Dimetindene Succinate 627

tration was correlated with frequency or extent of symp­ Childrcns Cough, Cold & Allergyt: Childrens liquid Allergy; Multi�ingredient Preparations. Austria: Eucillin; Prurimix; Belg.: toms.1 The most common symptom was impaired con­ Dipheni�t; Dormax; Dormex; Dormiphen; Extra Stength Sleep Rhini-San; Canad.: Creo-Rectal; Ger.: Tempil Nt; Hong Kong: sciousness; psychosis, seizures, antimuscarinic symptoms Aid; Insomnal; Jack & Jill Bedtime; Jack & Jill Thin Strips Phenahist; India: Cinaryl; Eskold Expectorant; Eskold; Mex.: such as mydriasis, tachycardia, and tachyarrhythmias, and Cough & Coldt: Nadryl; Neocitran Nighttime Cough; Night Flumil; S.Afr. : Actophlem; Eskornadet; Solpbyllex; Theophen respiratory failure were also seen. The positive association Cough; Nytol; Simply Sleep; Sleep Aid; Sleep-Eze D; Sominext; Comp; Switz. : Arbidt. & Runny Nose; Unisom; between dose and frequency and severity of symptoms Triaminic Thin Strips Nighttime Cough Chile: Jaquedryl; Somol; Cz.: Psilo-Balsam; Denm.: Benylan; was confirmed in a more recent study;2 it was also found Fr. : Butix; Nautamine; Ger.: Betadorm D; Dolestan; Revert­ that severe symptoms were more likely to occur when g Donn; Moradorm; nervo OPT N; Sediat; Sedopretten; Vivinox Doxylamine Succinate (BANM r!NNM) or more of diphenhydramine had been taken. I Sleep; Gr.: Benadryl; Hong Kong: Bendol; Bendrolt; Calmitcht; Deksilarr-,in Suksinat; Deksiiamino·vandeniiio sukcinatas; There have been reports3.4 of rhabdomyolysis as an effect Diphenaminet; Histergant; Unisomt; Hung.: Psilo-Balsam; Deksylamiinivetysuksinaatti; DexHamina, succin te de; of oral diphenhydramine overdosage. The liberal applica­ India: Benacof; Benadryl; Cofryl; Kuffdryl; Novadryl; Indon.: tion of a lotion containing diphenhydramine produced Arcodryl; Benadrylt: Otcde; Paradryl; Recodryl; Sidiadrylt; Doxilamin-hidrogen-szukciniit: Doxylamine a acute delirium with visual and auditory hallucinations in a Valdres; Israel: Nytol; Ital.: Aliserin; Allergan; Jpn: Venapasta; Succinate; Doxylamine. hydregenesuccinate HydrogenDoxyl­ 9-year-old boy5 and similar effects were seen in 3 children Mex. : Benadryl; Bionaryl; Bonanoti; Drafen; Glicodril; Hista­ amine, Succinate de; [)exylamir.hydregensuccinat;de; Doxyla­ with varicella -zoster infection after the topical application of dryl; Indumir; Lurispan; Nytol; Ulcoid; NZ: Unisom; Philipp.: min-hydrogen-sukcinat: Doxylami"i Hydrogenosuccinas; diphenhydramine (2 of these children also received oral Alerace; AHerin AH; Benadryl Antihistamine; Benaxil; Drame­ Doxylamini Succinas; Doxylaminium Succinate; Doxylamif1- lin; Tussicon; Port.: Benaderma; Benergina; Codilergit; Rus.: diphenhydramine) . 6 vil!esuccinat; Histadoxylamlne Succinate; Succinate de Psilo-Balsam (IIcnno-EaJib3aM); S.Afr. : Betasleep; Sleepeze-PM; 1. KOppel C, Tenczer J. Clinical symptomatology of diphenhydramine dbxilamina; CWCYIHJT. overdose: an evaluation of 136 cases in 1982 to 1985. Clin Toxicol 1987; Singapore: Benadryl; Bendrol; Paxidorm; Spain: Benadrylt; NN-Dimethyl-2-[JleKCYln3MYlH3t:t-rnethyi-o-(2-pyridyl)benzylexy ]ethylamine 25: 53-70. Neosayomol; Sonodor; Swed.: Desentol; Switz. : Benoaen; ' 2. Radovanovic D, et al. Dose-dependent toxicity of diphenhydramine Bonox; Nardyl Sommeil; Thai.: Benadryl; Cabana; Codiphen; hydrogen succinate. overdose. Hum E'xp Toxicol 2000; 19: 489-95. Dibendryl; Sedatab; Sedi; Tussodryl; Turk. : Allenik; Allerjint; 3. Hampel G, et al. Myoglobinuric renal failure due to drug-induced Benadryl; Benison; Difedrin; Fenotral; UAB: Amydramine II; C,,H;zN20,C,Hc0""'388.5 succin­ rhabdomyolysis. Hum Toxicol 1983; 2: 197-203. 