Avalide Uses, Dosage, Side Effects, FAQ - MedicinesFAQ (2023)

Avalide Oral tablet

Irbesartan: Angiotensin II is a potent vasoconstrictor formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the RAS and also stimulates aldosterone synthesis and secretion by adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth. Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to the AT1angiotensin II receptor. There is also an AT2receptor in many tissues, but it is not involved in cardiovascular homeostasis.

Irbesartan is a specific competitive antagonist of AT1receptors with a much greater affinity (more than 8500-fold) for the AT1receptor than for the AT2receptor, and no agonist activity.

Blockade of the AT1receptor removes the negative feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II do not overcome the effects of irbesartan on blood pressure.

Irbesartan does not inhibit ACE or renin or affect other hormone receptors or ion channels known to be involved in the cardiovascular regulation of blood pressure and sodium homeostasis. Because irbesartan does not inhibit ACE, it does not affect the response to bradykinin; whether this has clinical relevance is not known.

Hydrochlorothiazide: Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.


Irbesartan & Hydrochlorothiazide tablet are used for the treatment of hypertension. This tablet may be used in patients whose blood pressure is not adequately controlled on monotherapy. This tablet may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. The choice of Irbesartan & Hydrochlorothiazide tablets as initial therapy for hypertension should be based on an assessment of potential benefits and risks.

Patients with stage 2 (moderate or severe) hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. The decision to use a combination as initial therapy should be individualized and may be shaped by considerations such as the baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy.

Avalide is also used to associated treatment for these conditions: Acidosis, Renal Tubular, Calcium Nephrolithiasis, Cirrhosis of the Liver, Congestive Heart Failure (CHF), Diabetes Insipidus, Edema, High Blood Pressure (Hypertension), Hypertension,Essential, Hypokalemia caused by diuretics, Nephrotic Syndrome, Premenstrual tension with edema, Sodium retention, Stroke, Prophylaxis of preeclampsiaDiabetic Nephropathy, High Blood Pressure (Hypertension)

How Avalide works

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).

Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.

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Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Irbesartan prevents angiotensin II binding to the AT1 receptor in tissues like vascular smooth muscle and the adrenal gland. Irbesartan and its active metabolite bind the AT1 receptor with 8500 times more affinity than they bind to the AT2 receptor. Irbesartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation and prevents the secretion of aldosterone, lowering blood pressure.

Angiotensin II would otherwise bind to the AT1 receptor, inducing vasoconstriction and aldosterone secretion, raising blood pressure.


Trade Name Avalide
Generic Irbesartan + Hydrochlorothiazide
Weight 12.5mg + 150mg, 12.5mg + 300mg,
Type Oral tablet
Therapeutic Class Combined antihypertensive preparations
Available Country Canada, United States,
Last Updated: June 23, 2021 at 12:34 pm


Avalide Uses, Dosage, Side Effects, FAQ - MedicinesFAQ (1)

Table Of contents

  • Avalide
  • Uses
  • Dosage
  • Side Effect
  • Precautions
  • Interactions
  • Uses during Pregnancy
  • Uses during Breastfeeding
  • Accute Overdose
  • Food Interaction
  • Half Life
  • Volume of Distribution
  • Clearance
  • Interaction With other Medicine
  • Contradiction
  • Storage


Avalide dosage

Initial therapy: Irbesartan 150 mg & Hydrochlorothiazide 12.5 mg orally once a day; may increase after 1 to 2 weeks.

Add-on/Replacement therapy: Irbesartan 150 to 300 mg & Hydrochlorothiazide 12.5 to 25 mg orally once a day

Maximum dose: Irbesartan 300 mg & Hydrochlorothiazide 25 mg orally once a day

Side Effects

Irbesartan:Hyperkalemia (19%), Chest pain (2%), Tachycardia (1%), Abnormal urination (2%), Musculoskeletal pain (6%), Flu-like syndrome (3%), Edema (3%), Tachycardia (1%), Chest pain (2%), Creatinine increased (1%), Increased BUN (2%), Dizziness (10%), URI (9%), Orthostatic hypotension (5%), Fatigue (4%), Diarrhea (3%), Dyspepsia (2%)

Hydrochlorothiazide:Anorexia, Epigastric distress, Hypotension, Orthostatic hypotension, Photosensitivity, Anaphylaxis, Anemia, Confusion, Erythema multiforme, Stevens-Johnson syndrome, Exfoliative dermatitis including toxic epidermal necrolysis, Dizziness, Hypokalemia and/or hypomagnesemia, Hyperuricemia, Headache

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The oral LD50 of hydrochlorothiazide is >10g/kg in mice and rats.

Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.

The oral TDLO in humans is 30mg/kg/6W.

Symptoms of overdose include hypotension and tachycardia or bradycardia. Terlipressin may be given to treat hypotension and tachycardia if conventional vasopressors fail to control blood pressure.


