natgillin/translations-raw huggingface dataset:
Lansoprazol er en syrepumpehæmmer, der hæmmer syresekretionen i ventriklen og anvendes til behandling af ulcus duodeni og benignt ulcus ventriculi, gastro- øsofageal reflukssygdom og tilknyttede lidelser.
Lansoprazole is a proton pump inhibitor that inhibits gastric acid secretion and is used for the treatment of duodenal and benign gastric ulcers, gastro- oesophageal reflux disease and associated conditions.
Den 30. november 2006 blev ansøgningen indbragt for voldgift i henhold til artikel 29 i direktiv 2001/ 83/ EF, med senere ændringer.
On 30 November 2006, the application has been referred and submitted for arbitration according to Article 29 of Directive 2001/ 83/ EC, as amended.
Referencemedlemsstaten godkendte produktet på grundlag af resultaterne af undersøgelsen i fastende tilstand, hvor bioækvivalens klart blev påvist, idet 90% sikkerhedsintervallerne for AUC og Cmax lå inden for det acceptable bioækvivalensinterval på 80- 125%.
The RMS approved the product on the basis of the results of the fasted study showed unequivocal equivalence as shown by the 90% confidence intervals (CI) for the AUC and Cmax which were within the conventional 80-125% bioequivalence range.
78– 110%) lå uden for de sædvanlige acceptable grænser, opfylder de det bredere 75- 133% kriterium.
78– 110%) were outside the conventional limits they comply with the wider 75-133% criterion.
Dette bredere kriterium fandtes i dette tilfælde at kunne anvendes på grund af den ekstremt høje intra- individuelle variation (70- 82%), der blev påvist postprandialt i undersøgelsen.
It was considered that this wider criterion can be applied in this case because of the extremely high intra-subject variability (70- 82%) under fed conditions shown in this study.
Resultaterne blev endvidere anset for acceptable af kliniske grunde, da lansoprazols virkning stort set er dosisuafhængig i dette terapeutiske dosisinterval.
The results were also considered acceptable on clinical grounds as lansoprazole’ s efficacy is largely independent of dose at this therapeutic dose range.
Den dokumentation, der blev forelagt for CHMP, viser, at test - og referenceprodukterne i det væsentlige svarer til hinanden.
Documentation presented to the CHMP shows that the test and reference products are essentially similar.
For begge produkter er der udtalt effekt af fødeindtagelse, idet effekten dog synes at være størst for det generiske produkt, hovedsagelig som følge af den store intra - individuelle variation.
Both products show pronounced food effect although the generic product appears to be more affected largely because of the high intra-subject variability.
Resultaterne af disse postprandiale undersøgelser viser, at lansoprazols biotilgængelighed ikke kun nedsættes markant ved fødeindtagelse, men at absorptionen i forbindelse med fødeindtagelse kan være meget uregelmæssig.
The results of these fed studies demonstrate that Lansoprazole’ s bioavailability is not only markedly reduced when taken with food, but that its absorption, in the presence of food, can be very erratic.
Det har også en flad dosis- responskurve, dvs. virkningen er i vid udstrækning dosisuafhængig.
It also has a flat dose/ response curve i. e. its efficacy is largely independent of the dose.
Det betyder, at den lille forskel i serumkoncentration mellem reference - og testprodukt, der blev fundet postprandialt, er uden klinisk betydning.
This means that the small difference in blood levels between the reference and test products shown under fed conditions is of no clinical significance.
6 CHMP anbefalede udstedelse af markedsføringstilladelse( r).
The CHMP has recommended the granting of the Marketing Authorisation(s).
PRODUKTRESUME, ETIKETTERING OG INDLÆGSSEDDEL
SUMMARY OF PRODUCT CHARACHTERITICS, LABELLING AND PACKAGE LEAFLET
8 De gældende tekster til produktresumé, etikettering og indlægsseddel er de endelige versioner, der er fastlagt ved behandlingen i koordinationsgruppen.
