Advant tabl. #28
Manufacturer: Getz Pharma, Pakistan
Composition: candesartan 8.0 mg
How is candesartan cilexetil absorbed and metabolized?
Candesartan cilexetil is a prodrug that is rapidly and completely bioactivated by ester hydrolysis during absorption from the gastrointestinal tract to candesartan. It is converted to its active form, candesartan, during absorption and undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite.
What is the bioavailability of candesartan?
The absolute bioavailability of candesartan after administration of candesartan cilexetil is estimated to be 15%.
How does food affect the bioavailability of candesartan?
Food with a high-fat content does not affect the bioavailability of candesartan after candesartan cilexetil administration.
What is the peak serum concentration (Cmax) of candesartan after tablet ingestion?
The peak serum concentration (Cmax) is reached after 3 to 4 hours following tablet ingestion.
How is candesartan distributed in the body?
Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells. Its volume of distribution is 0.13 L/kg.
How long is the elimination half-life of candesartan?
The elimination half-life of candesartan is approximately 9 hours.
How is candesartan excreted from the body?
Approximately 26% of the dose is excreted unchanged in the urine. The total plasma clearance of candesartan is 0.37 mL/min/kg, with a renal clearance of 0.19 mL/min/kg.
How does the pharmacokinetics of candesartan differ in the elderly?
Plasma concentrations of candesartan are higher in the elderly (Cmax is approximately 50% higher, and AUC is approximately 80% higher) compared to younger subjects administered with the same dose. However, the pharmacokinetics of candesartan are linear in the elderly, and candesartan and its inactive metabolite do not accumulate in the serum of these subjects upon repeated, once-daily administration.
How does the pharmacokinetics of candesartan differ in patients with renal insufficiency?
Serum concentrations of candesartan are elevated in hypertensive patients with renal insufficiency. After repeated dosing, the AUC and Cmax are approximately doubled in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73 m2) compared to patients with normal kidney function. The pharmacokinetics of candesartan in hypertensive patients undergoing hemodialysis are similar to those in hypertensive patients with severe renal impairment.
How does the pharmacokinetics of candesartan differ in patients with hepatic insufficiency?
The increase in AUC for candesartan was 30% in patients with mild hepatic impairment (Child-Pugh A) and 145% in patients with moderate hepatic impairment (Child-Pugh B). The increase in Cmax for candesartan was 56% in patients with mild hepatic impairment and 73% in patients with moderate hepatic impairment. The pharmacokinetics after candesartan cilexetil administration have not been investigated in patients with severe hepatic impairment.
What drug interactions should be considered when administering Advant (Candesartan Cilexetil)?
Since both ACE inhibitors and angiotensin receptor blockers (ARBs) can increase potassium levels in the blood, caution should be exercised when using candesartan with other medications that can increase potassium levels, such as spironolactone and potassium supplements. Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors and some angiotensin II receptor antagonists. An increase in serum lithium concentration has been reported during concomitant administration of lithium with candesartan cilexetil, so careful monitoring of serum lithium levels is recommended during concomitant use.
What are the most common adverse reactions associated with Advant (Candesartan Cilexetil)?
The adverse effects reported with candesartan are usually mild and transient, including headache and dizziness.
What are the potentially important adverse events reported with Advant (Candesartan Cilexetil)?
Potentially important adverse events that have been reported, whether or not attributed to treatment, with an incidence of 0.5% cannot be determined whether these events were causally related to candesartan cilexetil. These include: asthenia, fever, paresthesia, vertigo, dyspepsia, gastroenteritis, tachycardia, palpitation, increased creatinine phosphokinase, hyperglycemia, hypertriglyceridemia, hyperuricemia, myalgia, epistaxis, anxiety, depression, somnolence, dyspnea, rash, increased sweating, hematuria.
What are the rare adverse events reported with Advant (Candesartan Cilexetil)?
Rare adverse events include: abnormal hepatic function, hepatitis, neutropenia, leukopenia, agranulocytosis, hyperkalemia, hyponatremia, renal impairment, renal failure, pruritis, and urticaria.
What are the risks associated with using Advant (Candesartan Cilexetil) during pregnancy?
When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, candesartan cilexetil should be discontinued as soon as possible.
Is it safe to use Advant (Candesartan Cilexetil) while breastfeeding?
It is not known whether candesartan is excreted in human milk, but 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.
What are the symptoms of Advant (Candesartan Cilexetil) overdosage?
The most likely manifestation of overdosage with candesartan cilexetil would be hypotension, dizziness, and tachycardia. Bradycardia could occur from parasympathetic (vagal) stimulation.
How should Advant (Candesartan Cilexetil) overdosage be treated?
If symptomatic hypotension should occur, supportive treatment should be instituted. Candesartan cannot be removed by hemodialysis.