Candesartan Cilexetil 8 mg Tablets

Indications

• Hypertension
• Heart failure
• Left ventricular dysfunction post-myocardial infarction

Dosage

Children: For children aged 1 to 17 years, the dose is based on body weight. The recommended starting dose is 0.05 to 0.1 mg/kg once daily, with a maximum dose of 0.4 mg/kg or 32 mg, whichever is lower.

Adults: The typical adult starting dose for hypertension is 8 mg once daily, which may be increased to a maximum of 32 mg once daily based on blood pressure response.

Mechanism of action

Candesartan selectively antagonizes the type I angiotensin II receptor (AT1), preventing angiotensin II from exerting its vasoconstrictive and aldosterone-secreting effects. This inhibition allows for vasodilation and decreased aldosterone release, promoting sodium excretion and lowering blood pressure. Candesartan does not affect the degradation of bradykinin, thus minimizing the common side effects associated with ACE inhibitors, such as cough and angioedema.

Pharmacodynamics

Candesartan effectively reduces systemic vascular resistance and lowers blood pressure, which can lead to a decrease in myocardial oxygen demand. Its long duration of action allows for once-daily dosing, and it has shown efficacy in both monotherapy and in combination with other antihypertensive agents. It also demonstrates cardioprotective effects, making it beneficial in the management of heart failure.

Pharmacokinetics

Candesartan is well-absorbed following oral administration, with peak plasma concentrations occurring approximately 1 to 3 hours after dosing. It has a bioavailability of around 15% due to extensive first-pass metabolism. Candesartan is primarily excreted via the kidneys, with a half-life of about 9 hours. The presence of food does not significantly affect its absorption.

Contra-indications

• Hypersensitivity to candesartan or any of its excipients
• Severe hepatic impairment
• Pregnancy

Adverse effects

• Dizziness
• Fatigue
• Hypotension
• Hyperkalemia
• Renal impairment
• Angioedema

Interactions

• Other antihypertensive agents may increase the hypotensive effect
• Potassium-sparing diuretics or potassium supplements may increase the risk of hyperkalemia
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect and increase the risk of renal impairment

Precautions

• Caution in patients with renal artery stenosis
• Monitor renal function, especially in patients with pre-existing renal impairment
• Caution in patients with aortic stenosis or hypertrophic cardiomyopathy
• Use with caution in patients with a history of angioedema

Pregnancy

Candesartan is contraindicated in pregnancy due to potential harm to the fetus, particularly in the second and third trimesters.

Breast-feeding

Candesartan is excreted in breast milk, and caution should be exercised when administering to breastfeeding women.

Storage

Store below 25°C in a dry place, protect from light.

Formulations

• Tablets: 4 mg, 8 mg, 16 mg, 32 mg

Indications

• Schizophrenia
• Psychotic disorders
• Mood disorders

Dosage

Children: Refer to specific clinical guidelines or product information for paediatric dosing, as it is essential to tailor treatment based on age, weight, and clinical status.

Adults: Refer to specific clinical guidelines or product information for adult dosing as it may vary based on the clinical condition and individual patient factors.

Mechanism of action

Cilexitil functions primarily as a selective antagonist at the dopamine D2 receptors in the brain. By binding to these receptors, it inhibits the action of dopamine, a key neurotransmitter involved in mood regulation and psychotic disorders. This mechanism is thought to help alleviate symptoms of schizophrenia, such as hallucinations and delusions, by rebalancing dopaminergic neurotransmission.

Pharmacodynamics

As a dopamine D2 receptor antagonist, cilexitil exhibits dose-dependent effects on neurotransmission and neuronal signaling pathways. This modulation of dopaminergic pathways contributes to its antipsychotic properties, which may also involve interactions with serotonin receptors, particularly 5-HT2A, thereby enhancing its therapeutic efficacy and reducing side effects commonly associated with traditional antipsychotics, such as extrapyramidal symptoms.

Pharmacokinetics

Cilexitil is absorbed following oral administration, with peak plasma concentrations typically reached within a few hours. The drug is extensively metabolized in the liver, with its metabolites being primarily excreted via the kidneys. The half-life of cilexitil is variable, influenced by individual patient factors such as age, liver function, and concurrent medications. Dosing adjustments may be necessary in populations with altered pharmacokinetics.

Pregnancy

Cilexitil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There is limited data on its safety in pregnancy.

Breast-feeding

Cilexitil is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Mechanism of action

Although these agents /angiotensin II receptor antagonists/ are similar to ACE inhibitors in that they decrease the effects of angiotensin II, rather than decreasing the formation of angiotensin II, drugs antagonize angiotensin II at the type I angiotensin receptor. This allows the drugs to inhibit the vasoconstrictive and aldosterone promoting effects of angiotensin II without interfering with bradykinin degradation, significantly reducing the adverse effects of cough and angioedema seen with ACE inhibitor therapy. ... /Angiotensin II receptor antagonists/ Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathways for angiotensin II synthesis. There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity (>10,000-fold) for the ATI receptor than for the AT2 receptor. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of candesartan on blood pressure.