natgillin/translations-raw huggingface dataset:
Der blev udført følsomhedstest i overensstemmelse med en modifikation af såvel Clinical and Laboratory Standards Institute (CLSI tidligere kendt som National Committee for Clinical Laboratory Standards [NCCSL]) M38- A- metoden (for Aspergillusarter) og M27- A- metoden (for Candidaarter).
Susceptibility testing was performed according to a modification of both the Clinical and Laboratory Standards Institute (CLSI, formerly known as the National Committee for Clinical Laboratory Standards [NCCLS]) method M38-A (for Aspergillus species) and method M27-A (for Candida species).
Hos nogle patienter er der set Candida mutationer med reduceret følsomhed overfor caspofungin under behandling.
Mutants of Candida with reduced susceptibility to caspofungin have been identified in some patients during treatment.
Standardiserede teknikker for følsomhedstest for antimykotiske midler, inklusiv beta (1, 3) - D - glucansyntesehæmmere, er dog ikke fastlagt.
However, standardised techniques for susceptibility testing for antifungal agents, including beta (1,3)-D-glucan synthesis inhibitors, have not been established.
MIC værdier for caspofungin bør ikke anvendes til at forudsige klinisk resultat, idet der ikke er etableret sammenhæng mellem MIC værdier og klinisk resultat.
MIC values for caspofungin should not be used to predict clinical outcome, since a correlation between MIC values and clinical outcome has not been established.
Udvikling af in vitro resistens over for caspofungin af Aspergillusarter er ikke identificeret.
Development of in vitro resistance to caspofungin by Aspergillus species has not been identified.
I begrænset klinisk erfaring er resistens overfor caspofungin ikke set hos patienter med invasiv aspergillose.
In limited clinical experience, resistance to caspofungin in patients with invasive aspergillosis has not been observed.
Incidensen af resistens overfor caspofungin af forskellige kliniske isolater af Candida og Aspergillus er ukendt.
The incidence of resistance to caspofungin by various clinical isolates of Candida and Aspergillus is unknown.
Invasiv Candidiasis hos voksne patienter:
Invasive Candidiasis in Adult Patients:
Der er inkluderet 239 patienter i en undersøgelse med henblik på at sammenligne caspofungin med amphotericin B til behandling af invasiv candidiasis.
Two hundred thirty-nine patients were enrolled in a study to compare caspofungin and amphotericin B for the treatment of invasive candidiasis.
24 patienter havde neutropeni.
Twenty-four patients had neutropaenia.
Den hyppigste diagnose var blodforgiftning (candidaæmi) (77%, n=186) og Candida- peritonitis (8%, n=19); patienter med Candida endocarditis, osteomyelitis eller meningitis blev holdt ude af denne undersøgelse.
The most frequent diagnoses were bloodstream infections (candidaemia) (77%, n=186) and Candida peritonitis (8%, n=19); patients with Candida endocarditis, osteomyelitis, or meningitis were excluded from this study.
Der administreredes, efter en bolusdosis på 70 mg, caspofungin 50 mg, én gang dagligt, mens amphotericin B administreredes med 0, 6- 0, 7 mg/ kg/ dag til patienter uden neutropeni og 0, 7- 1, 0 mg/ kg/ dag til patienter med neutropeni.
Caspofungin 50 mg once daily was administered following a 70 mg loading dose, while amphotericin B was administered at 0.6 to 0.7 mg/ kg/ day to non-neutropaenic patients or 0.7 to 1.0 mg/ kg/ day to neutropaenic patients.
Gennemsnitsvarigheden af intravenøs behandling var 11, 9 dage, med et variationsområde på 1- 28 dage.
The mean duration of intravenous therapy was 11.9 days, with a range of 1 to 28 days.
Et gunstigt respons krævede både resolution af symptomer og mikrobiologisk clearance af candida- infektionen.
A favourable response required both symptom resolution and microbiological clearance of the Candida infection.
224 patienter blev inkluderet i den primære effektanalyse (MITT analyse) af respons efter afslutning af IV- behandling; positive responsrater for behandling af invasiv candidiasis var sammenlignelige for caspofungin (73% [80/ 109]) og amphotericin B (62% [71/ 115]) [% forskel 12, 7 (95, 6% CI - 0, 7, 26, 0)].
