natgillin/translations-raw huggingface dataset:
• Inovelon 200 mg tabletterer lyserøde, ovale, let hvælvede filmovertrukne tableter med delekærv på begge sider, præget med ‘ Є262 ’ på den ene side og blanke på den anden side.
• Inovelon 200 mg tablets are pink, oval, slightly convex film-coated tablets, scored on both sides, embossed ‘Є 262’ on one side and blank on the other side.
• Inovelon 400 mg tabletter er lyserøde, ovale, let hvælvede filmovertrukne tabletter med delekærv på begge sider, præget med ‘ Є263 ’ på den ene side og blanke på den anden side.
• Inovelon 400 mg tablets are pink, oval, slightly convex film-coated tablets, scored on both sides, embossed ‘Є 263’ on one side and blank on the other side.
Eisai Ltd., Mosquito Way, Hatfield, Herts, AL10 9SN, Storbritannien.
Eisai Ltd, Mosquito Way, Hatfield, Herts, AL10 9SN, UK.
Fremstiller:
49 Manufacturer:
Eisai Manufacturing Ltd, Mosquito Way, Hatfield, Herts, AL10 9SN, Storbritannien
Eisai Manufacturing Ltd, Mosquito Way, Hatfield, Herts, AL10 9SN, United Kingdom
Hvis De vil have yderligere oplysninger om Inovelon, skal De henvende Dem til den lokale repræsentant:
For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
49 Danmark Eisai AB Tlf: +46 (0) 8 501 01 600 (Sverige)
Danmark Eisai AB Tlf: +46 (0)8 501 01 600 (Sverige)
50 Lietuva Eisai Ltd.
Lietuva Eisai Ltd.
De kan finde yderligere information om Inovelon på Det europæiske Lægemiddelagenturs (EMEA) hjemmeside http: // www. emea. europa. eu
Detailed information on this product is available on the European Medicines Agency (EMEA) website http: / /www. emea. europa. eu
Insulatard er en række suspensioner af insulin til injektion.
Insulatard is a range of insulin suspensions for injection.
Insuman leveres i hætteglas, cylinderampuller (Penfill) og fyldte injektionspenne til engangsbrug (InnoLet, NovoLet og FlexPen).
Insulatard is supplied in vials, cartridges (Penfill), or pre-filled pens (InnoLet, NovoLet and FlexPen).
Det aktive stof i Insulatard er humant insulin (rDNA).
Insulatard contains the active substance insulin human (rDNA).
Insulatard anvendes hos patienter med sukkersyge.
Insulatard is used in patients with diabetes.
Insulatard indsprøjtes subkutant (under huden), sædvanligvis i låret.
Insulatard is given subcutaneously (under the skin) by injection, usually in the thigh.
Hvis det hensigtsmæssigt, kan det også indgives i bugvæggen (maven), sædemuskelregionen (balderne) eller deltamuskelregionen (skulderen).
If convenient, it may also be given in the abdominal wall (tummy), the gluteal region (buttocks) or the deltoid region (shoulder).
Patientens blodglukose skal kontrolleres regelmæssigt for at fastsætte den effektive minimumsdosis.
The patient's blood glucose (sugar) should be tested regularly to find the lowest effective dose.
Insulatard er et langtidsvirkende insulin, der kan indgives som injektion en eller to gange dagligt med eller uden hurtigtvirkende insulin (ved spisetid) efter lægens anvisninger.
It can be given as a once- or twice-daily injection, with or without a fast-acting insulin (at meal times), according to the doctor’ s recommendation.
Sukkersyge er en sygdom, hvor kroppen ikke producerer tilstrækkeligt med insulin til at regulere blodglukosen.
Diabetes is a disease in which the body does not produce enough insulin to control the blood glucose.
Insulatard er et erstatningsinsulin, der er identisk med det insulin, der produceres af bugspytkirtlen.
Insulatard is a replacement insulin which identical to the insulin made by the pancreas.
