Arzneimittelinteraktionen bei der medikamentösen Epilepsietherapie

D. Schmidt; G. Eckermann; U. Fuhr; G. Luef; B. J. Steinhoff; C. E. Elger

doi:10.1055/s-0038-1626950

Nervenheilkunde, Table of Contents

Nervenheilkunde 2007; 26(11): 969-980
DOI: 10.1055/s-0038-1626950

Arbeiten zum Schwerpunkt - Theme Articles

Schattauer GmbH

Arzneimittelinteraktionen bei der medikamentösen Epilepsietherapie

Ein kritischer ÜberblickDrug interactions and epilepsy treatment: A critical review

D. Schmidt

¹Arbeitsgruppe Epilepsieforschung, Berlin

,

G. Eckermann

²Fachkrankenhaus für Psychiatrie, Psychotherapie, Neurologie und Psychosomatik, Kaufbeuren

,

U. Fuhr

³Institut für Pharmakologie, Klinikum der Universität zu Köln

,

G. Luef

⁴Medizinische Universität Innsbruck, Österreich

,

B. J. Steinhoff

⁵Epilepsiezentrum Kork, Kehl-Kork

,

C. E. Elger

⁶Klinik für Epileptologie, Universität Bonn

› Author Affiliations

Abstract

Zusammenfassung

Interaktionen von Antiepileptika untereinander und mit Medikamenten für andere Erkrankungen oder mit körpereigenen Substanzen sind eine häufige, klinisch wichtige und oft vermeidbare Ursache für Komplikationen der oft lebenslangen Behandlung epilepsiekranker Menschen. Obwohl Interaktionen für einige Patienten auch vorteilhaft sein können, kommt es nach der derzeitigen, noch lückenhaften Datenlage bei 6% aller Patienten unter der Kombination mehrerer Antiepileptika zu klinisch relevanten, unerwünschten Wirkungen. Zudem kann infolge einer Interaktion auch ein Wirkungsverlust auftreten. Bei Interaktionen von enzyminduzierenden Antiepileptika mit anderen Medikamenten oder mit körpereigenen Substanzen kann es ebenfalls zu einer wesentlichen Wirkungsabschwächung kommen, beispielsweise bei onkologischen Behandlungen. Daher wird zur Prävention von unerwünschten Interaktionen empfohlen, falls möglich schon in der Ersttherapie vorher unbehandelter Patienten mit Epilepsie bevorzugt im Vergleich zu den klassischen Medikamenten gleich wirksame, aber interaktionsfreie oder interaktionsarme Antiepileptika einzusetzen.

Summary

Interactions among antiepileptic drugs, with medications used for other disorders or with endogenous substances are a common and important cause of clinically relevant and often preventable complications in chronic treatment of patients with epilepsy. Although interactions may also be beneficial in some patients, the available evidence suggests that in 6% of patients experiencing adverse effects an interaction is responsible. In addition drug interactions may lead to clinically relevant loss of therapeutic effect. Interaction of enzyme inducing AEDs with other medications or endogenous substances may also lead to clinically relevant loss of therapeutic effects, for example in oncology. To prevent undesirable interactions, we recommend to start treatment with antiepileptic drugs for epilepsy that are efficacious as classical AEDs but are not involved or less involved in drug interactions.

Schlüsselwörter

Epilepsietherapie - Antiepileptika - Arzneimittelinteraktionen - Kombinationstherapie - Wirkungsverlust - unerwünschte Wirkungen

Keywords

Epilepsy treatment - drug interactions - antiepileptic drugs - loss of effect - adverse effects - combination therapy