Two hundred twenty-four patients were included in the primary efficacy analysis (MITT analysis) of response at the end of IV study therapy; favourable response rates for the treatment of invasive candidiasis were comparable for caspofungin (73% [80/ 109]) and amphotericin B (62% [71/ 115]) [% difference 12.7 (95.6% CI -0.7, 26.0)].
Blandt patienter med candidaæmi, var den positive respons rate efter endt IV- behandling sammenlignelig for caspofungin (72% (66/ 92)) og amphotericin B (63% (59/ 94)) i den primære effektanalyse (MITT analyse) [% forskel 10, 0 (95, 0% CI - 4, 5, 24, 5)] Data fra patienter med ikke- blod infektionssteder var mere begrænsede.
Data in patients with non-blood sites of infection were more limited.
Gunstige responsrater hos patienter med neutropeni var 7/ 14 (50%) i caspofungin- gruppen og 4/ 10 (40%) i amphotericin B- gruppen..
Favourable response rates in neutropaenic patients were 7/ 14 (50%) in the caspofungin group and 4/ 10 (40%) in the amphotericin B group.
Invasiv Aspergillose hos voksne patienter:
Invasive Aspergillosis in Adult Patients:
69 voksne patienter (i alderen 18- 80) med invasiv aspergillose blev inkluderet i en åben, non- komparativ undersøgelse, med henblik på at vurdere sikkerhed, tolerabilitet samt effekt af caspofungin.
Sixty-nine adult patients (age 18-80) with invasive aspergillosis were enrolled in an open-label, non-comparative study to evaluate the safety, tolerability, and efficacy of caspofungin.
Patienterne skulle være enten refraktære (sygdomsprogression eller manglende bedring ved andre antimykotiske behandlinger givet i mindst 7 dage) (84% af de inkluderede patienter), eller intolerante (16% af de inkluderede patienter) over for andre antimykotiske standardbehandlinger.
Patients had to be either refractory to (disease progression or failure to improve with other antifungal therapies given for at least 7 days) (84% of the enrolled patients) or intolerant of (16% of enrolled patients) other standard antifungal therapies.
Der anvendtes faste definitioner, fastsat efter ” Mycoses Study Group ” kriterier, til at diagnosticere invasiv aspergillose og til behandlingsrespons (gunstigt respons krævede klinisk signifikant radiografisk forbedring såvel som forbedring i tegn og symptomer).
Stringent definitions, modelled after the Mycoses Study Group Criteria, were used for diagnosis of invasive aspergillosis and for response to therapy (favourable response required clinically significant improvement in radiographs as well as in signs and symptoms).
Den gennemsnitlige varighed af behandlingen var 33, 7 dage, inden for en ramme af 1- 162 dage.
The mean duration of therapy was 33.7 days, with a range of 1 to 162 days.
Et uafhængigt ekspertpanel fastslog, at 41% (26/ 63) af patienterne, der fik mindst én dosis caspofungin, havde gunstigt respons.
An independent expert panel determined that 41% (26/ 63) of patients receiving at least one dose of caspofungin had a favourable response.
Af de patienter der fik mere end 7 dages behandling med caspofungin, havde 50% (26/ 52) gunstigt respons.
For those patients who received more than 7 days of therapy with caspofungin, 50% (26/ 52) had a favourable response.
Raterne af gunstigt respons for patienter som enten var refraktære eller intolerante overfor tidligere behandlinger var hhv.
The favourable response rates for patients who were either refractory to or intolerant of previous therapies
Selvom doserne af tidligere anvendt antimykotisk behandling for
8 were 36% (19/ 53) and 70% (7/ 10), respectively.
8 5 af patienterne, der var inkluderet som refraktære, var lavere end de doser der ofte gives for invasiv aspergillose, var raterne af gunstigt respons under caspofunginbehandling for disse patienter magen til dem set for resten af de refraktære patienter (henholdsvis 2/ 5 og 17/ 48).
Although the doses of prior antifungal therapies in 5 patients enrolled as refractory were lower than those often administered for invasive aspergillosis, the favourable response rate during therapy with caspofungin was similar in these patients to that seen in the remaining refractory patients (2/ 5 versus 17/ 48, respectively).
47% (21/ 45) og 28% (5/ 18).
The response rates among patients with pulmonary disease and extrapulmonary disease were 47% (21/ 45) and 28% (5/ 18), respectively.
