natgillin/translations-raw huggingface dataset:
A single-dose, open-label study was conducted to evaluate the pharmacokinetics of a reduced dose of sitagliptin (50 mg) in patients with varying degrees of chronic renal impairment compared to normal healthy control subjects.
A single dose, open label study was conducted to evaluate the pharmacokinetics of a reduced dose of sitagliptin (50 mg) in patients with varying degrees of chronic renal impairment sitagliptin/metformin in patients with type 2 diabetes mellitus and moderate renal impairment.
Κύπρος
Summary
A 24-week placebo-controlled study involving 660 patients was designed to evaluate the insulin-sparing efficacy and safety of sitagliptin (100 mg once daily) added to insulin glargine with or without metformin (at least 1,500 mg) during intensification of insulin therapy.
SmPC A 24 week placebo-controlled study involving 660 patients was designed to evaluate the insulin-sparing efficacy and safety of sitagliptin (100 mg once daily) added to insulin glargine with or without metformin (at least 1,500 mg)
DATE OF REVISION OF THE TEXT
Commission Decision Issued amended on
LABELLING AND PACKAGE LEAFLET
Update of Summary of Product Characteristics and Package Leaflet
Do not pass it on to others.
Opinions are issued for all other procedures.
Frequency not known pain in extremity
The majority of these adverse events of pain in extremity were non-serious in nature.
MSD
The CD
A. LABELLING
Labelling and PL
Sími: +354 535 7000
WS/0535
NAME OF THE MEDICINAL PRODUCT
Product Information affected
There have been post-marketing reports of bullous pemphigoid in patients taking DPP-4 inhibitors including sitagliptin.
09/06/2017 15/12/2017 SmPC and PL There have been post-marketing reports of bullous pemphigoid in patients taking DPP-4 inhibitors including sitagliptin.
EU/1/10/620/009
WS/0009
Metformin is contraindicated.
This was accepted by the CHMP.
BATCH NUMBER
Application number
Sitagliptin and metformin
SmPC and PL
EU/1/10/620/016 EU/1/10/620/018
24/06/2010 06/08/2010 SmPC and PL
OTHER
PL
Patients treated with sitagliptin had a modest increase in body weight (+1.1 kg) compared to those given placebo.
Body weight was increased in both treatment groups: 1.3 kg in the sitagliptin group vs. 1.1 kg in the placebo group.
An updated RMP should be submitted
Consequently, the RMP version 8 has also been updated accordingly.
UNIQUE IDENTIFIER - HUMAN READABLE DATA
Monograph - Updated certificate from an already approved manufacturer
Hepatic impairment Ristfor must not be used in patients with hepatic impairment (see section 5.2).
The statement "Sitagliptin is not recommended for use in patients with moderate to severe renal impairment including those with ESRD since experience in these patients is too limited (see section 4.2)."
Metabolism and nutrition disorders hypoglycaemia
Addition of an alternate Metformin Hydrochloride active substance manufacturer
Frequency categories are based on information available from metformin Summary of Product Characteristics available in the EU.
For detailed posology recommendations please refer to the Summary of Product Characteristics.
Distribution
location
Sitagliptin
Scope
Name and address of the manufacturer(s) responsible for batch release
A.5.b - Administrative change - Change in the name and/or address of a manufacturer of the finished product, including quality control sites (excluding manufacturer for batch release)
5.2 Pharmacokinetic properties
or national pharmacopoeia of a Member State
Merck Sharp & Dohme Ltd. Shotton Lane, Cramlington Northumberland NE23 3JU United Kingdom
Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands
In addition, osteoarthritis and pain in extremity were reported with frequency uncommon (> 0.5 % higher among sitagliptin users than that in the control group).
In addition, “bullous pemphigoid” and “arthopathy” as adverse reactions (frequency ‘unknown) were also added to section 4.8 as a result of PSUR assessment (PSUR procedure
However, more patients in the sitagliptin group discontinued due to lack of efficacy than in the glipizide group.
Numerically lower incidences of peripheral oedema were reported in the sitagliptin group than in the placebo group.
Following a [
This was an application for a variation following a
4.6 Fertility, pregnancy and lactation
SmPC, Labelling and PL
Metabolism may play a more significant role in the elimination of sitagliptin in the setting of severe renal impairment or end-stage renal disease (ESRD).
