Но-шпа и беременность

[vestamo]

Уважаемые коллеги!
У меня следующий вопрос.
В нашей стране ПОВСЕМЕСТНО при ведении беременности используется препарат но-шпа (дротаверина гидрохлорид). Как правило не только в стационарах при угрозе прерывания, но и назначаются врачами в ЖК, а также зачастую принимаются беременными самостоятельно.
Но как выясняется, препараты дротаверина широко популярны уже 40 лет в странах бывшей Восточного региона, в странах же Западной Европы и Америки он даже не зарегистирован (нет препаратов на основе дротаверина). Мне ещё не удалось выяснить - является ли она запрещённым или просто не зарегистрированным. FDA (USA) не рассматривает результаты тех испытаний, которые проводились фирмой?
В связи с этим два вопроса: какая же тактика ведения подобных беременных на Западе? какие препараты используются вместо наших популярных магнеВ6 (но речь сейчас пока не о нём) и дротаверина?
Если подскажите ссылки на упоминание drotaverina (его эффективности/безопасности) в западных источниках - буду очень благодарна.

[Dr.Vad]

все в кучу:

Eur J Drug Metab Pharmacokinet. 1996 Jul-Sep;21(3):217-21.
Pharmacokinetics and bioavailability of drotaverine in humans.

Bolaji OO, Onyeji CO, Ogundaini AO, Olugbade TA, Ogunbona FA.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.

The pharmacokinetics and bioavailability of drotaverine was studied in 10 healthy volunteers after administration of single 80 mg oral and intravenous doses of the HCl salt of the drug, in a crossover fashion. Plasma and urine samples were analyzed for the unchanged drug by HPLC. The pharmacokinetic parameters, such as elimination half-life, plasma clearance, renal clearance and apparent volume of distribution, were not influenced by the route of drug administration. The drug was mainly eliminated by non-renal routes since renal clearance accounted for only 0.31 +/- 0.13% of the total plasma clearance. The absolute bioavailability was variable and ranged from 24.5-91% with a mean of 58.2 +/- 18.2% (mean +/- SD). It is suggested that the high variation in the bioavailability of drotaverine HCl after oral administration may result in significant interindividual differences in therapeutic response.

Int J Gynaecol Obstet. 2001 Sep;74(3):255-60.
Drotaverine hydrochloride vs. valethamate bromide in acceleration of labor.

Sharma JB, Pundir P, Kumar A, Murthy NS.

Department of Obstetrics and Gynecology, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India. [Ссылки доступны только зарегистрированным пользователям ]

OBJECTIVES: To compare the efficacy and safety of drotaverine hydrochloride and valethamate bromide in shortening the duration of labor. METHODS: In a randomized controlled trial of 150 nulliparous women in established labor with cervical dilation of 4 cm, 50 women were given drotaverine (group I), 50 women were given valethamate (group II) and another 50 women were not given any medication (group III). Duration of labor, mode of delivery, side effects, and neonatal outcome were measured in all cases. Appropriate non-parametric tests and chi(2) tests were used for assessment of statistical significance. RESULTS: In the three groups, 100%, 96% and 46% women delivered within 6 h, respectively. The injection-to-delivery interval was significantly reduced in the drotaverine group (193.96 min) in contrast to the valethamate group (220.68 min) and control group (412.84 min). The rate of cervical dilation was highest in the drotaverine group (2.04 cm/h) compared with the valethamate bromide group (1.86 cm/h) and control group (1.01 cm/h). There were no major maternal or fetal adverse effects in any group, but minor side effects were more common in the valethamate group. CONCLUSION: Both intramuscular drotaverine hydrochloride and valethamate bromide are effective in acceleration of labor; however, drotaverine accelerates labor more rapidly and is associated with less side effects.

Orv Hetil. 2002 Mar 17;143(11):559-62.
[Safety profile of NO-SPA]

[Article in Hungarian]

Tar A, Singer J.

Chinoin Rt.-a Sanofi-Synthelabo vallalatcsoport tagja, Budapest.

