Cavazide 300 mg+12.5 mg

Indications
Cavazide tablets are prescribed for the treatment of hypertension in patients who are candidates for combination therapy.

Take this medication as per the advice of a registered healthcare professional.

Pharmacology

Irbesartan:
Irbesartan works by blocking the effects of Angiotensin II, a potent vasoconstrictor. Angiotensin II is produced from Angiotensin I through the action of angiotensin-converting enzyme (ACE). This molecule plays a significant role in elevating blood pressure and stimulating aldosterone secretion, which increases sodium retention in the kidneys, promotes sympathetic nervous system activity, and stimulates smooth muscle cell growth. Irbesartan specifically binds to the AT1 receptors of Angiotensin II, preventing its vasoconstrictor and aldosterone-secreting effects.

Irbesartan is a highly selective antagonist of the AT1 receptor, with more than 8500 times greater affinity for this receptor compared to the AT2 receptor. This results in no agonistic activity from Irbesartan at the AT2 receptor.

Blocking the AT1 receptor removes the feedback inhibition of renin secretion by Angiotensin II. This causes an increase in plasma renin activity and circulating Angiotensin II, but the blood pressure-lowering effects of Irbesartan are still maintained.

Irbesartan does not inhibit ACE or renin and does not affect other ion channels or hormone receptors involved in cardiovascular function and sodium balance. Since it does not inhibit ACE, it does not influence the bradykinin response, and whether this has clinical significance is not fully known.

Hydrochlorothiazide:
Hydrochlorothiazide is a thiazide diuretic that affects the renal tubules by inhibiting sodium and chloride reabsorption. This leads to an increased excretion of these electrolytes. Additionally, the diuretic effect reduces plasma volume, which indirectly raises plasma renin activity, increases aldosterone secretion, increases potassium loss, and decreases serum potassium levels. However, when combined with an Angiotensin II receptor antagonist like Irbesartan, the potassium loss caused by hydrochlorothiazide is typically reversed.

Dosage and Administration
For patients whose hypertension is not adequately controlled with either Irbesartan or Hydrochlorothiazide alone, Cavazide can be switched to a once-daily regimen to minimize dose-dependent side effects. Recommended starting doses, based on the desired effect, are as follows:

• 150 mg Irbesartan / 12.5 mg Hydrochlorothiazide (one Cavazide 150 tablet)
• 300 mg Irbesartan / 12.5 mg Hydrochlorothiazide (one Cavazide 300 tablet)
• 300 mg Irbesartan / 25 mg Hydrochlorothiazide (two Cavazide 150 tablets)

Typically, the most significant effect is seen when transitioning from monotherapy to Cavazide 150-12.5 mg (one tablet). Blood pressure stabilization typically occurs within 2-4 weeks after changing the dose. The standard dosage is one tablet of Cavazide 150 daily, and taking more than two tablets a day is not recommended. Maximum antihypertensive effects are achieved about 2-4 weeks after starting treatment.

Use in Patients with Renal Impairment:
Cavazide therapy can be continued in patients with creatinine clearance greater than 30 mL/min. There is no need for dosage adjustment in patients with hepatic impairment.

Take this medication as per the advice of a registered healthcare professional.

Interactions

Irbesartan:
Irbesartan does not interact significantly with drugs metabolized by cytochrome P450 isoenzymes such as CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, or CYP3A4. It is primarily metabolized by CYP2C9. Clinical studies have shown no significant interactions when Irbesartan is co-administered with warfarin (also metabolized by CYP2C9). Irbesartan does not affect the pharmacokinetics of digoxin, Nifedipine, or Hydrochlorothiazide. However, a reversible increase in lithium levels has been reported in rare cases. If Irbesartan and lithium are used together, serum lithium levels should be carefully monitored.

Hydrochlorothiazide:
Taking alcohol, barbiturates, or narcotics with Hydrochlorothiazide can cause orthostatic hypotension. Dosage adjustments may be needed for diabetic patients using oral antidiabetic agents or insulin. Co-administration with other antihypertensive medications may have an additive effect.

Contraindications
Cavazide is contraindicated for patients who are hypersensitive to Irbesartan, Hydrochlorothiazide, or any of the tablet’s components. It is also contraindicated during pregnancy.

Side Effects

• Gastrointestinal: Anorexia, nausea, vomiting, cramps, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, and salivary gland inflammation.
• Central Nervous System: Dizziness, vertigo, headache, and yellow vision.
• Cardiovascular: Rhythm disturbances, flushing, ECG abnormalities, cardiac murmurs, orthostatic hypotension, bradycardia, hypotension, syncope, conduction disorders, and myocardial infarction.

Pregnancy and Lactation
Cavazide is contraindicated in pregnancy, especially during the second and third trimesters, as it may cause harm or even death to the developing fetus. Thiazides are present in human milk, so breastfeeding should be discontinued if the drug is deemed necessary.

Precautions and Warnings
In patients whose renal function depends on the renin-angiotensin-aldosterone system (e.g., those with renal artery stenosis or severe heart failure), Cavazide can lead to oliguria, progressive azotemia, and rarely acute renal failure or death. Thus, careful monitoring of renal function and potassium levels is advised in such patients. Hyperkalemia may occur, especially in patients with kidney impairment or heart failure. The safety of Irbesartan in heart failure is not fully established, and caution is required when treating such patients.

Therapeutic Class
Combined antihypertensive preparations.

Storage Conditions
Store below 30°C, away from light and moisture. Keep out of reach of children.