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Profile Profile Profile Profile Uses and Administration Adverse Effects And 1330 Cardiovascular 2. Shawkett S, et a!. Prolonged effect of CGRP in Raynaud's patients: a I up to 6 years: initially 200 micrograms/kg daily, • double-blind randomised comparison with prostacyclin. Br J Clin adjusted according to response to 50 to 400 micro­ Pharmacol i99I; 32: 209-13. 3. Shekhar YC, et a!. Effects of prolonged infusion of human alpha grams/kg daily calcitonin gene-related peptide on haemodynamics, renal blood flow 6 up to 17 years and weighing less than 50 kg: initially 4 • Profile and hormone levels in congestive heart failure. Am J Cardiol i99I; 67: to 8 mg daily, adjusted according to response to 2 to 732-6. 16mg daily Butizide is a thiazide diuretic with properties similar to those 4. European CGRP in Subarachnoid Haemorrhage Study Group. Effect of 6 up to 17 years and weighing more than 50 kg: initially 8 of hydrochlorothiazide (p. 1403.2). It is used for oedema, calcitonin-gene-related peptide in patients with delayed postoperative • including that associated with heart failure (p. 1262.3), and cerebral ischaemia after aneurysmal subarachnoid haemorrhage. Lancet to 16 mg daily, adjusted according to response to 4 to 1992; 339: 831-4. lor hypertension (p. 1251.1). 32 mg daily 5. Bunker CB, et al. Calcitonin gene-related peptide in treatment of severe Butizide is given orally, usually with spironolactone; the peripheral vascular insufficiency in Raynaud's phenomenon. Lancet usual maintenance dose for oedema or hypertens:cn is 5 to 1993; 342: 80-2. Administration in hepatic impairment. The elimination of 10 mg daily. It has also been given with other aatihyper­ 6. Feuerstein G, et al. Clinical candesartan cilexetil is reduced in patients with hepatic peptide pharmacology. Can tensive drugs. impairment. For patients with hypertension, an initial oral 7. Gherardini G, et al. Venous ulcers: improved healing by iontophoretic dose of 4mg once daily is recommended in the UK in administration of calcitonin gene-related peptide and vasoactive those with mild or moderate impairment. In the USA, no Preparations intestinal peptide. Plast Reconstr Surg 1998; 101: 90-3. ............ .......... .... M3rquez-Rodas I, Pathophysiology and therapeutic possibilities of adjustment is considered necessary for patients with mild . 8. et a/. Proprietary Preparations (details are given in Volume B) calcitonin gene-related peptide in hypertension. J Physiol Biochem 2006; impairment; an initial oral dose of 8 mg once daily is 62: 45-'56. recommended for those with moderate impairment. Multi-ingredient Preparations. Austria: Aldactone Saltudn; 9. Recober A, Russo AF. Calcitonin gene-related peptide: an update on the For patients with heart fa ilure, no dose adjustments are Indon.: Aldazide; Ita!. : Kadiur; Mex. : Aldazida; Philipp.: Alda­ biology. Curr Opin Neurol 2009; 22: 241-6. zide; S.Afr. : Aldazide; Switz.: Aldozonet. considered necessary in those with mild to moderate impairment as initial doses are lower for this condition (see Candesartan Cilexetil Uses and Administration, above). Cadralazine (BAN, r/NNJ There is no experience of use in patients with severe hepatic impairment. Administration in renal impairment. The elimination of candesartan cilexetil is reduced in patients with renal impairment (including patients on haemodialysis1) and lower doses may therefore be required. For patients with hypertension, an initial oral dose of 4 mg once daily is recommended in the UK, including for patients on haemodialysis. In the USA, no initial dose adjustment is recommended for renal impairment, although dose reduction may be considered if patients are volume depleted. cadralazine. For patients with heart fa ilure, dose adjustments are not necessary as initial doses are lower for this condition (see Profile Uses and Administration, above). Candesartan may also have adverse effects on renal Cadralazine is a vasodilator with actions and uses similar to Ph. Eur.8: (Candesartan Cilexetil). A white or ahnost white function and regular monitoring is advised; treatment may those of hydralazine (p. 1401.2). It used has been in the powder. It exhibits polymorphism. Practically insoluble in need to be withheld or stopped if renal function management of hypertension. water; slightly soluble in dehydrated alcohol; freely soluble deteriorates. Reviews. in dichloromethane. 