Insulinet produceres af gærceller, der har fået indsat et gen (DNA), som gør dem i stand til at producere insulin.
The active substance in Insulatard, insulin human (rDNA), is produced by a method known as ‘ recombinant technology’: the insulin is made by a yeast that has received a gene (DNA), which makes it able to produce insulin.
Insulatard indeholder insulin blandet med et andet stof, protamin, i en form, der kaldes "isophan", som optages langsommere dagen igennem.
Insulatard contains insulin mixed with another substance, protamine, in an ‘ isophane’ form which is absorbed much more slowly during the day.
Erstatningsinsulinet virker på samme måde som naturligt produceret insulin og bevirker, at glukosen fra blodet føres ind i cellerne.
The replacement insulin acts in same way as naturally produced insulin and helps glucose enter cells from the blood.
Gennem regulering af blodglukosen mindskes symptomerne og komplikationerne ved sukkersygen.
By controlling the blood glucose, the symptoms and complications of diabetes are reduced.
Insulatard blev undersøgt i fire kliniske hovedundersøgelser med i alt 557 patienter med type 1 - diabetes, hvor bugspytkirtlen ikke kan producere insulin (to undersøgelser, som omfattede 81 patienter), eller type 2- diabetes, hvor kroppen ikke kan udnytte insulinet effektivt (to undersøgelser, som omfattede 476 patienter).
Insulatard has been studied in four main clinical trials, which included a total of 557 patients with type 1 diabetes, when the pancreas cannot produce insulin (two studies involving 81 patients), or type 2 diabetes, when the body is unable to use insulin effectively (two studies involving 476 patients).
Hos størstedelen af patienterne blev Insulatard sammenlignet med andre typer humant insulin eller insulinanaloger.
In most patients, Insulatard was compared with other types of human insulin or insulin analogues.
I undersøgelserne måltes det fastende blodsukker eller 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
The studies measured the levels of fasting blood glucose or a substance in the blood called 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 86 68 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged koncentrationen af et stof (glykosyleret hæmoglobin, HbA1c), der giver et fingerpeg om, hvor velreguleret blodglukosen er.
(44-20) 74 18 84 00 Fax (44-20) 74 18 86 68 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.
Der blev gennemført yderligere undersøgelser af 225 patienter, som sammenlignede injektion af Insulatard med kanyle med brug af en fyldt pen (InnoLet, NovoPen eller FlexPen).
Further studies were also carried out in 225 patients comparing injecting Insulatard using a syringe, or using a pre-filled pen (InnoLet, NovoPen or FlexPen).
Insulatard har bevirket et fald i indholdet af HbA1c som tegn på, at blodglukosen er blevet reguleret til et niveau svarende til det, der opnås med andre humane insuliner.
Insulatard led to a decrease in the level of HbA1c, indicating that blood sugar levels had been controlled to a similar level to that seen with other human insulins.
Insulatard var effektiv til såvel type 1 - som type 2- diabetes og ved anvendelsen af en standardinjektion eller en af pennene.
Insulatard was effective for both type 1 and type 2 diabetes, and when using a standard injection or one of the pens.
Insulatard kan som alle andre insuliner medføre hypoglykæmi (for lav blodglukose).
As with all insulins, Insulatard may cause hypoglycaemia (low blood glucose).
Den fuldstændige liste over alle de indberettede bivirkninger ved Insulatard fremgår af indlægssedlen.
For the full list of all side effects reported with Insulatard, see the Package Leaflet.
Insulatard må ikke anvendes hos patienter, der kan være overfølsomme (allergiske) over for humant insulin (rDNA) eller andre af indholdsstofferne.
Insulatard should not be used in people who may be hypersensitive (allergic) to insulin human (rDNA) or to any of the other ingredients.
Det kan desuden være nødvendigt at justere doseringen af Insulatard, når det gives sammen med en række andre lægemidler, der kan påvirke blodglukosen (den fuldstændige liste fremgår af indlægssedlen).
The full list is available in the Package Leaflet.
