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1344 Cardiovascular Drugs 1344 Cardiovascular Drugs Molsidomine is metabolised to linsidomine (p.1325), an active Moracizine Hydrochloride (BANM, rINNM) 2. Mehta AV, et al. Experience with moricizine HCl in children metabolite. with supraventricular tachycardia. Int J Cardiol 1996; 57: 31–5. Hidrocloruro de moracizina; Moracizine, Chlorhydrate de; 3. Geller JC, et al. Efficacy and safety of moricizine in the mainte- Carcinogenicity. Molsidomine tends to degrade into morpho- Moracizinhydroklorid; Moracizini Hydrochloridum; Morasitsiini- nance of sinus rhythm in patients with recurrent atrial fibrilla- line (even when protected from the light), a compound consid- hydrokloridi. tion. Am J Cardiol 2001; 87: 172–7. ered potentially carcinogenic. This finding led to the suspension Preparations 1 Морацизина Гидрохлорид of marketing of one molsidomine formulation; an earlier tempo- C H N O S,HCl = 464.0. USP 31: Moricizine Hydrochloride Tablets. rary suspension was related to evidence of carcinogenicity in 22 25 3 4 CAS — 29560-58-5. Proprietary Preparations (details are given in Part 3) some animals, although this has not been confirmed in humans. ATC — C01BG01. USA: Ethmozine†. 1. Anonymous. Corvaton Tropfen. Dtsch Apotheker Ztg 1989; 129 ATC Vet — QC01BG01. (49): VI. Pharmacopoeias. In Chin. and US. Myocardial infarction. Although intravenous nitrates (glycer- USP 31 (Moricizine Hydrochloride). A white to off-white crys- Moxisylyte Hydrochloride (BANM, rINNM) yl trinitrate or sodium nitroprusside) may be used in the manage- talline powder. Soluble in water and in alcohol. Store in airtight ment of acute myocardial infarction (p.1175), molsidomine and containers. Hidrocloruro de moxisilita; Moksisylyyttihydrokloridi; Moxisilita its active metabolite linsidomine (a nitric oxide donor) had no Clorhidrato; Moxisylyte, Chlorhydrate de; Moxisylythydroklorid; effect on mortality.1 Adverse Effects Moxisylyti Hydrochloridum; Moxisylytum Hydrochloridum; Thy- The most common adverse effects associated with moracizine moxamine Hydrochloride. 4-(2-Dimethylaminoethoxy)-5-iso- 1. European Study of Prevention of Infarct with Molsidomine affect the CNS and the gastrointestinal tract and include dizzi- (ESPRIM) Group. The ESPRIM trial: short-term treatment of propyl-2-methylphenyl acetate hydrochloride. acute myocardial infarction with molsidomine. Lancet 1994; ness, headache, fatigue, nausea, and abdominal pain. Other ad- 344: 91–7. verse effects include dyspnoea, dry mouth, blurred vision, impo- Моксизилита Гидрохлорид tence, and urinary-tract disorders. There have been occasional C16H25NO3,HCl = 315.8. The pharmacokinetics of molsidomine Pharmacokinetics. reports of fever, thrombocytopenia, hepatic dysfunction, hypo- CAS — 54-32-0 (moxisylyte); 964-52-3 (moxisylyte hydro- have been reviewed.1 Molsidomine is metabolised in the liver to thermia, and skin rash. chloride). linsidomine and other morpholine derivatives. Prolonged elimi- Like other antiarrhythmics moracizine can provoke or worsen ATC — C04AX10; G04BE06. nation half-lives of molsidomine and linsidomine due to reduced ATC Vet — QC04AX10; QG04BE06. plasma clearance have been reported in patients with liver cirrho- arrhythmias. This may range from an increase in the frequency sis.2 of premature ventricular contractions to induction or worsening of ventricular tachycardia. 1. Rosenkranz B, et al. Clinical pharmacokinetics of molsidomine. CH3 Clin Pharmacokinet 1996; 30: 372–84. An increased mortality rate occurred when moracizine was test- 2. Spreux-Varoquaux O, et al. Pharmacokinetics of molsidomine ed in the control of asymptomatic ventricular arrhythmias in CH O CH3 and its active metabolite, linsidomine, in patients with liver cir- post-infarction patients (see Cardiac Arrhythmias under Uses 3 rhosis. Br J Clin Pharmacol 1991; 32: 399–401. and Administration, below). N O Preparations Effects on body temperature. Fever with elevated creatine O H3C Proprietary Preparations (details are given in Part 3) phosphokinase and hepatic transaminase concentrations was as- Arg.: Molsicor; Molsidaine; Austria: Molsidolat; Molsihexal; Belg.: Coruno; sociated with moracizine in 2 patients.1 The fever abated within Corvatard†; Corvaton; Cz.: Corvaton; Molsihexal; Molsiket; Fr.: Corvasal; 48 hours of stopping moracizine and recurred within 24 hours of H3C CH3 Ger.: Corvaton; duracoron†; Molsi-Azu†; Molsi-Puren; Molsi†; Molsibeta; rechallenge in both patients. Results suggested a similarity to the Molsihexal; molsiket; Hung.: Corvaton; Port.: Corvaton†; Rus.: Dilasidom (moxisylyte) (Диласидом); Sydnopharm (Сиднофарм); Spain: Corpea; Molsidain; neuroleptic malignant syndrome that is associated with other Switz.: Corsifar†; Corvaton. phenothiazine derivatives. 