EZAPRIL-CO
Enalapril Maleate 20 mg + Hydrochlorothiazide 12.5 mg
1. Disclaimer
This monograph is intended for general educational and reference purposes only. It does not replace the current official Egyptian package leaflet, prescribing information, or individualized advice from a qualified physician or pharmacist. Drug information, approved indications, formulations, and regulatory status may change over time and may differ between countries.
We do not guarantee the accuracy, currency or completeness of information regarding medications or medical products, and official sources should be verified before making any decisions. Readers are responsible for independently verifying the information before relying on it.
The information below describes the active ingredients and the identified Egyptian-market product strength and should not be interpreted as authorization to initiate, discontinue, or modify treatment.
2. Summary
EZAPRIL-CO is an oral fixed-dose combination containing enalapril maleate 20 mg and hydrochlorothiazide 12.5 mg per tablet. It combines an angiotensin-converting enzyme (ACE) inhibitor with a thiazide diuretic, providing complementary antihypertensive effects. The current manufacturer information identifies EZAPRIL-CO in Egypt as a 20 mg/12.5 mg film-coated tablet.
The combination is primarily used for the treatment of hypertension, generally when treatment with the individual components or an appropriate combination regimen is clinically appropriate. Modern prescribing information for enalapril/hydrochlorothiazide fixed-dose products states that the combination is not intended as initial therapy in every patient, particularly when the dose requirements of each component have not yet been established.
3. Brand Name
EZAPRIL-CO
The Egyptian regulatory naming guidance itself uses Ezapril Co as an example of a combination trade name containing an additional active ingredient.
4. Category
Therapeutic category: Antihypertensive.
Pharmacological category:
ACE inhibitor + thiazide diuretic.
ATC classification: C09BA02 — Enalapril and diuretics.
5. Active Ingredient
Each tablet contains:
- Enalapril maleate — 20 mg
- Hydrochlorothiazide — 12.5 mg
The 20 mg/12.5 mg strength is documented in the current manufacturer product information for EZAPRIL-CO.
Enalapril maleate is a prodrug that is converted after absorption to enalaprilat, the pharmacologically active ACE inhibitor. Hydrochlorothiazide is a thiazide diuretic.
6. Pharmaceutical Form & Strength
Pharmaceutical form: Film-coated tablet for oral administration.
Strength:
Enalapril maleate 20 mg + hydrochlorothiazide 12.5 mg per tablet.
The current manufacturer listing specifically identifies EZAPRIL-CO as a 20 mg + 12.5 mg film-coated tablet.
Current Egyptian-market listings identify both:
- EZAPRIL-CO 20/12.5 mg — 20 tablets
- EZAPRIL-CO 20/12.5 mg — 30 tablets
as products manufactured by Multi-Apex.
7. Manufacturer & Marketing Authorization Holder
Manufacturer: Multi-Apex Pharma, Egypt.
The historical product leaflet identifies the manufacturing site as Multi-Apex Pharma, Badr City, Cairo, and current manufacturer-controlled information continues to list EZAPRIL-CO under the company's pharmaceutical product portfolio.
Marketing authorization holder: The publicly accessible sources reviewed for this monograph do not provide a sufficiently explicit, current statement separately identifying a legal entity as the marketing authorization holder. Therefore, no separate MAH designation is asserted here beyond the documented manufacturer/brand owner information.
8. Mechanism of Action
Enalapril
Enalapril is an ACE inhibitor and prodrug. After oral absorption it is hydrolyzed to enalaprilat, which inhibits angiotensin-converting enzyme.
ACE inhibition decreases formation of angiotensin II, thereby reducing angiotensin-II-mediated vasoconstriction and aldosterone secretion. The resulting reduction in systemic vascular resistance and sodium/water-retaining effects contributes to lowering blood pressure. ACE inhibition also reduces degradation of bradykinin, which is relevant to both pharmacological effects and the characteristic ACE-inhibitor adverse effect of cough.
Hydrochlorothiazide
Hydrochlorothiazide inhibits sodium and chloride reabsorption in the distal convoluted tubule, increasing urinary sodium and water excretion. Its diuretic action reduces extracellular fluid volume and contributes to antihypertensive activity.
Thiazide-induced volume depletion tends to activate the renin-angiotensin-aldosterone system and can increase potassium loss; enalapril inhibits this pathway and may therefore partially offset the potassium-losing effect of hydrochlorothiazide. Clinical studies demonstrate approximately additive blood-pressure-lowering effects from the combination.
