(and dosage form):


CAPOZIDE 50/25 is a combination of
captopril 50 mg, designated chemically as D-3-mercapto-2-methylpropanoyl-L-proline (captopril), and 25 mg hydrochlorothiazide, a thiazide diuretic antihypertensive agent, per tablet.

Category A 7.1.3 - Other hypotensives.

CAPOZIDE 50/25 is a combination of an angiotensin-converting enzyme inhibitor (captopril) and a diuretic (hydrochlorothiazide).
With diuretic treatment, blood pressure and blood volume fall resulting in a rise in angiotension II levels which tend to blunt the hypotensive effect. Captopril blocks this rise in angiotensin II. Since captopril and hydrochlorothiazide lower blood pressure by different, though complementary mechanisms, their antihypertensive effects are additive, and, concurrent administration may permit the use of lower doses of each drug. Because captopril reduces the production of aldosterone, its combination with hydrochlorothiazide may also minimise diuretic induced hypokalemia. Captopril may also interfere with the degradation of the vasodepressor peptide, bradykinin. Increased concentrations of bradykinin or prostaglandin E2 may also have a role in the therapeutic effect of captopril.
Thiazides increase excretion of sodium and chloride in approximately equal amounts.Natriuresis causes a secondary loss of potassium and bicarbonate.
After oral administration of therapeutic doses of captopril, rapid absorption occurs with peak blood levels at about one hour. The presence of food in the gastrointestinal tract reduces absorption by about 30 to 40%; captopril should therefore be given one hour before meals. Average minimal absorption is approximately 75%. In a 24-hour period, over 95% of the absorbed dose is eliminated in the urine; 40 - 50% is unchanged drug.
Approximately 25 to 30% of the circulating drug is bound to plasma proteins . The apparent elimination half-life in blood is probably less than 3 hours. In patients with renal impairment, however, retention of captopril occurs.
Administration of captopril results in a reduction of peripheral arterial resistance in hypertensive patients with either no change, or an increase in cardiac output. There is an increase in renal blood flow following administration of captopril and glomerular filtration rate is usually unchanged. Reductions of blood pressure are usually maximal 60 to 90 minutes after oral administration of an individual dose of captopril. The duration of effect is dose-related and is extended in the presence of a thiazide-type diuretic. The full effect of a given dose may be attained after 6-8 weeks. The blood pressure lowering effects of captopril and thiazide-type diuretics are additive. Blood pressure is lowered to about the same extent in both standing and supine positions.
Administration of hydrochlorothiazide results in an onset of diuresis in two hours and a peak effect at about four hours. Its action persists for approximately six to twelve hours. The mean plasma half-life has been reported to be approximately 2,5 hours. Hydrochlorothiazide is eliminated rapidly by the kidney, and excreted unchanged (>95%) in the urine.

CAPOZIDE 50/25 is indicated for the treatment of mild to moderate hypertension in patients who have been stabilised on the individual components given in the same proportions.

CAPOZIDE 50/25 is contraindicated in:
Patients with anuria or a hypersensitivity to captopril, or other angiotensin-converting enzyme inhibitors, thiazides, or any sulphonamide-derived drug.
Patients with a history of angioneurotic oedema relating to previous treatment with an ACE-inhibitor. (See WARNINGS).
Bilateral renal artery stenosis.
Severe renal and liver impairment.
Concomitant use of potassium-sparing diuretics.
Pregnancy and lactation.
Safety and effectiveness in individuals less than 18 years of age have not been established.

