natgillin/translations-raw huggingface dataset:
5. 2).
No dosage adjustment is necessary based on gender or race (see section 5.2).
2 Dosering til børn (12 måneder til 17 år) Hos børn (i alderen 12 måneder til 17 år) bør doseringen baseres på patientens legemsareal (se Instructions for Use in Paediatric Patients, Mosteller 1 Formula).
2 Dosage in paediatric patients (12 months to 17 years) In paediatric patients (12 months to 17 years of age), dosing should be based on the patient’ s body surface area (see Instructions for Use in Paediatric Patients, Mosteller 1 Formula).
For alle indikationer bør en enkelt bolusdosis på 70 mg/ m2 (som ikke må overstige en egentlig dosis på 70 mg) administreres på Dag 1 efterfulgt af 50 mg/ m2 dagligt (som ikke må overstige en egentlig dosis på 70 mg dagligt).
For all indications, a single 70-mg/ m2 loading dose (not to exceed an actual dose of 70 mg) should be administered on Day 1, followed by 50 mg/ m2 daily thereafter (not to exceed an actual dose of 70 mg daily).
Hvis den daglige dosis på 50 mg/ m2 tåles godt men ikke giver tilstrækkelig klinisk respons, kan den daglige dosis øges til 70 mg/ m2 dagligt (som ikke må overstige den egentlige daglige dosis på 70 mg).
If the 50- mg/ m2 daily dose is well tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70 mg/ m2 daily (not to exceed an actual daily dose of 70 mg).
Effekt og sikkerhed for CANCIDAS er ikke tilstrækkeligt undersøgt i kliniske undersøgelser med nyfødte og spædbørn under 12 måneder.
The efficacy and safety of CANCIDAS have not been sufficiently studied in clinical trials involving neonates and infants below 12 months of age.
Begrænsede data tyder på, at CANCIDAS 25 mg/ m2 dagligt til nyfødte og spædbørn (under 3 måneder) og 50 mg/ m2 dagligt til små børn (3- 11 måneder) kan overvejes.
Limited data suggest that CANCIDAS at 25 mg/ m2 daily in neonates and infants (less than 3 months of age) and 50 mg/ m2 daily in young children (3 to 11 months of age) can be considered (see section 5.2).
Varighed af behandlingVarigheden af empirisk behandling skal baseres på patientens kliniske respons.
Duration of treatment Duration of empirical therapy should be based on the patient’ s clinical response.
Behandlingen bør fortsættes op til 72 timer efter resolution af neutropeni (ANC≥500).
Therapy should be continued until up to 72 hours after resolution of neutropaenia (ANC≥ 500).
Behandlingens varighed fastsættes individuelt og bør baseres på patientens kliniske og mikrobiologiske respons.
Duration of treatment of invasive candidiasis should be based upon the patient’ s clinical and microbiological response.
Behandlingens varighed for invasiv aspergillose fastsættes individuelt og bør baseres på sværhedsgraden af patientens primærsygdom, restitution efter immunosuppression og klinisk respons.
Duration of treatment of invasive aspergillosis is determined on a case by case basis and should be based upon the severity of the patient’ s underlying disease, recovery from immunosuppression, and clinical response.
30% hos ældre patienter (≥65 år).
Dosage in elderly patients In elderly patients (65 years of age or more), the area under the curve (AUC) is increased by approximately 30%.
Erfaring med behandling af patienter ≥65 år er begrænset.
There is limited treatment experience in patients 65 years of age and older.
5. 2).
Dosage in patients with renal impairment No dosage adjustment is necessary based on renal impairment (see section 5.2).
Dosering til patienter med leverinsufficiens Det er ikke nødvendigt at justere dosis til voksne patienter med mild leverinsufficiens (Child- Pugh score 5- 6).
Dosage in patients with hepatic insufficiency For adult patients with mild hepatic insufficiency (Child-Pugh score 5 to 6), no dosage adjustment is needed.
Til voksne patienter med moderat leverinsufficiens (Child- Pugh score 7- 9) anbefales CANCIDAS 35 mg dagligt på baggrund af farmakokinetiske data.
For adult patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), CANCIDAS 35 mg daily is recommended based upon pharmacokinetic data.