Blandt patienterne med ekstrapulmonær sygdom havde 2 ud ad 8 patienter, der også havde konstateret, formodentlig eller mulig CNS inddragning, gunstigt respons.
Among patients with extrapulmonary disease, 2 of 8 patients who also had definite, probable, or possible CNS involvement had a favourable response.
Empirisk behandling af febrile voksne patienter med neutropeni:
Empirical Therapy in Febrile, Neutropaenic Adult Patients:
Disse blev behandlet enten med caspofungin 50 mg én gang daglig efter bolusdosis på 70 mg caspofungin eller liposomal amphotericin B 3, 0 mg/ kg/ dag.
A total of 1111 patients with persistent fever and neutropaenia were enrolled in a clinical study and treated with either caspofungin 50 mg once daily following a 70 mg loading dose or liposomal amphotericin B 3.0 mg/ kg/ day.
Egnede patienter havde fået kemoterapi mod malignitet eller havde fået hæmatopoietisk stamcelle transplantation, og havde neutropeni (< 500 celler/ mm3 i 96 timer) og havde haft feber (> 38, 0 °C) uden respons i mere end 96 timer til parenteral antibakteriel behandling.
Eligible patients had received chemotherapy for malignancy or had undergone hematopoietic stem-cell transplantation, and presented with neutropaenia (< 500 cells/mm3 for 96 hours) and fever (> 38.0°C) not responding to ≥ 96 hours of parenteral antibacterial therapy.
Hvis lægemidlet var veltolereret, men feberen var vedholdende og den kliniske tilstand forværredes efter 5 dages behandling, kunne doseringen af studiemedicinen øges til 70 mg/ dag caspofungin (13, 3% af de behandlede patienter) eller til 5, 0 mg/ kg/ dag liposomal amphotericin B (14, 3% af de behandlede patienter).
If the drug was well tolerated but the patient’ s fever persisted and clinical condition deteriorated after 5 days of therapy, the dosage of study drug could be increased to 70 mg/ day of caspofungin (13.3% of patients treated) or to 5.0 mg/ kg/ day of liposomal amphotericin B (14.3% of patients treated).
Der inkluderedes 1. 095 patienter i den primære MITT (modificeret intention til at behandle) effekt analyse af generelt fordelagtigt respons; caspofungin (33, 9%) var lige så effektivt som liposomal amphotericin B (33, 7%) [% forskel 0, 2 (95, 2% CI - 5, 6, 6, 0)].
There were 1095 patients included in the primary Modified Intention-To-Treat (MITT) efficacy analysis of overall favourable response; caspofungin (33.9%) was as effective as liposomal amphotericin B (33.7%) [% difference 0.2 (95.2% CI – 5.6, 6.0)].
Et samlet fordelagtigt respons krævede at alle 5 kriterier var opfyldt:
An overall favourable response required meeting each of 5 criteria:
(1) succesfuld behandling af enhver baseline svampeinfektion (caspofungin 51, 9% [14/ 27], liposomal amphotericin B 25, 9% [7/ 27]), (2) ingen ny - eller genopstået svampeinfektion under administration af studiemedicinen og i op til 7 dage efter endt behandling (caspofungin 94, 8% [527/ 556], liposomal amphotericin B 95, 5% [515/ 539]), (3) overlevelse i 7 dage efter afsluttet behandling med studiemedicin (caspofungin 92, 6% [515/ 556], liposomal amphotericin B 89, 2% [481/ 539]), (4) ingen afbrydelse af behandling med studiemedicinen på grund af lægemiddelrelateret toksicitet eller manglende effekt caspofungin 89, 7% [499/ 556], liposomal amphotericin B 85, 5% [461/ 539]), og (5) resolution af feber i perioden med neutropeni (caspofungin 41, 2% [229/ 556], liposomal amphotericin B 41, 4% [223/ 539]).
