Topiramate Decreases Lamotrigin Concentrations

Wnuk, W; Volanski, A; Foletti, G.

doi:10.1097/00007691-199908000-00094

Cited by 18 publications

(12 citation statements)

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“…TPM in bitherapy did not show any effect on LTG metabolism and also did not affect the inhibitive effect of VPA in triple therapy. Lack of influence of TPM on LTG metabolism, similarly to our studies, was described previously by Berry et al and Doose et al Contrary to that, Wnuk et al mentioned inductive effect of TPM on LTG in a seven‐patient study. Reimers et al described weak inhibitory effect of LEV in children, while, similarly to our findings, Otoul et al reported no effect in children, but their samples were taken 2‐8 hours after drug ingestion.…”

Section: Discussionsupporting

confidence: 90%

Lamotrigine drug interactions in combination therapy and the influence of therapeutic drug monitoring on clinical outcomes in paediatric patients

Kořístková

Grundmann

Brozmanová

et al. 2019

Basic Clin Pharma Tox

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The aim was to study the impact of therapeutic drug monitoring (TDM) on paediatric patients on lamotrigine therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations. During the period of 2001‐2015, 1308 pre‐dose samples were taken from 430 patients <15 years of age as part of routine TDM. Drug interactions were evaluated using calculation of lamotrigine clearance. Valproic acid decreased lamotrigine clearance by 54% in bitherapy, and by 21% in triple therapy with carbamazepine. Carbamazepine increased lamotrigine clearance by 191% in bitherapy. Levetiracetam and topiramate had no effect. The upper limit of lamotrigine therapeutic range (TR) was exceeded in 2% of cases in monotherapy, and in 6%‐7% of cases in bi‐ or triple therapy. About 61% of plasma levels were found within the TR during 2001‐2005, compared to 75% and 74% during 2006‐2010 and 2011‐2015, respectively. Adverse drug reactions (ADRs) were reported in 22 cases. Higher number of supratherapeutic levels in combination therapy led to a 3‐fold increase in incidence of ADRs. Seizures occurred more often daily and monthly during 2001‐2005 and in patients with three or four antiepileptic drugs in combination. Carbamazepine only partially compensated for the inhibitory effect of valproic acid. Lamotrigine clearance in monotherapy in children is similar to adults, but in polytherapy was found higher susceptibility to induction. A significantly higher number of supratherapeutic lamotrigine levels were found in combinations with valproate. Despite poor correlation with TR, both seizure frequency and ADRs declined after the implementation of TDM.

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Section: Discussionsupporting

confidence: 90%

Lamotrigine drug interactions in combination therapy and the influence of therapeutic drug monitoring on clinical outcomes in paediatric patients

Kořístková

Grundmann

Brozmanová

et al. 2019

Basic Clin Pharma Tox

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“…There are no previous reports of studies that have investigated whether there is a pharmacokinetic interaction between TPM and LTG. However, after the preliminary presentation of the current results in 1998 (11), Wnuk et al (12) reported a small study of seven patients who were maintained on stable LTG treatment of 350-800 mg/day while the TPM dose was escalated to 100-800 mg/day. The LTG and TPM doses were similar to those used in our study.…”

Section: Discussionmentioning

confidence: 94%

Lack of an Effect of Topiramate on Lamotrigine Serum Concentrations

Berry

Besag²,

Pool³

et al. 2002

Epilepsia

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Summary:Purpose: Pharmacokinetic interactions between the older antiepileptic drugs (AEDs) and topiramate (TPM) were assessed during the clinical development of this drug. Lamotrigine (LTG) has become established as an important new drug in treating a wide spectrum of seizure types, but there are no published data on whether LTG serum concentrations change when TPM is added to treatment.Methods: Escalating doses of TPM were added to stable LTG treatment in 24 young patients (8-21 years) with epilepsy. Blood samples taken before the morning dose were collected for drug-concentration measurement in all patients before starting treatment with TPM and after stabilisation at each dose escalation. Several patients had been maintained on unchanged therapy with drug-concentration monitoring for many months before introducing TPM, and a sequence of baseline LTG serum concentrations were available on these patients. Results:The mean of all baseline LTG concentrations for the group as a whole was 10.4 ± 4.4 mg/L compared with 9.7 ± 4.3 mg/L after addition of TPM. A comparison of last baseline LTG concentration with first test LTG concentration (i.e., after 2 weeks' TPM treatment) gave mean values of 10.7 ± 4.7 and 10.8 ± 4.6 mg/L, respectively. The mean LTG concentration for patients while taking their highest TPM dose was 9.5 ± 4.3 mg/L. The analysis-of-variance modeling for the effect of TPM on LTG concentration yielded a mean LTG concentration ratio (with TPM vs. without TPM) of 94.2%, with a 90% confidence interval of 89.5-99.1%.Conclusions: TPM did not cause a significant change in LTG serum concentration in this group of patients.

