1468 Cardiovascular Phenindione may discolour the urine pink orange and OT in severe shock (p. 1279.3) and in the treatment of urinary r ti this is independent of any haematuria. retention (p. 2349.2). P.r.�P.(]. <:J ?n.� ....... ............... ............. .................... Phenoxybenzamine is used as the hydrochloride. It is ProprietaryPreparations (details are given in Volume B) Effects on the gastrointestinal tract. There haw been given orally or by intravenous infusion as a dilute solution. Single·ingredient Prepara�ons. Austral.: Dibenylinet; Austria: cases of paralytic ileus, one fatal, associated wiLh phen­ In phaeochromocytoma it is used to control the Dibenzyran; Ger.: Dibenzyran; Gr.: Dibenyline; Dibenzyran; indione.1·2 hypertension associated with excessive catecholamine Hong Kong: Dibelinet; Dibenyline; India: Biophenox; Feno­ ben; Fenoxene; Israel: Dibenyline; NZ: Dibenyline; S.Afr. : 1. Menon IS. Phenindione and paralytic ileus. Lanat l966; i: 1421- release during the pre-operative period and in patients 2. Nash AG. Phenindione and paralytic ileus. ii: 5�-2. whose tumours are inoperable. A beta blocker may also be Dibenylinet; UK: Dibenyline; USA: Dibenzyline. given to control tachycardia, but not before alpha blockade PharmacopoeialPrepara�ons Precautions has completely suppressed the pressor effects of the BP 2014: Phenoxybenzamine Capsules; USP 36: Phenoxybenzamine Hydrochloride Capsules. As for Warfarin Sodium, p. 1529.2. phaeochromocytoma. The usual initial oral dose of Phenindione is not recommended in prcgnmr:y. phenoxybenzamine hydrochloride is 10 mg once or twice daily, increased gradually, according to the patient's Breast feeding. Phenindione is distributed into response, to a usual dose of 1 to 2 mglkg daily in 2 divided milk, with reported concentrations micro­ doses. It may be given intravenously for operative cover in l I to 5 patients with phaeochromocytoma in a daily dose of grams/mL after a single dose of 50 or 15 rug. A wmnan I mglkg in 200 mL of sodium chloride 0. 9% infused over at given phenindione 50mg each morning ann 50 and 25 mg on alternate nights breast fed her infant son,2 who least 2 hours. A similar intravenous dose in 200 to 500 mL of required a herniotomy at 5 weeks. After surgery he had sodium chloride 0.9% has been given in the n1anagement of an enormous scrotal haematoma with ooLing frmn the severe shock. wound and was found to have extended prothrombin and For urinary retention due to neurogenic bladder an partial thromboplastin times. Last available guidance from oral dose of lOmg twice daily has been given. the American Academy of Pediatrics therefore considered3 that phenindione should be given with GlL�don to breast­ feeding mothers. Adverse Effects and Treatment Gognel M, et a!. Therapeutique antico g du l. a ulante e� alliliu:nwnt:f'1"11de The adverse effects of phenoxybenzamine are mainly due to Uses and Administration de Ia phCnyl-2-dioxo, 1,3 iml.ane dans k ]<lit. matcwel. Rev Fr Obstet 1970; 65: 409-12. its alpha-adrenoceptor blocking activity. They include Phenprocoumon is an oral coumarin anticoagulant with HB, Jack B. Breast-feeding and anticoagui.Jn< orthostatic hypotension and dizziness, reflex tachycardia, 2. tbci·c,py. Lancet actions similar to those of warfarin (p. 1527.2). It is used in 1970; 672-3. i: nasal congestion, and miosis. Inhibition of ejaculation may the management of thromboembolic disorders (p. 1273.2). occur. These effects may be minimised by using a low initial Initial doses are upto 9 mgon the first day followed by 6 mg dose, and may diminish with continued use, but the on the second day. Maintenance doses are usually from 1.5 hypotensive effect can be exaggerated by exercise, heat, a to 6 mg daily, depending on the response. large meal, or alcohol ingestion. Other adverse effects include dry mouth, decreased sweating, drowsiness, fatigue, Adverse-- .. ····- Effects, Treatment, and Precautions Interactions and confusion. Gastrointestinal effects are usually slight. ··-······ When phenoxybenzamine is given intravenously, idiosyn� As for Warfarin Sodium, p. 1528.2. The interactions associated with oral anticoagulants are cratic profound hypotension can occur within a few described in detail under warfarin (p. 1529.3), Specific Effects on the liver. A woman who had twice previously references to interactions involving phenindione can be minutes of starting the infusion. Convulsions have been developed jaundice while taking phenprocoumon devel­ found there under tbe headings for the following drug reported after rapid intravenous infusion of phenoxybenz­ oped jaundice and parenchymal liver damage when, after groups: antibacterials; antifungals; antiplatelets; anxiolytic amine. some years, phenprocoumon was again given. 