Should a woman become pregnant while receiving an ACE-inhibitor, the treatment must be stopped promptly and switched to a different medicine. Should a woman contemplate pregnancy, the doctor should consider alternative medication.
ACE-inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. Oligohydramnios as well as hypotension, oliguria and anuria in newborns have been reported after administration of ACE-inhibitors in the second and third trimester. Cases of defective skull ossification have been observed.
Prematurity and low birth mass can occur.
Head and neck Angioedema:
Angioedema involving the extremities, face, eyes, lips, mucous membranes, tongue, glottis or larynx has been reported. Patients should be advised to immediately report to their physician any signs or symptoms suggesting angioedema (eg swelling of face, eyes, lips, tongue, larynx and extremities; difficulty in swallowing or breathing; hoarseness) and to discontinue therapy. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Emergency therapy, including but not necessarily limited to, subcutaneous administration of a 1:1000 solution of adrenaline should be promptly instituted. Swelling confined to the face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuation of captopril; some cases required medical therapy (see SIDE EFFECTS AND SPECIAL PRECAUTIONS).
Intestinal Angioedema: Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan, or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anaphylactoid reactions during desensitisation: Two patients undergoing desensitising treatment with hymenoptera venom while receiving an ACE Inhibitor, enalapril, sustained life-threatening anaphylactiod reactions. In the same patients, these reactions were avoided when the ACE inhibitor was temporarily withheld, but they reappeared upon inadvertent rechallenge. Therefore, caution should be used in patients treated with ACE inhibitors undergoing such desensitisations procedures.
Anaphylactoid reactions during high-flux dialysis/lipoprotein apheresis membrane exposure: Anaphylactoid reactions have been reported in patients hemodialyzed with high-flux dialysis membranes.
Anaphylactoid reactions have also been reported inpatients undergoing low-densitylipoprotein apheresis with dextran sulfate absorption. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of medication.
Haematological: Neutropenia/Agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving captopril, usually within three months after treatment has started.
During treatment, all patients should be instructed to report any sign of infection (eg persistent sore throat, fever), when a differential white blood cell count should be performed. CAPOZIDE 50/25 and other concomitant medication should be withdrawn if neutropenia (neutrophils less than 1000/mm3) is detected or suspected. In most patients neutrophil counts rapidly returned to normal upon discontinuing captopril.
Neutropenia/Agranulocytosis: Neutropenia (<1000/mm³) with myeloid hypoplasia has resulted from use of captopril. About half of the neutropaenic patients developed systemic or oral cavity infections or other features of the syndrome of agranulocytosis.
The risk of neutropenia is dependent on the clinical status of the patient.
In clinical trials in patients with hypertension who have normal renal function (serum creatinine less than 141,44 micromoles/L (and no collagen vascular disease), neutropenia has been seen in one patient out of over 8,600 exposed.
In patients with some degree of renal failure (serum creatinine at least 141,44 micromoles/L) but no collagen vascular disease, the risk of neutropenia in clinical trials was about 1 per 500, a frequency over 15 times that for uncomplicated hypertension.
In patients with collagen vascular diseases (e.g., systemic lupus erythematosus, scleroderma) and impaired renal function, neutropenia occurred in 3.7 percent of patients in clinical trials. The neutropenia has usually been detected within three months after captopril was started. In general, neutrophils returned to normal in about two weeks after Capozide was discontinued, and serious infections were limited to clinically complex patients . About 13 percent of the cases of neutropenia have ended fatally, but almost all fatalities were in patients with serious illness, having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a combination of these complicating factors.
Hypotension: In patients who are receiving diuretic therapy, particularly those with severe, renin dependent hypertension (eg renovascular hypertension), exaggerated hypotensive responses have occurred, usually within one hour of the initial dose of captopril. This transient fall in blood pressure may occur after any of the first several doses of captopril producing either no symptoms or brief mild light-headedness, and may be associated with arrhythmia or conduction defects. The possibility of this occurrence can be lessened in these patients by discontinuing diuretic therapy or significantly reducing the diuretic dose for 4 to 7 days prior to initiating CAPOZIDE 50/25 therapy. The exaggerated hypotensive response can be anticipated by medical supervision, during the first hour after initial dosing; and if necessary it can be rapidly reversed by intravenous infusion of normal saline. A hypotensive episode following the initial dose of CAPOZIDE 50/25 does not preclude further episodes.
Total urinary proteins greater than 1 g per day were seen in about 0.7 percent of patients receiving captopril. About 90 percent of affected patients had evidence of prior renal disease or received relatively high doses of captopril (in excess of 150 mg/day), or both. Since most cases of proteinuria occurred by the eighth month of therapy with captopril, patients with prior renal disease or those receiving captopril at doses greater than 150 mg per day, should have urinary protein estimation (dip-stick on first morning urine) prior to treatment, and periodically thereafter.
Evaluation of the hypertensive or heart failure patient should always include assessment of renal function.
If captopril is used in patients with impaired renal function, white blood cell and differential counts should be evaluated prior to starting treatment and at approximately two-week intervals for about three months, then periodically.
In patients with collagen vascular disease or who are exposed to other drugs known to affect the white cells or immune response, particularly when there is impaired renal function, captopril should be used only after an assessment of benefit and risk, and then with caution.
All patients treated with captopril should be told to report any signs of infection (e.g., sore throat, fever). If infection is suspected, white cell counts should be performed without delay.
Since discontinuation of Capozide has generally led to return within two weeks of the white count to normal, upon confirmation of neutropenia (neutrophil count<1000/mm3) the physician should withdraw captopril and closely follow the patient’s course .
Hepatic Failure
Capozide has been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and death. The mechanism of this syndrome is not understood. Patients receiving ACE Inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Thiazides are contraindicated in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the medicine may develop in patients with impaired renal function. Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma. Exacerbation or activation of systemic lupus erythematosus has been reported.
Lithium should not be given with diuretics (see PRECAUTIONS, Interactions).