Initial bolusdosis på 70 mg bør administreres på Dag 1.
An initial 70 mg loading dose should be administered on Day-1.
Der er ingen klinisk erfaring hos voksne patienter med svær leverinsufficiens (Child- Pugh score større end 9) og hos børn med alle grader af leverinsufficiens (se pkt.
There is no clinical experience in adult patients with severe hepatic insufficiency (Child-Pugh score greater than 9) and in paediatric patients with any degree of hepatic insufficiency.
Samtidig administration af induktorer af metaboliske enzymer Begrænsede data tyder på, at det bør overvejes at øge den daglige dosis af CANCIDAS til 70 mg efter bolusdosis på 70 mg, når CANCIDAS hos voksne patienter administreres samtidigt med visse induktorer af metaboliske enzymer (se pkt.
Co-administration with inducers of metabolic enzymes Limited data suggest that an increase in the daily dose of CANCIDAS to 70 mg, following the 70 mg loading dose, should be considered when co-administering CANCIDAS in adult patients with certain inducers of metabolic enzymes (see section 4.5).
4. 5), bør en dosis CANCIDAS på 70 mg/ m2 dagligt overvejes (som ikke må overstige en egentlig dosis på 70 mg).
When CANCIDAS is co-administered to paediatric patients (12 months to 17 years of age) with these same inducers of metabolic enzymes (see section 4.5), a CANCIDAS dose of 70-mg/ m2 daily (not to exceed an actual daily dose of 70 mg) should be considered.
N Engl j Med 1987 Oct 22; 317( 17): 1098 (letter)
N Engl J Med 1987 Oct 22; 317(17):1098 (letter)
3 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
Hypersensitivity to the active substance or to any of the excipients.
Begrænsede data tyder på at mindre almindelige ikke- Candida gærsvampe og ikke- Aspergillus skimmelsvampe ikke dækkes af caspofungin.
Limited data suggest that less common non-Candida yeasts and non-Aspergillus moulds are not covered by caspofungin.
Samtidig administration af CANCIDAS og ciclosporin er blevet evalueret hos raske voksne frivillige og hos patienter.
Concomitant use of CANCIDAS with cyclosporin has been evaluated in healthy adult volunteers and in adult patients.
Nogle raske voksne frivillige, der fik ciclosporin 2 doser á 3 mg/ kg sammen med caspofungin, viste forbigående stigninger i alanin transaminase (ALAT) og aspartat transaminase (ASAT) på op til 3 gange den øvre grænse i normalområdet, som svandt ved seponering.
Some healthy adult volunteers who received two 3 mg/ kg doses of cyclosporin with caspofungin showed transient increases in alanine transaminase (ALT) and aspartate transaminase (AST) of less than or equal to 3-fold the upper limit of normal (ULN) that resolved with discontinuation of the treatment.
I en retrospektiv undersøgelse af 40 patienter, som blev behandlet med CANCIDAS efter markedsføringen og ciclosporin i 1- 290 dage (median 17, 5 dage), blev der ikke observeret nogen alvorlige hepatologiske bivirkninger.
In a retrospective study of 40 patients treated during marketed use with CANCIDAS and cyclosporin for 1 to 290 days (median 17.5 days), no serious hepatic adverse events were noted.
Disse data tyder på, at CANCIDAS kan anvendes hos patienter, der behandles med ciclosporin, hvis de potentielle fordele overstiger de potentielle risici.
These data suggest that CANCIDAS can be used in patients receiving cyclosporin when the potential benefit outweighs the potential risk.
Tæt monitorering af leverenzymerne skal overvejes, hvis CANCIDAS og ciclosporin administreres samtidigt.
Close monitoring of liver enzymes should be considered if CANCIDAS and cyclosporin are used concomitantly.
20 og 75%.
In adult patients with mild and moderate hepatic impairment, the AUC is increased about 20 and 75%, respectively.
Der er ingen klinisk erfaring med voksne med svært nedsat leverfunktion eller med børn med alle grader af leverinsufficiens.
There is no clinical experience in adults with severe hepatic insufficiency or in paediatric patients with any degree of hepatic insufficiency.
4. 2 og 5. 2).