4. Haas CE, et al. Rhabdomyolysis and acute renal failure following an UK: Adult Chesty Cough; Boots Skin Allergy Relief; Child C4S - 469-2/·6 (dol(ylamine;� 562- 10-7 {doxylamine ethanol and diphenhydramine overdose. Ann Pharmacother 2003; 37: Chesty Cough; Dreemon; Histergan; Mandalyn Paediatric; arej. 538-42. Nightcalm; Nytol; Paxidorm; Sleep Aid; Sleepeaze; Ukr. : Der- 1 ATC - R06AA09. 5. Filloux F. Toxic encephalopathy caused by topically applied diphen­ modrin (,lJ;epMa,Lq)HH); Psilo-Balsam (IIcrnm-EaJih3aM); USA: 40 hydramine. J Pediatr 1986; 108: 1018-20. Winks; Aler-Dryl; AllerMax; Altaryl Childrens Allergy; Bano­ ATC Ve t-- QR06AA09. 6. Chan CYJ, Wallander KA. Diphenhydramine toxicity in three children phen Allergy; Ben-Tannt; Benadryl Allergy; Benadryl Chil­ flNII � V9.8!985Y12. with varicella-zoster infection. DlCP Ann Pharmacother 1991; 25: 130-2. Pharmacopoeias. In Eur. (see p. vii) and US. drens Allergy; Benadryl Itch; Benadryl; Childrens PediaCare Nighttime Cough; Compoz Night-time Sleep Aid; Derma-Pax; Ph. Eur. 8: (Doxylamine Hydrogen Succinate; Doxylamine Pregnancy. A pregnant woman who was receiving Dermamycin; Diphen AF; Diphenhist; Dormin; Dytant; Dytuss; Succinate BP 2014). A white or almost white powder. Very diphenhydramine hydrochloride 150mg daily for a pruri­ Genahist; Maximum Strength Sleepinal; Maximum Strength soluble in water; freely soluble in alcohol. It shows tic rash gave birth to an infant who developed diarrhoea Unisom SleepGels; Miles Nervine; Nytol; Q-dryl; Scot-Tussin polymorphism. and generalised tremulousness 5 days later.1 The delay in Allergy; Siladryl; Silpben; Simply Sleep; Sleep-Ettes D; Sleep­ USP 36: (Doxylamine Succinate). A white or creamy-white appearance of withdrawal symptoms was considered to be ettes Nighttime Sleep Aid; Sleepwell 2-nite; Snooze Fast; powder having a characteristic odour. Soluble in 1 of due to reduced activity of glucuronyl conjugating enzymes Sominex; Triaminic Children's Allergyt; Triaminic Cough & water, 1 in 2 of alcohol and of chloroform, and 1 lin 3 70 of in the first few days of life. Runny Noset; Tusstat; Twilite; Unisom SleepMelts; ZzzQuil; ether; very slightly soluble in benzene. Protect from light. For discussion of the use of antihistamines in pregnancy, Venez. : Benadryl. including a suggestion of a relationship between inguinal hernia or genitowurinary malformations and diphenhydrw Multi-ingredient Preparations. Numerous preparations are listed Uses and Administration in Volume B. amine exposure, see p. 614.2. See also under Interactions, Doxylamine succinate, a monoethanolamine derivative, is a below, for a report of perinatal death possibly associated Pharmacopoeial Preparations sedating antihistamine with antimuscarinic and pro­ with temazepam and diphenhydramine. BP 2014: Diphenhydramine Oral Solution; Diphenhydramine nounced sedative effects. I. Parkin DE. Probable Benadryl withdrawal manifestations in a new-born Tablets; Doxylamine succinate is given for the symptomatic relief infant. J Pediatr 1974; 85: 580. USP 36: Acetaminophen and Diphenhydramine