Dosage must be individualised.
See WARNINGS regarding hypotension in salt and volume depleted patients.
In the treatment of hypertension, CAPOZIDE 50/25 may be used for patients requiring individual doses of captopril and a diuretic.
This usual dose is one CAPOZIDE 50/25 tablet (captopril 50/hydrochlorithiazide 25 mg) once a day. If a satisfactory reduction of blood pressure has not been achieved after 6 –8 weeks, the dose of captopril (given as CAPOTEN tablets) may be increased to not more than 150 mg per day, in divided daily doses. Daily doses of hydrochlorothiazide for hypertension should not exceed 50 mg. A significant number of patients may achieve long-term control of their blood pressure on half a CAPOZIDE 50/25 tablet per day (captopril 25 mg/hydrochlorothiazide 12,5 mg), particularly in the elderly patients.
Patients with Renal Function Impairment:
These patients may respond to smaller or less frequent doses of CAPOZIDE . When concomitant diuretic therapy is required in patients with severe renal impairment, a loop diuretic, rather than a thiazide diuretic should be for used with captopril.
Therefore, CAPOZIDE is not recommended for use in patients with renal impairment.

Skin: A rash may occur which is usually pruritic and maculopapular, but rarely urticarial and generally occurs during the first 4 weeks of treatment. It may be accompanied by fever, arthralgia, eosinophilia and positive ANA titres. It usually is self-limited and reversible and may respond to antihistamine therapy. Pruritus, flushing, a reversible pemphigoid-like lesion, photosensitivity and angioedema have also been reported.
Photosensitivity, flushing and pallor have also been reported.
Gastro-intestinal: Patients may develop a diminution or loss of taste perception. Taste impairment is reversible and usually self-limited (2 to 3 months). In most patients the condition resolved with the continuation of therapy at the same or reduced dosage. Weight loss may be associated with the loss of taste. Stomatitis, resembling aphthous ulcers, has been reported.
Hepatobiliary: Elevation of liver enzymes has been noted in patients receiving the medicine although no causal relationship has been found. Cases of hepatocellular injury with or without cholestasis and jaundice have been reported in association with captopril administration.
Renal: Proteinuria (see WARNINGS), renal insufficiency, renal failure, nephrotic syndrome, polyuria, oliguria and urinary frequency.
Haematologic: Neutropenia/agranulocytosis has occurred (see WARNINGS). Cases of anaemia, aplastic anaemia, thrombocytopenia and pancytopenia have been reported during captopril therapy.
Cardiovascular: Hypotension may occur after initiation of captopril therapy in patients with heart failure, renin-dependent hypertension or who are significantly volume depleted (see WARNINGS). Tachycardia has been observed in volume-depleted patients. Chest pain, palpitations, angina pectoris, myocardial infarction, Raynaud’s syndrome and congestive heart failure have also been reported.
Anaphylactoid Reactions: There is an association of hypersensitivity-like (anaphylactoid) reactions during hemodialysis with high-flux dialysis membranes (eg AN69) in patients receiving ACE-inhibitors as medication. Therefore, special attention should be given to these patients; and in particular, to those having already shown similar reactions.
Angioedema: Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been reported. Angioedema involving the upper airways has caused fatal airway obstruction. (See WARNINGS).
Cough: Cough has been reported in 4-11% of patients treated with captopril.
Other: The following have been reported in about 0,5-2% of patients: gastric irritation, abdominal pain, nausea, vomiting, diarrhoea, anorexia, constipation, aphthous ulcers, peptic ulcers, dizziness, headache, malaise, fatigue, insomnia, dry mouth, dyspnea, alopecia, paresthesias.
Other clinical adverse effects reported since the drug was marketed are listed below by body system. In this setting, an incidence or causal relationship cannot be accurately determined.
General: Asthenia, gynecomastia.
Cardiovascular: Cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.
Dermatologic: Bullous pemphigus, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis.
Gastrointestinal: Pancreatitis, glossitis, dyspepsia.
Hematologic: Anaemia, including aplastic and haemolytic.
Hepatobiliary: Jaundice, hepatitis, including rare cases of necrosis, cholestasis.
Metabolic: Symptomatic hyponatremia.
Musculoskeletal: Myalgia, myasthenia.
Nervous/Psychiatric: Ataxia, confusion, depression, nervousness, somnolence.
Respiratory: Bronchospasm, eosinophilic pneumonitis, rhinitis.
Special Senses: Blurred vision.
Urogenital: Impotence.
A syndrome has been reported which may include: fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash or other dermatologic manifestations, eosinophilia and an elevated erythrocyte sedimentation rate (ESR).
CAPOZIDE 50/25 should be used only with extreme caution in patients with aortic stenosis because of the potentially harmful consequences of reduced coronary perfusion secondary to the reduced blood pressure.
Patients treated for severe congestive heart failure should be cautioned to increase their physical activity slowly.