A higher exposure than in moderate hepatic insufficiency is expected and CANCIDAS should be used with caution in these patients (see sections 4.2 and 5.2).
Der er begrænsede sikkerhedsoplysninger for behandlinger af mere end 4 ugers varighed.
The safety information on treatment durations longer than 4 weeks is limited.
Patienter med sjælden, arvelig fructoseintolerance eller sucrase- isomaltasemangel bør ikke anvende dette lægemiddel.
Patients with rare hereditary problems of fructose intolerance or sucrase– isomaltase insufficiency should not take this medicinal product.
In- vitro undersøgelser viser, at caspofunginacetat ikke hæmmer noget enzym i cytokrom P450 (CYP) systemet.
Studies in vitro show that caspofungin acetate is not an inhibitor of any enzyme in the cytochrome P450 (CYP) system.
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.
35%.
In two clinical studies performed in healthy adult subjects, cyclosporin A (one 4 mg/ kg dose or two 3 mg/ kg doses 12 hours apart) increased the AUC of caspofungin by approximately 35%.
CANCIDAS øgede ikke ciclosporins plasmaniveauer.
CANCIDAS did not increase the plasma levels of cyclosporin.
Der sås, ved samtidig administration af CANCIDAS og ciclosporin, forbigående stigninger i lever ALAT og ASAT, på op til 3 gange i normalområdet, som svandt ved seponering.
There were transient increases in liver ALT and AST of less than or equal to 3-fold the upper limit of normal (ULN) when CANCIDAS and cyclosporin were co-administered, that resolved with discontinuation of the medicinal products.
I en retrospektiv undersøgelse af 40 patienter, som blev behandlet med CANCIDAS efter markedsføringen og ciclosporin i 1- 290 dage (median 17, 5 dage), blev der ikke observeret nogen alvorlige hepatologiske bivirkninger (se pkt.
In a retrospective study of 40 patients treated during marketed use with CANCIDAS and cyclosporin for 1 to 290 days (median 17.5 days), no serious hepatic adverse events were noted (see section 4.4).
CANCIDAS reducerede mindste målte koncentration af tacrolimus med 26% hos frivillige raske voksne.
CANCIDAS reduced the trough concentration of tacrolimus by 26% in healthy adult volunteers.
Kliniske undersøgelser med raske voksne frivillige viser, at itraconazol, amphotericin B, mycophenolat, nelfinavir eller tacrolimus ikke ændrer farmakokinetikken for CANCIDAS i klinisk relevant grad.
Clinical studies in healthy adult volunteers show that the pharmacokinetics of CANCIDAS are not altered to a clinically relevant extent by itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus.
Caspofungin havde ingen indvirkning på farmakokinetikken for amphotericin B, itraconazol, rifampicin eller mycophenolat mofetil.
4 rifampicin or mycophenolate mofetil.
4 Rifampicin forårsagede en 60% øgning i AUC og 170% øgning i mindste målte koncentration af caspofungin på den første dag med co- administration når lægemidlerne blev initieret samtidigt hos raske voksne frivillige.
Rifampicin caused a 60% increase in AUC and 170% increase in trough concentration of caspofungin on the first day of co-administration when both medicinal products were initiated together in healthy adult volunteers.
Efter to ugers administration havde rifampicin begrænset effekt på AUC, mens det mindste målte niveau var 30% lavere end hos voksne patienter, som fik caspofungin alene.
After two weeks’ administration rifampicin had limited effect on AUC, but trough levels were 30% lower than in adult subjects who received caspofungin alone.
Begrænsede data fra populations- farmakokinetiske undersøgelser indikerer, at samtidig administration af CANCIDAS og induktorerne efavirenz, nevirapin, rifampicin, dexamethason, fenytoin eller carbamazepin kan resultere i et fald i caspofungins AUC.
Limited data from population pharmacokinetics studies indicate that concomitant use of CANCIDAS with the inducers efavirenz, nevirapine, rifampicin, dexamethasone, phenytoin, or carbamazepine may result in a decrease in caspofungin AUC.
4. 2).
When co-administering inducers of metabolic enzymes, an increase in the daily dose of CANCIDAS to 70 mg, following the 70 mg loading dose, should be considered in adult patients (see section 4.2).