The corresponding text was deleted from the SmPC for sitagliptin during variation WS-0179, which resulted in approval for use of lower doses of sitagliptin in patients with moderate or severe renal impairment or End Stage Renal Disease (ESRD).
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
A.7 - Administrative change - Deletion of manufacturing sites
The incidence of hypoglycaemia was 24.9 % for patients treated with sitagliptin, metformin, and insulin and 37.8 % for patients treated with placebo, metformin, and insulin.
The incidence of hypoglycaemia was 25.2 % in patients treated with sitagliptin and insulin (with or without metformin) and 36.8 % in patients treated with placebo and insulin (with or without metformin).The difference was mainly due to a higher percentage of patients in the placebo group experiencing 3 or more episodes of hypoglycaemia (9.4 vs 19.2%).
Reporting of suspected adverse reactions
Opinion/ Notification issued on
This leaflet was last revised in {MM/YYYY}.
The Package Leaflet was updated accordingly.
Onset of these reactions occurred within the first 3 months after initiation of treatment with sitagliptin, with some reports occurring after the first dose.
The profile over time for this group showed a reduction in FPG levels within the first 6 weeks of treatment with sitagliptin; and generally stable FPG was observed over the remaining double blind treatment period with only a minor trend towards baseline between Weeks
MSD France
N/0079
Frequency not known back pain
The majority of these adverse events of back pain were non-serious.
Ristfor 50 mg 1,000 mg
IG/0250
NN:
Update of:
In a 52-week study, comparing the efficacy and safety of the addition of sitagliptin 100 mg once daily or glipizide (a sulphonylurea) in patients with inadequate glycaemic control on metformin monotherapy, sitagliptin was similar to glipizide in reducing HbA1c (-0.7 % mean change from baselines at week 52, with baseline HbA1c of approximately 7.5 % in both groups).
The study showed that for patients with inadequate glycaemic control on dual combination therapy with metformin and pioglitazone, the addition of sitagliptin 100 mg provided a statistically significant lowering in HbA1c, compared to placebo at Week 26: difference in mean change -0.75 (95% CI -0.95, -0.54) (FAS/LOCF).
Medicinal product subject to medical prescription.
Certificate of Suitability to the relevant Ph. Eur.
MSD SHARP & DOHME GMBH Tel: 0800 673 673 673 (+49 (0) 89 4561 2612) e-mail@msd.de
Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
Procedural steps taken and scientific information after the authorisation
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any subsequent updates of the RMP.
In addition, the MAH took the opportunity to make editorial changes and to update the SPC and Package Leaflet in line with the latest QRD template (version 7.3).
Slovenská republika Merck Sharp & Dohme, s. r. o. Tel.: +421 2 58282010 dpoc_czechslovak@merck.com
Section 5.2 of the SmPC in order to delete information regarding renal impairment to allign the PI with sitagliptin PI as per variation EMEA/H/C/0722/WS/0179 (CD 22/12/2011).
2 years.
In 42 cases
Opaque blisters (PVC/PE/PVDC and aluminum).
3 SmPC (Summary of Product Characteristics), Annex II, Labelling, PL (Package Leaflet).
Table 1: The frequency of adverse reactions identified from placebo-controlled clinical studies of sitagliptin and metformin alone, and post-marketing experience
Furthermore, following the CHMP request, MAH applied to re-structure section 4.8 and present the adverse reactions identified from clinical studies and from post-marketing experience in one table with reduced footnotes in order to present clearer safety information.
Ristfor contains two different medicines called sitagliptin and metformin.
The MAH has received 91 postmarketing reports of “back pain”, in patients treated with sitagliptin (80 reports) or sitagliptin/metformin FDC (11 reports).
Read the package leaflet before use.
The Package Leaflet has been updated accordingly.
EU/1/10/620/001
IG/0016
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
C.I.11.b - Introduction of, or change(s) to, the obligations and conditions of a marketing
There have been no therapeutic clinical trials conducted with Ristfor tablets however bioequivalence of Ristfor with co-administered sitagliptin and metformin has been demonstrated (see section 5.2).
There was a low incidence of hypoglycaemia with no statistically significant or clinically meaningful differences between groups; this is reflected in section 5.1 of the SmPC.
