1570 Cough Suppressants Expectorants Mucolytics and Nasal Decongestants of a link between UK products containing phenylpropanolamine 90% of a dose is excreted unchanged in the urine with- Interactions and haemorrhagic stroke was weak (phenylpropanolamine is not in 24 hours. The half-life has been reported to be about Use of pholcodine with alcohol or other CNS depres- licensed as an appetite suppressant in the UK and the maximum recommended dose of 100 mg daily was lower than the 150 mg 3 to 5 hours. sants may increase the effects on the CNS. daily recommended in the USA). It was therefore suggested by ◊ References. UK commentators that use of licensed doses, with appropriate Uses and Administration 2 1. Simons FER, et al. Pharmacokinetics of the orally administered precautions, posed no additional risk. However, subsequently, decongestants pseudoephedrine and phenylpropanolamine in Pholcodine is a centrally acting cough suppressant that UK preparations containing phenylpropanolamine have either children. J Pediatr 1996; 129: 729–34. has actions and uses similar to those of dextromethor- been reformulated (mainly with pseudoephedrine) or withdrawn 2. Chester N, et al. Elimination of ephedrines in urine following by the manufacturers. multiple dosing: the consequences for athletes, in relation to phan (p.1556). It is given orally in a usual dose of 5 to doping control. Br J Clin Pharmacol 2004; 57: 62–7. 1. Lake CR, et al. Adverse drug effects attributed to phenylpropa- 10 mg three or four times daily. For children’s doses, nolamine: a review of 142 case reports. Am J Med 1990; 89: see Administration in Children, below. The citrate has 195–208. Uses and Administration also been used. Pholcodine polistirex (a pholcodine 2. Moffatt T, et al. Phenylpropanolamine: putting the record Phenylpropanolamine is a mainly indirect-acting sym- and sulfonated diethenylbenzene-ethenylbenzene co- straight. Pharm J 2000; 265: 817. pathomimetic (p.1408) with an action similar to that of 3. Kernan WN, et al. Phenylpropanolamine and the risk of hemor- polymer complex) has been used in modified-release rhagic stroke. N Engl J Med 2000; 343: 1826–32. ephedrine (p.1559) but less active as a CNS stimulant. preparations. 4. Ernst ME, Hartz A. Phenylpropanolamine and hemorrhagic Phenylpropanolamine has been given orally as the hy- stroke. N Engl J Med 2001; 344: 1094. Administration in children. Although pholcodine is licensed drochloride for the symptomatic treatment of nasal for use in children, over-the-counter cough and cold preparations 5. Wolowich WR, et al. Phenylpropanolamine and hemorrhagic stroke. N Engl J Med 2001; 344: 1094–5. congestion (p.1548). It has frequently been used in containing cough suppressants (including pholcodine) should be used with caution and generally avoided in those under 2 years 6. Stier BG, Hennekens CH. Phenylpropanolamine and hemorrhag- combination preparations for the relief of cough and ic stroke in the Hemorrhagic Stroke Project: a reappraisal in the cold symptoms. of age (see p.1547). The following oral doses of pholcodine are context of science, the Food and Drug Administration, and the given in the BNFC for use in children: law. Ann Epidemiol 2006; 16: 49–52. In the management of nasal congestion, phenylpropa- • 2 to 5 years: 2 mg three times daily 7. Committee on Safety of Medicines/Medicines Control Agency. nolamine hydrochloride has been given in oral doses of • 5 to 12 years: 2 to 5 mg three or four times daily Phenylpropanolamine and haemorrhagic stroke. Current Prob- up to 50 mg twice daily as modified-release prepara- lems 2001; 27: 5–6. Also available at: http://www.mhra.gov.uk/ home/idcplg?IdcService=GET_FILE&dDocName= tions. Preparations CON007458&RevisionSelectionMethod=LatestReleased (ac- BP 2008: Pholcodine Linctus; Strong Pholcodine Linctus. cessed 04/01/07) Other uses of phenylpropanolamine have included the control of urinary incontinence in some patients (see Proprietary Preparations (details are given in Part 3) p.2180). It has also been given in the management of Austral.: Actifed CC Dry; Actuss†; Duro-Tuss; Logicin Cough Suppres- Interactions sant†; Nyal Plus+ Dry Cough†; Ordov Dry Tickly Cough†; Pholtrate†; As for Sympathomimetics, p.1407. For a comment that some forms of priapism (see under Metaraminol, Tussinol; Cz.: Neocodin†; Fin.: Tuxi; Fr.: Biocalyptol; Broncorinol toux p.1333). Phenylpropanolamine has been used to sup- seche†; Codotussyl Toux Seche; Dimetane; Humex; Pharmakod toux drug interactions were likely to have been involved in seche; Respilene; Rhinathiol Toux Seche Pholcodine; Sirop des Vosges Toux many adverse events associated with phenylpropa- press appetite in the management of obesity (p.2149) Seche; Hong Kong: Duro-Tuss; Uni-Pholco; Irl.: Expulin Dry