8 The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination group procedure.
15. september 2005 EMEA/ CHMP/ 230471/ 2005
15 September 2005 EMEA/ CHMP/ 230471/ 2005
21, OM Lansoprazol Hexal 15 mg og 30 mg Internationalt fællesnavn (INN):
OPINION FOLLOWING AN ARTICLE 29(2)1 REFERRAL FOR Lansoprazol HEXAL 15 mg and 30 mg International Non-Proprietary Name (INN):
Den hæmmer sekretion af mavesyre og anvendes til behandling af duodenalt og gatrisk ulcus, reflux øsofagitis, gastro- øsofageal reflukssygdom, behandling og profylakse af NSAID- relaterede gastriske og duodenale ulcera, Zollinger- Ellison syndrom og i kombination med passende antibakterielle behandlinger til udryddelse af Helicobacter pylori og forebyggelse af recidiv af peptiske ulcera hos patienter med H. pylori - relaterede ulcera.
Lansoprazol HEXAL (lansoprazole) is a proton pump inhibitor that inhibits gastric acid secretion and is used for treatment of duodenal and gastric ulcer, reflux oesophagitis, gastro-oesophageal reflux disease, treatment and prophylaxis of NSAID-associated gastric and duodenal ulcers, Zollinger-Ellison syndrome, and in combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori and prevention of relapse of peptic ulcers in patients with H. pylori associated ulcers.
Der er tidligere udstedt en markedsføringstilladelse for Lansoprazol Hexal (15 mg og 30 mg) til Hexal AG i Finland den 7. november 2003.
A Marketing Authorisation for Lansoprazol HEXAL (15 mg and 30 mg) was previously granted to Hexal AG in Finland on 7 November 2003.
Der er identificeret signifikante forskelle i forhold til referenceproduktet i afsnittet om indikationer i produktresuméet.
Significant differences in comparison to the reference product have been identified with regard to the indications’ section of the SPCs.
Produktresuméet for referenceproduktet i Tyskland indeholder ikke indikationerne for samtidig anvendelse af NSAID’ er og behandling og forebyggelse af gastrisk og duodenal ulceration forårsaget af disse præparater.
The SPC of the reference product in Germany does not contain the indications related to the concomitant use of NSAIDs and the treatment and prevention of gastric and duodenal ulceration caused by these compounds.
På sit møde i juni 2005 var CHMP på grundlag af de samlede forelagte oplysninger og den faglige drøftelse i udvalget af den opfattelse, at benefit/ risk- forholdet var gunstigt for Lansoprazol Hexal.
During its June 2005 meeting, the CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, was of the opinion that the benefit/ risk ratio is favourable for Lansoprazol HEXAL.
Indikationerne for samtidig anvendelse af NSAID’ er samt behandling og forebyggelse af gastrisk og duodenal ulceration forårsaget af disse præparater blev understøttet.
The indications related to the concomitant use of NSAIDs and the treatment and prevention of gastric and duodenal ulceration caused by these compounds were supported.
Enterokapsel
Gastro-resistant capsule, hard
Lansohexal 15 mg - Hartkapseln
Lansohexal 15 mg Hartkapseln
Lansohexal 30 mg - Hartkapseln
Lansohexal 30 mg Hartkapseln
SAMLET RESUMÉ AF DEN FAGLIGE VURDERING AF LANSOPRAZOL HEXAL 15 MG, 30 MG GASTRO- RESISTENTE KAPSLER, HÅRDE (se bilag I)
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF LANSOPRAZOL HEXAL 15 MG, 30 MG GASTRO-RESISTANT CAPSULES, HARD (see Annex I)
Lansoprazol HEXAL 15 mg, 30 mg, gastro- resistente kapsler, hårde, blev indbragt til voldgiftsafgørelse i henhold til artikel 29 i Rådets direktiv 2001/ 83/ EF, med senere ændringer, efter at Tyskland havde givet udtryk for betænkeligheder under en procedure om gensidig anerkendelse med Finland som referencemedlemsstat.
Lansoprazol HEXAL 15 mg, 30 mg, gastro-resistant capsules, hard were referred for arbitration according to Article 29 of Council Directive 2001/ 83/ EC, as amended, following concerns raised by Germany during a Mutual Recognition Procedure with Finland acting as Reference Member state.
Produktresuméet for referenceproduktet i Tyskland indeholder ikke indikationerne for samtidig anvendelse af NSAID’ er samt behandling og forebyggelse af gastrisk og duodenal ulceration forårsaget af disse præparater.
