Transfer of Propranolol and Sotalol Across the Human Placenta

Erkkola, Risto; Lammintausta, Risto; Liukko, P.; Anttila, Markku

doi:10.3109/00016348209156947

Cited by 39 publications

(12 citation statements)

References 13 publications

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“…Control of the arrhythmia was achieved in 10/14 foetuses. In foetuses without hydrops, sotalol given orally to the mothers has been demonstrated to pass the placenta resulting in a foetal concentration corresponding to 50-100% of the maternal concentration (11,12). The present study also confirms that lack of adequate response of foetal SVT to digoxin therapy alone is most frequently related to the presence of foetal hydrops.…”

Section: Discussionsupporting

confidence: 79%

Foetal supraventricular tachycardia treated with sotalol

Sonesson¹,

Jc²,

Wesslen-Eriksson³

et al. 1998

SPAE

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This retrospective study (1991-95) presents our experience with sotalol in the treatment of 14 foetuses with supraventricular tachycardia (SVT). SVT was diagnosed in a structurally normal heart at a gestational age of 24-35 (median 28) weeks. In eight foetuses, hydrops was evident at presentation. In all patients pharmacological conversion with digoxin was tried before sotalol treatment was started. Sotalol was given orally to the mothers in a dose of 80-160 mg x 2. Cardioversion was obtained in 10 foetuses. In seven of these patients re-entry tachycardia and in five pre-excitation could be documented after birth. In two foetuses not responding to sotalol a long RP tachycardia was demonstrated; even when using digoxin, sotalol, flecainide and/or propafenone in different combinations after birth complete suppression of the arrhythmia was not obtained. Two severely hydropic foetuses died 1 and 10 d, respectively, after starting with sotalol. The 12 surviving infants were doing well except for one infant, with a cerebral lesion probably related to the arrhythmia. These findings demonstrate that sotalol can be useful in the treatment of foetal SVT.

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Section: Discussionsupporting

confidence: 79%

Foetal supraventricular tachycardia treated with sotalol

Sonesson¹,

Jc²,

Wesslen-Eriksson³

et al. 1998

SPAE

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“…Sotalol has been shown to readily cross the placenta (O'Hare et al 1980;Erkkola et al 1982). It is reasonable to assume that the sotalol-exposed rabbit embryos die as a consequence of embryonic bradyarrhythmia/cardiac arrest, in the same way as has been proposed to happen after embryonic exposure to Ikr blockers in the rat.…”

Section: Discussionmentioning

confidence: 99%

Developmental Toxicity in the Pregnant Rabbit by theClass III Antiarrhythmic Drug Sotalol

Sköld

Danielsson

2001

Pharmacology & Toxicology

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The purpose of this study was to investigate the potential of sotalol to cause developmental toxicity in the pregnant rabbit. Sotalol is a b-adrenoceptor blocking drug which also has class III antiarrhythmic properties via Ikr channel blockade. Experiment 1: Nine pregnant New Zealand White rabbits were given doses of either 300, 225, or 150 mg/kg of sotalol during gestational days, called Days, 13-16 which resulted in total litter loss. Experiment 2: A single dose of sotalol, 100 or 150 mg/kg was administered during Days 8-17 to 15 rabbits. Dosing on Day 8, 9, or 10 resulted in a slightly higher incidence of embryonic death compared to historical controls. There was marked increased embryonic death of 55-90% (four does with total litter loss), decreased number of live foetuses per litter, and elevated mean foetal weight after dosing during Days 12-16. Experiment 3: 16 pregnant rabbits were administered single doses of sotalol of either 100, 85, 75, 60 or 50 mg/kg on Day 14. The main finding was increased embryonic death, which ranged from total litter loss to ∂30% at 50 mg/kg. At 50 mg/kg, the maternal C max , AUC 1-24 hr , and t 1/2 were approximately 45 mM, 340 mmol¿hr/l, and 6 hr, respectively. In conclusion, sotalol treatment resulted in embryonic death in the rabbit in early pregnancy in the same way as has been seen for other drugs with Ikr blocking properties (class III antiarrhythmics) in rodents. The observed developmental toxicity in the rabbit is most likely secondary to embryonic arrhythmia as has been shown in rodent studies. The results may indicate that Ikr blocking agents are developmental toxicants across species including man.