TECOS Cardiovascular Safety Study
Periodic Safety Update EU Single assessmentmetformin hydrochloride / sitagliptin
- The active substances are sitagliptin and metformin.
To introduce 2 new manufacturing sites for the production of sitagliptin active substance and a synthetic intermediate.
In studies performed with the individual active substances, both sitagliptin and metformin are excreted in the milk of lactating rats.
The adverse drug reactions associated with the combination of sitagliptin and rosiglitazone which were previously included in the SmPC have been deleted.
Digoxin: Sitagliptin had a small effect on plasma digoxin concentrations.
Some specific adverse events occurred at a slightly higher incidence in the sitagliptin group relative to the placebo group.
In a 24-week placebo-controlled factorial study of initial therapy, sitagliptin 50 mg twice daily in combination with metformin (500 mg or 1,000 mg twice daily) provided significant improvements in glycaemic parameters compared with either monotherapy.
Update of section 5.1 of the SmPC with the results of study MK-0431 PN260 which examined the insulin-sparing effect of sitagliptin 100 mg once-daily compared with placebo over 24 weeks in participants with type 2 diabetes mellitus who have inadequate glycaemic control on insulin alone or in combination with metformin.
Intravascular administration of iodinated contrast agents may lead to contrast-induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis.
Agency on the adequacy of the current recommendations for metformin containing products with respect to the use in patients with moderate renal failure, taking into account the available information on the risk of lactic acidosis.
- This medicine has been prescribed for you only.
The notification for the procedure is appended to this opinion.
- hypersensitivity to the active substances or to any of the excipients listed in section 6.1 (see sections 4.4 and 4.8); - any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis); - diabetic pre-coma; - severe renal failure (GFR< 30 mL/min) (see section 4.4); - acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock, intravascular administration of iodinated contrast agents (see section 4.4); - acute or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure, recent myocardial infarction, shock; - hepatic impairment; - acute alcohol intoxication, alcoholism; - breast-feeding.
C.I.4 - Variations related to significant modifications of the SPC due in particular to new quality, pre-clinical, clinical or pharmacovigilance data C.I.4 - Variations related to significant modifications of the SPC due in particular to new quality, pre-clinical, clinical or pharmacovigilance data C.I.4 - Variations related to significant modifications of the SPC due in particular to new quality, pre-clinical, clinical or pharmacovigilance data the time to onset was reported, and in 28 (67%) of these cases time to onset (TTO) was <30 days.
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
For more information, please refer to the Summary of Product Characteristics.
Ristfor must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable (see sections 4.3 and 4.4).
The variation concerns an update of section 4.8 of the SPC to add the adverse reaction impaired renal function including acute renal failure under post-marketing data. Section 4 of the Package Leaflet has been updated accordingly.
The printed package leaflet of the medicinal product must state the name and address of the manufacturer responsible for the release of the concerned batch.
arrangements and quality control testing of the FPReplacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing
Tel: + 386 1 5204201 msd_slovenia@merck.com
28/01/2016 12/12/2016 SmPC, Annex II and PL
Table 2: HbA1c results in placebo-controlled combination therapy studies of sitagliptin and metformin*
B.II.b.2.b.1 - Change to batch release arrangements and quality control testing of the FP - Not including batch control/testing
Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin.
Section 5.1 of the SmPC has also been updated to reflect the results of study P128, and results of the study of sitagliptin in combination with rosiglitazone have been deleted.
België/Belgique/Belgien MSD Belgium BVBA/SPRL Tél/Tel: +32 (0)27766211 dpoc_belux@merck.com
C.I.3.b: Update of sections 4.4 of the SmPC in order to add a warning on bullous pemphigoid following the PRAC assessment outcome of EMEA/H/C/PSUSA/2711/201408; the Package Leaflet
The observed incidence of hypoglycaemia in patients treated with sitagliptin was similar to placebo.
The incidences of drug-related adverse events and serious adverse events were numerically lower in the sitagliptin group relative to the placebo.
Incidence rate per patientyears* N (%)
or with a national pharmacopoeia of a Member State - AS
By inhibiting the DPP-4 enzyme, sitagliptin increases the levels of two known active incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
Update of section 4.4 of the SmPC and update of the RMP, upon request by the CHMP, to implement the CHMP recommendations of the Art. 5(3) referral procedure regarding GLP-1-based therapies and pancreatic safety.