The SPC of the reference product in Germany does not contain the indications related to the concomitant use of NSAIDs and the treatment and prevention of gastric and duodenal ulceration caused by these compounds.
• behandling af godartede gastriske og duodenale ulcera i tilknytning til anvendelse af anti - inflammatoriske analgetika hos patienter, som kræver løbende antiinflammatorisk, analgetisk behandling.
• Treatment of benign gastric and duodenal ulcers associated with the use of anti-inflammatory analgesics in patients requiring continued anti-inflammatory analgesic treatment.
Mavesyre er en vigtig faktor for opståen af gastroduodenale ulcera, og det er påvist, at hæmning af syre er effektiv til heling af NSAID - inducerede ulcera.
Gastric acid is central in the pathogenesis of gastroduodenal ulcers and acid inhibition has been shown to effectively heal NSAID induced ulcers.
Hos patienter, som fortsætter med at tage NSAID’ er, forsinkes helingen.
In patients who continue to take NSAID medication healing is delayed.
Agrawal m. fl. gennemførte en dobbeltblind RCT- undersøgelse af 353 patienter med gastrisk ulcus, som fortsatte med at få konstante doser af NSAID.
Agrawal et al conducted a double-blind RCT in 353 patients with gastric ulcer and who continued to receive stable doses of NSAIDs.
Efter 8 ugers behandling blev der observeret heling hos 61 (53%) af 115, 81 (69%) af 118 og 85 (73%) af 117 patienter, som modtog henholdsvis ranitidin, lansoprazol 15 mg og lansoprazol 30 mg (P < 0, 05 for ranitidin vs. begge lansoprazol- doser).
After 8 weeks of treatment, healing was observed in 61 (53%) of 115, 81 (69%) of 118, and 85 (73%) of 117 patients receiving ranitidine, lansoprazole 15 mg, and lansoprazole 30 mg, respectively (P < 0.05 for ranitidine vs. both lansoprazole doses).
Efter 4 uger var de tilsvarende helingsrater 30%, 47% og 57%.
At 4 weeks, the corresponding healing rates were 30%, 47% and 57%.
For duodenal ulcera (n=46) var helingsraterne mellem 81% - 93% efter uge 8 i den 3. behandlingsgruppe.
For duodenal ulcers (n=46), the healing rates were between 81%-93% at week 8 in the 3 treatment groups.
Matsukawa m. fl. undersøgte i en ukontrolleret undersøgelse virkningen af lansoprazol 15 mg og 30 mg hos 47 patienter med NSAID - inducerede gastroduodenale ulcera.
Matsukawa et al evaluated in an uncontrolled study the efficacy of lansoprazole 15 mg and 30 mg in 47 patients with NSAID induced gastroduodenal ulcers.
Patienter med duodenale ulcera (n=3) blev behandlet i 6 uger og patienter med gastriske ulcera (n=42) eller multiple ulcera (n=5) i 8 uger.
Patients with duodenal ulcers (n=3) were treated for 6 weeks and patients with gastric ulcers (n=42) or multiple ulcers (n=5) for 8 weeks.
Den samlede helingsrate var i følge Sakitas’ s klassifikation 95%.
Overall rate of healing according to Sakitas classification was 95%.
S2- helingsraten (god heling) var 35%.
The rate of S2-healing (good healing) was 35%.
Campell m. fl. undersøgte i samlede analyser af to identiske dobbeltblinde RCT- undersøgelser, hvori lansoprazol blev sammenlignet med ranitidine, indvirkningen af forudgående behandling for Helicobacter pylori - (H. pylori) infektion på helingsraterne for gastrisk ulcus hos patienter, der fik NSAID og sekrethæmmende medicin.
Campell et al evaluated the effect of pre-treatment of Helicobacter pylori (H. pylori) infection on gastric ulcer healing rates in patients receiving NSAIDs and antisecretory medication in pooled analyses of two identical double-blind RCT comparing lansoprazole with ranitidine.
66%, 74% og 50% i grupperne med lansoprazol 15 mg, 30 mg og ranitidin; P < 0. 001).
Simple healing rates (independent of H. pylori status) were at 8 weeks, 66%, 74% and 50% in the lansoprazole 15 mg, 30 mg and ranitidine groups, respectively; P < 0.001).