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at fordelene ved Insulatard til behandling af sukkersyge er større end risiciene.
The Committee for Medicinal products for Human Use (CHMP) decided that Insulatard’ s benefits are greater than its risks for the treatment of diabetes.
Udvalget anbefalede udstedelse af markedsføringstilladelse for Insulatard.
The Committee recommended that Insulatard be given marketing authorisation.
Andre oplysninger om Insulatard:
Other information about Insulatard:
Europa- Kommissionen udstedte en markedsføringstilladelse for Insulatard med gyldighed i hele Den Europæiske Union til Novo Nordisk A/ S den 7. oktober 2002.
The European Commission granted a marketing authorisation valid throughout the European Union for Insulatard to Novo Nordisk A/ S on 7 October 2002.
Den fuldstændige EPAR for Insulatard findes her.
The full EPAR for Insulatard is available here.
1 hætteglas
Invented Name
40 IE/ ml
Strength
EU/ 1/ 02/ 233/ 003
Pharmaceutical Form
Injektionsvæske, Subkutan anvendelse suspension
Route of administration Packaging
Injektionsvæske, Subkutan anvendelse suspension
Content (concentration) Package size
EU/ 1/ 02/ 233/ 005
EU/ 1/ 02/ 233/ 001 EU/ 1/ 02/ 233/ 002 EU/ 1/ 02/ 233/ 003 EU/ 1/ 02/ 233/ 004 EU/ 1/ 02/ 233/ 005 EU/ 1/ 02/ 233/ 006 EU/ 1/ 02/ 233/ 007
Insulatard Penfill
Insulatard Insulatard Insulatard Insulatard Insulatard Penfill Insulatard Penfill Insulatard Penfill
100 IE/ ml
40 IU/ ml 40 IU/ ml 100 IU/ ml 100 IU/ ml 100 IU/ ml 100 IU/ ml 100 IU/ ml
Injektionsvæske, Subkutan anvendelse suspension
Suspension for injection Suspension for injection Suspension for injection Suspension for injection Suspension for injection Suspension for injection Suspension for injection
Injektionsvæske, Subkutan anvendelse suspension
Subcutaneous use Subcutaneous use Subcutaneous use Subcutaneous use Subcutaneous use Subcutaneous use Subcutaneous use
5 cylinderampuller
Vial (glass) Vial (glass) Vial (glass) Vial (glass) Cartridge (glass) Cartridge (glass) Cartridge (glass)
Injektionsvæske, Subkutan anvendelse suspension
10ml (1.4 mg/ ml) 10 ml (1.4 mg/ ml) 10 ml (3.5 mg/ ml) 10 ml (3.5 mg/ ml) 3 ml (3.5 mg/ ml) 3 ml (3.5 mg/ ml) 3 ml (3.5 mg/ ml)
10 cylinderampuller
1 vial 5 vials 1 vial 5 vials 1 cartridge 5 cartridges 10 cartridges
EU/ 1/ 02/ 233/ 008
EU/ 1/ 02/ 233/ 008
Cylinderampul (glas) i fyldt pen
Subcutaneous use
Hætteglas
Subcutaneous use
10 ml (1. 4 mg/ ml)
vial (glass) 10 ml (1.4 mg/ ml)
10 ml (3. 5 mg/ ml)
vial (glass) 10 ml (3.5 mg/ ml)
Insulatard 40 IE/ ml injektionsvæske, suspension i et hætteglas
Insulatard 40 IU/ ml suspension for injection in a vial.
Insulatard er en suspension af isophan( NPH) insulin.
Insulatard is a suspension of isophane (NPH) insulin.
Insulatard kan bruges alene eller blandes med hurtigtvirkende insulin.
Insulatard may be used alone or mixed with fast-acting insulin.
Ved intensiv insulinbehandling kan suspensionen anvendes som basal insulin (injektion aften og/ eller morgen) med hurtigtvirkende insulin til måltiderne.
