1878 Gastrointestinal
Effects on the skin. Reports of skin reactions associated sion of myopia. In a study3 involving 3 53 children with with phenolphthalein include fixed drug eruptions, I,, myopia, pirenzepine 2% gel given once or twice daily into erythema multiforrne reactions, u and toxic epidermal the lower eyelid for l year was associated with reduced necrolysis.4•5 progression: at 12 months myopia had progressed by a mean of 0,7 and 0.47 dioptres in children assigned to once l. Baer RL, Harris H. Types of cutaneous reactions to drugs. JAMA 1967; 202: 710-13. and twice daily dosage respectively, compared with 2. Savin JA. Current causes of fixed drug eruptions. BrJ Dermatol l970; 83: 0.84 dioptres in those given placebo. The gel was generally 546-9. well tolerated, the most frequent adverse effects being 3. Shelley WB, et al. Demonstration of intercellular immunofluorescence and epidermal hysteresis in bullous fixed drug eruption _due to Profile development of papillae or follicles, or abnormalities of phenolphthalein. Br l Dermato! I972; 86: llB-2 5. accommodation such as mydriasis or cycloplegia, Of 55 Piperidolate hydrochloride is a tertiary amine antimusca 4. Kar PK, et al. Toxic epidermal necrolysis in a patient induced by patients who failed to complete the study, 31 did so as a phenolphthalein. J Indian Med Assoc 1986; 189-93. rinic with effects similar to those of atropine (p, 1312,!), It 84: result of adverse effects, 5. Artymowicz RJ, et al. Phenolphthalein-induced toxic epidermal has been given in the symptomatic treatment of smooth necrolysis. Ann Pharmacother 1997; 31: 1157-9. muscle spasm associated with gastrointestinal disorders. 1. Bartlett JD, et a!. A tolerability study of pirenzepine ophthalmic gel in myopic children. J Ocul Phannacol Ther 2003; 19: 271-9. Overdosage. The most likely consequence of phenolph 2. Siatkowski RM, et al. US Pirenzepine Study Group. Safety and efficacy of i 2% pirenzepine ophthalmic gel in children with myopia: a 1-year. ....Prepa...... rat..ons...... thalein overdosage is excessive purgation, which may ...... multicenter, double-masked, placebo-controlled parallel study. Arch require fluid and electrolyte replacement. However, a pos ProprietaryPreparations (details are given in Volume B) Ophthalmol1004; 122: 1667-74. 3. Tan DTH, et al. Asian Pirenzepine Study Group. One-year multicenter, sible association with acute pancreatitis occurred in a 34- Single-ingredient Preparations. Jpn: Dactiran; Mex. : Dactil OB, year-old man who inadvertently ingested phenolphthalein double-masked, placebo-controlled, parallel safety and efficacy study of Braz.: Dactil OB, 2% pirenzepine ophthalmic gel in children with myopia. Ophthalmology 2 g, There was complete recovery with no sequelae from Multi-ingredientPreparations. 2005; 112: 84--91. the pancreatitis.1 Widespread organ failure with dissemi 4. Siatkowsk.i et al. U.S. Pirenzepine Study Group. Two-year RM, nated intravascular coagulation, massive liver damage, multicenter, randomized, double-masked, placebo-controlled, parallel pulmonary oedema, renal failure, and myocardial damage Pipethanate Ethobromide (r!NNM) safety and efficacy study of 20/r, pirenzepine ophthalmic gel in children with myopia. J AAPOS 2008; 12: 332-9. in a second patient2 were attributed to self-poisoning with Ethy!p)petfianJte Btoh1ide; Etobr:OmurQ . Oe plj:ietan�t(): an unknown quantity of phenolphthalein-containing . Pfperil.ate i; hol? romid�; Pi"pe anato, etobromuro de; laxative, although the diagnosis was problematic The � ( Plp�t apate, . tho rprnu re. djii; !'ipeth.iln�tl .Et ()brom.\QU[J;(:· Adverse Effects and Precautions patient died despite intensive support. � s t:; .. � . f:lJ.ine a Sl}(}6P()M>IJ,l . . .· · · · . .. · J�I-\ Til . < ·. · ·· . . Antirnuscarinic adverse effects such as dry mouth and l. Lambrianides AL, Rosin RD. Acute pancreatitis complicating excessive . ••.•. ·· • ...... •. ·· .. . •.•. ; ; <. .• intake of phenolphthalein. Postgrad Med J 1984; 60: 491-2. i·-(2-B�0�11ilW>wethxth1 ,�tn$'lpl�erictirrit-:rn• bf9m.id�. blurred vision have been reported but are less common with . . Sidhu PS, Fatal phenolphthalein poisoning with fulminant hepatic . . 