Drug Interaction:
Angiotensin II Receptor Antagonists-
Candesartan, Eposartan, Irbestan, Losartan metabolite, Olmesatran, Telmistran, Valsartan
Prior treatment with diuretics increases risk of excessive hypotension, use a lower initial dose.
Potassium, potassium-sparing diuretics, cyclosporin may increase risk of hyperkalaemia, monitor potassium.
NSAIDs (including COX-2 inhibitors) may reduce antihypertensive response risk of hyperkalaemia or acute renal failure.
Excretion of lithium may be reduced; monitor lithium concentration
Indication:
Hypertension
Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Candesartin Antihypertensive 31-08-2000
FIXED DOSE COMBINATIONS APPROVED BY DCG(I)
FROM JANUARY 1961 TILL NOVEMBER 2014
Name of Drug Indication Date of Approval
1.Candesartan Cilexetil 16mg+ 13-01-2002
Hydrochlorthiazide 12.5mg tablet
Essential hypertension (not for initial therapy)
Angiotensin II Receptor Antagonists-
Candesartan, Eprosartan, Irbestan, Losartan metabolite, Olmesatran, Telmistran, Valsartan
Adverse Reaction:
Angiotensin II Receptor Antagonists-
Candesartan, Eprosartan, Irbestan, Losartan metabolite, Olmesatran, Telmistran, Valsartan
Adverse Reactions-
CANDESARTAN-
CNS-
Dizziness 4% , Headache,Fatigue, Anxiety/nervousness Depression < 1%
GI -
Diarrhea > 1% Dyspepsia/heartburn > 0.5%, Nausea/vomting >1% Adominal pain >1%
Musculoskeletal-
Arthalgia >1% Pain 3% Myalgia >0.5%
Respiratory -
Upper Res tract infn 6 % Cough >1 % Sinusitis >1% Pharyngitis 2%, Bronchitis >1%
Miscellaneous -
Chest pain >1% Rash > 0.5%Tacycardia > 0.5% Peripheral edema >1%
Albuminurea > 1% Hypertriglyceridemia > 0.5%
Creatinine phosphokinase increase > 0.5% .Hypperglycemia > 0.5%
Hematuria > 0.5%
Contra-Indications:
Hypersensitivity reactions. Patients with a history of angioedema, including angioedema following use of ACE inhibitors.
Special precautions:
Patients with sodium depletion and aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy as severe hypotension may occur.
Patients with renal artery stenosis, there is a risk of impaired renal function and precipitation of acute renal failure.
Patients with primary hyperaldosteronism may poorly respond to anyihypertensive effect of the drug.
Women of reproductive potential, avoid use of this drug in women who are likely to become pregnant
Dosages/ Overdosage Etc:
Date of approval August 2000
Indication-
Hypertension
Dosage
Blood pressure response is dose related over a range of 2 to 32mg once daily
Most of the anti-hypertensive effect is present within 2 weeks amd maximal blood pressure reduction obtained wihin 4 to 6 weeks of treatment with candesartan
Patient Information:
1.Women of reproductive potential, avoid use of this drug in women who are likely to become pregnant
2.Food does not affect the bioavailability of candesartan
Pharmacology/ Pharmacokinetics:
Angiotensin II Receptor Antagonists-
Candesartan, Eprosartan, Irbestan, Losartan metabolite, Olmestaran, Telmistran, Valsartan
Ref- Drug Facts and Comparison (2010)
Pharmacology:
Candesartan blocks the binding of angiotension II to type I angiotension (AT) receptors and
therefore blocks the effects of angiotensin more selectively than do the ACE inhibitors, reduces angiosin-induced vassoconstriction, sodium readsorption and aldosterone release.
Pharmacokinetics:
After oral administration, candesartan cilexetil is rapidly and completely metabolised to the active compound candesartin during absorption from gastro-intestinal tract. Peak plasma concentration reaches at approx 3 to 5 hours. Food does not affect the bioavailability. Within 72 hours about 90% of the dose is excreted. The terminal half-life ranged from approx 9 to 13 hours.
Angiotensin II Receptor Antagonists Pharmacoknetics
Parameters Candesartran Eprosartan Irbesartan Losartan
metabolite
Bioavailability 15% ~13% 60% to 80% ~ 33%
Food effect no effect <25% no effect 10% 14%
AUC /Cmax)
Plasma bound >99% ~ 98% 90% 98.7% (99.8%)
Tmax 3 to 4h 1to 2 1.5 to 2h 1h(3 to 4h)
Volume 0.13L/kg 308L 53to 93L ~34L(~12L)
distribution
Converted to minor minor <20% ~14%
metabolite
Metabolism O-demeth glucoron CYP2C9 CYP2C9/
lation idation CYP3A4
Terminal ~9hr 5 to 9h 11 to 15h ~2h(6 to 9h)
half-life
Total Plasma 0.37mL/ ~130mL/min 157 to ~600mL/min
clearance min/kg 176mL/min (~50mL/min)
Renal 0.19mL/ ~30 to 40 3 to 3.5 ~75mL/min
clearance min/kg mL/min mL/min (~25mL/min)
Recovered ~33% ~7% ~20% ~45/~35%
in urine (IV/oral)
Recovered ~67% ~90% ~80% ~50~60%
in feces (IV/oral)
Olmesartan Telmisartan Valsartan
Bioavailability ~26% 42% /58% ~25%
(40mg/160mg)
Food effect no effect 6%/20% 40%/50%
(AUC/Cmax) (40mgAUC/
160mg AUC)
Plasma 99% >99.5% 95%
bound
Tmax 1 to 2 0.5 to 1h 2 to 4h
Volume of ~17L ~500L 17L
distribution
Convereted none ~11% ~20%
to metabolite
Metabolism none conjugation unknown
Terminal ~13hr ~24hr ~6hr
half life
Total plasma 1.3L/h >800mL/min ~2L/h
clearance
Renal 0.6L/h nd 0.62L/h
clearance
Recovered 35% to 50% 0.91%/ ~13%
in urine 0.49%(IV/oral)
Recovered 50% to65% >97% ~83%
in feces
Interaction with Food:
Food does not affect the bioavailability of candesartan
Pregnancy and lactation:
Insufficient information available on pregnancy and lactation.
Women of reproductive potential, avoid use of this drug in women who are likely to become pregnant
Manufacturer Details