In intensive insulin therapy the suspension may be used as basal insulin (evening and/ or morning injection) with fast-acting insulin given at meals.
Dosisjustering kan også blive nødvendig, hvis patienter skifter fra et insulinpræparat til et andet (se
2 Dosage adjustment may be necessary when transferring patients from one insulin preparation to another (see section 4.4).
Insulatard administreres subkutant i låret.
Insulatard is administered subcutaneously in the thigh.
Maveregionen, bagdelen eller deltoideusregionen kan også anvendes.
If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used.
Hvis en justering er nødvendig ved skift til Insulatard, kan det vise sig ved første dosis eller inden for de første adskillige uger eller måneder.
If an adjustment is needed when switching the patients to Insulatard, it may occur with the first dose or during the first several weeks or months.
I sjældne tilfælde kan reaktioner på injektionsstedet nødvendiggøre ophør af behandling med Insulatard.
On rare occasions, injection site reactions may require discontinuation of Insulatard.
3 Før en udlandsrejse bør patienten kontakte sin læge, da tidsforskellen mellem landene kan betyde, at det er nødvendigt at tage insulin og indtage måltider på andre tidspunkter end patienten plejer.
Before travelling between different time zones, the patient should be advised to consult the physician, since this may mean that the patient has to take insulin and meals at different times.
Insulatard indeholder metacresol, som kan forårsage allergiske reaktioner.
Insulatard contains metacresol, which may cause allergic reactions.
Lægen bør derfor overveje mulige interaktioner, samt altid spørge sine patienter, om de anvender andre lægemidler.
The physician must therefore take possible interactions into account and should always ask his patients about any medicinal products they take.
Det kan dog være nødvendigt at justere Insulatard- dosis.
However, the Insulatard dosage may need to be adjusted.
4 markedsføringen varierer frekvensen i forhold til patientpopulation og dosisregime.
In clinical trials and during marketed use, the frequency varies with patient population and dose regimens.
Frekvensen af bivirkninger fra de kliniske forsøg, som kan betragtes at være relateret til Insulatard, er angivet nedenfor.
Frequencies of adverse drug reactions from clinical trials that are considered related to Insulatard are listed below.
Frekvenserne er defineret således: ikke almindelig (≥ 1/ 1. 000 til, < 1/ 100).
The frequencies are defined as: uncommon (≥ 1/ 1,000 to < 1/ 100).
Nervesystemet Meget sjælden - Perifer neuropati Hurtig forbedring af blodglucosekontrollen kan være forbundet med en tilstand kaldet ” akut smertefuld neuropati ”, som sædvanligvis er reversibel.
Nervous system disorders Very rare - Peripheral neuropathy Fast improvement in blood glucose control may be associated with a condition termed “ acute painful neuropathy”, which is usually reversible.
Øjne Meget sjælden - Refraktionsanomalier Refraktionsanomalier kan forekomme ved initiering af insulinterapi.
Eye disorders Very rare - Refraction disorders Refraction anomalies may occur upon initiation of insulin therapy.
Ikke almindelig - Diabetisk retinopati Blodglucosekontrol forbedret gennem lang tid nedsætter risikoen for forværring af diabetiskretinopati.
Uncommon - Diabetic retinopathy Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.
Immunsystemet Ikke almindelig - Nældefeber, udslæt Meget sjælden - Anafylaktiske reaktioner Symptomer på almen hypersensibilitet kan indbefatte hududslæt, kløe, svedtendens, gastrointestinalt ubehag, angioneurotisk ødem, åndedrætsbesvær, hjertebanken, blodtryksfald og besvimelse/ tab af bevidsthed.
Immune system disorders Uncommon - Urticaria, rash Very rare - Anaphylactic reactions Symptoms of generalised hypersensitivity may include generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation, reduction in blood pressure and fainting/ loss of consciousness.
Der findes ingen specifikke definitioner på insulinoverdosering.