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“…Evidence regarding the effect of TPM on LTG pharmacokinetics is mixed. In a small study of seven patients receiving stable LTG treatment (350–800 mg/day) (Wnuk et al., 1999), four of the seven patients comedicated with LTG and TPM had LTG concentrations 40–50% lower compared with those during monotherapy. Other studies have reported no effect of TPM on LTG pharmacokinetics at mean doses of <400 mg/day (Berry et al., 2002; Doose et al., 2003).…”

Section: Discussionmentioning

confidence: 99%

The effect of age and comedication on lamotrigine clearance, tolerability, and efficacy

et al. 2011

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SUMMARYPurpose: To compare pharmacokinetics, tolerability, and efficacy of lamotrigine (LTG) in older versus younger adults. Methods: We studied 686 adult outpatients seen at our center over 5 years. We compared apparent clearance (CL) of LTG in the youngest (16-36 years; n = 247) and oldest (55-92 years; n = 155) tertiles. We analyzed oneyear retention for younger and older adults newly started on LTG, frequency of adverse effects causing intolerability, and rates of specific adverse effects. We also investigated 6-month seizure freedom. Key Findings: Median LTG CL of older adults taking LTG in monotherapy was approximately 22% lower compared to younger adults (28.8 vs. 36.5 ml/h/kg; p < 0.001). LTG CL in older adults was lower compared to younger adults in patients on polytherapy and on polytherapy without enzyme inducers or valproate. One-year retention for LTG was comparable in older (78.1%, 121/155) and younger (72.4%, 179/247) adults. Intolerability to LTG was higher in older (34.8%) versus younger adults (24.2%; p = 0.005). Imbalance, drowsiness, and dizziness were common intolerable side effects in both groups. Older patients had higher rates of intolerability due to imbalance (16% vs. 4%), drowsiness (13% vs. 7%), and tremor (5% vs. 2%) compared with younger patients. Rates of 6-month seizure freedom were comparable, and small numbers of each group benefited from very high levels of LTG (>15 lg/ml). Significance: LTG CL in monotherapy in older adults is approximately 20% lower than in younger adults. For a given serum LTG level, older adults are twice as likely to have significant adverse effects compared to younger adults. Older patients are more likely to experience imbalance, drowsiness, and tremor than younger patients. Younger adults tolerate LTG better than older adults, but one-year retention is comparable. Some patients may benefit from high serum levels of LTG. KEY WORDS: Antiepileptic drug, Older adults, Drug interactions, Elderly, Pharmacokinetics.Lamotrigine (LTG) is a commonly used antiepileptic drug (AED) that received approval by the U.S. Food and Drug Administration (FDA) in 1994 as adjunctive therapy for partial seizures in adults and later in pediatric patients (at least 2 years of age). In addition, LTG has been approved for conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), primidone (PRM), or valproate (VPA) as the single AED (August, 2005;Gilliam et al., 1998) and for adjunctive treatment of primary generalized tonic-clonic seizures and generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients aged 2 years or older.The clinical management of seizures in older adults is often complicated by an increased likelihood of adverse effects (AEs) and potential interactions with multiple comedications. The effect of age and comedication on LTG pharmacokinetics in older adults has not been well studied. In this study we investigated drug and nondrug predictors of LTG clearan...

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Topiramate Decreases Lamotrigin Concentrations

Cited by 18 publications

References 0 publications

Lamotrigine drug interactions in combination therapy and the influence of therapeutic drug monitoring on clinical outcomes in paediatric patients

Lamotrigine drug interactions in combination therapy and the influence of therapeutic drug monitoring on clinical outcomes in paediatric patients

Lack of an Effect of Topiramate on Lamotrigine Serum Concentrations

The effect of age and comedication on lamotrigine clearance, tolerability, and efficacy

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