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“…In long VA tachycardia, a type III anti-arrhythmic agent was our first choice. We opted for sotalol because its electrophysiological actions on the immature mammalian heart have been studied (Houyel et al, 1992), and also because of its good placental transfer (Erkkola et al, 1982), its relatively short half-life and weak beta-blocker effect. We always start with an oral dose of 80 mg of sotalol twice a day, usually for 24 to 48 h, followed by the usual regimen of 160 mg twice a day.…”

Section: Commentsmentioning

confidence: 99%

Fetal arrhythmias: the Saint‐Justine hospital experience

Fouron

2004

Prenatal Diagnosis

109

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We intend to review our experience with the investigation and management of foetal arrhythmia on the basis of superior vena cava/ascending aorta (SVC/AA) Doppler flow velocity recordings. Irregular rhythms n = 307. Premature atrial and ventricular contractions were easily identified and generally self-limited in time. Sustained bradycardia n = 19. Four had sinus bradycardia, six presented with blocked atrial bigeminism, three showed 2:1, and five had a complete atrio-ventricular (AV) block. Another foetus that presented with first-degree AV block developed a Luciani-Wenckebach phenomenon 1 week later. These different types of bradycardia were all identified on SVC/AA Doppler recordings. Tachyarrhythmia n = 30. Five types of tachyarrhythmia were observed: Type I: Short ventriculo-atrial (VA) tachycardia (VA < AV), n = 11. Ten foetuses of this group presented a distinctive Doppler flow velocity pattern characterised by 1:1 AV conduction and a tall atrial wave ('a' wave) superimposed on the aortic ejection wave. They were considered to have re-entrant tachycardia through a fast-conducting AV accessory pathway; all 10 responded to digoxin therapy. The eleventh foetus with short VA tachycardia had atrial ectopic tachycardia with AV node dysfunction; he was treated successfully with sotalol. Type II: Long VA tachycardia (VA > AV): n = 8. In seven cases, an 'a' wave of normal amplitude with normal AV time interval could be clearly identified in front of the aortic ejection wave: one foetus in this group was considered to be in sinus tachycardia based on the variability of its heart rate; in another, sudden onset of tachycardia triggered by extrasystoles led to the possibility of permanent junctional reciprocating tachycardia (PJRT). The five other foetuses had atrial ectopic tachycardia. The last foetus presented with AV and VA intervals of the same duration and a heart rate of 210 beats/min; he did not respond either to digoxin or to sotalol, and was found after birth to have PJRT. The drug of first choice in this group was sotalol. Type III: Simultaneous onset of atrial and ventricular contractions: n = 3. These foetuses were classified as junctional ectopic tachycardia. Two responded to amiodarone. The other foetus converted spontaneously to sinus rhythm. Type IV: Flutter: n = 7. All presented with 2:1 AV relationship except one who had a variable block. Digoxin was prescribed as a first choice associated with sotalol in three cases. Conversion to sinus rhythm was documented in all; however, one hydropic foetus with advanced cardiomyopathy died one day after birth. Type V: Ventricular tachycardia: n = 1. This 30-week foetus presented alternance of AV dissociation (atrial rate: 130, ventricular rate: 170 beats/min) and atrial capture (ventricular rate of 138 beats/min). The arrhythmia responded well to propanol, and no recurrence was recorded after birth. Precise prenatal identification of arrhythmia type can be achieved with the SVC/AA Doppler approach. Such information allows for a better management and a rational c...

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Transfer of Propranolol and Sotalol Across the Human Placenta

Cited by 39 publications

References 13 publications

Foetal supraventricular tachycardia treated with sotalol

Foetal supraventricular tachycardia treated with sotalol

Developmental Toxicity in the Pregnant Rabbit by theClass III Antiarrhythmic Drug Sotalol

Fetal arrhythmias: the Saint‐Justine hospital experience

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