Child: Do not nurse

Lactation: Discontinue drug or do not nurse


Other antihypertensives, lithium, K-sparing diuretics, K supplements, salt substitutes containing K. CNS depressants, antidiabetics, cholestyramine & colestipol resins, corticosteroids, ACTH, digitalis glycosides, antiarrhythmics, NSAIDs, tubocurarine, antigout medications, Ca salts. Alcohol; diazoxide, atropine, beperiden, amantadine, cyclophosphamide, methotrexate.

Volume of Distribution

The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.

The volume of distribution of irbesartan is 53-93L.

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Elimination Route

An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a Tmax of 1-5 hours, and a Cmax of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, Cmax is 20% lower, and Tmax increases from 1.6 to 2.9 hours.

Irbesartan is 60-80% bioavailable with a Tmax of 1.5-2hours. Taking irbesartan with food does not affect the bioavailability.

In one study, healthy subjects were given single or multiple oral doses of 150mg, 300mg, 600mg, and 900mg of irbesartan. A single 150mg dose resulted in an AUC of 9.7±3.0µg\•hr/mL, a Tmax of 1.5 hours, a half life of 16±7 hours, and a Cmax of 1.9±0.4µg/mL. A single 300mg dose resulted in an AUC of 20.0±5.2µg\•hr/mL, a Tmax of 1.5 hours, a half life of 14±7 hours, and a Cmax of 2.9±0.9µg/mL. A single 600mg dose resulted in an AUC of 32.6±11.9µg\•hr/mL, a Tmax of 1.5 hours, a half life of 14±8 hours, and a Cmax of 4.9±1.2µg/mL. A single 900mg dose resulted in an AUC of 44.8±20.0µg\•hr/mL, a Tmax of 1.5 hours, a half life of 17±7 hours, and a Cmax of 5.3±1.9µg/mL.

Multiple 150mg doses resulted in an AUC of 9.3±3.0µg\•hr/mL, a Tmax of 1.5 hours, a half life of 11±4 hours, and a Cmax of 2.04±0.4µg/mL. Multiple 300mg doses resulted in an AUC of 19.8±5.8µg\•hr/mL, a Tmax of 2.0 hours, a half life of 11±5 hours, and a Cmax of 3.3±0.8µg/mL. Multiple 600mg doses resulted in an AUC of 31.9±9.7µg\•hr/mL, a Tmax of 1.5 hours, a half life of 15±7 hours, and a Cmax of 4.4±0.7µg/mL. Multiple 900mg doses resulted in an AUC of 34.2±9.3µg\•hr/mL, a Tmax of 1.8 hours, a half life of 14±6 hours, and a Cmax of 5.6±2.1µg/mL.

Half Life

The plasma half life of hydrochlorothiazide is 5.6-14.8h.

The terminal elimination half life of irbesartan is 11-15 hours.


The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.

Total plasma clearance of irbesartan is 157-176mL/min while renal clearance is 3.0-3.5mL/min.

Elimination Route

Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide.

20% of a radiolabelled oral dose of irbesartan is recovered in urine, and the rest is recovered in the feces. 10

Pregnancy & Breastfeeding use

Pregnancy Category D. Use of drugs that acton the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Irbesartan and Hydrochlorothiazide as soon as possible.

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Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Nursing Mothers: It is not known whether irbesartan is excreted in human milk, but irbesartan or some metabolite of irbesartan is secreted at low concentration in the milk of lactating rats.

Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.


Irbesartan and Hydrochlorothiazide tablets are contraindicated in patients who are hypersensitive to any component of this product. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Do not coadminister aliskiren with Irbesartan and Hydrochlorothiazide tablets in patients with diabetes

Special Warning

Renal Dose Adjustments:

  • Mild to moderate renal dysfunction (CrCl 30 mL/min or greater): No adjustment recommended
  • Severe renal dysfunction (CrCl less than 30 mL/min): Not recommended

Liver Dose Adjustments: Caution recommended

Acute Overdose

Irbesartan: No data are available in regard to overdosage in humans. However, daily doses of 900 mg for 8 weeks were well tolerated. The most likely manifestations of overdosage are expected to be hypotension and tachycardia; bradycardia might also occur from overdose. Irbesartan is not removed by hemodialysis.To obtain up-to-date information about the treatment of overdosage, a good resource is a certified regional Poison Control Center. Telephone numbers of certified Poison Control Centers are listed in thePhysicians’ Desk Reference(PDR). In managing overdose, consider the possibilities of multiple-drug interactions, drug-drug interactions, and unusual drug kinetics in the patient.Laboratory determinations of serum levels of irbesartan are not widely available, and such determinations have, in any event, no established role in the management of irbesartan overdose.Acute oral toxicity studies with irbesartan in mice and rats indicated acute lethal doses were in excess of 2000 mg/kg, about 25- and 50-fold the MRHD (300 mg) on a mg/m2basis, respectively.

Hydrochlorothiazide: The most common signs and symptoms of overdose observed in humans are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The oral LD50of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

Storage Condition

Should be stored in cool and dry place


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