Hos patienter med H. pylori- infektion, som fik NSAID’ er, fremmede det sekretionshæmmende middel helingen af gastrisk ulcus væsentligt (70% vs 61%, P < 0. 05).
In patients receiving NSAIDs with H. pylori infection gastric ulcer healing with an antisecretory agent was significantly enhanced (70% vs 61%, P < 0.05).
44% og 51% for dosis på 15 mg og 30 mg.
At week 4 the healing rates were 44% and 51% for the 15 mg and 30 mg dose, respectively.
Alle tre har et meget begrænset potentiale for lægemiddelinteraktion på CYP- niveau (Unge og Andersson 1997).
All three have a very limited potential for drug interactions at the CYP level (Unge and Andersson 1997).
Interaktion med NSAID’ er ikke blevet antydet.
Interaction with NSAIDs has not been suggested.
• Profylakse af gastriske og duodenale ulcera i tilknytning til anvendelse af anti- inflammatoriske midler samt lindring af symptomer hos patienter, der kræver fortsat anti- inflammatorisk behandling.
• Prophylaxis of gastric and duodenal ulcer associated with the use of anti-inflammatory agents and relief of symptoms in patients requiring continuous anti-inflammatory therapy
Der er fremlagt 3 offentliggjorte dokumenter om den kliniske dokumentation for forebyggelse af NSAID - relaterede ulcera.
Three published papers on the clinical evidence for prevention of NSAID related ulcers are submitted.
Lai m. fl. undersøgte 123 patienter smittet med H. pylori og med ulcerkomplikationer, 4 som var relateret til anvendelse af lav- dosis aspirin.
Lai et al studied 123 patients with ulcer complications relating to the use of low dose aspirin and who were infected by H. pylori.
Under opfølgningen havde 9/ 61 patienter (14, 8%) i placebo- gruppen recidiverende ulcuskomplikationer i forhold til 1/ 62 patients (1, 6%) i lansoprazol- gruppen (P=0, 008).
During follow-up, 9/ 61 patient (14.8%) in the placebo group had recurrence of ulcer complications compared with 1/ 62 patients (1.6%) in the lansoprazole group (P=0.008).
Graham m. fl. gennemførte en prospektiv, dobbeltblind RCT - undersøgelse af 537 patienter uden H. pylori - infektion med langtidsbrug af NSAID og endoscopisk bekræftet gastrisk ulcus.
Graham et al conducted a prospective; double blind RCT 4 among 537 patients without H. pylori infection who were long-term users of NSAIDs with a history of endoscopically documented gastric ulcer.
Ulcus - status blev bestemt efter en endoskopisk undersøgelse i uge 4, 8 og 12.
Ulcer status was determined by endoscopy at week 4, 8, and 12.
Procenttallene for gastrisk ulcusfri patienter var 51%, 93%, 80% og 82% for hhv. placebo, misoprostol, lansoprazol 15 mg og lansoprazol 30 mg- gruppen.
By week 12, the percentages of gastric ulcer-free patients were 51%, 93%, 80% and 82% for the placebo, misoprostol, lansoprazole 15 mg and lansoprazole 30 mg group, respectively.
Anvendelsen af antacid var betydeligt mindre blandt patienter i lansoprazo - gruppen end blandt patienter i misoprostol - og placebo- grupperne.
Antacid use was significantly less among patients in the lansoprazole groups compared with patients in the misoprostol and placebo groups.
Patienter i lansoprazol- gruppen havde betydeligt færre abdominale smerter i forhold til patienter i misoprostol- gruppen.
Patients in the lansoprazole groups had significantly less abdominal pain compared with patients in the misoprostol group.
Den kumulative incidens af symptomatiske og komlicerede ulcera i uge 8 var 4, 5% i lansoprazol - gruppen og 42, 9% i gruppen, der ingen behandling modtog (P=0. 0025).
The cumulative incidence of symptomatic and complicated GD ulcers at week 8 was 4.5% in the lansoprazole group and 42.9% in the no treatment group (P=0.0025).
Benefit/ risk- forholdet:
Benefit/ Risk considerations
De bibliografiske oplysninger fremlagt af ansøgeren viser, at lansoprazol hos patienter, der fortsætter med at få NSAID, er mere virksomt til at hele gastriske ulcera end H2- receptor - antagonisten, og helingsraterne er acceptable, selv om de er lidt lavere end dem, der er indberettet for omeprazol.