2. et al. CnH.;o�rl'\iQ3�A .. • ·. . < .. •. .. , ••.... . · · pirenzepine than with atropine (see p, !312,1), Pirenzepine . . ·· · . failure and disseminated intravascular coagulation. Hum Toxicol l9B9; 8: (J\S · 4:546-39:8· lpipethanate); 23 1.8246f9 (DiJOetlianr1te· should be used with caution in patients with renal 381-4. -'-' ethq/jronlltfe) impairment, particularly those with end-stage renal failure, Pharmacokinetics Profile Effects on the blood. Thrombocytopenia in one patient Up to 15% of phenolphthalein given orally is subsequently and agranulocytosis in another was probably associated Pipethanate ethobromide is an antirnuscarinic with actions excreted in the urine. Enterohepatic circulation occurs and with the use of pirenzepine.1 similar to those of atropine (p, !312,1), It has been used in the glucuronide is excreted in the bile. Elimination may take I. Stricker BHC, et a!. Blood disorders associated with pirenzepine. BM.J the symptomatic treatment of visceral spasms in oral doses several days. 1986; 293: l074. of up to 160 mg daily in divided doses, Pipethanate ethobromide has been given intramuscularly or intrave nously in doses of l 0 to 20 mg daily; it has also been given Interactions Proprietary Preparations(details are given in Volume B) rectally. As for antimuscarinics in general (see Atropine Sulfate, Single-ingredient Preparations, Arg, : Fructines: India: Jaglax; p, !312,3). Israel: Easylax; S.Afr. : Brooklaxt; Dr Mackenzies Veinoidst; P epara ions ...r...... t ...... Laxadort; Laxenet; SB Strong-Laxt; Super-Tabst; Surget; ProprietaryPreparations (details are given in Volume B) Thai. : Phenolax; Regulimt; Turk. : Alin; Laksafenol. Pharmacokinetics Single�ingredient Preparations. Chile: Nospasmin; Ital. : Spasmo Multi-ingredient Preparations. Arg.: Cascara Sagrada Bouzen; dil; Venez. : Flespan. Pirenzepine is absorbed from the gastrointestinal tract but Cascara Sagrada Puler; Genolaxante; Veracolatet; Austral.: the bioavailability is reported to be only about 20 to 30%, Ford Pillst; Austria: Waldheim Abfuhrdragees fortet; Chile: Multi-ingredient Preparations. Chile: Nospasmin Compuesto. and is decreased to about l 0 to 20% when taken with food, Agarolt; Bulgarolaxt; Fenokomp 39; Oblax A-1-1; India: Very little pirenzepine is metabolised, About 10% of an oral Coslax; Jetomisol-P; Indon.: Laxadine; Israel: Laxative Com dose is excreted unchanged in the urine, the remainder pound; Port.: Doce Alivio; S.Afr. : Brooklax Pillst; SB 3 Triple Piren:zepine Hydrochloride being excreted in the faeces. Action Pillst; Singapore: Beagarol; Spain: Laxante Bescansa (BANM, USAN, r!NNM) Aloicot; Switz. : Paragar; Thai.: Anson; Emulax; Heroanson; Pirenzepine has an elimination half-life of about 12 hours and is about 12% bound to plasma proteins. Diffusion Patarcolate; Taeniacide; Veracolatet; Zenda; Turk. : Fenolaks; Hidrodoruio dfi orienzepina;. LS-sr� .( pir��zepine); l.%19· Karboseptin; Musilaks; UK: Fam-Lax; USA: Agoral. Cl2; ··Rirentsepiinidit\ydro�ioridimpnoi'JYdraa.tti; .Pirenzepinil< across the blood-brain barrier is poor and only minimal amounts are present in breast milk. hidrodoro.rode; Pirenz:epi(H1ihidro�lorld1'!1Qnohidrat; PJ ren� ze in"Cliliy(jroch!orld rno0ohydtat;· Plrenzepindlhy!Jroklorld• p . Pipen:zolate Bromide (BAN, riNNI Pirertzepine, de; Pirenzepine Renol impairment. The renal clearance and total plasma �onOh')fdti!t; Chlorhydrat� .••. Brorh;�lo de (:)lpenzolatD;· !'lpeflzolat BrornUr; f'i�nzolau( \Clichlo!hy�rate de) monohydrate; )'trenzel:\lni <::lipYdror;:hlor. clearance of pirenzepine may be significantly reduced in . patients with renal impairment, 1.2 with clearance decreas Br rnure. de; •• Pipe zol�te Methyloromide; Pipen�ol.ati i�U,I'n f:(\Onohy�rlc\JfD; Pirenzeptni Hyd or::l'iloridum; ·Pir�nz � . � .. . � ':' ing proportionately with the degree of renal impairment. 8romidurn; Plpenzo!a!o, bf.OJ'flurode; nV!n H30flil.Tq 6poMfM. pint:. <;li hidr chlort�as m:o �ohidratas� flVtpe�?etH4lolq � � . The half-life of pirenzepine is increased with reported . · . . . 3-!lenzi!oylo ·l·ethyl-1-methylpiperidinium. bromide: f,V�J,lpo�Jiop0,[1. ,: • < • >. , . ·. , •.. . < • •.. • · • � . . · . values ranging from 14 to 20 hours.1-3 Plasma concentra C22H,,BrN�= 5 1.1 :Dil;\)! ro-,1 1 �(4cmetf1ylpiperazin'1 ·yla<:e 0py.rido[2,3·bl. 434A • : (,l ty . rponohydra;e: tions of pirenzepine may be reduced by up to about 50% CA S . . IJ473c3B·6 (plpeJ")ZOiate); (1.4JI;)enz.odia;;�pli'\c6·o\')� dit1ydror::hloride •.• · . during haemodialysis.2·3 .G,gHnNs0,,2HCJ.r\20=442,?. . · . . . · · :··• • . ·· ·· ·. .. .. ·. ·. . . : . bromide/ . : y l. Krakamp B, et a!. Steady-state intravenous pharmacokinetics of 28797-6 1·7 2986fJ,
All cross-references refer to entries in Volume A