natgillin/translations-raw huggingface dataset:
Ritonavir bør ikke gives som en farmakokinetisk forstærker til patienter med inkompenseret leversygdom.
Ritonavir should not be given as a pharmacokinetic enhancer to patients with decompensated liver disease.
Da der ikke er gennemført farmakokinetiske forsøg på patienter med stabil alvorlig nedsat leverfunktion (Child- Pugh klasse C) uden dekompensation, bør der udvises forsigtighed, når ritovanir anvendes som en farmakokinetisk forstærker, da forhøjede niveauer af den proteasehæmmer, der gives sammen med ritonavir, kan forekomme.
In the absence of pharmacokinetic studies in patients with stable severe hepatic impairment (Child Pugh Grade C) without decompensation, caution should be exercised when ritonavir is used as a pharmacokinetic enhancer as increased levels of the co-administered PI may occur.
Den anbefalede dosis af miksturen er 600 mg (7, 5 ml) to gange daglig peroralt.
The recommended dosage of Norvir solution is 600 mg (7.5 ml) twice daily by mouth.
Gradvis dosisforøgelse af ritonavir i behandlingens begyndelse kan medvirke til at øge tolerancen. Behandling bør indledes med 300 mg (3, 75 ml) to gange daglig i en periode på 3 dage og øges gradvist med 100 mg (1, 25 ml) to gange daglig op til 600 mg to gange daglig over en periode på højst 14 dage.
Treatment should be initiated at 300 mg (3.75 ml) twice daily for a period of three days and increased by 100 mg (1.25 ml) twice daily increments up to 600 mg twice daily over a period of no longer than 14 days.
Den anbefalede dosering af Norvir mikstur til børn er 350 mg/ m2 peroralt to gange daglig og bør ikke overskride 600 mg to gange daglig.
Paediatric use (2 years of age and above): the recommended dosage of Norvir solution in children is 350 mg/ m² by mouth twice daily and should not exceed 600 mg twice daily.
Norvir bør påbegyndes med 250 mg/ m2 og øges efter 2 til 3 dages interval med 50 mg/ m2 to gange daglig.
Norvir should be started at 250 mg/ m² and increased at 2 to 3 day intervals by 50 mg/ m² twice daily.
Om muligt skal dosis indgives med en kalibreret doseringssprøjte.
When possible, dose should be administered using a calibrated dosing syringe.
Pædiatrisk doseringsvejledning
Paediatric Dosage Guidelines
0, 25 0, 50 1, 0 1, 25 1, 5
Body Surface area* (m²) 0.25 0.50 1.00 1.25 1.50
0, 8 ml (62, 5 mg) 1, 6 ml (125 mg) 3, 1 ml (250 mg) 3, 9 ml( 312, 5 mg) 4, 7 ml (375 mg)
Twice daily dose 250 mg/ m² 0.8 ml (62.5 mg) 1.6 ml (125 mg) 3.1 ml (250 mg) 3.9 ml (312.5 mg) 4.7 ml (375 mg)
1, 1 ml (87, 5 mg) 2, 2 ml (175 mg) 4, 4 ml (350 mg) 5, 5 ml( 437, 5 mg) 6, 6 ml (525 mg)
Twice daily dose 350 mg/ m² 1.1 ml (87.5 mg) 2.2 ml (175 mg) 4.4 ml (350 mg) 5.5 ml (437.5 mg) 6.6 ml (525 mg)
BSA (m2) = √ (højde (cm) x vægt (kg) / 3600).
* Body surface area can be calculated with the following equation BSA (m²) = √ (Height (cm) X Weight (kg) / 3600)
Doser til overfladestørrelser, der ikke er anført i ovennævnte tabel, kan beregnes som følger:
To calculate the volume to be administered (in ml) the body surface area should be multiplied by a factor of:
For at beregne den nødvendige dosis (i ml) skal kroppens overflade ganges med 3, 1 for doser på 250 mg / m2, med 3, 8 for doser på 300 mg / m2, og med 4, 4 for 350 mg / m2.
3.1 for a dose of 250 mg/ m²; 3.8 for one of 300 mg/ m²; and by 4.4 for 350 mg/ m².
Derfor forventes der ikke noget fald i kroppens samlede clearance hos patienter med nedsat nyrefunktion.
The renal clearance of ritonavir is negligible; therefore, a decrease in the total body clearance is not expected in patients with renal impairment.
Farmakokinetiske data indikerer at dosisjustering ikke er nødvendig hos patienter med mild eller moderat nedsat leverfunktion (se afsnit 5. 2).
Pharmacokinetic data indicate that no dose adjustment is necessary in patients with mild to moderate 3 hepatic impairment (see section 5.2).