EU/1/10/620/008 EU/1/10/620/017
EMEA/H/C/PSUSA/00002711/201408).
Gastrointestinal disorders diarrhoea
including batch control/testing
Study of sitagliptin in combination with metformin and a PPAR agonist A 26-week placebo-controlled study was designed to evaluate the efficacy and safety of sitagliptin (100 mg once daily) added to the combination of pioglitazone and metformin.
15/11/2012 18/12/2012 SmPC and PL Study P128 was a Phase III, multicentre, randomised, double-blind placebo controlled study that evaluated the safety and efficacy of sitagliptin in patients with T2DM and inadequate glycaemic control on combination therapy with metformin and pioglitazone.
For patients inadequately controlled on maximal tolerated dose of metformin monotherapy For patients not adequately controlled on metformin alone, the usual starting dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) plus the dose of metformin already being taken.
For patients with moderate renal impairment and a GFR of 45-49 mL/min, the maximum sitagliptin daily dose of 100 mg can be used.
Tel. +48 22 721 40 00 bioinfo@bioton.pl
21/07/2011 24/08/2011 SmPC, Annex II and PL
In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention.
The adverse events were generally mild to moderate in intensity and did not lead to discontinuation of study drug.
The following statements reflect the pharmacokinetic properties of the individual active substances of Ristfor.
To introduce a new manufacturing route for production of sitagliptin active substance.
• medicines which increase urine production (diuretics)
C.I.z - Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation
Gastrointestinal symptoms were reported very commonly in clinical studies and post-marketing use of metformin.
Following the review of the PSUR 7-8 the CHMP requested to include arthralgia and myalgia as adverse drug reactions reported during post-marketing period.
tmax is between 3 and 8 hours.
tmax är mellan 3 och 8 timmar.
Diagnosis should be made according to current guidelines.
Diagnos bör ställas enligt gällande riktlinjer.
You may experience increased symptoms as described in section 4.
Du kan få ökade symtom som beskrivs i avsnitt 4.
In another case of a large overdose, the patient also survived and recovered.
I ett annat fall med stor överdosering överlevde också patienten och återhämtade sig.
The potential risk for humans is unknown.
Eventuell risk för människa är inte känd.
The solution should be taken with a little water.
Lösningen ska tas med lite vatten.
To benefit from your medicine you should take it regularly every day at the same time of the day.
För att du ska ha nytta av din medicin måste du ta den regelbundet varje dag vid samma tid på dagen.
Oral solution 50 ml
Oral lösning 50 ml
As a consequence, only limited data are available and patients with these conditions should be closely supervised.
Till följd av detta finns endast begränsade uppgifter tillgängliga och patienter med dessa tillstånd bör övervakas noga.
SYSTEM ORGAN CLASS
ORGANSYSTEM KLASS
There is a possible relationship between this accumulation and the vacuolisation observed in lungs.
Det finns ett möjligt samband mellan denna ackumulering och den vakuolisering som har observerats i lungor.
No specific antidote for intoxication or overdose is available.
Det finns ingen specifik antidot mot intoxikation eller överdosering.
This effect was only observed at high doses in rodents.
Denna effekt observerades endast vid höga doser på gnagare.
Mon → Tue → Wed → Thu → Fri → Sat → Sun
Mån → Tis → Ons → Tor → Fre → Lör → Sön
Some factors that may raise urine pH (see section 5.2 “Elimination”) may necessitate careful monitoring of the patient.
Vissa faktorer som kan höja urinens pH (se avsnitt 5.2 ”Eliminering”) kan göra det nödvändigt med noggrann övervakning av patienten.
The volume of distribution is around 10 l/kg.
Distributionsvolymen är omkring 10 l/kg.
CARTON AND LABEL FOR BOTTLE
KARTONG OCH ETIKETT FÖR FLASKA
In the event of overdose, treatment should be symptomatic.
I händelse av överdosering ska behandlingen vara symtomatisk.
Memory loss in Alzheimer's disease is due to a disturbance of message signals in the brain.
Minnesförlust vid Alzheimers sjukdom beror på en störning av meddelandesignaler i hjärnan.
