Cavazide 75-MG Tablet

This tablet is indicated for the treatment of hypertension for patients in whom combination therapy is appropriate.

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 AT1 angiotensin II receptor. There is also an AT2 receptor in many tissues, but it is not involved in cardiovascular homeostasis.

Irbesartan is a specific competitive antagonist of AT1 receptors with a much greater affinity (more than 8500-fold) for the AT1 receptor than for the AT2 receptor, and no agonist activity.

Blockade of the AT1 receptor 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.

A patient whose blood pressure is inadequately controlled by irbesartan or Hydrochlorothiazide alone may be switched to once daily to minimize dose independent side effects. Recommended doses are (irbesartan and hydrochlorothiazide)

• 150-12.5 mg (one 150 tablet),
• 300-12.5 mg (one 300 tablet), and
• 300-25 mg (two 150 tablet).

The largest incremental effect will likely be in the transition from monotherapy to 150-12.5 mg (one 150 tablet). It takes 2-4 weeks for the blood pressure to stabilize after a change in the dose of this tablet.

The usual dose- 150 is one tablet once daily More than two tablets once daily is not recommended.

The maximal antihypertensive effect is attained about 2-4 weeks after initiation of therapy.

Use in Patients with Renal Impairment: The usual regimens of therapy may be followed as long as the patient’s creatinine clearance iss 30 mVmin. Patients with Hepatic impairment No dosage adjustment is necessary in patients with hepatic impairment.

Irbesartan: Based on in vitro data, no interactions with irbesartan would be expected to occur with drugs whose metabolism is dependent upon cytochrome P450 isoenzymes GYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1 or CYP3A4. irbesartan is primarily metabolized by CYP2C9, however, during clinical interaction studies, no significant pharmacokinetic and pharmacodynamic interactions were obsen/ed when irbesartan was co-administered with warfarin (a drug metabolized by CYP2C9). irbesartan does not affect the pharmacokinetics of digoxin. The pharmacokinetics of irbesartan are not affected by coadministration with Nifedipine or Hydrochlorothiazide. Reversible increase in lithium concentrations have been rarely reported with irbesartan. Therefore, if co-administration of irbesartan and lithium proves necessary, careful monitoring of senrm lithium is necessary.

Hydrochlorothiazide: Alcohol, Barbiturates, Narcotics: potential of orthostatic hypotension may occur. Antidiabetic drugs (oral agents and insulin: dosage adjustment of the antidiabetic drug may be required. Other antihypertensive drugs: additive effect or potentiation.

irbesartan and Hydrochlorothiazide tablet is contra-indicated in patients who are hypersensitive to irbesartan, Hydrochlorothiazide, and in pregnancy.

Gastro-intestinal system: Anorexia, gastric irritation, nausea, vomiting, cramps, diarrhoea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, salivary gland inflammation. Central nen/ous system: Dizziness, vertigo, headache, yellow vision.

Cardiovascular: Subjective rhythm disturbance, flushing, ECG abnormality cardiac murmur, cardiac rhythm disturbance, orthostatic hypotension, atrial rhythm disturbance, bradycardia, hypotension, syncope, conduction disorder, myocardial infarction.

Irbesartan and Hydrochlorothiazide is contra- indicated in pregnancy When used during the second and third trimesters of pregnancy, irbesartan can cause injury and even death ofthe developing baby Thiazides appear in human milk. If use of the drug is seemed essential, the patient should stop breast feeding.

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function depends on the activity of the renin-angiotensin- aldosterone system (e.g. hypertensive patients with renal artery stenosis in one or both kidneys, or patients with severe congestive heart failure), treatment with drugs that affect this system has been associated with oliguria andlor progressive azotemia and (rarely) with acute renal failure andlor death. The possibility of a similar effect occurring with the use of an angiotensin ll receptor antagonist, including irbesartan, cannot be excluded. Experience is limited with irbesartan in patients with moderate to severe renal impairment; careful monitoring of renal function and potassium in such patients is advised. While hyperkalaemia in uncomplicated patients with hypertension has not been reported with irbesartan, hyperkalaemia may occur during treatment with other drugs that affect the renin-angiotensin-aldosterone system, especially in the presence of renal impairment and/or heart failure. Adequate monitoring of serum potassium in patients at risk is recommended. The safety of irbesartan in the presence of heart failure has not been fully defined. Sudden death has oocuned in some studies of patients with heart failure, and although such deaths may have reflected the natural history of the underlying heart failure, caution is recommended when treating such patients with irbesartan. At this time, experience is limited with irbesartan in the treatment of patients with ventricular dysfunction or cardiac arrythmias; caution is advised.

Combined antihypertensive preparations

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.