Resultaterne fra regressionsanalyser af farmakokinetiske data tyder på, at samtidig administration af dexamethason og CANCIDAS kan medføre klinisk betydningsfulde fald i dalkoncentrationer af caspofungin hos børn.
In paediatric patients, results from regression analyses of pharmacokinetic data suggest that co-administration of dexamethasone with CANCIDAS may result in clinically meaningful reductions in caspofungin trough concentrations.
Når CANCIDAS administreres til børn (12 måneder til 17 år) sammen med induktorer af lægemiddelelimination, som rifampicin, efavirenz, neviparin, phenytoin, dexamethason eller carbamazepin, bør en dosis CANCIDAS på 70 mg/ m2 dagligt overvejes (må ikke overstige en egentlig daglig dosis på 70 mg).
When CANCIDAS is co-administered to paediatric patients (12 months to 17 years of age) with inducers of drug clearance, such as rifampicin, efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a CANCIDAS dose of 70-mg/ m2 daily (not to exceed an actual daily dose of 70 mg) should be considered.
Der findes ingen kliniske data om graviditet for CANCIDAS.
For CANCIDAS, no clinical data on exposed pregnancies are available.
Der er ikke tilstrækkelig data vedrørende anvendelse af caspofungin til gravide kvinder.
There are no adequate data from the use of caspofungin in pregnant women.
Undersøgelser med dyr har vist bivirkninger (se afsnit 5. 3).
Developmental studies in animals have shown adverse effects (see section 5.3).
Caspofungin er vist at passere placentabarrieren i dyreundersøgelser.
Caspofungin has been shown to cross the placental barrier in animal studies.
Den potentielle risiko for det menneskelige foster er ukendt.
The potential risk to the human foetus is unknown.
Caspofungin udskilles i mælken hos diegivende dyr.
Caspofungin is excreted in milk of lactating animals.
Det vides ikke om det udskilles i modermælk.
It is not known whether it is excreted in human milk.
Der er ikke lavet undersøgelser af, hvorvidt CANCIDAS påvirker evnen til at føre bil eller betjene maskiner.
No studies on the effects on the ability to drive and use machines have been performed.
Voksne patienter I alt 1. 440 voksne personer modtog i kliniske undersøgelser enkeltdoser eller gentagne doser af CANCIDAS:
Adult patients In clinical studies, 1440 adult individuals received single or multiple doses of CANCIDAS:
564 patienter med febril neutropeni (undersøgelse med empirisk behandling), 125 patienter med invasiv candidiasis, 72 patienter med invasiv aspergillose, 285 patienter med lokaliserede Candida infektioner og 394 personer blev inkluderet i fase I undersøgelser.
564 febrile neutropaenic patients (empirical therapy study), 125 patients with invasive candidiasis, 72 patients with invasive aspergillosis, 285 patients with localised Candida infections, and 394 individuals enrolled in Phase I studies.
Patienterne i undersøgelsen med empirisk behandling havde modtaget kemoterapi for malignitet eller havde fået hæmatopoietisk stamcelle transplantation (inklusiv 39 allogene transplantationer).
In the empirical therapy study patients had received chemotherapy for malignancy or had undergone hematopoietic stem-cell transplantation (including 39 allogeneic transplantations).
I undersøgelserne med patienter med dokumenterede Candida infektioner havde de fleste patienter med invasive Candida- infektioner alvorlige primærsygdomme (for eksempel hæmatologisk eller anden malignitet, nyligt større kirurgisk indgreb, HIV), med behov for adskillige samtidige behandlingsregimer.
In the studies involving patients with documented Candida infections, the majority of the patients with invasive Candida infections had serious underlying medical conditions (e. g., haematologic or other malignancy, recent major surgery, HIV) requiring multiple concomitant medications.
Patienterne i den non- komparative Aspergillus- undersøgelse havde ofte alvorlige prædisponerende tilstande (for eksempel knoglemarvs - eller stamcelletransplantation, malign hæmatologisk sygdom, solide tumorer eller organtransplantation), med behov for adskillige samtidige behandlingsregimer.
Patients in the non-comparative Aspergillus study often had serious predisposing medical conditions (e. g., bone marrow or peripheral stem cell transplants, haematologic malignancy, solid tumours or organ transplants) requiring multiple concomitant medications.
