門診處方討論 Nifedipine 用於安胎 主講者 : 黃意文

Nifedipine ❃ OVERVIEW A. Nifedipine is a calcium channel antagonist. B. Nifedipine is a vasodilator with antianginal and antihypertensive effects. It acts by blocking the post- excitation release of calcium ions into cardiac and vascular smooth muscle, thereby inhibiting the activation of ATPase on myofibril contraction. C. The usual adult oral dose in angina and hypertension is 10 to 20 milligrams (mg) three times daily or 30 to 60 mg extended release daily; doses above 180 mg/day regular release or 90 to 120 mg extended release are not recommended. A maximum daily dose of 60 mg immediate-release nifedipine for patients with essential hypertension or chronic angina pectoris has been recommended in 1997 by the German Health Authority (BfArM) due to a dose-dependent increase in heart-related complications and incidence of death.

Premature labor

❄ PREMATURE LABOR 1.OVERVIEW: FDA APPROVAL: Adult, no; pediatric, no USP RATING: Not rated EFFICACY: Adult, effective DOCUMENTATION: Adult, good 2.SUMMARY: Tocolytic effect similar to standard beta- mimetic agents Minimal maternal/fetal adverse effect Investigation status; not recommended for general use

PRETERM LABOR TREATMENT SUMMARY  A. GENERAL: Treatment is aimed at termination of premature uterine contractions with tocolytics, administration of steroids for fetal lung maturation, and, when appropriate, group B streptococcus prophylaxis to decrease risk of maternal and neonatal infection. Bedrest, hydration, and pelvic rest have not been proved effective and are not recommended routinely.  B. TOCOLYTICS: Cornerstone of primary pharmacologic management. May lengthen duration of pregnancy by several days to allow time for steroid administration and possible transfer to a tertiary care facility. Choice of agent should be based on maternal condition, drug side effects, and gestational age. Use in consultation with obstetrician.

Nifedipine GENERAL INFORMATION: With their potential efficacy for inhibiting contractility in myometrial tissue, calcium channel blockers may be useful in prolonging PRETERM LABOR leading to improved survivability and morbidity in premature infants. Current data suggests this is achieved with minimal adverse effects to the mother or fetus. Nifedipine is the most widely studied member of this class, and it has shown comparable effectiveness when compared to standard beta sympathomimetic agents such as ritodrine and terbutaline. Additionally, some evidence suggests that calcium antagonists might be combined with standard therapies to control maternal side effects induced by sympathomimetics. However, general application cannot be recommended and their use as tocolytics should be considered inconclusive and investigational (Steer, 1999; Monga & Creasy, 1995; McCombs, 1995; Higby et al, 1993; Leonardi & Hankins, 1992).

建議劑量 CALCIUM CHANNEL BLOCKERS: NIFEDIPINE: ADULTS: 30 mg loading dose, then 10 to 20 mg orally Q4-6H.

Nifedipine 與 Ritodrine 的比較 A randomized trial (n=52) failed to demonstrate an efficacy difference between ritodrine (0.05 to 0.35 milligram/minute IV for 12 hours, then 5 mg every 3 hours orally) and nifedipine (loading dose of 10 mg sublingually plus 20 mg orally, then 10 to 20 mg orally every 4 to 6 hours) in terms of postponing delivery or neonatal outcomes. However, nifedipine-treated subjects experienced significantly fewer and less severe adverse effects (Garcia-Velasco et al, 1998). Data from another trial (n=102) also support equivalent tocolytic efficacy of nifedipine and ritodrine. Dosing consisted of 0.2 to 0.4 milligram/minute IV ritodrine with conversion to oral ritodrine 80 mg 3 times daily, or 30 mg sublingual nifedipine followed by oral nifedipine 40 to 120 mg daily. During the first 7 days of therapy, the incidence of adverse effects was significantly higher in the ritodrine group (Koks et al, 1998).

Nifedipine 與 Ritodrine 的比較 Nifedipine was just as effective as ritodrine for delaying delivery for either 48 hours, 7 days, or until the 36th week of gestation (Kupferminc et al, 1993; Ferguson et al, 1990). Regimens compared sublingual nifedipine (10 to 50 mg), with a maintenance dose of 20mg every 4 to 8 hours. Ritodrine was initiated at 50 mcg/minute, increased by 15 to 50 mcg/minute until a maximum of 300 to 350 mcg/minute was administered, uterine contractions stopped, or unacceptable side effects occurred. Delivery was delayed more than 48 hours in 83% to 84% of the patients treated with nifedipine and 72% to 77% in patients treated with ritodrine. Maternal side effects were less frequent with nifedipine. Fetal and neonatal outcomes were similar for both treatments and studies.

Summery 1. 目前 FDA 核准用於安胎藥物只有 Ritodrine 2.Nifedipine-treated subjects experienced significantly fewer and less severe adverse effects 3.Maternal side effects were less frequent with nifedipine

資料來源 ~ 1.Micromedex 2.Obstetrics and Gynecology: November 2002 Volume 100, Number 5, Part 1 Pages