Gastrointestinal system: Anorexia, gastric irritation, nausea, vomiting, cramping, diarrhoea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis and sialadenitis.
Central nervous system: dizziness, vertigo, paresthesias, headache and xanthopsia.
Haematologic: Leucopenia, agranulocytosis, thrombocytopenia, aplastic anaemia and haemolytic anaemia have occurred with the use of thiazide.
Cardiovascular: orthostatic hypotension
Hypersensitivity: purpura, photosensitivity, rash. urticaria, necrotising angiitis (vasculitis; cutaneous vasculitis), fever, respiratory distress including pneumonitis and anaphylactic reactions.
Other: hyperglycaemia, glycosuria, hyperuricaemia, muscle spasm, weakness, restlessness, jaundice, interstitial nephritis, glycosurea, electrolyte imbalance, including hyponatremia, hypochloraemic alkylosis, transient blurred vision, and impotence have been reported in patients receiving thiazides.
Whenever adverse reactions are moderate to severe, thiazide dosage should be reduced or therapy withdrawn.
CAPOZIDE 50/25 should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alternations of fluid and electrolyte balance may precipitate hepatic coma. Cholistatic jaundice and pancreatitis may occur.
Patients receiving CAPOZIDE 50/25 should be observed for clinical signs of thiazide induced fluid or electrolyte imbalance. Hypokalemia, should it occur, can sensitise or exaggerate the response of the heart to the toxic effects of digitalis (eg increased ventricular irritability). Because captopril reduces the production of aldosterone, its combination with hydrochlorothiazide may minimise the diuretic-induced hypokalemia. However, some patients may still require potassium supplements.
Thiazide diuretics should not be given to patients with Addison's Disease.
Hyperuricaemia may occur or frank gout may be precipitated by thiazides in certain patients. Insulin requirements in diabetic patients may be altered by thiazides and latent diabetes mellitus may emerge.
Pathologic changes in the parathyroid gland with hypercalcaemia and hypophosphatemia have been observed in a few patients during prolonged thiazide therapy.
A rise in serum cholesterol has been noted after use of diuretics. Hypomagnesia has also occurred.
Sensitivity reactions to thiazide may occur in patients with a history of allergy or bronchial asthma. Pulmonary oedema and pneumonitis has also occurred.
The possibility of exacerbation or activation of systemic lupus erythematosus has been reported with thiazide therapy.
Altered laboratory findings:
Serum electrolytes: Hyperkalemia and hyponatremia .
BUN/Serum creatinine: Elevations of BUN or serum creatinine especially in volume or salt depleted patients or those with renovascular hypertension, may occur.
Haematologic: Positive ANA has been reported.
Liver function test: Elevations of liver transaminases, alkaline phosphates and serum bilirubin have occurred.

