Re: procardia and magnesium

From: Efrain Ramirez (eramirezt@coqui.net)
Thu May 15 13:12:22 2008


This might help..

Ef

Pharmacokinetics and MetabolismPROCARDIA is rapidly and fully absorbed after oral administration. The drug is detectable inserum 10 minutes after oral administration, and peak blood levels occur in approximately30 minutes. Bioavailability is proportional to dose from 10 to 30 mg; half-life does not changesignificantly with dose. There is little difference in relative bioavailability when PROCARDIA capsules are given orally and either swallowed whole, bitten and swallowed, or bitten and held sublingually. However, biting through the capsule prior to swallowing does result in slightlyearlier plasma concentrations (27 ng/mL 10 minutes after 10 mg) than if capsules are swallowed intact. It is highly bound by serum proteins. PROCARDIA is extensively converted to inactive metabolites and approximately 80 percent of PROCARDIA and metabolites are eliminated viathe kidneys. The half-life of nifedipine in plasma is approximately two hours. Since hepatic biotransformation is the predominant route for the disposition of nifedipine, the pharmacokinetics may be altered in patients with chronic liver disease. Patients with hepaticimpairment (liver cirrhosis) have a longer disposition half-life and higher bioavailability of

-------------------------------------------------------------------------------- Page 3 -------------------------------------------------------------------------------- 3nifedipine than healthy volunteers. The degree of serum protein

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binding of nifedipine is high(92–98%).  Protein binding may be greatly
reduced in patients with renal or hepatic impairment.  In healthy
subjects, the elimination half-life of a BID sustained release
nifedipine formulation [that was neither Procardia Capsules nor
Procardia XL (nifedipine) Extended Release Tablets]was longer in elderly
subjects (6.7 h) compared to young subjects (3.8 h) following oral
administration.  A decreased clearance was also observed in the elderly
(348 ml/min) followingintravenous administration.  Co-administration of
nifedipine with grapefruit juice resulted in approximately a 2-fold
increasein nifedipine AUC and Cmax with no change in half-life.  The
increased plasma concentrations are most likely due to inhibition of CYP
3A4 related first-pass metabolism

Thu, 15 May 2008, Glen Elrod wrote: > >I understand that and even questioned our local MFM on mag. He still does occasionally. I didn't end up using it in this case and restarted her procardia the next morning, but I'm still curious from a scientific perspective how long to wait between procardia dose and magnesium start IF you were go >>ing to do it. > >Glen >

>>----- Original Message ---- >From: Efrain Ramirez <eramirezt@coqui.net> >To: Multiple recipients of list OB-GYN-L <ob-gyn-l@mail.obgyn.net> >Sent: Thursday, May 15, 2008 12:30:06 AM >Subject: Re: procardia and magnesium > >I stopped using MagS04 for TPL .. > >Ef > >Magnesium sulphate for preventing preterm birth in threatened preterm >labour >Crowther CA, Hiller JE, Doyle LW >Bookmark this: > more ... loading... please wait Summary >Magnesium sulphate given to women who go into labour too early does not >prevent their babies being born too soon and is associated with an >increased risk of the baby dying >Even short-term postponement of birth when labour begins early (before >37 weeks) can help improve outcomes for babies, as the woman can take >steroid drugs to help develop the baby's lungs in a short time. >Magnesium sulphate is one of the drugs used to try to stop the uterus >contracting in women who go into labour too soon. The review of trials >did not find that magnesium sulphate, given to women who go into labour >too soon, reduced the risks of the baby being born early or developing >serious health problems. More babies died when women took magnesium >sulphate. > >This is a Cochrane review abstract and plain language summary, prepared >and maintained by The Cochrane Collaboration, currently published in The >Cochrane Database of Systematic Reviews 2008 Issue 2, Copyright © 2008 >The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The >full text of the review is available in The Cochrane Library (ISSN >1464-780X). >This record should be cited as: Crowther CA, Hiller JE, Doyle LW. >Magnesium sulphate for preventing preterm birth in threatened preterm >labour. Cochrane Database of Systematic Reviews 2002, Issue 4. Art. >No.: CD001060. DOI: 10.1002/14651858.CD001060 > >This version first published online: October 21. 2002 >Date of last subtantive update: August 27. 2002 > >Abstract >Background >Magnesium sulphate is used to inhibit uterine activity in women in >preterm labour to prevent preterm birth. > >Objectives >To assess the effectiveness and safety of magnesium sulphate therapy >given to women in threatened preterm labour with the aim of preventing >preterm birth and its sequelae. > >Search strategy >We searched the Cochrane Pregnancy and Childbirth Group trials register >(May 2002) and the Cochrane Controlled Trials Register (The Cochrane >Library, Issue 2, 2002). > >Selection criteria >Types of participants: Women thought to be in preterm labour. > >Types of interventions: Magnesium sulphate as the only tocolytic, >administered intravenously or orally, compared with either placebo, no >treatment or alternative tocolytic therapy. > >Types of outcome measures: Measures of effectiveness, complications, >women's satisfaction with their care and health service use. > >Data collection and analysis >Assessments of trial eligibility, quality and data extractions were done >by at least two of the reviewers. > >Main results >Over 2000 women were recruited into the 23 included trials. Only nine >trials were rated of high quality for the concealment of allocation. In >the magnesium sulphate versus control (all studies) no difference was >seen for the risk of birth within 48 hours of treatment for women given >magnesium sulphate compared with controls when using a random effects >model (relative risk (RR) 0.85, 95% confidence interval (CI) 0.58-1.25, >11 trials, 881 women). No benefit was seen for magnesium sulphate on >the risk of giving birth preterm (<37 weeks) or very preterm (<34 >weeks). The risk of death (fetal and paediatric) was higher for infants >exposed to magnesium sulphate (RR 2.82, 95% CI 1.20-6.62, 7 trials, 727 >infants). There were only two fetal deaths, both in the magnesium >sulphate group in one study. The six other trials reported there were >no fetal deaths. No differences for total paediatric mortality were >shown in the six trials with data. > >No beneficial effect was seen from using magnesium sulphate on the risk >of other neonatal morbidity. A non-significant reduction in the risk of >cerebral palsy was reported at follow up at 18 months corrected age (RR >0.14, 95% CI 0.01-2.60, 1 trial, 99 children). > >Authors' conclusions >Magnesium sulphate is ineffective at delaying birth or preventing >preterm birth, and its use is associated with an increased mortality for >the infant. Any further trials should be of high quality, large enough >to assess serious morbidity and mortality, compare different dose >regimens, and provide neurodevelopmental status of the child. > >At Wed, 14 May 2008, Glen Elrod wrote: >> >>I know that procardia and magnesium should not be given together. But, does anyone know how long you need to have a patient off procardia before starting mag? For instance, someone on procardia for preterm labor and presents with breakthrough labor. >> >>Thanks, >> >>Glen >

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