Ritonavir bør ikke gives til patienter med alvorlig nedsat leverfunktion( se afsnit 4. 3).
Ritonavir should not be given to patients with severe hepatic impairment (see section 4.3).
3 Særlige populationer:
Special Populations:
Farmakokinetiske data indikerer, at det ikke er nødvendigt med dosis - justering hos ældre patienter (se pkt 5. 2).
Pharmacokinetic data indicated that no dose adjustment is necessary for elderly patients (see section 5.2).
Overfølsomhed over for det aktive stof eller ét eller flere af hjælpestofferne.
Hypersensitivity to the active substance or to any of the excipients.
In vitro og in vivo undersøgelser har vist, at ritonavir i betydelig grad hæmmer CYP3A - og CYP2D6 - medierede biotransformationer.
In vitro and in vivo studies have demonstrated that ritonavir is a potent inhibitor of CYP3A- and CYP2D6- mediated biotransformations.
Anvendelse af følgende lægemidler er kontraindiceret, når de anvendes sammen med ritonavir og, medmindre andet er angivet, er kontraindikationen baseret på ritonavirs evne til at hæmme metabolismen af det samtidigt indgivne lægemiddel, hvilket medfører øget eksponering over for det samtidigt indgivne lægemiddel samt risiko for klinisk signifikante bivirkninger.
The following medicines are contraindicated when used with ritonavir and unless otherwise noted, the contraindication is based on the potential for ritonavir to inhibit metabolism of the co-administered drug, resulting in increased exposure to the co-administered drug and risk of clinically significant adverse effects.
For nogle produkter, kan kontraindikationer være mere relevante, når ritonavir anvendes som et antiretroviralt stof end når ritonavir anvendes som farmakokinetisk forstærker (f. eks. rifabutin og voriconazol):
For some products, contraindications may be more relevant when ritonavir is used as an antiretroviral agent than when ritonavir is used as a pharmacokinetic enhancer (eg rifabutin and voriconazole):
Lægemiddelklasse
Drug Class
Lægemiddel i klassen
Drugs within Class
Rationale
Rationale
Forhøjet niveau af samtidigt indgivet lægemiddel α1- Adrenoreceptor antagonister
Concomitant Drug Levels Increased α 1-Adrenoreceptor Antagonist
4. 5).
Increased plasma concentrations of alfuzosin which may lead to severe hypotension (see section 4.5).
Meperidin, piroxicam, propoxyfen
Meperidine, piroxicam, propoxyphne
Forhøjede plasmakoncentrationer af normeperidin, piroxicam og propoxyfen.
Increased plasma concentrations of normeperidine, piroxicam and propoxyphene.
Amiodaron, bepridil, encainid, flecainid, kinidin, propafenon
Amiodarone, bepridil, encainide, flecanide, propafenone, quinidine
Forhøjede plasmakoncentrationer af amiodaron, bepridil, encainid, flecainid, kinidin, propafenon.
Increased plasma concentrations of amiodarone, bepridil, encainide, flecanide, propafenone, quinidine.
Derved forøges risikoen for arytmier eller andre alvorlige virkninger af disse midler.
Thereby, increasing the risk of arrhythmias or other serious adverse effects from these agents.
Samtidig anvendelse af ritonavir (400 mg to gange daglig eller mere) og voriconazol er kontraindiceret på grund af nedsættelse af plasmakoncentrationerne af voriconazol og muligvis tab af effekt (se pkt.
Concomitant use of ritonavir (400 mg twice daily and more) and voriconazole is contraindicated due to a reduction in voriconazole plasma concentrations and possible loss of effect (see section 4.5)
4. 5).
4
4 Antihistaminer
Antihistamines
Forhøjede plasmakoncentrationer af astemizol og terfanadin.
Increased plasma concentrations of astemizole and terfenadine.
Antimykobakteriel
Antimycobacterial
4. 4).
Concomitant use of ritonavir dosed as an antiretroviral agent (600 mg twice daily) and rifabutin due to an increase of rifabutin serum concentrations and risk of adverse events including uveitis (see section 4.4).
4. 5.
Recommendations regarding use of ritonavir dosed as a pharmacokinetic enhancer with rifabutin are noted in section 4.5
Antipsykotika / Neuroleptika
Antipsychotics/ Neuroleptics
Ergotaminderivater
Ergot Derivatives
Peristaltikfremmende middel
GI motility agent
HMG Co- A Reduktasehæmmere
HMG Co-A Reductase Inhibitor
Lovastatin, simvastatin
Lovastatin, simvastatin
4. 5).