9. Spectrum of Activity
EZAPRIL-CO is not an antimicrobial medicine, so the concept of an antimicrobial spectrum does not apply.
Its therapeutic activity is directed toward blood-pressure reduction through inhibition of the renin-angiotensin-aldosterone system and promotion of natriuresis/diuresis. It has no antibacterial, antiviral, antifungal, or antiparasitic spectrum.
10. Pharmacokinetics
Enalapril
Following oral administration, peak serum concentrations of enalapril occur at approximately 1 hour. Approximately 60% of an oral dose is absorbed based on urinary recovery data. Food does not materially affect enalapril absorption. Enalapril is subsequently hydrolyzed to enalaprilat, with peak serum enalaprilat concentrations occurring approximately 3–4 hours after an oral dose.
Enalaprilat is eliminated predominantly through the kidneys. An effective accumulation half-life of approximately 11 hours has been reported after repeated dosing. Renal impairment, particularly when glomerular filtration rate falls to approximately 30 mL/min or below, increases enalaprilat exposure and prolongs its disposition. Enalaprilat is dialyzable.
Hydrochlorothiazide
Hydrochlorothiazide is absorbed from the gastrointestinal tract and is not significantly metabolized. It is eliminated predominantly by the kidneys as unchanged drug. Reported plasma elimination half-life is approximately 5.6–15 hours, although pharmacodynamic effects persist longer than the plasma half-life.
Combination
Concomitant administration of enalapril and hydrochlorothiazide generally has little or no clinically important effect on the bioavailability of either component, and combination tablets have been demonstrated in several products to be bioequivalent to administration of the corresponding individual components.
11. Indications
The well-established therapeutic indication for the enalapril/hydrochlorothiazide fixed-dose combination is:
• Treatment of hypertension.
The combination may be appropriate when an ACE inhibitor and a thiazide diuretic are both clinically indicated and the required doses of the components have been established.
Important clarification regarding congestive heart failure
The older EZAPRIL-CO leaflet supplied with the original material lists congestive cardiac failure as an indication. Enalapril itself is an established treatment for symptomatic heart failure, but the current authoritative prescribing information reviewed for fixed-dose enalapril/hydrochlorothiazide identifies hypertension as the indication and does not establish this fixed-dose combination as a general heart-failure treatment. Therefore, congestive heart failure should not be presented as an independently confirmed current indication for EZAPRIL-CO without reference to the current Egyptian approved product information. Enalapril as an individual drug, however, has an established heart-failure indication.
12. Administration
EZAPRIL-CO is administered orally.
The tablet may generally be taken with or without food. It should be taken consistently at approximately the same time each day and swallowed according to the product instructions. Because hydrochlorothiazide increases urine production, administration earlier in the day is often practical to reduce interference with nighttime sleep.
Dosage
The exact dose must be individualized according to the patient's blood-pressure response, renal function, prior antihypertensive therapy, volume status, and tolerance.
The supplied historical leaflet states 1–2 tablets once daily or as prescribed, but this wording should not be treated as an independent universal dosing instruction for the current product. Fixed-dose enalapril/hydrochlorothiazide combinations are commonly used after the individual component requirements have been established, rather than automatically being used as initial treatment.
Patients with significant renal impairment require particular caution because both components are substantially dependent on renal handling, and the fixed-dose combination may not provide the flexibility required for initial dose adjustment.
13. Method of Preparation
No preparation or reconstitution is required.
EZAPRIL-CO is supplied as a finished film-coated tablet for oral administration.
The current manufacturer information identifies the product as a film-coated tablet.
14. Contraindications
EZAPRIL-CO/enalapril-hydrochlorothiazide should be avoided or considered contraindicated in patients with:
- Known hypersensitivity to enalapril, hydrochlorothiazide, or any component of the product.
- Previous ACE-inhibitor-associated angioedema.
- Hereditary or idiopathic angioedema.
- Anuria.
- Hypersensitivity to sulfonamide-derived drugs, in accordance with the product labeling.
- Concomitant therapy with a neprilysin inhibitor such as sacubitril; the combination must not be given within the specified 36-hour interval when switching to or from sacubitril/valsartan.
- Concomitant use of aliskiren in patients with diabetes is contraindicated according to the cited prescribing information.