The aim of the safety analysis performed by Chinoin Drug Safety Unit was to summarise the safety profile of NO-SPA (drotaverine hydrochloride), the Hungarian spasmolytic well known in Hungary and abroad. Authors collected the safety data from clinical studies between 1964-1998 for the determination of the adverse event frequency. Based on the data of 12111 patients treated with NO-SPA in 37 clinical trials 0.9% frequency of adverse events was found. The value indicates uncommon (0.1-1%) adverse event frequency according to the criteria for frequency categories. The benefit-risk ratio of NO-SPA is favourable, since the therapeutic effect does not include frequent adverse reaction occurrence.



...Recently, a controlled open, phase IV clinical trial has been performed demonstrating prominent effects for drotaverine on some parameters of human deliveries (Demeter, 1998). Drotaverine, given at a dose of 40 mg (i.m.) in the stage of cervical dilatation phase to parturients, significantly (P=0.005) shortened the time course of dilatation stage and highly significantly (P=0.001) lowered the incidence of cervical ruptures, which led to decreased obstetrical complications. No increase in the risk of atonia was observed. Although drotaverine caused some lowering in the blood pressure, this effect may be of beneficial influence on the stress accompanying labor (Demeter et al., 1999).

Demeter, 1998. J. Demeter , Smooth muscle spasm in obstetrical and gynecological practice. In: A. Pap, Editor, The Management of Smooth Muscle Spasm, Onix Nyomda Kft, Debrecen, Hungary (1998), pp. 234–240.

Demeter et al., 1999. J. Demeter, G. Oszoli, Zs. Turi, A. Pal and Gy. Blaskó , Effect of intramuscularly administered NO-SPA injection on the dilatation stage of physiological deliveries. Magy. Noorv. Lapja 62 (1999), pp. 349–353

ИЗ: European Journal of Pharmacology
Volume 449, Issues 1-2 , 2 August 2002, Pages 55-60
Drotaverine interacts with the L-type Ca2+ channel in pregnant rat uterine membranes.
Zsuzsanna Tömösközi, , Olivier Finance1 and Péter Arányi
Internal Medicine Department, Sanofi-Synthelabo CHINOIN, Tó utca 1-5, Budapest, H-1045, Hungary.

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Wien Med Wochenschr. 1993;143(19-20):519-21.
[Calcium antagonists in pregnancy as an antihypertensive and tocolytic agent]
[Article in German]
Lechner W.
Universitatsklinik fur Frauenheilkunde, Innsbruck.
In pregnancy calcium antagonism is of great importance. The uterus-relaxing properties of verapamil are well known, diltiazem shows an excellent tokolytic efficacy and is also effective as hypotensive in pregnancy-induced hypertension. In contrast to verapamil and diltiazem the dihydropyridines were not clinically successful as tokolytic or hypotensive in pregnancy. Magnesium is a therapy of first choice in the EPH-gestosis.


J Matern Fetal Med. 1998 Sep-Oct;7(5):217-21.
Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial.

El-Sayed YY, Holbrook RH Jr, Gibson R, Chitkara U, Druzin ML, Baba D.

Department of Gynecology and Obstetrics, Stanford University, California, USA.

The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

[vestamo]

Спасибо. Статьи восточных и африканских авторов по дротаверину тоже находила, интересна индийская статья. А за американских авторов спасибо - я никак не могла "ключевые" слова подобрать, чтобы адекватный поиск вести.

Удивило применение БМКК. Согласно классификации FDA в USP DI от 2000 они относятся к категории С:
"Изучение репродукции на животных выявило неблагоприятное действие на плод, а адекватных и строго контролируемых исследований у беременных женщин не проведено, однако потенциальная польза, связанная с применением ЛС у беременных, может оправдать его использование, несмотря на возможный риск."

Впрочем для дротаверина видела упоминание в одном из форумов ([Ссылки доступны только зарегистрированным пользователям ]), где также указывается только его применение при родах, но не при беременности.

Теперь буду знать "ключевые" слова и авторов для поиска