Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk

Nitsun, Martin; Szokol, Joseph W.; Saleh, Hesham; Murphy, Glenn S.; Vender, Jeffery S.; Luong, L.; Raikoff, Kiril; Avram, Michael J.

doi:10.1016/j.clpt.2006.02.010

Cited by 93 publications

(60 citation statements)

References 32 publications

(51 reference statements)

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“…Methods using HPLC-UV, [12][13][14][15] GC-MS, 16) and LC-MS, [17][18][19][20][21][22] have been used to determine the fentanyl concentration in plasma [18][19][20]22) and breast milk. 21) Liquid chromatographytandem mass spectrometry (LC-MS/MS) provides a rapid, sensitive, and specific analysis.…”

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confidence: 99%

A Simple Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Plasma Fentanyl Concentration in Rats and Patients with Cancer Pain

Hisada

Katoh

Hitoshi

et al. 2013

Biological & Pharmaceutical Bulletin

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A fentanyl patch is widely used for the treatment of cancer pain. Its few adverse effects include constipation and drowsiness. The absorption volume of transdermally applied fentanyl may differ according to its site of application and variability in patch adhesion. Since fentanyl is predominantly metabolized by the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 in the liver, its concentration may vary in cases of physiologically reduced CYP3A4 activity in the liver (liver disease and aging) or on co-administration of drugs. The clinical significance of measuring plasma concentration of fentanyl is high, but conventional methods require complicated processes such as solid-phase extraction and liquid-liquid extraction before the sample is injected into an HPLC system. In this study, a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determining plasma fentanyl concentrations by deproteinization with acetonitrile. A recovery test was conducted using an absolute calibration curve to confirm the method's linearity and inter-and intra-day reproducibility. The required plasma volume for detection was reduced from 1 mL in the conventional method to 20 µL in the present study, and a good calibration curve was obtained in the concentration range from 0.05 to 5 ng/mL. These findings suggest that the method for sample preparation and quantification developed in this study are appropriate for measuring fentanyl concentration in human plasma in clinical settings.

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confidence: 99%

A Simple Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Plasma Fentanyl Concentration in Rats and Patients with Cancer Pain

Hisada

Katoh

Hitoshi

et al. 2013

Biological & Pharmaceutical Bulletin

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“…16 A return to baseline mentation and strength suggests that sedating medications have redistributed from the plasma and milk compartment to the adipose and muscle and are being slowly released back into the plasma. For additional safety, mothers should closely monitor their infant for signs and symptoms of behavioral changes while consuming medications.…”

Section: Resultsmentioning

confidence: 99%

“…Given the low bioavailability of fentanyl and its short duration of action, the authors recommended resuming breastfeeding in the postoperative period when the mother is alert with reasonable intraoperative fentanyl doses. 16,18 There is no literature regarding morphine and hydromorphone as part of a "balanced anesthetic" during cesarean delivery. Their analgesia data and suggestions are provided in the following section on postpartum analgesia.…”

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confidence: 99%

“…15 In a study of five breastfeeding mothers, 2 mg of midazolam was administered with general anesthesia and breast milk samples were collected during a 24-hour period and analyzed for midazolam concentration. 16 A 24-hour breast milk collection contained 0.004% (0.08 ug) of the maternal dose of midazolam. The authors concluded that breastfeeding should not be interrupted because of midazolam usage.…”

mentioning

confidence: 99%

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Breastfeeding after Anesthesia: A Review for Anesthesia Providers Regarding the Transfer of Medications into Breast Milk