Increased plasma concentrations of lovastatin and simvastatin; thereby, increasing the risk of myopathy including rhabdomyolysis (see section 4.5).
4. 5).
(For caution on parenterally administered midazolam, see section 4.5).
Formindsket Ritonavir lægemiddelniveau Naturlægemidler
Ritonavir Drug Level Decreased Herbal Preparation
Prikbladet perikum
John’ s Wort
Naturlægemidler som indeholder prikbladet perikum (Hypericum perforatum) på grund af risikoen for formindskelse af plasmakoncentrationer og reduceret klinisk effekt af ritonavir (se pkt.
Herbal preparations containing St John’ s wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of ritonavir (see section 4.5).
4. 5).
5 4.4 Special warnings and precautions for use
Ritonavir helbreder hverken HIV- 1- infektion eller AIDS.
Ritonavir is not a cure for HIV-1 infection or AIDS.
Patienter, der får ritonavir eller anden antiretroviral behandling, kan fortsat udvikle opportunistiske infektioner og andre komplikationer af HIV- 1- infektion.
Patients receiving ritonavir or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV-1 infection.
Patienter bør informeres om, at den nuværende antiretrovirale behandling ikke har vist sig at hindre risiko for overførsel af HIV til andre gennem blod eller ved seksuel kontakt.
Patients should be advised that current antiretroviral therapy has not been proven to prevent the risk of transmission of HIV to others through blood or sexual contact.
Der skal fortsat tages passende forholdsregler.
Appropriate precautions should continue to be used.
5 Når ritonavir anvendes som en farmakokinetisk forstærker med andre proteasehæmmere, bør de fuldstændige oplysninger vedrørende advarsler og forsigtighedsregler, der gælder for netop den proteasehæmmer, tages i betragtning, og derfor skal produktresuméet for den konkrete proteasehæmmer konsulteres.
When ritonavir is used as a pharmacokinetic enhancer with other PIs, full details on the warnings and precautions relevant to that particular PI should be considered, therefore the Summary of Product Characteristics for the particular PI must be consulted.
Patienter med kronisk diarré eller malabsorption:
Patients with chronic diarrhoea or malabsorption:
Den relativt hyppige forekomst af diarré under ritonavirbehandling kan hæmme optagelsen og virkningen (på grund af nedsat compliance) af ritonavir eller andre lægemidler, der indtages samtidig.
The relatively high frequency of diarrhoea during treatment with ritonavir may compromise the absorption and efficacy (due to decreased compliance) of ritonavir or other concurrent medications.
Alvorlig vedvarende opkastning og/ eller diarré i forbindelse med ritonavir kan også påvirke nyrefunktionen.
Serious persistent vomiting and/ or diarrhoea associated with ritonavir use might also compromise renal function.
Der er rapporteret forøget blødning, herunder spontane hudhæmatomer og hæmartrose hos patienter med hæmofili type A og B, som er behandlet med proteasehæmmere.
Haemophilia: there have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in haemophiliac patients type A and B treated with protease inhibitors.
Nyopdaget diabetes mellitus, hyperglykæmi eller forværring af allerede eksisterende diabetes mellitus er rapporteret hos patienter i behandling med proteasehæmmere.
New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors.
Hos nogle af disse var hyperglykæmien alvorlig og hos nogle også ledsaget af ketoacidose.
In some of these the hyperglycaemia was severe and in some cases also associated with ketoacidosis.
Mange patienter havde vildledende medicinske tilstande, hvoraf nogle krævede behandling med stoffer, som har været tillagt betydning i udviklingen af diabetes mellitus eller hyperglykæmi.
Many patients had confounding medical conditions, some of which required therapy with agents that have been associated with the development of diabetes mellitus or hyperglycaemia.
Antiretroviral kombinationsbehandling er blevet associeret med omfordeling af kropsfedt (lipodystrofi) hos HIV- patienter.
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients.
Langtidsvirkningerne af disse bivirkninger er ukendte.
The long-term consequences of these events are currently unknown.
Der er fremført en hypotese om en forbindelse mellem lipomatose i indre organer og proteasehæmmere og lipoatrofi og nukleosid revers transkriptasehæmmere (NRTI).
A connection between visceral lipomatosis and PIs and lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs) has been hypothesised.
En højere risiko for lipodystrofi er forbundet med individuelle faktorer, f. eks. højere alder, og med lægemiddelrelaterede faktorer som længere varighed af antiretroviral behandling og hermed forbundne metaboliske forstyrrelser.
A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances.
I kliniske undersøgelser bør indgå en vurdering af fysiske tegn på omfordeling af fedt.
Clinical examination should include evaluation for physical signs of fat redistribution.