Impaired Renal Function: Some patients with renal disease, particularly those with severe renal artery stenosis, have developed increases in BUN and serum creatinine after reduction of blood pressure with captopril. Captopril dosage reduction and/or discontinuation of diuretic may be required. For some patients, it may not be possible to normalise blood pressure and maintain adequate renal perfusion. (See DOSAGE AND DIRECTIONS FOR USE, ADVERSE REACTIONS [Altered Laboratory Findings])
Hyperkalemia: Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including captopril. When treated with ACE Inhibitors, patients at risk for the development of hyperkalemia include those with: renal insufficiency; diabetes mellitus; and those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes: or other drugs associated with increases in serumpotassium (e.g., heparin). (See SIDE EFFECTS, Altered laboratory findings, captopril)
Cough: Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE Inhibitor-induced cough should be considered as part of the differential diagnosis of cough.
Surgery/Anaesthesia: In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, captopril will block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
Orthostatic effects and tachycardia are infrequent but may occur more frequently in volume-depleted patients. Abrupt withdrawal of captopril has been associated with a rapid increase in blood pressure. Captopril does not cross the blood-brain barrier to any significant extent.

All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance, namely: hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids.
Hypokalemia can sensitise or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Because captopril reduces the production of aldosterone, concomitant therapy with captopril reduces the diuretic-induced hypokalemia.
Any chloride deficit is generally mild and usually does not require specific treatment. Dilutional hyponatremia may occur in edematous.
Hyperuricaemia may occur or frank gout may be precipitated.
Latent diabetes mellitus may become manifest during thiazide administration.
If progressive renal impairment becomes evident, as indicated by a rising nonprotein nitrogen or blood urea nitrogen (BUN), a careful reappraisal of therapy is necessary with consideration given to withholding or discontinuing diuretic therapy.
Thiazides may decrease Protein Bound Iodine (PBI) levels without signs of thyroid disturbance. Calcium excretion is decreased by thiazides. Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. Thiazides should be discontinued before carrying out tests for parathyroid function. Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Laboratory Tests
Serum electrolyte levels should be regularly monitored. (See WARNINGS and SPECIAL PRECAUTIONS).

