| Composition |
Each tablet contains 10 mg enalapril maleate and 25 mg hydrochlorothiazide.
Each tablet contains 20 mg enalapril maleate and 12.5 mg hydrochlorothiazide. |
| Pharmacodynamics properties |
As a result of its diuretic effects, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, and decreases serum potassium.
Administration of enalapril maleate blocks the renin-angiotensin aldosterone axis and tends to reverse the potassium loss associated with the diuretic.
In clinical studies, the extent of blood pressure reduction seen with the combination of enalapril maleate and hydrochlorothiazide was approximately additive.
The antihypertensive effect of Clandopril & Clandopril-D was usually sustained for at least 24 hours.
Enalapril Maleate:
Mechanism of Action: Enalapril, after hydrolysis to enalaprilat, inhibits angiotensin-converting enzyme (ACE).
ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion.
Removal of angiotensin II negative feedback on rennin secretion leads to increased plasma rennin activity.
ACE is identical to kininase, an enzyme that degrades bradykinin.
So using enalapril will increase the levels of bradykinin, a potent vasodepressor peptide
(its role in the therapeutic effect remains to be elucidated).
Hydrochlorothiazide:
The mechanism of the antihypertensive effect of thiazides is unknown.
Thiazides do not usually affect normal blood pressure. Hydrochlorothiazide is a diuretic and antihypertensive.
It affects the distal renal tubular mechanism of electrolyte reabsorption.
Hydrochlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts.
Natriuresis may be accompanied by some loss of potassium and bicarbonate.
After oral use diuresis begins within two hours, peaks in about four hours and lasts about 6 to 12 hours. |
| Therapeutic indications |
| Clandopril & Clandopril-D is indicated for the treatment of hypertension. |
| Side effect |
In clinical trials with Clandopril & Clandopril-D no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have
occurred have been limited to those that have been previously treated with
enalapril and hydrochlorothiazide. The most frequent clinical adverse
experiences in controlled trials were: dizziness, headache, fatigue and cough.
Generally, adverse experiences were mild and transient in nature.
Clinical adverse experiences occurring in 0.5 to 2.0 % of patients in controlled
trials included: Body as a Whole: Syncope, chest pain, abdominal pain.
Cardiovascular: Orthostatic hypotension, palpitation, tachycardia. Digestive:
Vomiting, dyspepsia, constipation, flatulence, dry mouth. Nervous/Psychiatric:
Insomnia, nervousness, paresthesia, somnolence, vertigo. Skin: Pruritus, rash.
Other: Dyspnea, gout, back pain, arthralgia, diaphoresis, decreased libido,
tinnitus, urinary tract infection and angioedema. |
| Warnings and precautions |
WARNINGS:
Enalapril Maleate:
Hypotension: Excessive hypotension was rarely seen in uncomplicated hypertensive patients but is a possible consequence of enalapril use in severely salt/volume depleted persons such as those treated vigorously with diuretics or patients on dialysis.
In patients with severe congestive heart failure, with or without associated renal insufficiency, excessive hypotension has been observed and may be associated with oliguria and/or progressive azotemia, and rarely with acute renal failure.
Because of the potential fall in blood pressure in these patients, therapy should be started under very close medical supervision.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor.
Neutropenia / Agranulocytosis: Available data from clinical trials of enalapril are insufficient to show that enalapril does not cause agranulocytosis at similar rates.
Periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease should be considered.
Hydrochlorothiazide:
Thiazides should be used with caution in severe renal disease.
In patients with renal disease, thiazides may precipitate azotemia.
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 a history of allergy or bronchial asthma.
PRECAUTIONS:
Enalapril Maleate:
Aortic Stenosis / Hypertrophic Cardiomyopathy: As with all vasodilators, enalapril should be given with caution to patients with obstruction in the outflow tract of the left ventricle.
Impaired Renal Function: In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldersterone system, treatment with angiotensin converting enzyme inhibitors, including enalapril, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure.
Hydrochlorothiazide:
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.
Hypokalemia may develop, especially with diuresis, when severe cirrhosis is present, or after prolonged therapy.
Although any chloride deficit is generally mild and usually does not require specific treatment except under; extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required.
Hyperglycemia may occur with thiazide diuretics.
Thiazides may decrease urinary calcium excretion causing intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism |
| Contraindication |
Clandopril & Clandopril-D are contraindicated in patients who are:
• Hypersensitive to any component of this product.
• Patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor.
• In patients with hereditary or idiopathic angioedema.
• Because of the presence of hydrochlorothiazide, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide derived drugs. |
| Pregnancy and lactation |
PREGNANCY:
Pregnancy Categories C (first trimester) and D (second and third trimesters).
When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus.
When pregnancy is detected, this drug should be discontinued as soon as possible.
NURSING MOTHERS:
Enalapril, enalaprilat, and hydrochlorothiazide have been detected in human breast milk. Because of the potential for serious reactions in nursing infants from either drug, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother. |
| Drug interactions |
Enalapril Maleate:
• Non-steroidal Anti-inflammatory Agents: In some patients with compromised renal function who are being treated with non-steroidal anti-inflammatory drugs, the coadministration of enalapril may result in a further deterioration of renal function.
These effects are usually reversible.
• Other Cardiovascular Agents: Enalapril has been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine and prazosin without evidence of clinically significant adverse interactions.
• Agents Increasing Serum Potassium: Enalapril attenuates diuretic-induced potassium loss. Potassium sparing diuretics (e.g., spironolactone, triameterene, or amiloride), potassium supplements, or potassium containing salt substitutes may lead to significant increases in serum potassium.
Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia they should be used with caution and with frequent monitoring of serum potassium.
Hydrochlorothiazide:
When administered concurrently the following drugs may interact with thiazide diuretics:
• Alcohol, barbiturates, or narcotics: potentiation of orthostatic hypotension may occur.
• Antidiabetic drugs (oral agents and insulin): dosage adjustment of the antidiabetic drug may be required.
• Other antihypertensive drugs: additive or potentiation effect.
• Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired.
• Corticosteroids, ACTH: intensified electrolyte depletion, particularly hypokalemia.
• Pressor amines (e.g., norepinephrine): possible decreased response to pressor amines but not sufficient to preclude their use.
• Skeletal muscle relaxants, non-depolarizing (e.g., tubocurarine): possible increased responsiveness to the muscle relaxant.
• Lithium: should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
• Non-steroidal Anti-inflammatory Drugs: In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic,and antihypertensive effects of diuretics. Therefore, when Clandopril/ Clandopril-D and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
ADVERSE REACTIONS:
In clinical trials with Clandopril & Clandopril-D no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred have been limited to those that have been previously treated with enalapril and hydrochlorothiazide. The most frequent clinical adverse experiences in controlled trials were: dizziness, headache, fatigue and cough.
Generally, adverse experiences were mild and transient in nature.
Clinical adverse experiences occurring in 0.5 to 2.0 % of patients in controlled trials included: Body as a Whole: Syncope, chest pain, abdominal pain.
Cardiovascular: Orthostatic hypotension, palpitation, tachycardia. Digestive:
Vomiting, dyspepsia, constipation, flatulence, dry mouth. Nervous/Psychiatric:
Insomnia, nervousness, paresthesia, somnolence, vertigo. Skin: Pruritus, rash.
Other: Dyspnea, gout, back pain, arthralgia, diaphoresis, decreased libido, tinnitus, urinary tract infection and angioedema |
| DOSAGE & ADMINISTRATION |
The usual dosage range of enalapril is 10 to 40 mg per day administered in a single or two divided doses.
Hydrochlorothiazide is effective in doses of 12.5 to 50 mg daily.
A patient whose blood pressure is not adequately controlled with either enalapril or hydrochlorothiazide monotherapy may be given one tablet of Clandopril & Clandopril-D. Further increases of enalapril, hydrochlorothiazide or both depend on clinical response.
Use in Renal Impairment: The usual regimens of therapy with Clandopril / Clandopril-D do not need to be adjusted as long as the patient’s creatinine clearance is > 30 mL/min/m2.
In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so enalapril maleate-hydrochlorothiazide is not recommended. |
| Overdose |
No specific information is available on the treatment of overdosage with Clandopril & Clandopril-D. Treatment is symptomatic and supportive.
Therapy with Clandopril / Clandopril-D should be discontinued and the patient observed
closely.
Suggested measures include induction of emesis and/or gastric lavage, and correction of
dehydration, electrolyte imbalance and hypotension by established procedures. |
| Package |
| 2 X 10 tablets packed in PVC/Aluminum blister inside a carton box with a leaflet. |
| Storage |
| Store between (15-30)°C, Keep away from children. |