5 A specific overdose of insulin cannot be defined.
Det anbefales derfor, at diabetespatienterne bærer nogle sukkerknalder, slik, småkager eller sukkerholdig frugtjuice på sig. • Svær hypoglykæmi, hvor patienten er blevet bevidstløs, kan behandles med glucagon (0, 5 - 1 mg) indgivet intramuskulært eller subkutant af en instrueret person eller med glucose indgivet
It is therefore recommended that the diabetic patients carry some sugar lumps, sweets, biscuits or sugary fruit juice. • Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a person who has received appropriate instruction, or by glucose given intravenously by a medical professional.
Insuliner og analoger til injektion, middellang virkningstid, insulin (human).
Insulins and analogues for injection, intermediate-acting, insulin (human).
24 timer.
Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire duration of action is approximately 24 hours.
Flere faktorer har indflydelse på denne proces (f. eks. insulindosis, injektionsmåde og sted, tykkelsen af det subkutane fedtlag, diabetestype).
This process is influenced by several factors (e. g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes).
Absorption Maksimal plasmakoncentration for insulinet opnås 2- 18 timer efter subkutan indgivelsesmåde.
Absorption The maximum plasma concentration of the insulin is reached within 2-18 hours after subcutaneous administration.
Den endelige halveringstid (t½) er derfor et mål for absorptionen og ikke for den egentlige eliminering af insulin fra plasma (insulin i blodet har en t½ på nogle få minutter).
6 insulin from plasma (insulin in the blood stream has a t½ of a few minutes).
6 Zinkchlorid Glycerol Metacresol Phenol Dinatriumphosphatdihydrat Natriumhydroxid (til pH- justering) Saltsyre (til pH- justering) Protaminsulphat Vand til injektionsvæsker
Zinc chloride Glycerol Metacresol Phenol Disodium phosphate dihydrate Sodium hydroxide (for pH adjustment) Hydrochloric acid (for pH adjustment) Protamine sulphate Water for injections
30 måneder hvis det opbevares mellem 2°C- 8°C.
30 months when stored between 2°C - 8°C.
4 uger hvis det bruges eller opbevares ved stuetemperatur (under 25°C).
4 weeks when used or stored at room temperature (below 25°C).
Opbevares i køleskab (2°C- 8°C).
Before use: store in a refrigerator (2°C - 8°C).
10 ml hætteglas (type 1) lukket med en gummiskive af brombutyl/ polyisopren og en beskyttelsesplastikhætte, som sikrer mod utilsigtet åbning.
10 ml glass vial (type 1) closed with a bromobutyl/ polyisoprene rubber stopper and a protective tamper-proof plastic cap.
1 og 5 hætteglas x 10 ml og en multipakning 5 x (1 x 10 ml) hætteglas.
1 and 5 vials x 10 ml and a multipack with 5 x (1 x 10 ml) vials.
Efter, at Insulatard hætteglasset er taget ud af køleskabet, bør hætteglasset opnå stuetemperatur (ikke over 25°C) inden insulinet opblandes, som beskrevet første gang.
7 After removing Insulatard vial from the refrigerator it is recommended to allow the vial to reach room temperature (not above 25°C) before resuspending the insulin as instructed for first time use.
EU/ 1/ 02/ 233/ 001, 002, 016
EU/ 1/ 02/ 233/ 001-002, 016
Insulatard 100 IE/ ml injektionsvæske, suspension i et hætteglas
Insulatard 100 IU/ ml suspension for injection in a vial.
Dosisjustering kan også blive nødvendig, hvis patienter skifter fra et insulinpræparat til et andet (se
9 Dosage adjustment may be necessary when transferring patients from one insulin preparation to another (see section 4.4).
Nogle få patienter, som har oplevet hypoglykæmiske reaktioner efter skift fra animalsk insulin, har rapporteret, at de tidlige advarselssymptomer på hypoglykæmi var mindre udtalte eller forskellige fra
10 A few patients who have experienced hypoglycaemic reactions after transfer from animal source insulin have reported that early warning symptoms of hypoglycaemia were less pronounced or different from those experienced with their previous insulin.
