Pharmacology: Irbesartan is a specific competitive antagonist of angiotensin I (AT1) receptors with a much greater affinity (>8500-fold) for the AT1 receptor than for the AT2 receptor and no agonist activity. It is a potent antihypertensive drug which is administered orally, and may be given alone or in combination with diuretics and/or other antihypertensive agents.
Hydrochlorothiazide is a moderately potent diuretic and exert this effect by reducing the reabsorption of electrolytes from the renal tubules, thereby increasing the excretion of sodium and chloride ions, and consequently water.
Pharmacokinetics: Irbesartan is an orally active agent that does not require biotransformation into an active form. It is rapidly absorbed from the gastrointestinal tract with an oral bioavailability of 60-80%. Peak plasma concentrations of irbesartan occur 1.5-2 hrs after an oral dose. Irbesartan is about 96% bound to plasma proteins. It undergoes some metabolism in the liver, primarily by the cytochrome P-450 isoenzyme CYP2C9, to inactive metabolites. It is excreted as unchanged drug and metabolites in the bile and in urine. The terminal elimination t½ is about 11-15 hrs.
Hydrochlorothiazide is fairly rapidly absorbed from the gastrointestinal tract with an oral bioavailability of 65-70%. It has been estimated to have a plasma t½ of between 5 and 15 hrs and appears to be preferentially bound to red blood cells. It is excreted mainly unchanged in the urine.
Treatment of essential hypertension and for adults who have hypertension (high blood pressure) that is not adequately controlled by irbesartan or hydrochlorothiazide alone.
Hypertension: 150 mg once daily, increased to 300 mg once daily, if necessary. Elderly >75 Years, Patients with Intravascular Volume Depletion and Those Receiving Hemodialysis: A lower initial dose of 75 mg once daily may be considered. Children 6-12 Years: 75 mg once daily, increased to 150 mg once daily, if necessary.
Renal Disease in Hypertensive Type II Diabetes: Initial Dose: 150 mg once daily, increased to 300 mg once daily for maintenance. Hydrochlorothiazide is normally effective at 12.5 mg daily dose but may be increased to 25-50 mg, if necessary. Irbesartan is normally given in the morning so that sleep is not interrupted by diuresis.
No data are available, in regard to overdosage in humans. However, daily doses of irbesartan 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.
The side effects of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-dependent phenomena (eg, pancreatitis), the former much more common than the latter.
Hypersensitivity to irbesartan, hydrochlorothiazide and any other component of Co-Ivyzar.
Use in pregnancy: Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected, irbesartan should be discontinued as soon as possible.
Hepatic/Renal Impairment: Hydrochlorothiazide should be used with caution on patients with these conditions. It should not be used when the creatinine clearance is <30 mL/min.
Use in lactation: Hydrochlorothiazide has been shown to pass into breast milk, while the excretion of irbesartan in breast milk has not yet been established. The American Academy of Pediatrics consider hydrochlorothiazide usually compatible with breastfeeding. Caution should be taken when administering Co-Ivyzar to lactating mothers.
Use in children: Pharmacokinetic parameters in pediatric subjects (6-16 years) were comparable to adults. At doses up to 150 mg daily for 4 weeks, irbesartan was well-tolerated in hypertensive children and adolescents.
Use in the elderly: While there is no overall differences in effectiveness or safety of irbesartan observed between these subjects and younger subjects, some older individuals are at risk in fluid and electrolyte balance due to hydrochlorothiazide. Use with caution on elderly.
Use in pregnancy: Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected, irbesartan should be discontinued as soon as possible.
Use in lactation: Hydrochlorothiazide has been shown to pass into breast milk, while the excretion of irbesartan in breast milk has not yet been established. The American Academy of Pediatrics consider hydrochlorothiazide usually compatible with breastfeeding. Caution should be taken when administering Co-Ivyzar to lactating mothers.
Treatment with angiotensin II receptor antagonists is associated with dizziness and headache. Hypotension, characterized as orthostatic and dose-related, was seen in patients with volume depletion eg, those receiving high-dose diuretics.
Other adverse effects associated with the use of irbesartan include gastrointestinal disturbance, fatigue, muscle and joint pains, congestion, hyperkalemia, back pain, vertigo, migraine, cough, acute pancreatitis and increase in liver enzymes.
Hypersensitivity reactions eg, rash, urticaria, pruritus and angioedema have been reported with the use of irbesartan.
No significant drug-drug pharmacokinetic (or pharmacodynamic) interactions have been found in interaction studies of irbesartan with digoxin, warfarin and nifedipine.
In vitro studies show significant inhibition of the formation of oxidized irbesartan metabolites with the known cytochrome CYP2C9 substrates/inhibitors sulphenazole, tolbutamide and nifedipine. However, in clinical studies, the consequences of concomitant irbesartan on the pharmacodynamics of warfarin were negligible. Based on in vitro data, no interaction would be expected with drugs whose metabolism is dependent upon CYP450 isozymes 1A1, 1A2, 2A6, 2B6, 2D6, 2E1 or 3A4.
Many of the interactions of hydrochlorothiazide are due to its effect on fluid and electrolyte balance. Diuretic-induced hypokalemia may enhance the toxicity of digitalis glycosides and may also increase the risk of arrhythmias with drugs that prolong the QT interval eg, astemizole, terfenadine, halofantrine, pimozide and sotalol. It may also enhance the neuromuscular blocking action of competitive neuromuscular blockers eg, atracurium. Its potassium-depleting effect may be enhanced by corticosteroids, corticotropin, β2-agonists eg, salbutamol, carbenoxolone, amphotericin B or reboxetine. Hydrochlorothiazide may enhance the nephrotoxicity of NSAIDs. It has also been reported to diminish the response to pressor amines eg, noradrenaline. It should not be used with lithium to prevent reaching toxic blood level. Increased toxicity has been reported when administered with allopurinol and tetracyclines.
Store at temperatures not exceeding 30°C.
C09DA04 - irbesartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.
Co-Ivyzar tab 150 mg/12.5 mg
100's (P25/tab)
Co-Ivyzar tab 300 mg/12.5 mg
100's (P40/tab)
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