1. Ottosson P, et al. Candesartan cilexetil in haemodialysis patients. Clin l. McTavish D, et at. Cadralazinc: a review of its pharmacodynamic and Drug Invest 2003; 23: 545-50. pharmacokinetic properties, and therapeutic potential in the treatment USP 36: (Candesartan Cilexetil). A white to off-white of hypertension. Drugs 1990; 40: 543-60. powder. Practically insoluble in water; sparingly soluble in For mention of the potential use methyl alcohol. Store in airtight containers at a temperature Diabetic complications. of angiotensin II receptor antagonists, including candesar­ between 20 degrees and 25 degrees, excursions permitted tan, in the management oi diabetic complications such as between 15 degrees and 30 degrees. retinopathy see under Losartan, p. 1423.1. Uses and Administration Migraine. For reference to the use of angiotensin II recep­ Candesartan is an angiotensin II receptor antagonist with tor antagonists, including candesartan, in the prophylaxis actions similar to those of losartan (p. 1422.2). It is used in of migraine, see under Losartan, p. 1423.3. the management of hypertension (p. 1251.1) and may also be used in heart failure in patients with impaired left Adverse Effects and Precautions ventricular systolic function, either when ACE inhibitors As for Losartan Potassium, p. 1424.1. are not tolerated, or in addition to ACE inhibitors, (see under Losartan Potassium, p. 1423.2). Porphyria. The Drug Database for Acute Porphyria, com­ Candesartan is given orally as the ester prodrug piled by the Norwegian Porphyria Centre (NAPOS) and candesartan cilexetil. Onset of antihypertensive action the Porphyria Centre Sweden, classifies candesartan as not occurs about 2 hours after a dose and the maximum effect is porphyrinogenic; it may be used as a drug of first choice achieved within about 4 weeks of starting therapy. and no precautions are needed. 1 Profile In the management of hypertension the usual initial dose of candesartan cilexetil is 8 mg once daily in the UK, or 1. The Drug Database for Acute Porphyria. Available at: http://www. drugs-porphyria.org (accessed 13/10/ll) Cafedrine hydrochloride is a derivative of theophylline 16 mg once daily in the USA. The dose should be adjusted (p. 1229.3), used mainly in preparations with theodrenaline according to response; the usual maintenance dose is 8 mg Interactions hydrochloride in the treatment of hypotensive states. once daily, but doses up to 32 mg daily, as a single dose or in 2 divided doses, may be used. Lower initial doses should be As for Losartan Potassium, p. 1424.3. P.r.�P.?.r?li()_n.S.. considered in patients with intravascular volume depletion; Proprietary Preparations (details are given in Volume B) in the UK an initial dose of 4 mg once daily is suggested. Pharmacokinetics Patients with renal or hepatic impairment n1ay also require Multi-ingredient Prepara�ons. Austria: Akrinort: Fr.: low initial doses (see below). For doses in children, see Candesartan cilexetil is an ester prodrug that is hydrolysed Ger.: Akrinor; Indon.: Akrinor; S.Afr. : Akrlnor. Administration in Children, below. to the active form candesartan during absorption from the In heart failure, candesartan cilexetil is given in an gastrointestinal tract. The absolute bioavailability for initial dose of 4 mg once daily. The dose should be doubled candesartan is about 40% when candesartan cilexetil is Calcitonin Gene-related Peptide at intervals of not less than two weeks up to 32 mg once given as a solution and about 14% when given as tablets. daily if tolerated; blood pressure should be monitored Peak plasma concentrations of candesartan occur about 3 to during dose increases. 4 hours after oral doses as tablets. Candesartan is more than 99% bound to plasma proteins. It is excreted in urine and Reviews. bile mainly as unchanged drug with a small amount as blocker. inactive metabolites. The terminal elimination half-life is 2. Easthope SE, Jarvis Candesartan cilexetil: an update of its use in about 9 hours. Candesartan is not removed by haemodia­ Profile 62: essential hypertension. Drugs 2002; 1253-87. lysis. Calcitonin gene-related peptide is an endogenous peptide 3. Fenton C, Scott U. Candcsartan cilexetil: a review of its use in the management of chronic heart failure. Drugs 2005; 65: 537-58. Reviews. derived £rmn the calcitonin gene. It has vasodilating activity 4. McKelvie RS. Candesartan for the of heart failure: more I. Gleiter CH, Mi:irikeKE. Clinical pharmacokinetics of candesartan. Clin and has been investigated in the management of peripheral than an alternative. Expert 7: 194'5-56. Pharmacokinet 2002; 41: 7-17. vascular disease (Raynaud's syndrome), heart failure, and 5. Meredith PA. Candesanan review of elfects on cardiovas- for ischaemia following neurosurgery for subarachnoid <."ular complications in hypertension and chronic heart failure. Cun Med Res Opin 2007; 23: 1693-1705. haemorrhage. The endogenous substance may be involved 6. Mendis B, Page SR. Candcsartan: Proprietary Preparations (details are given in Volume B) in the pathophysiology of headache and migraine, and angiotensin II receptor blocker? Expert Opin antagonists are under investigation in the 1nanagement of 1995-2007. Single-ingredient Preparations. Arg.: Atacand; Dacten; Tiadyl; these conditions. Austral.: Atacand; Austria: Atacand; Blopress; Belg.: Atacand; Administration in children. Candesartan cilexetil is used Braz.: Atacand; Blopress; Canad.: Atacand; Chile: Atacand; References. for the treatment of hypertension in children from 1 year (�1Z, JfX); Johnston FG, et a!. Effect of calcitonin-gene-related peptide on Bilaten; Blopress; Blox; Candex; China: Ao Bi Xin L (&,ii'>Wi); om"ooem,tivc neurological deficits aher subarachnoid haemorrhage. of age. It is given in the following oral doses, either as a Blopress Eo Li Gao (j;!l;/Jill'J); Da Mai (it:ia); Di Zhi 335: 869-72.
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