Pregnancy
ACE inhibitors, including enalapril, can cause serious fetal toxicity. When pregnancy is detected, enalapril-containing therapy should be discontinued as soon as possible and an appropriate alternative considered under medical supervision.
The wording in the original leaflet, “ascertained or supposed pregnancy,” is therefore more appropriately replaced by a modern, explicit fetal-toxicity warning.
15. Warnings & Precautions
Hypotension and volume depletion
Excessive hypotension may occur, particularly in patients who are volume- or sodium-depleted, receiving intensive diuretic therapy, or undergoing dialysis. Dehydration from vomiting, diarrhea, excessive sweating, or inadequate fluid intake may increase this risk.
Renal function
Renal function should be assessed and monitored where clinically appropriate. Increases in blood urea nitrogen and serum creatinine may occur, particularly in patients with pre-existing renal impairment or renovascular disease.
Hyperkalemia
Although hydrochlorothiazide can lower serum potassium, enalapril can increase potassium. Hyperkalemia may therefore occur, particularly in patients with renal impairment, diabetes, or concomitant use of potassium supplements, potassium-containing salt substitutes, or potassium-sparing diuretics. Periodic monitoring of serum potassium is appropriate when clinically indicated.
Electrolyte disturbances
Hydrochlorothiazide may cause hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis, as well as other electrolyte abnormalities. Monitoring is particularly important in susceptible patients and those receiving prolonged therapy.
Glucose and uric acid
Thiazide diuretics may cause hyperglycemia/glycosuria and may increase serum uric acid, potentially precipitating gout in susceptible patients.
Angioedema
ACE inhibitors may cause potentially life-threatening angioedema involving the face, lips, tongue, glottis, or larynx. It may occur at any time during treatment. EZAPRIL-CO should be discontinued and urgent medical management instituted if significant angioedema occurs.
Cough
A persistent, generally nonproductive cough is a recognized adverse effect of ACE inhibitors and may necessitate reassessment of therapy.
Rare hematologic reactions
ACE inhibitors have been associated with rare neutropenia/agranulocytosis and related hematologic abnormalities. Particular caution is warranted in patients with renal impairment or collagen vascular disease.
Photosensitivity and non-melanoma skin cancer
Hydrochlorothiazide is photosensitizing and has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma in the setting of substantial cumulative exposure. Patients receiving long-term hydrochlorothiazide should practice appropriate sun protection and be alert to suspicious skin lesions.
16. Drug Interactions
Important interactions include:
Lithium
ACE inhibitors and thiazide diuretics can increase lithium exposure and the risk of lithium toxicity. Concomitant use requires careful consideration and monitoring.
Potassium supplements and potassium-sparing diuretics
Potassium supplements, potassium-containing salt substitutes, spironolactone, triamterene, amiloride, and similar agents may increase the risk of hyperkalemia when used with enalapril.
Other antihypertensive agents
Additive blood-pressure lowering may occur with other antihypertensive drugs. Beta-blockers and several other cardiovascular agents can be co-administered when clinically indicated, but blood pressure should be monitored.
NSAIDs
Nonsteroidal anti-inflammatory drugs may reduce antihypertensive effects and, particularly in susceptible patients, increase the risk of deterioration in renal function when combined with ACE inhibitors and diuretics.
Cholestyramine and colestipol
These anion-exchange resins can reduce gastrointestinal absorption of hydrochlorothiazide. Appropriate separation of administration is therefore advisable when they are used together. Hydrochlorothiazide labeling reports marked reductions in absorption with these resins.
Digitalis glycosides
Hydrochlorothiazide-induced hypokalemia can increase susceptibility to digitalis-associated toxicity and arrhythmias.
Antidiabetic therapy
Hydrochlorothiazide may impair glycemic control and may require reassessment of antidiabetic treatment.
Sacubitril/valsartan and neprilysin inhibitors
Concurrent use with a neprilysin inhibitor is contraindicated. When switching between an ACE inhibitor and sacubitril/valsartan, a 36-hour washout period is required to reduce the risk of angioedema.
Aliskiren
Combination with aliskiren is contraindicated in patients with diabetes and is generally avoided in certain patients with renal impairment because of increased risk of hypotension, hyperkalemia, and renal dysfunction.
17. Side Effects
Adverse effects vary between patients and may result from either component.