Måling af fastende serumlipider og blodsukker bør overvejes.
Consideration should be given to measurement of fasting serum lipids and blood glucose.
Pankreatit:
Pancreatitis:
Pankreatit bør overvejes, hvis der optræder kliniske symptomer (kvalme, opkastning, mavesmerter) eller unormale laboratorieværdier (f. eks. forhøjede serumlipase - eller amylaseværdier), som kan tyde på pankreatit.
Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should occur.
4. 8).
Patients who exhibit these signs or symptoms should be evaluated and Norvir therapy should be discontinued if a diagnosis of pancreatitis is made (see section 4.8).
Hos HIV- inficerede patienter med svær immuninsufficiens kan der ved påbegyndelse af antiretroviral kombinationsbehandling (CART) opstå en inflammatorisk reaktion på asymptomatiske eller residuale opportunistiske patogener, som kan forårsage alvorlige kliniske tilstande eller forværring af symptomer.
Immune Reactivation Syndrome: in HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymtomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Typisk er sådanne reaktioner observeret inden for de første få uger eller måneder efter påbegyndelsen af CART.
Typically, such reactions have been observed within the first few weeks or months of 6 initiation of CART.
Relevante eksempler er cytomegalovirus retinitis, generaliserede og/ eller fokale mykobakterielle infektioner og pneumocystis carinii pneumoni.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and Pneumocystis carinii pneumonia.
Ritonavir bør ikke gives til patienter med inkompenseret leversygdom.
Ritonavir should not be given to patients with decompensated liver disease.
4. 2.
For patients with stable severe hepatic impairment (Child Pugh Grade C) without decompensation see section 4.2.
I tilfælde af
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse events.
6 samtidig antiviral behandling for hepatitis B eller C bør de relevante produktinformationer for disse lægemidler konsulteres.
In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products.
Nyresygdom:
Renal disease:
Eftersom nyreclearance af ritonavir er minimal, forventes der ikke noget fald i kroppens samlede clearance hos patienter med nedsat nyrefunktion.
Since the renal clearance of ritonavir is negligible, the decrease in the total body clearance is not expected in patients with renal impairment.
4. 2.
See also section 4.2.
Ritonavir oral opløsning indeholder ricinusolie polyoxyl, som kan forårsage maveonde og diarré.
Ritonavir oral solution contains castor oil polyoxyl which may cause stomach upset and diarrhoea.
Ritonavir oral opløsning indeholder alkohol (43% v/ v), dvs. op til 258 mg pr. maksimal dosis på 600 mg, svarende til 65 ml øl eller 27 ml vin pr. dosis.
Ritonavir oral solution contains alcohol (43% v/ v), ie up to 258 mg per maximum dose of 600 mg, equivalent to 65 ml beer, 27 ml wine per dose.
Hver 100 mg dosis indeholder op til 43 mg alkohol, og hver 200 mg dosis indeholder 86 mg alkohol.
Each 100 mg dose contains up to 43 mg alcohol and each 200 mg dose contains 86 mg alcohol.
Derfor bør anvendelse af Norvir samtidig med disulfiram eller lægemidler med disulfiram- lignende virkning (f. eks. metronidazol) undgås.
Therefore concomitant administration of Norvir with disulfiram or medicines with disulfiram-like reactions (eg metronidazole) should be avoided.
Dette bør også tages i betragtning i forbindelse med gravide eller ammende kvinder, børn og højrisikogrupper, f. eks. patienter med leversygdom eller epilepsi.
Also to be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.
Der er rapporteret tilfælde af osteonekrose hos patienter med fremskreden HIV- sygdom og/ eller i langvarig kombinationsbehandling med antiretrovirale lægemidler (CART).
Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported in patients with advanced HIV-disease and/ or long-term exposure to combination antiretroviral therapy (CART).
Ætiologien anses dog for at være multifaktoriel (omfattende anvendelse af kortikosteroider, alkoholforbrug, svær immunosuppression, højere Body Mass Index (BMI)).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Forlængelse af PR- interval: hos nogle raske voksne individer har ritonavir vist sig at forårsage beskeden asymptomatisk forlængelse af PR- intervallet.
PR interval prolongation: ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects.
Hos patienter, der får lopinavir/ ritonavir, er der rapporteret om sjældne tilfælde af 2. eller 3. grads atroventrikulær blok hos patienter med underliggende strukturel hjertesygdom og eksisterende overledningsforstyrrelser eller hos patienter, der får lægemidler, der er kendt for at forlænge PR- intervallet (sådan som verapamil eller atazanavir).
Rare reports of 2nd or 3rd degree atrioventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving drugs known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving ritonavir.