1. Miura DS, et al. Ethmozine toxicity: fever of unknown origin. J NOTE. MOX, formerly THY, is a code approved by the BP 2008 Clin Pharmacol 1986; 26: 153–5. for use on single unit doses of eye drops containing moxisylyte Precautions hydrochloride where the individual container may be too small Monteplase (rINN) to bear all the appropriate labelling information. As for Flecainide Acetate, p.1288. E-6010; Monteplasa; Montéplase; Monteplasum. Pharmacopoeias. In Br. Interactions BP 2008 (Moxisylyte Hydrochloride). A white, odourless or al- Монтеплаза Use of moracizine with other antiarrhythmics or arrhythmogenic most odourless, crystalline powder. Freely soluble in water and C2569H3896N746O783S39 = 59009.5. drugs may increase the incidence of cardiac arrhythmias. Mora- in chloroform; soluble in alcohol; practically insoluble in ether CAS — 156616-23-8. cizine undergoes metabolism in the liver and its activity may be and in petroleum spirit. A 5% solution in water has a pH of 4.5 Profile influenced by other drugs affecting the enzymes responsible for to 5.5. Protect from light. Monteplase is a thrombolytic related to alteplase (p.1207) that is its metabolism; it is an enzyme inducer and may also affect the activity of other hepatically-metabolised drugs. Adverse Effects used in acute myocardial infarction (p.1175) and venous throm- Moxisylyte hydrochloride may cause nausea, diarrhoea, head- boembolism (p.1189). For acute myocardial infarction, the usual Pharmacokinetics ache, vertigo, flushing of the skin, dry mouth, and nasal conges- dose is 27 500 units/kg given by intravenous injection as soon as Moracizine is readily and almost completely absorbed from the tion. Hepatotoxicity has been reported. Overdosage may cause possible after the onset of symptoms. For pulmonary embolism, gastrointestinal tract. It undergoes significant first-pass hepatic hypotension. the usual dose is 13 750 units/kg to 27 500 units/kg. metabolism so that the oral bioavailability is about 38%. Mora- Transient ptosis has occurred occasionally after ophthalmic ap- cizine is extensively metabolised and some of the numerous me- plication. Prolonged erections or priapism have occurred rarely ◊ References. tabolites may be active. It induces its own metabolism; the plas- after intracavernosal injection and systemic effects may also oc- 1. Kawai C, et al. A prospective, randomized, double-blind multi- ma elimination half-life is about 2 hours after multiple doses. center trial of a single bolus injection of the novel modified t-PA cur. E6010 in the treatment of acute myocardial infarction: compari- Although plasma concentrations are reduced with multiple dos- son with native t-PA. J Am Coll Cardiol 1997; 29: 1447–53. ing, clinical response is not affected. It is about 95% bound to Effects on the liver. Hepatic adverse reactions with moxisylyte 2. Inoue T, et al. A new thrombolytic agent, monteplase, is inde- plasma proteins. Moracizine is distributed into breast milk. first appeared in France after its use in benign prostatic hyperpla- pendent of the plasminogen activator inhibitor in patients with About 56% of a dose is excreted in the faeces and about 39% in sia, a condition in which relatively high doses were used (up to acute myocardial infarction: initial results of the COmbining the urine. 480 mg daily compared with up to 320 mg daily for peripheral Monteplase with Angioplasty (COMA) trial. Am Heart J 2002; vascular disease). Since then the UK CSM has received reports ◊ References. 144: E5. associated with lower doses.1 Thirteen hepatic reactions, ac- 3. Inoue T, et al. Long-term benefits of monteplase before coronary 1. Benedek IH, et al. Enzyme induction by moricizine: time course angioplasty in acute myocardial infarction. Am J Cardiol 2005; and extent in healthy subjects. J Clin Pharmacol 1994; 34: counting for 17% of all reports of suspected adverse reactions to 95: 506–8. 167–75. moxisylyte, had been received. These comprised 3 cases of 4. Inoue T, et al. Therapeutic potential of monteplase in acute my- hepatic function abnormalities, 3 of jaundice, 4 of cholestatic ocardial infarction. Am J Cardiovasc Drugs 2005; 5: 225–31. Uses and Administration jaundice, 2 of hepatitis, and 1 of hepatitis with jaundice. In most Moracizine is a phenothiazine compound that has class I an- Preparations cases the reaction occurred within 5 weeks of the start of treat- tiarrhythmic activity (p.1153) but does not readily fall into the ment and resolved on drug withdrawal. In 9 cases the dosage of Proprietary Preparations (details are given in Part 3) subclasses a, b, or c. It is used as the hydrochloride in the treat- moxisylyte was known and varied from 80 to 320 mg daily with Jpn: Cleactor. ment of serious symptomatic ventricular arrhythmias. Mora- 7 patients receiving 160 mg or less daily. cizine hydrochloride
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