Full Text

References

Literatur
1 Anderson GD. Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs. Neurology 2004; 63: 3-8.
2 Arzneimittelkommisssion der Deutschen Ärzteschaft. Carbamazepin-Intoxikation durch Wechselwirkung mit Lopinavir/Ritonavir. Deutsches Ärzteblatt 2007; 119: A1336.
3 Basile VS, Masellis M, McIntyre RS. et al. Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. J Clin Psych 2001; 62: 45-66.
4 Bates DW, Spell N, Cullen DJ. et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA 1997; 277 (04) 307-311.
5 Bauer J, Blumenthal S, Reuber M, Stoffel-Wagner B. Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy. Neurology 2004; 62 (02) 243-246.
6 Bauer J, Isojarvi JI, Herzog AG. et al. Reproductive dysfunction in women with epilepsy: recommendations for evaluation and management. J Neurol Neurosurg Psychiatry 2002; 73 (02) 121-125.
7 Besag FMC, Berry DJ, Pool F, Newbery JE, Subel B. Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction?. Epilepsia 1998; 39: 183-187.
8 Beyenburg S, Schmidt D. Patienten mit Epilepsie und Angsterkrankungen: Diagnose und Behandlung. Nervenarzt 2005; 76 (09) 1077-1078.
9 Bilo L, Meo R. Epilepsy and polycystic ovary syndrome: where is the link?. Neurol Sci 2006; 27 (04) 221-230 Review.
10 Brickell K, Porter D, Thompson P. Phenytoin toxicity due to fluorouyramides (5FU/capecitabine): three case reports. Br J Cancer 2003; 89: 615-616.
11 Burchell B, Brierley CH, Rance D. Specificity of human UDP-glucuronosyltransferases and xenobiotic glucuronidation. Life Sci 1995; 57: 1819-1831.
12 Calandre EP, Rodriguez-Lopez C, Blazquez A, Cano D. Serum lipids, lipoproteins and apoliproteins A and B in epileptic patients treated with valproic acid, carbamazepine or phenobarbital. Acta Neurol Scand 1991; 83: 250-253.
13 Connell JM, Rapeport WG, Gordon S, Brodie MJ. Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine. Eur J Clin Pharmacol 1984; 26: 453-456.
14 Cozza KL, Amstrong SC, Oesterheld JR. Concise guide to drug interaction principles for medical practice. Cytochrome P450s, UGTS, P-glycoproteins. 2nd edition. Washington DC, London: American Psychiatric Publishing Inc; 2003
15 Crawford P. Interactions between antiepileptic drugs and hormonal contraception. CNS Drugs 2002; 16 (04) 263-272.
16 Cummings SR, Nevitt MC, Browner WS. et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fracture Research Group. N Engl J Med 1995; 332: 767-773.
17 Dansky LV, Andermann E, Andermann F. Marriage and fertility in epileptic patients. Epilepsia 1980; 21: 261-227.
18 Eiris J, Novo-Rodriguez MI, Del Rio M. et al. The effects on lipid and apolipoprotein serum levels of long-term carbamazepine, valproic acid and phenobarbital therapy in children with epilepsy. Epilepsy Res 2000; 41: 1-7.
19 Ethell BT, Anderson GD, Burchell B. The effect of valproic acid on drug and steroid glucuronidation by expressed human UDP-glucuronosyltransferases. Biochem Pharmacol 2003; 65: 1441-1449.
20 Faber MS, Fuhr U. Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clin Pharmacol Ther 2004; 76 (02) 178-184.
21 Findlay KA, Kaptein E, Visser TJ, Burchell B. Characterization of the uridine diphosphate-glucuronosyltransferase-catalyzing thyroid hormone glucuronidation in man. J Clin Endocrinol Metab 2000; 85: 2879-2883.
22 Fuhr U, Weiss M, Kroemer HK. et al. Systematic screening for pharmacokinetic interactions during drug development. Int J Clin Pharmacol Ther 1996; 34: 139-151.
23 Fuhr U. Drug interactions with grapefruit juice. Extent, probable mechanism and clinical relevance.Drug Saf 1998; 18 (04) 251-272.
24 Fuhr U. Induction of drug metabolising enzymes: pharmacokinetic and toxicological consequences in humans. Clin Pharmacokinet 2000; 38 (06) 493-504.
25 Hahn TJ, Hendin BA, Scharp CR, Boisseau BA, Haddad Jr JG. Serum 25-hydroxycalciferol levels and bone mass in children on chronic anticonvulsant therapy. N Engl J Med 1975; 292 (11) 550-554.
26 Hesslinger B, Normann C, Langosch JM. et al. Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients. J Clin Psychopharmacol 1999; 19: 310-315.
27 Isojärvi JI, Rättyä J, Myllylä VV. et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 1998; 43: 446-451.