Common or clinically recognized effects
- Dizziness or lightheadedness
- Hypotension, including orthostatic hypotension
- Headache
- Fatigue or weakness
- Nausea or other gastrointestinal symptoms
- Dry cough
- Increased urination
- Electrolyte disturbances
- Hyperuricemia/gout
- Hyperglycemia
Hypotension, orthostatic effects, syncope, and cough are established adverse effects of the combination or its individual components.
Important serious reactions
- Angioedema, including potentially fatal airway obstruction
- Severe hypotension or syncope
- Significant renal dysfunction
- Hyperkalemia or serious electrolyte disturbances
- Severe hypersensitivity reactions
- Rare blood dyscrasias
- Severe cutaneous reactions
- Hydrochlorothiazide-associated photosensitivity and non-melanoma skin cancer risk with cumulative exposure
The original leaflet's statement that dizziness and “too much potassium loss” may be particularly likely in elderly patients is incomplete. Elderly patients may be more susceptible to volume depletion, hypotension, electrolyte disturbances, and renal impairment, and these risks should be assessed clinically.
18. Use in Special Populations
Pregnancy
Not recommended and potentially hazardous.
Enalapril and other drugs acting directly on the renin-angiotensin system can cause fetal renal injury, oligohydramnios, skull abnormalities, fetal/neonatal morbidity, and death, particularly during the second and third trimesters. Enalapril should be discontinued as soon as pregnancy is detected.
Breastfeeding
Enalapril is present in breast milk at very low levels, and current LactMed information indicates that the small amounts transferred to the infant generally have not produced adverse effects in the limited reported cases.
Hydrochlorothiazide at doses of 50 mg/day or less is considered compatible with lactation by LactMed, although large diuretic doses may reduce milk production through intense diuresis. The EZAPRIL-CO hydrochlorothiazide dose is 12.5 mg per tablet, but the overall clinical decision should take the mother's condition and total daily dosage into account.
Pediatric use
The safety and appropriate dosing of this particular fixed-dose combination in children are not sufficiently established for routine use. Pediatric antihypertensive treatment should be individually selected and dosed by an appropriately qualified clinician.
Elderly patients
Older adults may be more susceptible to hypotension, volume depletion, electrolyte abnormalities, and renal impairment. Renal function and blood pressure should therefore be assessed carefully.
Renal impairment
Particular caution is required because enalaprilat is primarily renally eliminated and hydrochlorothiazide also depends substantially on renal excretion. Significant renal impairment may make a fixed-dose combination unsuitable when individual component titration is needed.
Hepatic impairment
Patients with significant hepatic disease should be treated cautiously because disturbances in fluid and electrolyte balance may have greater clinical consequences. Specific dosing information for EZAPRIL-CO in hepatic impairment was not identified in the current publicly accessible manufacturer material reviewed for this monograph.
No additional high-confidence product-specific special-population information was identified in the reviewed sources.
19. Storage Conditions
Store the tablets in the original package, protected from excessive heat and moisture, and keep them out of the reach of children.
For exact temperature requirements, the current product package or official Egyptian leaflet should be followed because the publicly available current manufacturer webpage reviewed does not specify a numerical storage temperature. General references for the combination commonly specify room-temperature storage in a closed container protected from heat, moisture, and direct light.
20. Additional Sections
Current Egyptian-market presentations
Current Egyptian-market sources identify:
- EZAPRIL-CO 20/12.5 mg — 20 tablets
- EZAPRIL-CO 20/12.5 mg — 30 tablets
Both are identified with enalapril + hydrochlorothiazide and Multi-Apex as the manufacturer.
Important distinction from the historical leaflet
The historical leaflet supplied for this product describes several points using older terminology and older clinical assumptions. Current drug references support retaining the core composition but updating terminology, safety information, interaction warnings, pregnancy language, and the characterization of the approved indication. The current manufacturer listing confirms the 20 mg/12.5 mg film-coated tablet formulation.
Overdose
Excessive ingestion may produce hypotension, dehydration, electrolyte disturbances, and renal abnormalities. Severe hydrochlorothiazide overdose is principally associated with excessive diuresis and electrolyte depletion. Suspected overdose requires urgent medical assessment and supportive management rather than self-treatment.
21. Frequently Asked Questions (FAQ)
What is EZAPRIL-CO used for?
EZAPRIL-CO is a fixed-dose combination of enalapril and hydrochlorothiazide used primarily for the treatment of hypertension.
What are the active ingredients?