(1) successful treatment of any baseline fungal infection (caspofungin 51.9% [14/ 27], liposomal amphotericin B 25.9% [7/ 27]), (2) no breakthrough fungal infections during administration of study drug or within 7 days after completion of treatment (caspofungin 94.8% [527/ 556], liposomal amphotericin B 95.5% [515/ 539]), (3) survival for 7 days after completion of study therapy (caspofungin 92.6% [515/ 556], liposomal amphotericin B 89.2% [481/ 539]), (4) no discontinuation from the study drug because of drug-related toxicity or lack of efficacy (caspofungin 89.7% [499/ 556], liposomal amphotericin B 85.5% [461/ 539]), and (5) resolution of fever during the period of neutropaenia (caspofungin 41.2% [229/ 556], liposomal amphotericin B 41.4% [223/ 539]).
Responsraterne for caspofungin og liposomal amphotericin B for baseline infektioner grundet Aspergillus arter var henholdsvis 41, 7% (5/ 12) og 8, 3% (1/ 12), og Candida arter 66, 7% (8/ 12) og 41, 7% (5/ 12).
Response rates to caspofungin and liposomal amphotericin B for baseline infections caused by Aspergillus species were, respectively, 41.7% (5/ 12) and 8.3% (1/ 12), and by Candida species were 66.7% (8/ 12) and 41.7% (5/ 12).
Patienter i caspofungin - gruppen oplevede gennembrudsinfektioner ved følgende ikke- almindelige gær - og skimmelsvampe:
Patients in the caspofungin group experienced breakthrough infections due to the following uncommon yeasts and moulds:
Trichosporon arter (1), Fusarium arter (1), Mucor arter (1) og Rhizopus arter (1).
Trichosporon species (1), Fusarium species (1), Mucor species (1), and Rhizopus species (1).
Børn Sikkerhed og effekt for CANCIDAS blev vurderet hos børn i alderen 3 måneder til 17 år i to prospektive, kliniske multicenterundersøgelser.
Paediatric Patients The safety and efficacy of CANCIDAS was evaluated in paediatric patients 3 months to 17 years of age in two prospective, multicenter clinical trials.
5. 1).
The study design, diagnostic criteria, and criteria for efficacy assessment were similar to the corresponding studies in adult patients (see section 5.1).
Den første undersøgelse, som inkluderede 82 patienter i alderen 2- 17 år, var en randomiseret, dobbeltblind undersøgelse, som sammenlignede CANCIDAS (50 mg/ m2 iv en gang dagligt efter en 70 mg/ m2 bolusdosis på Dag 1 [som ikke må overstige 70 mg dagligt] med liposomal amphotericin B (3 mg/ kg iv dagligt) på en 2: 1 behandlingsmåde (56 på caspofungin, 26 på liposomal amphotericin B) som empirisk behandling hos børn med vedvarende feber og neutropeni.
The first study, which enrolled 82 patients between 2 to 17 years of age, was a randomized, double- blind study comparing CANCIDAS (50 mg/ m2 IV once daily following a 70-mg/ m2 loading dose on Day 1 [not to exceed 70 mg daily]) to liposomal amphotericin B (3 mg/ kg IV daily) in a 2:1 treatment fashion (56 on caspofungin, 26 on liposomal amphotericin B) as empirical therapy in paediatric patients with persistent fever and neutropenia.
Overordnet var succesraten i MITT- analyseresultaterne, justeret i henhold til risikostrata, følgende:
The overall success rates in the MITT analysis results, adjusted by risk strata, were as follows:
46, 6% (26/ 56 for CANCIDAS og 32, 2% (8/ 25) for liposomal amphotericin B.
46.6% (26/ 56) for CANCIDAS and 32.2% (8/ 25) for liposomal amphotericin B.
Den anden undersøgelse var en prospektiv, åben, ikke- komparativ undersøgelse til vurdering af caspofungins sikkerhed og effekt hos børn (i alderen 6 måneder til 17 år) med invasiv candidiasis, candidiasis i øsofagus og invasiv aspergillosis (som livsreddende behandling).
The second study was a prospective, open-label, non-comparative study estimating the safety and efficacy of caspofungin in paediatric patients (ages 6 months to 17 years) with invasive candidiasis, esophageal candidiasis, and invasive aspergillosis (as salvage therapy).
49 patienter blev inkluderet og fik CANCIDAS 50 mg/ m2 iv én gang dagligt efter en bolusdosis på 70 mg/ m2 på dag 1 (som ikke måtte overstige 70 mg dagligt), hvoraf 48 blev inkluderet i MITT- analysen.