Andre lokale reaktioner inkluderede erythem, smerter/ ømhed, kløe, væsken samt brændende fornemmelse.
Other local reactions included erythema, pain/ tenderness, itching, discharge, and a burning sensation.
5 Indberettede kliniske og laboratoriemæssige abnormaliteter, blandt voksne patienter, der er behandlet med CANCIDAS (i alt 989), var sædvanligvis milde og krævede sjældent seponering.
5 Reported clinical and laboratory abnormalities among all adult patients treated with CANCIDAS (total 989) were typically mild and rarely led to discontinuation.
[Meget almindelig (≥1/ 10), almindelig (≥1/ 100 til < 1/ 10)]
[Very common (≥ 1/ 10), Common (≥ 1/ 100, < 1/ 10)]
Anæmi
Common: anaemia
Hovedpine
Common: headache
Takykardi
Common: tachycardia
Phlebitis/ thrombophlebitis, rødmen
Common: phlebitis/ thrombophlebitis, flushing
Dyspnø
Common: dyspnoea
Abdominalsmerter, kvalme, diarré, opkastning
Common: abdominal pain, nausea, diarrhoea, vomiting
Almindelig:
Skin and subcutaneous tissue disorders:
Udslæt, pruritus, svedtendens
Common: rash, pruritus, sweating
Smerter, kuldegysninger, infusionsvenekomplikationer
Very common: fever Common: pain, chills, infused-vein complications
Forhøjede levertal (ASAT, ALAT, alkalisk phosphatase, direkte og total bilirubin), øget serum creatinin, nedsat hæmoglobin, nedsat hæmatokrit, nedsat kalium i blodet, hypomagnesiæmi, lavt albumin, reduceret antal hvide blodlegemer, øgede eosinophiltal, thrombocyttal nedsat, reduceret neutrophiltal, øget antal røde blodceller i urinen, øget partiel thromboplastintid, reduceret total serumprotein, øget urinprotein, øget prothrombintid, nedsat natrium i blodet, øget antal hvide blodceller i urinen og lavt calcium.
Common: elevated liver values (AST, ALT, alkaline phosphatase, direct and total bilirubin), increased serum creatinine, decreased haemoglobin, decreased haematocrit, blood potassium decreased, hypomagnesaemia, low albumin, decreased white blood cells, increased eosinophils, platelet count decreased, decreased neutrophils, increased urinary red blood cells, increased partial thromboplastin time, decreased total serum protein, increased urinary protein, increased prothrombin time, blood sodium decreased, increased urinary white blood cells and low calcium.
Højt calcium er blevet rapporteret som usædvanligt (≥1/ 1. 000, < 1/ 100).
High calcium has been reported as uncommon (≥ 1/ 1000, < 1/ 100).
Mulige histamin- medierede symptomer er blevet rapporteret inkluderende tilfælde af udslæt, hævelse af ansigtet, pruritus, varmefølelse eller bronchospasmer.
Possible histamine-mediated symptoms have been reported including reports of rash, facial swelling, pruritus, sensation of warmth, or bronchospasm.
Der er rapporteret anafylaksi under administration af CANCIDAS.
Anaphylaxis has been reported during administration of CANCIDAS.
Hos patienter med invasiv aspergillose er der også rapporteret lungeødem, ARDS (Adult Respiratory Distress Syndrome) og radiografiske infiltrationer.
Also reported in patients with invasive aspergillosis were pulmonary oedema, adult respiratory distress syndrome (ARDS), and radiographic infiltrates.
Børn I kliniske undersøgelser fik 171 børn enkelte eller flere doser CANCIDAS:
Paediatric Patients In clinical studies, 171 paediatric patients received single or multiple doses of CANCIDAS:
104 febrile patienter med neutropeni; 56 patienter med invasiv candidiasis; 1 patient med candidiasis i øsofagus; og 10 patienter med invasis aspergillosis.
104 febrile, neutropenic patients; 56 patients with invasive candidiasis; 1 patient with esophageal candidiasis; and 10 patients with invasive aspergillosis.
Overordnet er sikkerhedsprofilen for CANCIDAS generelt den samme hos børn som hos voksne.
