Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring

Landmark, Cecilie Johannessen; Johannessen, Svein I.; Tomson, Torbjörn

doi:10.1684/epd.2016.0880

Cited by 61 publications

(67 citation statements)

References 77 publications

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“…10,12 The interaction potential is therefore seen as low, even though interactions with some antacids and analgesics have been reported. 15 The reference range for GBP in epilepsy in Norway is 20-120 µmol/L under drug fasting conditions at steady state, 16 similar to international recommendations. 15 The reference range for GBP in epilepsy in Norway is 20-120 µmol/L under drug fasting conditions at steady state, 16 similar to international recommendations.…”

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confidence: 59%

“…This will then minimize the risk of adverse effects due to high concentrations, while still enabling adequate serum concentration at all times to avoid breakthrough seizures, as measured by the through concentration, drug fasting in the morning 7,15. Furthermore, concentrations that may have resulted in adverse effects such as tiredness or dizziness during the day may be tolerable at night.…”

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confidence: 99%

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Therapeutic drug monitoring of gabapentin in various indications

et al. 2019

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Objectives Gabapentin has been increasingly used in various indications in recent years. Despite variable pharmacokinetics, therapeutic drug monitoring (TDM) is scarcely described in other indications than epilepsy. The aim of the study was to investigate the use and pharmacokinetic variability of gabapentin in epilepsy and non‐epilepsy indications and to further evaluate the use of TDM in patients with restless legs syndrome (RLS). Materials & Methods Population‐based data from the Norwegian Prescription Database, retrospective TDM data from the section for Clinical Pharmacology, the National Center for Epilepsy, Norway, and prospective observational data on patients with RLS were used. Results The use of gabapentin increased by 30% from 2014 to 2017 (32 181 to 42 675 users). TDM data from 120 patients showed a 22‐fold pharmacokinetic variability in concentration/dose ratios, and this ratio was elevated in elderly patients (≥65 years). The majority of elderly used gabapentin for non‐epilepsy indications. In patients with RLS, intake in the evening/night only was common due to nocturnal symptoms, in contrast to regular dosing regimens in epilepsy. Thus, drug fasting concentrations do not reflect concentrations at the time of required therapeutic effect. TDM was still found useful in most patients to support dosage increase or evaluate adverse effects. Conclusion Due to extensive pharmacokinetic variability, TDM can benefit patients using gabapentin. Challenges with applying TDM in new indications such as RLS include different dosage regimens and consequently different interpretation of serum concentrations. Thus, TDM should be requested on clear clinical grounds and the service tailored according to the therapeutic indication.

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confidence: 99%

Therapeutic drug monitoring of gabapentin in various indications

et al. 2019

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“…Dose optimization based on measured blood concentration is called therapeutic drug monitoring (TDM) and can be valuable for drugs with a small therapeutic window, an established exposure–response relationship and large interpatient PK variability, all applicable for TKIs . TDM guided dosing is routinely used for anti‐epileptics, antibiotics, immunosuppressive agents and within oncology for methotrexate (MTX), mitotane and busulfan, but is less common for TKIs despite a similar level of available evidence that optimizing the dose will result in less toxicity or better efficacy . For an increasing number of TKIs a target threshold has been defined and TDM based dosing seems promising .…”

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confidence: 99%

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Westerdijk¹,

Desar²,

Steeghs

et al. 2020

Brit J Clinical Pharma

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Tyrosine kinase inhibitors (TKIs) are anti‐cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure‐treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic drug monitoring (TDM), can be valuable in increasing efficacy and reducing the toxicity of these drugs. In this review, an overview of the current knowledge on TDM guided individualized dosing of imatinib, sunitinib and pazopanib for the treatment of solid tumours is presented. We summarize preclinical and clinical data that have defined thresholds for efficacy and toxicity. Furthermore, PK models and factors that influence the PK of these drugs which partly explain the interpatient PK variability are summarized. Finally, pharmacological interventions that have been performed to optimize plasma concentrations are described. Based on current literature, we advise which methods should be used to optimize exposure to imatinib, sunitinib and pazopanib.

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“…12,13 It is not certain, however, that all people with JME need treatment with AEDs throughout life. 12,13 It is not certain, however, that all people with JME need treatment with AEDs throughout life.…”

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Antiepileptic drug withdrawal in juvenile myoclonic epilepsy

et al. 2018

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Juvenile myoclonic epilepsy (JME) is the most common type of epilepsy affecting adolescents, and it is hallmarked by myoclonic jerks, predominantly after awakening, aggravated by sleep deprivation and stress. 1 The majority of patients have occasional generalized tonicclonic seizures (GTCS), and about one-third have absence seizures. 2The antiepileptic drugs (AEDs) most commonly used in the treatment of JME are valproate, lamotrigine, levetiracetam, topiramate, and zonisamide. 3 Juvenile myoclonic epilepsy was initially considered a manageable type of epilepsy, with intellectual abilities within the normal range, normal neurologic examination, normal magnetic resonance imaging of the brain, and a favorable response to treatment in the majority of patients. 4,5 However, the rate of relapse upon withdrawal of AEDs was high, and the general advice was that these patients ought to continue medication throughout life. 5-7 Smaller, but more Objectives: Withdrawal of antiepileptic drugs (AEDs) has been discouraged in juvenile myoclonic epilepsy (JME). However, impulsivity as a consequence of executive dysfunction in JME may influence treatment adherence. The aim of the present study was to assess how common withdrawal of AEDs is in a large and representative JME group. Materials and methods:Patients with genetic generalized epilepsy (GGE) were identified through a retrospective search of medical records at Drammen Hospital, Norway, and invited to a clinical interview. Information related to AED withdrawal was analyzed in those classified as JME.Results: A total of 132 patients with GGE were interviewed (87 JME). Thirty-five patients with JME (40%) discontinued AEDs, of which 74% did so without consulting a doctor. The rate of self-withdrawal was significantly higher in JME than in other types of GGE. Having a parent with psychosocial difficulties was significantly overrepresented in the JME self-withdrawal group. Twelve of those who discontinued AEDs (34%) were free from generalized tonic-clonic seizures (GTCS) and without antiepileptic drugs >1 year. All but one of them withdrew AEDs without consulting a doctor. Age at first motor seizure was significantly higher in those with a favorable outcome of AED withdrawal. Conclusions: Self-withdrawal of AEDs is common in JME, especially in those with troublesome conditions at home. However, about 1/3 may remain free from GTCS without AEDs. The findings indicate a need for a stronger follow-up with appropriate information about the prognosis of the disorder. K E Y W O R D Sadherence, antiepileptic drugs, juvenile myoclonic epilepsy, withdrawal

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Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring

Cited by 61 publications

References 77 publications

Therapeutic drug monitoring of gabapentin in various indications

Therapeutic drug monitoring of gabapentin in various indications

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Antiepileptic drug withdrawal in juvenile myoclonic epilepsy

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