The effects of barbiturates and neuroleptics may be reduced.
Effekten av barbiturater och neuroleptika kan minska.
„Possible side effects“.
”Eventuella biverkningar”.
GENERAL CLASSIFICATION FOR SUPPLY 15.
ALLMÄN KLASSIFICERING FÖR FÖRSKRIVNING 15.
Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Din läkare kommer att tala om för dig om din sjukdom tillåter att du kör fordon och använder maskiner på ett säkert sätt.
Due to the pharmacological effects and the mechanism of action of memantine the following interactions may occur:
På grund av de farmakologiska effekterna och verkningsmekanismen för memantin kan följande interaktioner inträffa:
The treatment scheme is also indicated on the treatment initiation pack.
Behandlingsschemat anges också på förpackningen för inledande av behandling.
Memantine is eliminated in a monoexponential manner with a terminal t½ of 60 to 100 hours.
Memantin elimineras på ett monoexponentiellt sätt med en terminal t½ på 60 till 100 timmar.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia.
Behandlingen ska inledas och övervakas av en läkare med erfarenhet av diagnostik och behandling av Alzheimers demens.
The patient received symptomatic treatment and plasmapheresis.
Patienten erhöll symtomatisk behandling och plasmaferes.
Once daily
En gång dagligen
It is not known whether memantine is excreted in human breast milk but, taking into consideration the lipophilicity of the substance, this probably occurs.
Det är inte känt om memantin utsöndras i human bröstmjölk men med hänsyn till att substansen är lipofil inträffar detta förmodligen.
Date of first authorisation: 22 Nov 2012 Date of latest renewal: {DD month YYYY}
Första godkännande: 22 november 2012 Förnyat godkännande: {DD månad ÅÅÅÅ}
There is one published case report on a possible risk also for the combination of memantine and phenytoin.
Det finns en publicerad fallrapport om en möjlig risk även för kombinationen memantin och fenytoin.
The tablets should be swallowed with some water.
Tabletterna ska sväljas med lite vatten.
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Patienter med sällsynta ärftliga problem såsom fruktosintolerans ska inte ta detta läkemedel.
The tolerance and dosing of memantine should be reassessed on a regular basis, preferably within three months after start of treatment.
Tolerabiliteten och doseringen av memantin bör regelbundet utvärderas, helst inom tre månader efter behandlingens start.
Your doctor will advise you.
Din läkare kommer att underrätta dig om detta.
Instruction for proper use of the pump
Instruktioner för korrekt användning av pumpen
This effect is known from other active substances with cationic amphiphilic properties.
Denna effekt är känd från andra aktiva substanser med katjonaktiva amfifila egenskaper.
It modulates the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal dysfunction.
Den modulerar effekterna av patologiskt förhöjda toniska glutamatnivåer som kan leda till neuronal dysfunktion.
In general, the observed side effects are mild to moderate.
I allmänhet är de observerade biverkningarna lindriga till måttliga.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Om din läkare har sagt att du har intolerans mot vissa sockerarter, kontakta din läkare innan du tar detta läkemedel.
week 1
vecka 1
In the prospectively defined primary analysis statistical significance was not reached at the primary efficacy endpoint at week 24.
Vid den prospektivt definierade primära analysen uppnåddes ingen statistiskt signifikant skillnad för primär efficacy endpoint vid vecka 24.
About 45% of memantine is bound to plasma-proteins.
Ca 45 % memantin är bundet till plasmaproteiner.
The clinical relevance of these findings is unknown.
Den kliniska relevansen av dessa fynd är inte känd.
Hold a glass with a little water or a spoon below the nozzle.
Håll ett glas med lite vatten eller en sked under munstycket.
Take one tablet once a day.
Ta en tablett en gång dagligen.
There is no indication that food influences the absorption of memantine.
Det finns inget som tyder på att föda påverkar absorptionen av memantin.
If the pump does not function as described during intended use and according to instruction, the patient should consult the treating physician or a pharmacist.
Om pumpen inte fungerar som beskrivet under avsedd användning och enligt instruktioner ska patienten kontakta behandlande läkare eller apotekspersonal.
Check with your doctor or pharmacist if you are not sure.
Rådfråga din läkare eller apotekspersonal om du är osäker.