The bibliographic data submitted by the applicant show that in patients who continue to receive NSAID medication, lansoprazole is more effective in healing gastric ulcers than H2-receptor antagonist and the healing rates are acceptable although somewhat lower than reported for omeprazole.
Endvidere er der i interaktionsundersøgelser med omeprazol og flere NSAID’ er ingen interaktion påvist.
Furthermore, interaction studies performed with omeprazole and several NSAIDs have not shown any interaction.
De fremlagte bibliografiske data giver dokumentation til underbyggelse af indikationerne: • Behandling af NSAID- relaterede benigne gastriske og duodenale ulcera hos patienter, der kræver løbende behandling med NSAID • Profylakse mod NSAID- relaterede benigne gastriske og duodenale ulcera hos risikopatienter, der kræver løbende behandling med NSAID En indikation om lindring af symptomer i denne population var dog ikke tilstrækkeligt underbygget.
An indication that includes relief of symptoms in this population, however, is not sufficiently supported.
I forhold til placebo reducerer lansoprazol kun behovet for antacider i en af undersøgelserne, men der blev ikke påvist væsentlige forskelle med hensyn til symptomerne.
Compared with placebo, lansoprazole only reduced the need for antacids in one of the studies but significant difference with regard to symptoms was not shown.
Benefit- risk profilen af Lansoprazol HEXAL 15 mg, 30 mg til de ansøgte indikationer kan derfor anses for gunstig.
Therefore, the benefit-risk profile of Lansoprazol HEXAL 15 mg, 30 mg in the proposed indications can be considered favourable.
BEGRUNDELSER FOR ÆNDRING AF PRODUKTRESUMEET Ud fra følgende betragtninger:
GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS Whereas, The scope of the referral was to agree on a Summary of Products Characteristics in view of the indication.
Hensigten med henvisningen var at opnå enighed om et produktresumé med henblik på indikationen, det af ansøgeren foreslåede produktresumé er blevet vurderet på grundlag af den forelagte dokumentation og den faglige drøftelse i udvalget –
The Summary of Products Characteristic proposed by the applicant has been assessed based on the documentation submitted and the scientific discussion within the Committee. the CHMP has recommended the granting of the Marketing Authorisations with amendments of the Summary of Product Characteristics as set out in Annex III for Lansoprazol HEXAL and associated names (see Annex I).
(se bilag I).
5 ANNEX III
Lansopranzol og tilhørende navne (se Bilag I), 15 mg gastro- resistent kapsel, hård Lansopranzol og tilhørende navne (se Bilag I), 30 mg gastro- resistent kapsel, hård
Lansoprazole and associated names (see Annex I), 15 mg gastro-resistant capsule, hard Lansoprazole and associated names (see Annex I), 30 mg gastro-resistant capsule, hard
[Se Bilag I – udfyldes nationalt]
[See Annex I - to be completed nationally]
• Behandling af duodenalt og gatrisk ulcus bekræftet ved endoskopi eller røntgen. • Behandling af reflux øsofagitis. • Længerevarende profylakse mod reflux øsofagitis. • Zollinger- Ellison syndrom. • Behandling af NSAID- relaterede benigne gastriske og duodenale ulcera hos patienter, der kræver løbende behandling med NSAID. • Profylakse mod NSAID- relaterede benigne gastriske og duodenale ulcera hos risikopatienter, der kræver løbende behandling med NSAID.
• Treatment of duodenal and gastric ulcer confirmed by endoscopy or radiography. • Treatment of reflux oesophagitis. • Long-term prophylaxis of reflux oesophagitis. • Zollinger-Ellison syndrome. • Treatment of NSAID-associated benign gastric and duodenal ulcers in patients requiring continuous NSAID-treatment • Prophylaxis of NSAID-associated gastric and duodenal ulcer in patients at risk requiring continuous NSAID-treatment
8 Behandling af reflux øsofagitis:
7 Treatment of reflux oesophagitis:
Benigne NSAID- relaterede gastriske og duodenale ulcera:
Benign NSAID-associated gastric and duodenal ulcers:
For risikopatienter eller med ulcera, der er vanskelige at hele, bør et længere behandlingsforløb og/ eller en højere dosis overvejes.