Cough; Phol- but the use of stimulants is no longer recommended. codex; Pholcolin; Malaysia: Dhacodine; Duro-Tuss; Norw.: Tuxi; NZ: Ac- nolamine see under Adverse Effects and Precautions, tifed CC Dry†; Duro-Tuss; S.Afr.: Pholcolinct; Pholtex; Singapore: Duro- above. Due to its indirect action, hypertensive crisis is Phenylpropanolamine polistirex (a phenylpropa- Tuss; Spain: Trophires†; UK: Benylin Childrens Dry Coughs; Boots Dry Cough Syrup 1 Year Plus; Galenphol; Hill’s Balsam Dry Cough; Pavacol-D; a particular risk in patients receiving MAOIs. nolamine and sulfonated diethenylbenzene-ethenyl- Tixylix Daytime. benzene copolymer complex) has also been used, as Amantadine. Severe psychosis has been reported1 in a woman Multi-ingredient: Austral.: Chemists Own Kiddicol; Demazin Cough & taking amantadine with phenylpropanolamine. In another re- have phenylpropanolamine bitartrate, phenylpropa- Cold; Difflam Anti-inflammatory Lozenges with Cough Suppressant; Duro- 2 Tuss Cough Lozenges; Duro-Tuss Decongestant; Duro-Tuss Dry Cough port, a 39-year-old man had intense and recurrent déjà vu expe- nolamine maleate, and phenylpropanolamine sulfate. Plus Nasal Decongestant; Duro-Tuss Expectorant; Phensedyl†; Tixylix Nigh- riences after taking amantadine with phenylpropanolamine for Preparations time; Belg.: Broncho-pectoralis Pholcodine; Eucalyptine Pholcodine; Euca- viral influenza. The effect ceased when he stopped both drugs. lyptine Pholcodine Le Brun†; Folex†; Norhitis; Pectorhinyl; Pholco-Mere- The authors suggested that his symptoms were due to increased USP 31: Chlorpheniramine Maleate and Phenylpropanolamine Hydrochlo- prine; Cz.: Biocalyptol S†; Fr.: Atouxx; Broncalene; Clarix; Denoral†; ride Extended-release Capsules; Chlorpheniramine Maleate and Phenyl- Hexapneumine; Isomyrtine†; Polery; Trophires; Hong Kong: Biocalyptol†; dopamine activity caused by the combination. propanolamine Hydrochloride Extended-release Tablets; Phenylpropa- Duro-Tuss Decongestant; Duro-Tuss Expectorant; Hexapneumine; Tripe P; 1. Stroe AE, et al. Psychotic episode related to phenylpropa- nolamine Hydrochloride Capsules; Phenylpropanolamine Hydrochloride India: Tixylix; Irl.: Day Nurse; Expulin; Expulin Childrens Cough; Malay- nolamine and amantadine in a healthy female. Gen Hosp Psychi- Extended-release Capsules; Phenylpropanolamine Hydrochloride Extend- sia: Difflam Anti-Inflammatory Lozenges (with cough suppressant); Duro- atry 1995; 17: 457–8. ed-release Tablets; Phenylpropanolamine Hydrochloride Oral Solution; Tuss Expectorant; Phensedyl Dry Cough; Promedyl Plus; Rhynacol; Russedyl Phenylpropanolamine Hydrochloride Tablets. Plus; Tixylix†; NZ: Difflam Cough; Duro-Tuss Cough; Duro-Tuss Expecto- 2. Taiminen T, Jääskeläinen SK. Intense and recurrent déjà vu ex- rant; Duro-Tuss Lozenges; Phensedyl Dry Family Cough†; Tixylix; S.Afr.: periences related to amantadine and phenylpropanolamine in a Proprietary Preparations (details are given in Part 3) Contra-Coff; Docsed; Folcofen; Pholtex Linctus; Procof; Respinol Com- healthy male. J Clin Neurosci 2001; 8: 460–2. Fin.: Rinexin; Ger.: Boxogetten S; Recatol mono; Norw.: Rinexin; Philipp.: pound; Tixylix; Singapore: 3P†; Duro-Tuss Cough Lozenges; Duro-Tuss Decolgen; Desotap; Disudrin; Naldec; Nasadec; Nasaphen; Nasathera P; Decongestant; Duro-Tuss Expectorant; Spain: Caltoson Balsamico; Switz.: Antipsychotics. A 27-year-old woman with schizophrenia and Neo-Coldan; S.Afr.: Restaslim†; Swed.: Rinexin; Switz.: Kontexin†; Pecto-Baby; Phol-Tussil; Phol-Tux; Tussiplex†; UK: Boots Nightime Cough T-wave abnormality of the heart, who had responded to thiori- Merex†; Slim Caps. Syrup 1 Year Plus; Cough Nurse; Day & Night Nurse; Day Nurse; Expulin dazine 100 mg daily with procyclidine 2.5 mg twice daily, died Multi-ingredient: numerous preparations are listed in Part 3. Childrens Cough†; Nirolex Day Cold & Flu; Nirolex Night Cold & Flu; Tix- from ventricular fibrillation within 2 hours of taking a single ylix Cough & Cold; Tixylix Night-Time. dose of a preparation reported to contain chlorphenamine maleate 4 mg with phenylpropanolamine hydrochloride 50 mg (Contac C), concurrently with thioridazine.1 Pholcodine (BAN, rINN) Pipazetate (BAN, rINN) 1. Chouinard G, et al. Death attributed to ventricular arrhythmia in- duced by thioridazine in combination with a single Contac C Folcodina; Folkodiini; Folkodin; Folkodin monohydrát; Folkodinas; D-254; Pipazétate; Pipazetato; Pipazetatum; Pipazethate (USAN); capsule. Can Med Assoc J 1978; 119: 729–31. Pholcodinum; Pholcodinum Monohydricum. 3-O-(2-Morpholi- SKF-70230-A; SQ-15874. 2-(2-Piperidinoethoxy)ethyl pyri- noethyl)morphine monohydrate. do[3,2-b][1,4]benzothiazine-10-carboxylate. Antivirals. A patient taking an over-the-counter nasal decon- gestant preparation