1 Other sedatives; gastrointestinal drugs; lipid regulating drugs; and Severe hypotension may occur in overdose and treatment includes support of the circulation by postural cases of phenprocoumon -associated liver damage have sex hormones. - measures and parenteral fluid volume replacement. been reported.2 4 Sympathomimetics are considered to be of little value, and I. den Boer W, Loeliger EA. Phenprocoumon-induced jaundice. Lancet Pharmacokinetics adrenaline is contra-indicated since it also stilnulates beta 1976; i: 912. 2. Slagboom G, Loeliger EA. Coumarin-associated hepatitis: report of two Phenindione is completely absorbed from the gastrointest­ receptors causing increased hypotension and tachycardia. cases. Arch lntern Med 1980; 140: 1028-9. inal tract, with peak plasma levels attained after 1 to 3 hours Sources differ as to the value of noradrenaline in 3. Cordes A, et al. Phenprocoumon-induziertes Leberversagen. Dtsch Med and a half-life of 5 to 6 hours. It crosses the placenta 1nd is overcoming alpha-receptor blockade. Wochenschr 2003; 128: 1884-6. 4. Bulang T, et al. Akutes Leberversagen durch Phenprocoumon-drei distributed into breast milk. Metabolites phcnL..1di.one Phenoxybenzamine has been shown to be mutagenic in JI Fallberichte. Z Gastroenterol 2004; 42: 1055-8. excreted in the urine are responsible for any discoloration in vitro tests and carcinogenic in rodents. There have been that may occur. case reports of carcinoma in patients given long-term treatment with phenoxybenzamine for bladder dysfunc­ Interactions t tion; US licensed product information therefore advises The interactions associated with oral anticoagulants are P.r�p(]_r(]_ i?n.�..... against long-term use. discussed in detail under warfarin (p. 1529.3). Specific Proprietary Preparations (details are given in Volume B) references to interactions involving phenprocoumon can be Single-ingredient Preparations. Austral.: Dindevan; Gr, : Solu­ found there under the headings for the following drug thrombine; India: Dindevan; Rus.: Phenylin (<De1mmm) Precautions groups: analgesics; antiarrhythmics; antidepressants; antidiabetics; antigout drugs; antineoplastics; gastrointest­ Pharmacopoeial Preparations Phenoxybenzamine should be given with care to patients inal drugs; ljpid regulating drugs; and sex hormones. BP 2014: Pbenindione Tablets. with heart failure, ischaemic heart disease, cerebrovascular disease, or renal impairment, and should be avoided if a fall in blood pressure would be dangerous. Phenoxybenzamine Pharmacokinetics Phenoxybenzamine may aggravate the symptoms of respiratory infections. Phenprocoumon is readily absorbed from the gastrointest­ Hydrochloride !BANM. rtNNM! When given intravenously, phenoxybenzamine hydro­ inal tract and is extensively bound to plasma proteins. chloride should always be diluted and given by infusion. Metabolism is mediated partly by tbe cytochrome P450 Fenbksybenzaminy Chlorowodorek; l'enoHb�nz<1C'J'na, Intravenous fluids must always be given beforehand to isoenzyme CYP2C9, which shows genetic polymorphism. hidrodoruro de; Hidrocloruro de fenoxibenzarnina;. t'hen" ensure an adequate circulating blood volume and to prevent The half-life is around 6 days. It is excreted in the urine and oxybenzamitHo, Chlorhydrate . de;. Phenoxyb�nzilrnioi·Hydro: a precipitous fall in blood pressure. Care should be taken to faeces as conjugated hydroxy metabolites and parent . _ c!)loridum; SKF-68SA; CIJeHoKcl<16eK3iiM vt!ia I�t.IPOXJ10fJ>1J:l, avoid extravasation. Contamination of the skin should also compound. Phenprocoumon is given as a racemic mixture; !3enzyl(2:d1ioroethyi)(l"rnethyh2. -phenoxyethyllamine be avoided since contact sensitisation may occur. the S-isomer is more potent. The stereo-isomers have hyqrochlorlde; different pharmacokinetics. C,<H,2CINCJ,HCI�3403 References. _ Interactions I. Husted S, Andreasen F. Individual variation in the response to C45 � 59-·96- 1 (phieno.xyb;mz<Jmi,rye); phenprocoumon. Bur J Clin Pharmacol 1977; 11: 351-8. Since phenoxybenzamine only blocks alpha receptors, 2. Toon S, et a!. Metabolic fate of phenprocoumon in humans. J PharmSd leaving the beta receptors unopposed, use with drugs such 1985; 74: 1037-40. as adrenaline that also stimulate beta receptors may 3. Ufer M. Comparative pharmacokinetics of vitamin K antagonists: warfarin. phenprocoumon and acenocoumarol. Clin Pharmacokinet2005; enhance the cardiac-accelerating and hypotensive action of 44: 1227-46. phenoxybenzamine. 4. Werner D, et al. Pharmacogenetic characteristics of patients with 65: complicated phenprocoumon dosing. Bur 1 Clin Pharmacal 2009; BP 2014: (Phenoxybenzamine Hydrochloride). 783-8. almost white, odourless or almost odourlcss, crystalline Pharmacokinetics powder. Sparingly soluble in water; freely