Long-term Effect of Bariatric Surgery on the Use of Levothyroxine and Thyroid Levels.

BACKGROUND: The aim of this study was to evaluate the effect of bariatric surgery on the defined daily dose of levothyroxine (DDD LT4), thyroid-stimulating hormone (TSH), and free thyroxine (fT4) in female patients with hypothyroidism until 48 months after surgery. METHODS: A retrospective observational study of hypothyroid patients who underwent bariatric surgery. Changes in DDD LT4, TSH, and fT4 over a 48 month period after surgery were analyzed. RESULTS: Thirty-seven patients were included: 27 Roux-en-Y gastric bypass (RYGB), 6 sleeve gastrectomy (SG), 3 adjustable gastric band, and 1 one anastomosis gastric bypass. The median DDD LT4 decreased from 125 µg at baseline to 100 µg 12 months after surgery. From 24 to 48 months after surgery, the median DDD LT4 was stable at 125 µg. Most dose adjustments occurred during the first 24 months after surgery. In the time period of 24-48 months after surgery, the dose remained stable in 73.1% of the RYGB patients and in 60.0% of the SG patients. After 48 months in the RYGB group, no significant change in TSH and fT4 levels was observed. CONCLUSIONS: Bariatric surgery led to frequent dose adjustments during the first 2 years after surgery. However, 24-48 months after surgery in the majority of patients, the dosage remained stable. No significant change in TSH and fT4 was observed 48 months after RYGB. In the first 2 years after surgery, clinicians should frequently monitor TSH and fT4 for individual dose adjustment of levothyroxine. Thereafter, the frequency of monitoring may be decreased.

Therapeutic Drug Monitoring of Antiepileptic Drugs in Women with Epilepsy Before, During, and After Pregnancy.

During pregnancy, the pharmacokinetics of an antiepileptic drug is altered because of changes in the clearance capacity and volume of distribution. These changes may have consequences for the frequency of seizures during pregnancy and fetal exposure to antiepileptic drugs. In 2009, a review was published providing guidance for the dosing and therapeutic drug monitoring of antiepileptic drugs during pregnancy. Since that review, new drugs have been licensed and new information about existing drugs has been published. With this review, we aim to provide an updated narrative overview of changes in the pharmacokinetics of antiepileptic drugs in women during pregnancy. In addition, we aim to formulate advice for dose modification and therapeutic drug monitoring of antiepileptic drugs. We searched PubMed and the available literature on the pharmacokinetic changes of antiepileptic drugs and seizure frequency during pregnancy published between January 2007 and September 2018. During pregnancy, an increase in clearance and a decrease in the concentrations of lamotrigine, levetiracetam, oxcarbazepine's active metabolite licarbazepine, topiramate, and zonisamide were observed. Carbamazepine clearance remains unchanged during pregnancy. There is inadequate or no evidence for changes in the clearance or concentrations of clobazam and its active metabolite N-desmethylclobazam, gabapentin, lacosamide, perampanel, and valproate. Postpartum elimination rates of lamotrigine, levetiracetam, and licarbazepine resumed to pre-pregnancy values within the first few weeks after pregnancy. We advise monitoring of antiepileptic drug trough concentrations twice before pregnancy. This is the reference concentration. We also advise to consider dose adjustments guided by therapeutic drug monitoring during pregnancy if the antiepileptic drug concentration decreases 15-25% from the pre-pregnancy reference concentration, in the presence of risk factors for convulsions. If the antiepileptic drug concentration changes more than 25% compared with the reference concentration, dose adjustment is advised. Monitoring of levetiracetam, licarbazepine, lamotrigine, and topiramate is recommended during and after pregnancy. Monitoring of clobazam, N-desmethylclobazam, gabapentin, lacosamide, perampanel, and zonisamide during and after pregnancy should be considered. Because of the risk of teratogenic effects, valproate should be avoided during pregnancy. If that is impossible, monitoring of both total and unbound valproate is recommended. More research is needed on the large number of unclear pregnancy-related effects on the pharmacokinetics of antiepileptic drugs.