For patients at risk or with ulcers that are difficult to heal, a longer course of treatment and/ or a higher dose should be considered.
Profylakse mod NSAID- relaterede gastriske og duodenale ulcera hos patienter, de kræver løbende behandling med NSAID:
Prophylaxis of NSAID-associated gastric and duodenal ulcers in patients requiring continuous NSAID- treatment:
Symptomatisk gastro- øsofageal reflux- lidelse:
Symptomatic gastro-oesophageal reflux disease:
4. 4 ” Særlige advarsler og fosigtighedregler vedrørende brugen ”).
Due to the lack of data in patients with severely impaired hepatic function, these patients should not be treated with lansoprazole (see section 4.4 “ Special warning and precautions for use”).
Grundet forsinket elimination af lansoprazol hos de ældre, kan det være nødvendigt at indgive behandlingen i doser på 15 til 30 mg, justeret efter individuelle kra.
Due to delayed elimination of lansoprazole in the elderly it may be necessary to administer the treatment in doses of 15-30 mg adjusted to individual requirements.
9 4. 4.
4.4.
Reflux øsofagitis fremstår måske ikke som ulceration og/ elle visuel beskadigelse, hvorfor i visse tilfælde endoskopi alene ikke er tilstrækkelig.
Reflux oesophagitis may not present as ulceration and/ or visual damage, therefore in certain cases endoscopy alone may not be sufficient.
Muligheden for malign gastrisk tumor bør udelukkes, inden der indledes behandling af gastrisk ulcus med lansoprazol, da lansoprazol kan maskere symptomerne og forsinke diagnosen.
8 The possibility of malignant gastric tumour should be excluded before initiating treatment of gastric ulcer with lansoprazole, because lansoprazole can mask the symptoms and delay the diagnosis.
Hvis lansoprazol, i kombination med antibiotika, anvendes til udryddelsesbehandling af H. pylori, bør brugsanvisningerne for disse antibiotika også følges.
If lansoprazole, in combination with antibiotics, is used for eradication therapy of H. -pylori, then also instructions for the use of these antibiotics should be followed.
Administration af lansoprazol kan resultere i subterapeutiske koncentrationer af ketoconazol
Administration of lansoprazole may result in subtherapeutic concentrations of ketoconazol and itraconazol and the combination should be avoided.
Digoxin Samtidig administration af lansoprazol og digoxin kan lede til øgede plasmaniveauer af digoxin.
9 Digoxin Coadminitration of lansoprazole and digoxin may lead to increased digoxin plasma levels.
Carbamazepin Der tilrådes forsigtighed under samtidig behandling med carbamazepin (et CYP3A substrat) og lansoprazol.
Carbamazepine Caution is adviced during cotreatment with carbamazepin (a CYP3A substrate) and lansoprazole.
Klinisk signifikante interaktioner af lansoprazol med non- steroide antiinflammatoriske lægemidler eller diazpam er ikke blevet påvist.
Clinically significant interactions of lansoprazole with nonsteroidal anti-inflammatory drugs or diazepam have not been demonstrated.
Formelle interaktionundersøgelser med lansoprazol og NSAID’ er er ikke blevet gennemført.
Formal interaction studies with lansoprazole and NSAIDs have not been conducted.
Det kan ikke udelukkes, at lansoprazol kan påvirke tranport via dette protein givende anledning til øgede plasmakoncentrationer af P- gp substrater såsom digoxin.
It may not be excluded that lanzoprazole may affect transport via this protein giving rise to increased plasma concentrations of P-gp substrates such as digoxin.
11 Samtidigt administrerede lægemidler
Co-administered medicinal products
lansoprazol + amoxicillin lansoprazol + metronidazol
10 lansoprazole + amoxicillin lansoprazole + metronidazole
lansoprazol + clarithromycin + amoxicillin
lansoprazole + clarithromycin + amoxicillin
Øger biotilgængeligheden og halveringstiden for lansoprazol med 30% hver; øgede plasmaniveauer af en clarithromycinmetabolit med 30%
Increase bioaivalability and half-life of lansoprazole by 30% each; increased plasma levels of a clarithromycin metabolite by 30%