. Absolute bioavailability has been estimated to be between 64% and 90%. The volume of distribution is approximately 20 L/kg. Amlodipine's bioavailability is not altered by the presence of food.
Amlodipine is extensively (about 90%) converted to inactive metabolite via hepatic metabolism with 10% of the parent compound and 60% of the metabolite excreted in the urine. Studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination t½ of about 30-50 hrs. Steady state plasma levels of amlodipine are reached after 7-8 days of consecutive dosing.
Amlodipine inhibits calcium ion influx across cell membrane selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of dissolution with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and a decrease in blood pressure.
Hydrochlorothiazide: Hydrochlorothiazide (HCTZ), a thiazide diuretic, increases the excretion of water by inhibiting the reabsorption of sodium and chloride ions at the distal renal tubule. The excretion of potassium and magnesium is also increased while the elimination of calcium and uric acid is decreased. Thiazide diuretics usually do not affect the normal blood pressure. When chronically administered, thiazide diuretics decrease peripheral vascular resistance. The exact mechanism responsible for lowered peripheral resistance is not known, however, excretion of urinary sodium by the kidneys is required to achieve blood pressure reduction.
Indirectly, the diuretic action of HCTZ reduces plasma volume, with consequent increases in plasma renin activity, aldosterone secretion, urinary potassium loss, and decrease in serum potassium.
Diuresis begins with 2 hrs, peaks in about 4 hrs and lasts about 6-12 hrs after oral administration of HCTZ.
Pharmacokinetics: Amlodipine: After oral administration of therapeutic doses of amlodipine, peak plasma concentrations are reached between 6 and 12 hrs. Absolute bioavailability has been estimated to be between 64% and 90%. The volume of distribution is approximately 20 L/kg. Amlodipine's bioavailability is not altered by the presence of food.
Amlodipine is extensively (about 90%) converted to inactive metabolite via hepatic metabolism with 10% of the parent compound and 60% of the metabolite excreted in the urine. Studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination t½ of about 30-50 hrs. Steady state plasma levels of amlodipine are reached after 7-8 days of consecutive dosing.
MedsGo Class
Calcium Antagonists / Diuretics
Features
Brand
Amvasc Plus
Full Details
Dosage Strength
5mg / 12.5mg
Drug Ingredients
- Amlodipine
- Hydrochlorothiazide
Drug Packaging
Tablet 1's
Generic Name
Amlodipine Besilate / Hydrochlorothiazide
Dosage Form
Tablet
Registration Number
DR-XY38045
Drug Classification
Prescription Drug (RX)
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