The overall safety profile of CANCIDAS in paediatric patients is generally comparable to that in adult patients.
[Meget almindelig (≥1/ 10), almindelig (≥1/ 100 til < 1/ 10)]
6 [Very common (≥ 1/ 10), Common (≥ 1/ 100, < 1/ 10)]
6 Nervesystemet:
Nervous system disorders:
Rødmen, hypotension
Common: flushing, hypotension
Forhøjede leverenzymer (ASAT, ALAT)
Elevated liver enzyme levels (AST, ALT)
Udslæt, pruritus
Common: rash, pruritus
Feber Almindelig:
Very Common: fever Common: chills, catheter site pain
Nedsat kalium i blodet, hypomagnesiæmi, øget glucose, fald i phosphor, stigning i phosphor, øgede eosinophiltal.
Common: decreased potassium, hypomagnesemia, increased glucose, decreased phosphorus, increased phosphorus, and increased eosinophils.
Som hos voksne patienter er der set de samme histamin- medierede symptomer hos børn.
As in adult patients, similar histamine-mediated symptoms have also been reported in paediatric patients.
Erfaringer efter markedsføring:
Post-Marketing experience:
Følgende bivirkninger er rapporteret efter markedsføring:
The following post-marketing adverse events have been reported:
Almene symptomer og reaktioner på administrationsstedet Hævelser og perifere ødemer
Swelling and peripheral oedema
Der er rapporteret utilsigtet administration af op til 140 mg caspofungin i løbet af én dag.
Inadvertent administration of up to 140 mg of caspofungin in one day has been reported.
Disse tilfælde har ikke resulteret i klinisk vigtige bivirkninger.
These occurrences did not result in clinically important adverse experiences.
Antimykotikum til systemisk anvendelse ATC- kode:
Pharmacotherapeutic group: antimycotics for systemic use, ATC Code:
Caspofunginacetat hæmmer syntesen af beta (1, 3) - D- glucan, en vigtig bestanddel af cellevæggen i mange trådsvampe og i gær.
Caspofungin acetate inhibits the synthesis of beta (1,3)-D-glucan, an essential component of the cell wall of many filamentous fungi and yeast.
Beta (1, 3) - D- glucan findes ikke i pattedyrsceller.
Beta (1,3)-D-glucan is not present in mammalian cells.
Caspofungin virker fungicidt mod candidagær.
7 Fungicidal activity with caspofungin has been demonstrated against Candida yeasts.
7 Caspofungin virker in vitro mod Aspergillusarter (Aspergillus fumigatus [N = 75], Aspergillus flavus [N = 111], Aspergillus niger [N = 31], Aspergillus nidulans [N = 8], Aspergillus terreus [N = 52] og Aspergillus candidus [N = 3]).
Caspofungin has in vitro activity against Aspergillus species (Aspergillus fumigatus [N = 75], Aspergillus flavus [N = 111], Aspergillus niger [N = 31], Aspergillus nidulans [N = 8], Aspergillus terreus [N = 52], and Aspergillus candidus [N = 3]).
Caspofungin virker in vitro også mod Candidaarter (Candida albicans [N = 1032], Candida dubliensis [N = 100], Candida glabrata [N = 151], Candida guilliermondii [N = 67], Candida kefyr [N = 62], Candida krusei [N = 147], Candida lipolytica [N = 20], Candida lusitaniae [N = 80], Candida parapsilosis [N = 215], Candida rugosa [N = 1] og Candida tropicalis [N = 258]), inklusiv isolater med multiresistente transportmutationer og dem med erhvervet eller egenstimulerende resistens mod fluconazol, amphotericin B og 5- flucytosin.
Caspofungin also has in vitro activity against Candida species (Candida albicans [N = 1032], Candida dubliniensis [N = 100], Candida glabrata [N = 151], Candida guilliermondii [N = 67], Candida kefyr [N = 62], Candida krusei [N = 147], Candida lipolytica [N = 20], Candida lusitaniae [N = 80], Candida parapsilosis [N = 215], Candida rugosa [N = 1], and Candida tropicalis [N = 258]), including isolates with multiple resistance transport mutations and those with acquired or intrinsic resistance to fluconazole, amphotericin B, and 5-flucytosine.