Patienter bør rådes til at tage forholdsregler for at undgå hypoglykæmi, når de fører motorkøretøj.
11 Patients should be advised to take precautions to avoid hypoglycaemia whilst driving.
11 Hypoglykæmi er, som ved andre insulintyper, den oftest forekommende bivirkning.
As for other insulin products, in general, hypoglycaemia is the most frequently occurring undesirable effect.
Hud og subkutane væv Usædvanlig - Lipodystrofi Lipodystrofi kan forekomme på injektionsstedet som en konsekvens af ikke at skifte injektionssted inden for samme område.
Skin and subcutaneous tissue disorders Uncommon - Lipodystrophy Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
12 • Svær hypoglykæmi, hvor patienten er blevet bevidstløs, kan behandles med glucagon (0, 5 - 1 mg) indgivet intramuskulært eller subkutant af en instrueret person eller med glucose indgivet intravenøst af en medicinsk uddannet person.
It is therefore recommended that the diabetic patients carry some sugar lumps, sweets, biscuits or sugary fruit juice. • Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a person who has received appropriate instruction, or by glucose given intravenously by a medical professional.
Flere faktorer har indflydelse på denne proces (f. eks. insulindosis, injektionsmåde og – sted, tykkelsen af det subkutane fedtlag diabetestype).
This process is influenced by several factors (e. g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes).
Eliminering Den endelige halveringstid bestemmes af absorptionshastigheden fra det subkutane væv.
13 The terminal half-life is determined by the rate of absorption from the subcutaneous tissue.
13 6. 1 Hjælpestoffer
6.1 List of excipients
Insulinpræparater, som har været frosne, må ikke anvendes.
14 Insulin preparations which have been frozen must not be used.
Efter, at Insulatard hætteglasset er taget ud af køleskabet, bør hætteglasset opnå stuetemperatur (ikke over 25°C) inden insulinet opblandes, som beskrevet første gang.
After removing Insulatard vial from the refrigerator it is recommended to allow the vial to reach room temperature (not above 25°C) before resuspending the insulin as instructed for first time use.
Novo Nordisk A/ S
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
EU/ 1/ 02/ 233/ 003, 004, 017
EU/ 1/ 02/ 233/ 003-004, 017
Insulatard Penfill 100 IE/ ml injektionsvæske, suspension i en cylinderampul
Insulatard Penfill 100 IU/ ml suspension for injection in a cartridge.
Dosisjustering kan også blive nødvendig, hvis patienter skifter fra et insulinpræparat til et andet (se
16 Dosage adjustment may be necessary when transferring patients from one insulin preparation to another (see section 4.4).
Den detaljerede brugervejledning, der følger med dispenseringssystemet, skal følges.
Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed.
17 Før en udlandsrejse bør patienten kontakte sin læge, da tidsforskellen mellem landene kan betyde, at det er nødvendigt at tage insulin og indtage måltider på andre tidspunkter end patienten plejer.
Before travelling between different time zones, the patient should be advised to consult the physician, since this may mean that the patient has to take insulin and meals at different times.
Patienter bør rådes til at tage forholdsregler for at undgå hypoglykæmi, når de fører motorkøretøj.
18 Patients should be advised to take precautions to avoid hypoglycaemia whilst driving.
18 markedsføringen varierer frekvensen i forhold til patientpopulation og dosisregime.
In clinical trials and during marketed use, the frequency varies with patient population and dose regimens.
19 intravenøst af en medicinsk uddannet person.
19 4.9 Overdose
Eliminering Den endelige halveringstid bestemmes af absorptionshastigheden fra det subkutane væv.
20 The terminal half-life is determined by the rate of absorption from the subcutaneous tissue.
De prækliniske data viser ingen særlig risiko for mennesker vurderet ud fra konventionelle undersøgelser af sikkerhedsfarmakologi, toksicitet efter gentagne doser, genotoksicitet, karcinogenicitet, og reproduktionstoksicitet.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.