Each tablet contains enalapril maleate 20 mg and hydrochlorothiazide 12.5 mg.
Does EZAPRIL-CO contain a diuretic?
Yes. Hydrochlorothiazide is a thiazide diuretic.
Does EZAPRIL-CO contain an ACE inhibitor?
Yes. Enalapril is an ACE inhibitor.
Can EZAPRIL-CO cause cough?
Yes. A persistent dry cough is a recognized adverse effect associated with ACE inhibitors such as enalapril.
Can EZAPRIL-CO cause dizziness?
Yes. Dizziness and lightheadedness can occur, particularly when treatment lowers blood pressure excessively or during the early phase of therapy.
Can EZAPRIL-CO increase potassium?
It can. Although hydrochlorothiazide can lower potassium, enalapril may increase serum potassium. The net effect varies between patients, so potassium monitoring may be required.
Can EZAPRIL-CO be used during pregnancy?
ACE-inhibitor-containing treatment such as EZAPRIL-CO should not be used during pregnancy because of serious fetal toxicity risks. Enalapril should be discontinued as soon as pregnancy is detected.
Can EZAPRIL-CO be used while breastfeeding?
The individual components have relatively low reported exposure in breast milk, but the decision should be individualized. Current LactMed data consider enalapril compatible with breastfeeding in appropriate circumstances and hydrochlorothiazide doses of 50 mg/day or less generally acceptable, while noting that larger diuretic doses can reduce milk production.
Can EZAPRIL-CO cause angioedema?
Yes. Enalapril can cause angioedema involving the face, lips, tongue, or airway. This can be life-threatening and requires urgent medical attention.
Is EZAPRIL-CO an antibiotic?
No. It is an antihypertensive combination, not an antimicrobial drug.
Is congestive heart failure an indication for EZAPRIL-CO?
Enalapril itself has an established role in symptomatic heart failure, but the current fixed-dose enalapril/hydrochlorothiazide prescribing information reviewed for this monograph identifies hypertension as the indication. Therefore, the older statement that EZAPRIL-CO itself is routinely indicated for congestive heart failure should not be reproduced without confirmation from the current Egyptian approved leaflet.
22. References
- Apex / Multi-Apex Pharma. EZAPRIL-CO product information: Enalapril Maleate 20 mg + Hydrochlorothiazide 12.5 mg; current manufacturer product listing.
- Multi-Apex Pharma. EZAPRIL-CO historical product leaflet, including composition and original product information.
- DailyMed — Enalapril Maleate and Hydrochlorothiazide Tablets. Current professional prescribing information covering indications, contraindications, warnings, interactions, adverse reactions, and pharmacokinetics.
- DailyMed — VASOTEC (enalapril maleate). Updated pharmacokinetic and mechanism-of-action information for enalapril/enalaprilat.
- DailyMed — Enalapril Maleate. Current information concerning renal dose adjustment and heart-failure use of enalapril as an individual active ingredient.
- DailyMed — Hydrochlorothiazide. Current information on adverse effects, electrolyte disturbances, drug interactions, photosensitivity, and non-melanoma skin cancer risk.
- MedlinePlus. Enalapril and Hydrochlorothiazide drug information, including administration and general patient-use information.
- LactMed, National Library of Medicine. Enalapril; revision July 15, 2026.
- LactMed, National Library of Medicine. Hydrochlorothiazide; revision September 15, 2025.
- Egyptian Drug Authority / Central Administration for Pharmaceutical Products. Egyptian guidance on pharmaceutical trade-name conventions, including the example “Ezapril Co.”
- Vademecum International. Egyptian-market identification of EZAPRIL CO 20 mg + 12.5 mg, Multi-Apex, oral tablet, ATC C09BA02.
Final scientific verification
The original material has been corrected in the final version where it conflicted with current or higher-confidence sources. In particular, the monograph does not retain the old universal claim that EZAPRIL-CO is indicated for congestive heart failure, does not retain the old categorical statement that the medicine “does not interfere with driving,” and does not treat “1–2 tablets once daily” as a universal dose. The current 20 mg/12.5 mg composition and film-coated tablet formulation are confirmed, while safety information has been expanded to include contemporary ACE-inhibitor contraindications and warnings, neprilysin-inhibitor separation, potassium-related interactions, renal considerations, angioedema, and the recognized hydrochlorothiazide-associated non-melanoma skin-cancer risk.