Cobb

Liu

Valentine

et al. 2015

Transl Perioper & Pain Med

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Brief Summary:Doctors, nurses, and midwives often inform mothers to "pump and dump" their breast milk for 24 hours after receiving anesthesia to avoid passing medications to the infant. This advice, though cautious, is probably outdated. This review highlights the more recent literature regarding common anesthesia medications, their passage into breast milk, and medication effects observed in breastfed infants. We suggest continuing breastfeeding after anesthesia when the mother is awake, alert, and able to hold her infant. We recommend multiple types of medications for pain relief while minimizing sedating medications. Few medications can have sedating effects to the infant, but those medications are specifically outlined. For additional safety, anesthesia providers and patients may screen medications using the National Institute of Health' LactMed database. INTRODUCTIONThe positive impact of breastfeeding for both mothers and infants has been well established.1, 2 Given the difficulty of conducting randomized clinical trials in breastfeeding mothers and their infants however, there is a paucity of human data regarding the transfer of anesthesia and analgesia medications into breast milk. Available information remains limited to case studies, small sample observations, and animal studies, which may or may not accurately reflect conditions for lactating women. 3,4 This lack of knowledge may lead mothers who require medication to abandon nursing on their own accord or based on conservative advice from healthcare practitioners who are concerned about possible adverse effects in the infant. 5 In addition, physicians, hospitals, and even patients continue to rely on the information given by drug manufacturers concerning the use of drugs during breastfeeding, which is often restrictive or similarly contains contraindications for the lactation period. The lack of agreement among physicians, the FDA, and hospital policy has created different recommendations and practices regarding, 1) the interval between medication administration and breastfeeding, 2) when to "pump and dump", and most importantly, 3) which medications are safe. This review highlights the most recent medical literature concerning breastfeeding and the perioperative use of common medications by anesthesia providers during the intraoperative, intrapartum, postoperative and postpartum periods. 6 The review is focused only on opioid-naïve patients as evidence addressing recommendations in opioid-tolerant lactating mothers remain non-existent. Information presented in this review is written on the premise that data is limited and most medications administered in this patient population have not been rigorously screened by the FDA for safety and efficacy. EVIDENCEThe transfer of medications into breast milk depends on pharmacological properties including protein binding, lipid solubility, molecular weight, pKa, and maternal plasma level of the drug. 7 In general, medications that are highly lipid soluble, less protein-bound, of lower molecular weight, or wit...

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“…Following single intraoperative doses of midazolam (2 mg), propofol (2.5 mg/kg), and fentanyl (100 mcg), less than 0.1% of the drugs were excreted into milk within 24 hours, suggesting that interruption of breastfeeding may not be required (Nitsun et al, 2006 Level III-3).…”

Section: Pain Management During Lactationmentioning

confidence: 99%

Safety of opioid patch initiation in Australian residential aged care

Gadzhanova

Roughead

Pont

2015

Medical Journal of Australia

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Objective: To explore opioid use by aged care facility residents before and after initiation of transdermal opioid patches. Design: A cross‐sectional cohort study, analysing pharmacy data on individual patient supply between 1 July 2008 and 30 September 2013. Setting: Sixty residential aged care facilities in New South Wales. Participants: Residents receiving an initial opioid patch during the study period. Main outcome measure: The proportion of residents who were opioid‐naive in the 4 weeks prior to patch initiation was determined. In addition, the patch strength at initiation and the daily dose of transdermal patches and of additional opioids 1 month after initiation were determined. Results: An opioid patch was initiated in 596 of 5297 residents (11.3%: 2.6% fentanyl, 8.7% buprenorphine) in the 60 residential aged care facilities. The mean age at initiation was 87 years, and 74% of the recipients were women. The proportion of recipients who were opioid‐naive before patch initiation was 34% for fentanyl and 49% for buprenorphine. Most were initiated at the lowest available patch strength, and the dose was up‐titrated after initiation. Around 15% of fentanyl users and 10% of buprenorphine users needed additional regular opioids after patch initiation. Conclusions: The results suggest some inappropriate initiation of opioid patches in Australian residential aged care facilities. Contrary to best practice, a third of residents initiated on fentanyl patches were opioid‐naive in the 4 weeks before initiation.

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Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk

Abstract: The amount of midazolam, propofol, and fentanyl excreted into milk within 24 hours of induction of anesthesia provides insufficient justification for interrupting breast-feeding.

Cited by 93 publications

References 32 publications

A Simple Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Plasma Fentanyl Concentration in Rats and Patients with Cancer Pain

A Simple Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Plasma Fentanyl Concentration in Rats and Patients with Cancer Pain

Breastfeeding after Anesthesia: A Review for Anesthesia Providers Regarding the Transfer of Medications into Breast Milk

Safety of opioid patch initiation in Australian residential aged care

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