Forty-nine patients were enrolled and received CANCIDAS at 50 mg/ m2 IV once daily following a 70-mg/ m2 loading dose on Day 1 (not to exceed 70 mg daily), of whom 48 were included in the MITT analysis.
Den gunstige responsfordeling, i henhold til indikation, var ved afslutningen af
The favorable response rate, by indication, at the end of caspofungin therapy was as follows in the MITT
9 caspofunginbehandlingen følgende i MITT- analysen:
9 analysis:
81% (30/ 37) ved invasiv candidiasis, 50% (5/ 10) ved invasis aspergillosis og 100% (1/ 1) ved candidiasis i øsofagus.
81% (30/ 37) in invasive candidiasis, 50% (5/ 10) in invasive aspergillosis, and 100% (1/ 1) in esophageal candidiasis.
Distribution Caspofungin bindes i udstrakt grad til albumin.
Distribution Caspofungin is extensively bound to albumin.
Den ubundne fraktion af caspofungin i plasma varierer fra 3, 5% i raske frivillige til 7, 6% i patienter med invasiv candidiasis.
The unbound fraction of caspofungin in plasma varies from 3.5% in healthy volunteers to 7.6% in patients with invasive candidiasis.
Distributionen er hovedansvarlig for caspofungins plasmafarmakokinetik og er det hastighedskontrollerende trin i både alfa - og beta- dispositionsfasen.
Distribution plays the prominent role in caspofungin plasma pharmacokinetics and is the rate-controlling step in both the alpha- and beta-disposition phases.
Distribution til væv toppede 1, 5- 2 dage efter dosering, hvor 92% af dosis var distribueret til vævet.
The distribution into tissues peaked at 1.5 to 2 days after dosing when 92% of the dose was distributed into tissues.
Metabolisme Caspofungin nedbrydes spontant til en åben ringstruktur.
Metabolism Caspofungin undergoes spontaneous degradation to an open ring compound.
Yderligere metabolisme involverer peptidhydrolyse og N- acetylering.
Further metabolism involves peptide hydrolysis and N-acetylation.
Caspofungin er ikke et substrat for P- glycoprotein, og er et dårligt substrat for cytokrom P450 enzymer.
Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes.
Elimination og udskillelse Eliminationen af caspofungin fra plasma er langsom med en clearance på 10- 12 ml/ min.
Elimination and excretion The elimination of caspofungin from plasma is slow with a clearance of 10-12 ml/ min.
Plasmakoncentrationen af caspofungin falder i et polyfasisk mønster efter enkelt 1- times intravenøs infusion.
Plasma concentrations of caspofungin decline in a polyphasic manner following single 1-hour intravenous infusions.
Der opstår en kortvarig alfa- fase umiddelbart efter infusion, efterfulgt af en beta- fase med en halveringstid på 9- 11 timer.
A short alpha-phase occurs immediately post-infusion, followed by a beta-phase with a half- life of 9 to 11 hours.
Der opstår ligeledes yderligere en gamma- fase med en halveringstid på 45 timer.
An additional gamma-phase also occurs with a half-life of 45 hours.
75% af en radioaktivt mærket dosis blev genfundet i løbet af 27 dage:
Approximately 75% of a radioactive dose was recovered during 27 days:
41% i urinen og 34% i fæces.
41% in urine and 34% in faeces.
Udskillelsen er langsom, med en terminal halveringstid af radioaktivitet på 12- 15 dage.
Excretion is slow and the terminal half-life of radioactivity was 12 to 15 days.
1, 4% af dosis).
A small amount of caspofungin is excreted unchanged in urine (approximately 1.4% of dose).
Caspofungin udviser moderat non- lineær farmakokinetik med øget akkumulering ved stigende doser, og tiden indtil steady- state opnås, efter administration af gentagne doser.
Caspofungin displays moderate non-linear pharmacokinetics with increased accumulation as the dose is increased, and a dose dependency in the time to reach steady state upon multiple-dose administration.
Særlige populationer Der er set øget optagelse af caspofungin hos voksne patienter med nyreinsufficiens og mild leverinsufficiens, kvindelige patienter samt hos ældre patienter.
Special populations Increased caspofungin exposure was seen in adult patients with renal impairment and mild liver impairment, in female subjects, and in the elderly.
For voksne patienter med moderat leverinsufficiens eller høj vægt kan en dosisjustering være nødvendig (se nedenfor).