28 Isojärvi JI, Airaksinen KE, Mustonen JN. et al. Thyroid and myocardial function after replacement of carbamazepine by oxcarbazepine. Epilepsia 1995; 36: 810-816.
29 Isojärvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KTS, Myllylä VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993; 329: 1383-1388.
30 Isojärvi JI, Löfgren E, Juntunen K. et al. Effect of epilepsy and antiepileptic drugs on male reproductive health. Neurology 2004; 62: 247-253.
31 Isojärvi JI, Pakarinen AJ, Rautio A, Pelkonen O, Myllylä MV. Serum sex hormone levels after replacing carbamazepine with oxcarbazepine. Eur J Clin Pharmacol 1995; 47: 461-464.
32 Isojärvi JI, Turkka J, Pakarinen AJ. et al. Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy. Epilepsia 2001; 42: 9300-9343.
33 Isojarvi JL, Laatikainen TJ, Knip M. et al. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 1996; 39: 579-584.
34 Isojarvi JL. Reproductive dysfunction in women with epilepsy. Neurology 2003; 61 (6 Suppl 2): S27-34.
35 Jallon P, Picard F. Body weight gain and anticonvulsants: a comparative review. Drug Saf 2001; 24: 969-975.
36 Kaufman KR, Gerner R. Lamotrigine toxicity secondary to sertraline. Seizure 1998; 07: 163-165.
37 Krämer G. Antiepileptika-Interaktionen 2007. Bad Honnef: Hippocampus; 2007: 1-44.
38 Kruse R. Osteopathies in antiepileptic long-term therapy (preliminary report). Monatsschr Kinderheilkd 1968; 116 (06) 378-381.
39 Lakehal F, Wurden CJ, Kalhorn TF, Levy RH. Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19. Epilepsy Res 2002; 52: 79-83.
40 Levy RH, Bishop F, Streeter AJ. et al. Explanation and prediction of drug interactions with topiramate using CYP450 inhibition spectrum. Epilepsia 1995; 36 (Suppl. 04) 47.
41 Louma PV, Sotaniemi EA, Peklonen R, Myllylä VV. Plasma high-density lipoprotein cholesterol and hepatic cytochrome P450 concentrations in epileptics undergoing anticonvulsant treatment. Scand J Clin Lab Invest 1980; 40: 163-167.
42 Luef G, Abraham I, Trinka E. et al. Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate. Epilepsy Res 2002; 48 (1–2): 91-102.
43 Luef G, Abraham I, Haslinger M. et al. Polycystic ovaries, obesity and insulin resistance in women with epilepsy. A comparative study of carbamazepine and valproic acid in 105 women. J Neurol 2002; 49 (07) 835-841.
44 Luef G, Abraham I, Hoppichler F. et al. Increase in postprandial serum insulin levels in epileptic patients with valproic acid therapy. Metabolism 2002; 51: 1247-1248.
45 Luef GJ, Lechleitner M, Bauer G, Trinka E, Hengster P. Valproic acid modulates islet cell insulin secretion: a positive mechanism of weight gain in epilepsy patients. Epilepsy Res 2003; 32: 557-558.
46 Mackenzie PI, Owens IS, Burchell B. et al. The UDP glucuronosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 1997; 07: 255-259.
47 Manon-Espaillat R, Burnstine TH, Remler B, Reed RC, Osorio I. Antiepileptic drug intoxication: factors and their significance. Epilepsia 1991; 32 (01) 96-100.
48 Morrell MJ. Guidelines for the care of women with epilepsy. Neurology 1998; 51 (Suppl. 04) 21-27.
49 Oberndorfer S, Piribauer M, Marosi C. et al. P450 enzyme inducing and non-enzyme inducing antiepileptics in glioblastoma patients treated with standard chemotherapy. J Neurooncol 2005; 72 (03) 255-260.
50 Pack AM, Morrell MJ, Marcus R. et al. Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol 2005; 57 (02) 252-257.
51 Pack AM, Olarte LS, Morrell MJ. et al. Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy Behav 2003; 04: 169-174.
52 Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurology 2003; 02: 473-481.
53 Patsalos PN, Fröscher W, Pisani F, van Rijn CM. The importance of drug interactions in epilepsy therapy. Epilepsia 2002; 43 (04) 365-385.
54 Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol 2003; 02: 347-356.
55 Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol 2006; 61 (03) 246-255.
56 Petty SJ, O’Brien TJ, Wark JD. Anti-epileptic medication and bone health. Osteopor Int 2007; 18: 129-142.
57 Pisani F, Oteri G, Russo MF, Di Perri R, Perucca E, Richens A. The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia 1999; 40 (08) 1141-1146.