Citrate Tablets; of hypersensitivity reactions, in pruritic skin disorders Acetaminophen, Diphenhydramine Hydrochloride, and Pseudo­ (p. 612.1), as a hypnotic in the short-term treaunent of Interactions ephedrine Hydrochloride Tablets; Diphenhydramine and insomnia (p. 611.2), and as an ingredient of compound Pseudoephedrine Capsules; Diphenhydramine Citrate and preparations for symptomatic treatment of coughs and the As for the sedating antihistamines in general, p. 614.3. Ibuprofen Tablets; Diphenhydramine Hydrochloride Capsules; common cold (p. 611.2). Oral doses of up to 25 mg of Diphenhydramine inhibits the cytochrome P450 isoenzyme Diphenhydramine Hydrochloride Elixir; Diphenhydramine doxylamine succinate have been given every 4 to 6 hours to CYP2D6 that is partly responsible for the metabolism of Hydrochloride Injection. some beta blockers including metoprolol and the a maximum of 150 mg daily. The usual hypnotic dose is 25 mg orally, up to half an hour before bedtime, although antidepressant venlafaxine. this may be increased to 50 mg if necessary. Diphenylpyraline Hydrochloride Benzodiazepines. There has been a report1 suggesting It is also used in the management of nausea and vomiting (BANM. r!NNM) that a reduction in temazepam metabolism caused by of early pregnancy (p. 1814.3) in women who have not diphenhydramine may have contributed to perinatal responded to conservative management such as dietary and death after ingestion of these drugs by the mother. lifestyle modifications. (See p. 614.2 for the controversy that has surrounded the use in pregnancy of combination 1. Kargas GA, et at. Perinatal mortality due to interaction of diphenhydr- ! amine and temazepam. N Engl J Med 1985; 313: 1417-18. 1 products of doxylamine.) It is given orally as a modified­ release combination preparation with pyridoxine hydro­ chloride (see Vitamin B Substances, p. 2105.3); each tablet Pharmacokinetics contains doxylamine 6succinate 10 mg and pyridoxine Diphenhydramine hydrochloride is well absorbed from the hydrochloride 10mg. The recommended initial dose is 2 gastrointestinal tract, although high first �pass metabolism tablets at bedtime, taken on an empty stomach; if symptoms appears to affect systemic availability. Peak plasma �� -- are not adequately controlled, the dose may be gradually concentrations occur about to 4 hours after oral doses. TC Vet-- OR06/i)\07. increased, according to response, to a maximum of 4 tablets Diphenhydramine is widelyI distributed throughout the UNft Ci9FU7ffE87. daily in the morning and at mid-afternoon, and 2 at Pharmacopoeias. In Br. body including the CNS. It crosses the placenta and has been bedtime(I ). This preparation should be taken regularly and detected in breast milk. Diphenhydramine is highly bound BP 2014: (Diphenylpyraline Hydrochloride). A white or not on an as-required basis; the need for continued to plasma proteins. Metabolism is extensive. Diphenhydr� almost white, odourless or almost odourless powder. Freely treatn1ent should be reassessed as the pregnancy progresses amine is excreted mainly in the urine as metabolites; little is soluble in water, in alcohol, and in chloroform; practically and the dose gradually tapered when stopping treatment. excreted as unchanged drug. The elimination half-life has insoluble in ether. been reported to range from 2.4 to 9.3 