Agents increasing serum potassium: Since captopril decreases aldosterone production, elevation of serum potassium may occur, especially in patients with renal failure or diabetes mellitus. Potassium sparing diuretics such as spironolactone, triamterene and amiloride or other drugs associated with increases in serum potassium (eg heparin), if needed, should be used with caution since they may lead to a significant increase of serum potassium.
Potassium supplements should be given only for documented hypokalemia and then with caution since they may lead to a significant increase in serum potassium. Salt substitutes which contain potassium should also be used with caution.
Hypotension (patients on diuretic therapy): Patients on diuretics and especially those in whom diuretic therapy was recently instituted, as well as those on severe dietary salt restriction or dialysis, may occasionally experience a precipitous reduction of blood pressure usually within the first hour after receiving the initial dose of captopril. Medicalsupervision should be provided for at least one hour after the initial dose. If hypotension occurs, the patient should be placed in a supine position and if necessary, receive an intravenous infusion of normal saline. This transient hypotensive response is not a contraindication to further doses, which can be given once the blood pressure has increased after volume expansion.
Agents Having Vasodilator Activity: Data on the effect of concomitant use of other vasodilators in patients receiving captopril for heart failure are not available; therefore, nitroglycerin or other nitrates (as used for management of angina) or other drugs having vasodilator activity should, if possible, be discontinued before starting captopril. If resumed during captopril therapy, such agents should be administered cautiously, and perhaps at low dosage.
Agents Affecting Sympathetic Activity: The sympathetic nervous system may be especially important in supporting blood pressure in patients receiving captopril alone or with diuretics. Therefore, agents affecting sympathetic activity (eg ganglionic blocking agents or adrenergic neuron blocking agents) should be used with caution. Beta-adrenergic blocking drugs add some further antihypertensive effect to captopril, but the overall response is less than additive.
Inhibitors of Endogenous Prostaglandin Synthesis: It has been reported that indomethacin may reduce the antihypertensive effect of captopril, especially in cases of low renin hypertension. Other non-steroidal anti-inflammatory agents (eg aspirin) may also have this effect. The administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic and antihypertensive effect of thiazide diuretics.
Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These agents should be coadministered with caution and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, it may increase the risk of lithium toxicity.
Alcohol, barbiturates, or narcotics: potentiation of orthostatic hypotension may occur.
Amphotericin B, corticosteroids, or corticotropin (ACTH): hydrochlorothiazide may intensify electrolyte imbalance, particularly hypokalemia.
Anticoagulants (oral): dosage adjustments of anticoagulant medication may be necessary since hydrochlorothiazide may decrease their effects.
Anti-gout medications: dosage adjustments of anti-gout medication may be necessarysince hydrochlorothiazide may raise the level of blood uric acid.
Other antihypertensive medications (e.g., ganglionic or peripheral adrenergic blocking agents): dosage adjustments may be necessary since hydrochlorothiazide may potentiate their effects.
Antidiabetic drugs (oral agents and insulin): since thiazides may elevate blood glucose levels, dosage adjustments of antidiabetic agents may be necessary.
Calcium salts: increased serum calcium levels due to decreased excretion may occur when administered concurrently with thiazide diuretics.
Cardiac glycosides: enhanced possibility of digitalis toxicity associated with thiazide induced hypokalemia. Monitor potassium levels.
Cholestyramine resin and colestipol HCL: may delay or decrease absorption of hydrochlorothiazide. Sulphonamide diuretics should be taken at least one hour before or four to six hours after these medications.
Use of allopurinol concomitantly with captopril in patients with renal failure has been associated with neutropenia.
Diazoxide: enhanced hyperglycaemic, hyperuricemic, and antihypertensive effects when administered concurrently with thiazide diuretics.
MAO inhibitors: dosage adjustments of one or both agents may be necessary since hypotensive effects are enhanced.
Nondepolarizing muscle relaxants, preanesthetics and anaesthetics used in surgery (e.g., tubocurarine chloride and gallamine triethiodide): for hydrochlorothiazide, effects of these agents may be potentiated; dosage adjustments may be required. Monitor and correct any fluid and electrolyte imbalances prior to surgery if feasible.
Methenamine: possible decreased effectiveness of hydrochlorothiazide due to alkalinization of the urine.
Pressor amines (e.g., norepinephrine): decreased arterial responsiveness, but not sufficient to preclude effectiveness of the pressor agent for therapeutic use. Use caution in patients taking both medications who undergo surgery. Administer preanesthetic and anaesthetic agents in reduced dosage, and if possible, discontinue hydrochlorothiazide therapy one week prior to surgery.
Probenecid or sulfinpyrazone: increased dosage of these agents may be necessary since hydrochlorothiazide may have hyperuricemic effects.
Laboratory test interactions
Captopril may cause a false-positive urine test for acetone. Hydrochlorothiazide may cause diagnostic interference of the bentiromide test.

In the event of overdosage hypotension and electrolyte depletion would be the most important problem. Volume expansion with an intravenous infusion of normal saline is the treatment of choice to normalise the blood pressure.
Captopril is removed by hemodialysis. The degree to which hydrochlorothiazide is removed by hemodialysis has not been clearly established. In addition to the expected diuresis, overdosage of thiazides may produce varying degrees of lethargy which may progress to coma within a few hours, with minimal depression of respiration and cardiovascular function and without evidence of serum electrolyte changes or dehydration. The mechanism of thiazide-induced CNS depression is unknown. Gastrointestinal irritation and hypermotility may occur. Transitory increase in blood urea nitrogen (BUN) has been reported, and serum electrolyte changes may occur, especially in patients with impaired renal function.
In addition to gastric lavage and supportive therapy for stupor or coma, symptomatic treatment of gastrointestinal effects may be needed. Measures as required to maintain hydration, electrolyte balance, respiration and cardiovascular and renal function should be instituted.

–A white to off-white, biconvex oval tablet, 6,5 mm x 12,86 mm, which may be mottled, with a bisect bar on one side and “CAPOZIDE”over “50/25” on the other side.

Blister packs of 30 tablets each.

Store at room temperature not exceeding 25°C. Protect from moisture.

CAPOZIDE 50/25:        Y/7.1.3/379

47 van Buuren Road
Bedfordview. 2008

23 July 2002

Updated on this site: June 2005
Source: Pharmaceutical Industry

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