Stability of Direct Oral Anticoagulants and Antiarrhythmic Drugs in Serum Collected in Standard (Nongel) Serum Tubes Versus Tubes Containing Gel Separators.

BACKGROUND: Separation gels are often used in collection tubes, but adsorption of drugs onto the gel may cause falsely low concentrations in therapeutic drug monitoring. In this study, the stability of apixaban, edoxaban, rivaroxaban, flecainide, amiodarone, and desethylamiodarone was assessed in tubes, with and without gel separators. METHODS: Drug-free blood was spiked and stored for up to 7 days in nongel tubes and gel tubes from 2 manufacturers (Vacuette and Vacutainer). The samples were analyzed in triplicates using ultra-high-pressure liquid chromatography-tandem mass spectrometry. RESULTS: At ambient temperature conditions, the serum concentrations of apixaban, edoxaban, and rivaroxaban in a tube with acrylic-based gel had already decreased at baseline, whereas it took 6 hours to observe the same result in a tube with olefin-based gel. At 4°C, the reduction in serum concentration was considerably slower. For flecainide, the gel tube concentrations were stable at ambient temperature for 3 days, but decreased after 7 days in acrylic-based gel tubes. Amiodarone and desethylamiodarone stored in gel tubes at 4°C showed decrease in concentrations after 24 hours and 6 hours, respectively. CONCLUSIONS: Acrylic-based gel tubes should not be used for any of the tested drugs. Although olefin-based gel tubes may be used for anticoagulants and flecainide, it is advisable to prefer nongel tubes as a general precaution.

Transfer of triptans into human breast milk and estimation of infant drug exposure through breastfeeding.

Clinical data on the transfer of triptans into human breast milk remain scarce. In a lactation study including 19 breastfeeding women with migraine, we examined the excretion of six different triptans into milk. Following intake of a single dose, each participant collected seven breast milk samples at predefined intervals up to 24 hours after dose. Triptan concentrations in milk were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infant drug exposure was estimated by calculating the relative infant dose (RID). Twenty-two breast milk sample sets were obtained for sumatriptan (n = 8), rizatriptan (n = 5), zolmitriptan (n = 4), eletriptan (n = 3), almotriptan (n = 1) and naratriptan (n = 1). Based on the average concentration in milk throughout the day, estimated mean RIDs (with range in parenthesis) were as follows: eletriptan 0.6% (0.3%-0.8%), sumatriptan 0.7% (0.2%-1.8%), rizatriptan 0.9% (0.3%-1.4%), almotriptan 1.8% (-), zolmitriptan 2.1% (0.7%-5.3%) and naratriptan 5.0% (-). Infant drug exposure through breastfeeding appears to be low and indicates that use of the triptans in this study is compatible with breastfeeding. Naratriptan may not be first choice in breastfeeding mothers initiating triptans during the neonatal period.

Risk perception, beliefs about medicines and medical adherence among pregnant and breastfeeding women with migraine: findings from a cross-sectional study in Norway.

OBJECTIVES: To examine risk perception, beliefs about migraine medications and medical adherence among pregnant and breastfeeding women with migraine. DESIGN AND SETTING: Cross-sectional study conducted in Norway from October 2013 to February 2014. Data were collected via an anonymous, electronic questionnaire. PARTICIPANTS: Women with migraine, either pregnant or having delivered within the previous 18 months. MAIN OUTCOMES: Women's perception of teratogenic risk (numeric rating scale 0-10) was obtained for 14 different drugs/substances, including medications commonly used in the acute treatment of migraine. Women's perspectives on migraine drug therapy were assessed by 10 statements from the Beliefs about Medicines Questionnaire (BMQ-Specific) and six pregnancy/breastfeeding-specific statements. Adherence to migraine treatment during pregnancy and breastfeeding period was assessed by maternal self-report. RESULTS: The study population included 401 women with migraine, of which 140 were pregnant and 261 were new mothers. More than 70% of the women reported use of migraine medications during pregnancy. Still, the majority severely overestimated the risk associated with migraine medications and were concerned about using medications to manage their migraine during pregnancy and breastfeeding. Almost 9 out of 10 women had at some point deliberately avoided using migraine medications during their pregnancy. Women reporting use of migraine medications, however, were more positive and overestimated to a lesser extent the risks of using such medications in pregnancy compared with their counterparts. CONCLUSIONS: Women with migraine severely overestimated the risk associated with migraine pharmacotherapy in pregnancy. The majority of women were concerned about use of migraine medications during pregnancy and breastfeeding and reported non-adherence to needed treatment. More attention should be focused on women's beliefs and concerns regarding migraine pharmacotherapy during pregnancy and breastfeeding in order to improve management of disease, reduce unfounded concerns and enhance adherence to needed treatment.