58 Ragueneau-Majlessi I, Levy RH, Meyerhoff C. Lack of effect of repeated administration of levetiracetam on the pharmacodynamic and pharmacokinetic profiles of warfarin. Epilepsy Res 2001; 47: 55-63.
59 Rättyä J, Turkka J, Pakarinen AJ. et al. Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy. Neurology 2001; 56: 31-36.
60 Reddy MN. Effect of anticonvulsant drugs on plasma total cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A and B in children with epilepsy. Proc Soc Exp Biol Med 1985; 180: 359-363.
61 Relling MV, Pui CH, Sandlund JT. et al. Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia. Lancet 2000; 356 (9226): 285-290.
62 Rowan AJ, Ramsay RE, Collins JF. et al. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology 2005; 64 (11) 1868-1873.
63 Rowan AJ, Meijer JW, de Beer-Pawlikowski N, van der Geest P, Meinardi H. Valproate-ethosuximide combination therapy for refractory absence seizures. Arch Neurol 1983; 40 (13) 797-802.
64 Sabers A. et al. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsiy Res 2001; 47 (1–2): 151-154.
65 Schmid F. Osteopathien bei antiepileptischer Dauerbehandlung. Fortschr Med 1967; 85: 381-382.
66 Schmidt D, Elger CE. Praktische Epilepsiebehandlung. Stuttgart: Thieme; 2005
67 Schmidt D, Löscher W. Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms. Epilepsia 2005; 46 (06) 858-877.
68 Schmidt D, Elger CE, Steinhoff BJ. et al. Einsatz neuer Antiepileptika bei vorher unbehandelten Jugendlichen und Erwachsenen mit Epilepsie. Therapie-Empfehlungen. Nervenheilkunde 2004; 23: 354-362.
69 Sheth RD, Wesolowski CA, Jacob JC. et al. Effect of carbamazepine and valproate on bone mineral density. J Pediatr 1995; 127: 256-262.
70 Shimada T, Yamazaki H, Mimura M, Inui T, Guengerich FP. Interindividual variation in human liver cytochrome P450 enzymes involved in the oxidation of drugs, carcinogens, and toxic chemicals: studies with the microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 270: 414-423.
71 Sisodiya SM, Sander JW, Patsalos PN. Carbamazepine toxicity during combination with levetiracetam: a pharmacodynamic interaction. Epilepsy Res 2002; 48: 217-219.
72 Vainionpää LK, Mikkonen K, Rättyä J. et al. Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication. Epilepsia 2004; 45: 197-220.
73 Valimaki MJ, Tiihonen M, Laitinen K. et al. Bone mineral density measured by dual-energy X-ray absorptiometry and novel markers of bone formation and resorption in patients on antiepileptic drugs. J Bone Miner Res 1994; 09: 631-637.
74 Valmadrid C, Voorhees C, Litt B, Schneyer CR. Practice patterns of neurologists regarding bone and mineral effects of antiepileptic drug therapy. Arch Neurol 2001; 58 (09) 1369-1374.
75 Verrotti A, Basciani F, Morresi S. et al. Serum leptin changes in epileptic patients who gain weight after therapy with valproic acid. Neurology 1999; 53: 230-232.
76 Verrotti A, Basciani F, Morresi S, Morgese G, Chiarelli F. Thyroid hormones in epileptic children receiving carbamazepine and valproic acid. Pediatr Neurol 2001; 25: 43-46.
77 Victor A, Lundberg PO, Johansson ED. Induction of sex hormone binding globulin by phenytoin. BMJ 1977; 02: 934-935.
78 Wolf P. et al. Praxisbuch Epilepsien. Diagnostik– Behandlung – Rehabilitation. Stuttgart: Kohlhammer; 2003
79 Wong MC, Suite NDA, Labar DR. Seizures in human immunodeficiency virus infection. Arch Neurol 1990; 47: 640-642.
80 Wrighton SA, Stevens JC. The human hepatic cytochrome P450 involved in drug metabolism. Crit Rev Toxicol 1992; 22: 1-21.
81 Xu Y, Hashizume T, Shuhart MC. et al. Intestinal and hepatic CYP3A4 catalyze hydroxylation of 1 alpha,25-dihydroxyvitamin D(3): implications for drug-induced osteomalacia. Mol Pharmacol 2006; 69 (01) 56-65.
82 Yatham LN, Grossman F. et al. Mood stabilizers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial. Br J Psychiatry 2003; 182: 141-142.
83 Yin Ophelia QP. et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004; 14 (12) 841-850.
84 York DA, Singer L, Thomas S, Bray JA. Effect of topiramate on body weight and body composition of Osborne-Mendel rats fed a high-fat diet: alterations in hormones, neuropeptide, and uncouplingprotein mRNAs. Nutrition 2000; 16: 967-975.
85 Zhou S, Yung SChan, Cher BGoh. et al. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet 2005; 44 (03) 279-304.