hours. Adverse Effects and Precautions References. Profile I. Glazko et at. Metabolic disposition of diphenhydramine. Clin As for the sedating antihistamines in general, p. 613.1 and Pharmacol 1974; 16: 1066-76. Diphenylpyraline hydrochloride, a piperidine derivative, is p. 613.3, respectively. The controversy surrounding the use 2. Paton DM, Webster DR Clinical pharmacokinetics of H1-receptor a sedating antihistamine (p. 610. I) with antimuscarinic and in pregnancy of combination products of doxylamine is antagonists {the antihistamines). Clin Pharmacokinet 1985; 10: 477-97. significant sedative properties. discussed on p. 614.2. (includes studies indicating a correlation between plasma concentra­ tions and both antihistaminic and sedative effects). It bas been given for the symptomatic relief of allergic 3. Simons et al. Diphenhydramine: pharmacokinetics and pharmaco­ IU, conditions including rhinitis (p. 612.1), and in pruritic skin Overdosage. In an evaluation of 09 cases of intoxication dynamics in elderly adults, young adults, and children. Clin Pharmacol 1 disorders (p. 612.1). It has also been used in compound with doxylamine, 1 no correlation Iwas found between the 1990; 30: 665-71. preparations for the symptomatic treatment of coughs and 4. Scavone JM, et al. Pharmacokinetics and pharmacodynamics of amount ingested or plasma concentration and the fre­ diphenhydramine 25mg in young and elderly volunteers. Clin the common cold (p. 611.2). Diphenylpyraline and quency or extent of symptoms. The most common symp­ 1 Pharmar:ol 1998; 38: 603-9. diphenylpyraline hydrochloride have been applied topically tom was impaired consciousness. Psychotic behaviour, sei­ although, as with other antihistamines, there is a risk of zures, and antimuscarinic symptoms such as tachycardia Prep(lr(l_lion sensitisation. and mydriasis were also seen. Rhabdomyolysis occurred in �·················· Diphenylpyraline teoclate is piprinhydrinate (p. 638.1). one patient and was accompanied by transient impairment (details are given in Volume B) ProprietaryPreparations of renal function. The same group cornmented2 that rhab­ References. Arg. : Alerminat; Amodormin; Graham G, Bolt AG. Half-life of diphenylpyraline in man. J domyolysis had been noted in 7 of 442 cases of doxyl­ Single�ingredient Preparations. L Benadryl; Caladryl Dt; Fabolergic; Fadalex; Histaler; Klonadryl Pharmacokinet Biopharm 1974; 2: 191-5 (ranged from 24 to 40 hours). amine overdosage, with an associated rise in plasma crea­ Antialergico; Nelfigent; TheraFlu Alergiat; Austral.: Snuzaid; tine kinase and myoglobinuria, and suggested that Unisom; Austria: Calmaben; Dermodrin; Dibondrin; Histaxin; doxylamine has a direct toxic effect on striated muscle. Noctor; Azaron; Diphamine; Nustasium; R Calm; Preparations Belg. : Braz.: KOppel C, et al. Poisoning with over-the-counter doxylamine l. Difenidrin; Canad.: Aller-Aide; Allerdryl; Allergy Elixir; Allergy ProprietaryPreparations (details are given in Volume B) preparations: an evaluation of 109 cases. Hum Toxico/ 1987; 6: 155-9. Formula; Allergy Tablets; Allergy; Allemix; Anti-Itch; Benadryl; 2. KOppel C, et at. Rhabdomyolysis in doxylamine overdose. Lancet 1987; i: Benylin Night Caught; Calmex; Children's Allergy Formula; Single-ingredient Preparations, Gr.: Arbid-St. 442-3.

The symbol t denotes a preparation no longer actively marketed