In adult patients with moderate liver impairment or in higher weight patients, a dosage adjustment may be necessary (see below).
I populationsfarmakokinetiske undersøgelser hos voksne candidiasispatienter blev det fundet, at vægten havde en indvirkning på caspofungins farmakokinetik.
Weight was found to influence caspofungin pharmacokinetics in the population pharmacokinetic analysis in adult candidiasis patients.
4. 2).
The average exposure in an adult patient weighing 80 kg was predicted to be about 23% lower than in an adult patient weighing 60 kg (see section 4.2).
Der er ingen klinisk erfaring hos voksne patienter med svært nedsat leverfunktion og hos børn med alle grader af leverinsufficiens.
There is no clinical experience in adult patients with severe hepatic insufficiency and in paediatric patients with any degree of hepatic insufficiency.
Det er i en undersøgelse med gentagne doser vist, at en dosisreduktion af daglig dosis til 35 mg til voksne patienter med moderat leverinsufficiens giver et
In a multiple-dose study, a dose reduction of the daily dose to 35 mg in adult patients with moderate
4. 2).
10 hepatic impairment has been shown to provide an AUC similar to that obtained in adult subjects with normal hepatic function receiving the standard regimen (see section 4.2).
I en klinisk undersøgelse med enkeltdosis 70 mg, svarede caspofungins farmakokinetik hos raske voksne frivillige med mild nyreinsufficiens (creatininclearance 50 - 80 ml/ min) til hvad der sås hos kontrolgruppen.
In a clinical study of single 70 mg doses, caspofungin pharmacokinetics were similar in adult volunteers with mild renal insufficiency (creatinine clearance 50 to 80 ml/ min) and control subjects.
Moderat nyreinsufficiens (creatininclearance 31 - 49 ml/ min), fremskreden nyreinsufficiens (creatininclearance 5- 30 ml/ min) samt nyreinsufficiens i slutstadiet (creatininclearance < 10 ml/ min og dialyseafhængig) øgede i moderat grad plasmakoncentrationer af caspofungin efter administration af enkeltdosis (30 – 49% for AUC).
30 to 49% for AUC).
Hos voksne patienter med invasiv candidiasis, esophageal candidiasis eller invasiv aspergillose, som fik gentagne, daglige doser af CANCIDAS 50 mg, havde mild til fremskreden nyreinsufficiens dog ingen betydelig effekt på koncentrationen af caspofungin.
However, in adult patients with invasive candidiasis, oesophageal candidiasis, or invasive aspergillosis who received multiple daily doses of CANCIDAS 50 mg, there was no significant effect of mild to advanced renal impairment on caspofungin concentrations.
Det er ikke nødvendigt at justere dosis til patienter med nyreinsufficiens.
No dosage adjustment is necessary for patients with renal insufficiency.
Plasmakoncentrationer af caspofungin var gennemsnitligt 17- 38% højere hos kvinder end hos mænd.
Caspofungin plasma concentrations were on average 17-38% higher in women than in men.
Ældre patienter:
Elderly:
Der sås beskeden stigning i AUC (28%) og C24 t (32%) hos ældre, mandlige patienter sammenlignet med unge, mandlige patienter.
A modest increase in AUC (28%) and C24h (32%) was observed in elderly male subjects compared with young male subjects.
Patientfarmakokinetiske data indikerer at der ikke er set klinisk signifikante forskelle i caspofungins farmakokinetik hos patienter af europæisk, negroid, sydamerikansk og sydamerikansk/ indiansk afstamning.
Patient pharmacokinetic data indicated that no clinically significant differences in the pharmacokinetics of caspofungin were seen among Caucasians, Blacks, Hispanics, and Mestizos.
Børn:
Paediatric Patients:
70 mg dagligt), var caspofungins AUC0- 24t i plasma generelt den samme som hos voksne, der fik caspofungin 50 mg dagligt.
In adolescents (ages 12 to 17 years) receiving caspofungin at 50 mg/ m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr was generally comparable to that seen in adults receiving caspofungin at 50 mg daily.
Alle de unge fik doser > 50 mg dagligt, og faktisk fik 6 ud af 8 den maksimale dosis på 70 mg/ dag.
All adolescents received doses > 50 mg daily, and, in fact, 6 of 8 received the maximum dose of 70 mg/ day.