Norvir bør bruges med forsigtighed til sådanne patienter (se punkt 5. 1).
Norvir should be used with caution in such patients (see section 5.1).
Der skal tages hensyn til følgende advarsler og forsigtighedsregler, når ritonavir anvendes som et antiretroviralt stof.
The following Warnings and Precautions should be considered when ritonavir is used as an antiretroviral agent.
4. 4 i produktresuméet for den konkrete proteasehæmmer konsulteres for at afgøre, om nedenstående oplysninger er gældende.
When ritonavir is used as a pharmacokinetic enhancer, full details on the warnings and precautions relevant to that particular PI must be considered, therefore the Summary of Product Characteristics, section 4.4, for the particular PI must be consulted to determine if the information below is applicable.
PDE5- hæmmere:
7 PDE5 inhibitors:
Ordination af sildenafil, tadalafil eller vardenafil til patienter, som er i behandling med ritonavir, bør ske med særlig forsigtighed.
Particular caution should be used when prescribing sildenafil, tadalafil or vardenafil in patients receiving ritonavir.
4. 5).
Co-administration of ritonavir with these medicinal products is expected to substantially increase their concentrations and may result in associated adverse events such as hypotension and prolonged erection (see section 4.5).
HMG- CoA reduktasehæmmere:
HMG-CoA reductase inhibitors:
Samtidig anvendelse af ritonavir og simvastatin eller
The HMG-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A for metabolism, thus concomitant use of ritonavir with simvastatin or lovastatin is not recommended due to an increased risk of myopathy including rhabdomyolysis.
Der er imidlertid rapporteret om en stigning af rosuvastatin eksposition med samtidig administration af ritonavir.
While rosuvastatin elimination is not dependent on CYP3A, an elevation of rosuvastatin exposure has been reported with ritonavir co-administration.
4. 5).
The increased digoxin levels may lessen over time (see section 4.5).
Barrieremetoder eller andre ikke- hormonelle antikonceptionsmidler bør overvejes, når ritonavir indgives i terapeutiske eller lave doser, da ritonavir sandsynligvis vil nedsætte virkningen og ændre den uterine blødningsprofil ved indgift sammen med antikonceptionsmidler, som indeholder estradiol.
Barrier or other non-hormonal methods of contraception should be considered when administering ritonavir at therapeutic or low doses as ritonavir is likely to reduce the effect and change the uterine bleeding profile when co-administered with estradiol-containing contraceptives.
Samtidig anvendelse af ritonavir og fluticason eller andre glukokortikoider, som metaboliseres af CYP3A4, anbefales ikke, medmindre de potentielle fordele ved behandlingen opvejer risikoen for systemiske bivirkninger forårsaget af kortikosteroider, herunder Cushings syndrom og binyrebarksuppression (se pkt.
Concomitant use of ritonavir and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing’ s syndrome and adrenal suppression (see section 4.5).
4. 5). Trazodon:
Trazodone:
Trazodon er et CYP3A4- substrat, og samtidig indgift af ritonavir forventes at øge trazodonkoncentrationerne.
Trazodone is a CYP3A4 substrate and co-administration of ritonavir is expected to increase trazodone levels.
4. 5).
Adverse events of nausea, dizziness, hypotension and syncope have been observed in single dose interaction studies in healthy volunteers (see section 4.5)
Interaktionsprofilen for HIV- proteasehæmmere ved samtidig indgift af lave doser af ritonavir afhænger af den konkrete samtidigt indgivne proteasehæmmer.
The interaction profiles of HIV-protease inhibitors, co-administered with low dose ritonavir, are dependant on the specific co-administered protease inhibitor.
Højere doser af ritonavir har vist sig at være forbundet med en øget forekomst af bivirkninger.
Higher doses of ritonavir have been shown to be associated with an increased incidence of adverse events.
Samtidig indgift af saquinavir og ritonavir har ført til alvorlige bivirkninger, hovedsagelig diabetisk ketoacidose og leversygdomme, især hos patienter med en allerede eksisterende leversygdom.
8 Co-administration of saquinavir and ritonavir has led to severe adverse events, mainly diabetic ketoacidosis and liver disorders, especially in patients with pre-existing liver disease.
Saquinavir/ ritonavir bør ikke gives sammen med rifampicin på grund af risikoen for alvorlig levertoxicitet (viser sig ved forhøjede levertransaminaser), hvis de tre lægemidler gives sammen (se afsnit 4. 5).
Saquinavir/ ritonavir should not be given together with rifampicin, due to the risk of severe hepatotoxicity (presenting as increased hepatic transaminases) if the three medicines are given together (see section 4.5).