Systemic antibiotic prophylaxis prior to gastrointestinal surgery - is oral administration of doxycycline and metronidazole adequate?

BACKGROUND: Antibiotic prophylaxis is recommended prior to a wide range of gastrointestinal operations to reduce the rate of surgical site infections (SSIs). Traditional intravenous (IV) drugs are costly and their preparation strains nursing resources at the wards. While oral administration may attenuate these limitations, its use remains limited. We aimed to assess whether a dual oral antibiotic prophylaxis regimen provides adequate serum concentrations throughout the surgical procedure. METHODS: We measured serum concentrations of doxycycline and metronidazole following single oral doses of 400 mg doxycycline and 1200 mg metronidazole at first incision and repeated at wound closure in a cohort of patients undergoing elective gastrointestinal surgery. Both drugs were dispensed at least two hours before skin incision. Serum concentrations were compared to minimum inhibitory concentrations (MIC) and epidemiological cut-off values (ECOFFs) for relevant pathogens. RESULTS: Mean serum concentrations of doxycycline at first incision and at wound closure were 5.75 mg/L and 4.66 mg/L and of metronidazole 18.88 mg/L and 15.56 mg/L, respectively. Metronidazole concentrations were above ECOFF (2 mg/L) for relevant anaerobic species in 103/104 of patients in both samples. Doxycycline serum concentrations were above the ECOFF for common Enterobacteriaceae species (4 mg/L) in both samples in 58/104 patients (55.8%). CONCLUSIONS: A single dose of orally administered metronidazole provides adequate concentrations throughout surgery in a heterogeneous cohort of patients. Uncertainty persists regarding the adequacy of doxycycline concentrations, as the optimal serum level of doxycycline in a prophylactic setting has not been established.

Use of antimigraine medications and information needs during pregnancy and breastfeeding: a cross-sectional study among 401 Norwegian women.

PURPOSE: Migraine is highly prevalent among women of fertile age. The main objectives of this study were to describe the prevalence and patterns of use of antimigraine medications during pregnancy and breastfeeding and to identify maternal and migraine-related factors associated with medication use during pregnancy. METHODS: The study is a cross-sectional internet-based survey among pregnant women and new mothers with migraine conducted in Norway from October 1, 2013 to February 1, 2014. Descriptive statistics were used to explore patterns of medication use, and logistic regression analysis was performed to examine the association between maternal socio-demographic and migraine-related factors and use of antimigraine medications during pregnancy. RESULTS: Of the total 401 respondents, 34.9 % were pregnant and 65.1 % had delivered within the last 18 months. The majority reported use of antimigraine medications during pregnancy (73.3 %) and postpartum (64.8 %), yet less than a third considered their migraine to be optimally treated during pregnancy (31.7 %) and the breastfeeding period (27.2 %). The patterns of medication use markedly changed during pregnancy and postpartum. Women with moderate or severe migraine were more likely to use antimigraine medications during pregnancy compared to women with mild migraine. CONCLUSIONS: Despite the fact that antimigraine medications were commonly used, the majority of the women felt that their migraine was suboptimally treated during pregnancy and postpartum. There was a decline in the use of medicines in pregnancy and postpartum, and the patterns of use markedly changed. Efforts to improve treatment of women with migraine during pregnancy and breastfeeding should be undertaken.

Pharmacological treatment of migraine during pregnancy and breastfeeding.

Migraine affects up to 25% of women of reproductive age. In the majority of these women, migraine improves progressively during pregnancy, but symptoms generally recur shortly after delivery. As suboptimally treated migraine in pregnancy could have negative consequences for both mother and fetus, the primary aim of clinicians should be to provide optimal treatment according to stage of pregnancy, while minimising possible risks related to drug therapy. Nonpharmacological approaches are always first-line treatment, and should also be used to complement any required drug treatment. Paracetamol is the preferred drug for acute treatment throughout pregnancy. If paracetamol is not sufficiently effective, sporadic use of sumatriptan can be considered. NSAIDs such as ibuprofen can also be used under certain circumstances, though their intake in the first and third trimesters is associated with specific risks and contraindications. Preventive treatment should only be considered in the most severe cases. In women contemplating pregnancy, counselling is essential to promote a safe and healthy pregnancy and postpartum period for the mother and child, and should involve a dialogue addressing maternal concerns and expectations about drug treatment. This Review summarizes current evidence of the safety of the most common antimigraine medications during pregnancy and breastfeeding, and provides treatment recommendations for use in clinical practice.