Fragmin 5000 IE - Fertigspritzen

Fragmin darf nicht angewendet werden,

• wenn bei Ihnen eine Überempfindlichkeit oder Allergie gegen Dalteparin-Natrium oder einen der in Abschnitt 6. genannten sonstigen Bestandteile dieses Arzneimittels, andere niedermolekulare Heparine und/oder Heparin oder gegen Produkte aus Schweinefleisch bekannt ist.
• wenn bei Ihnen eine durch Heparin ausgelöste Thrombozytopenie (zu niedrige Anzahl von Blutplättchen) bekannt ist oder vermutet wird.
• Schwangere, die mit gerinnungshemmenden Arzneimitteln behandelt werden, dürfen während der Geburt auf keinen Fall eine Betäubung im Rückenmark (Kreuzstich) bekommen (siehe
  „Schwangerschaft und Stillzeit“).

• bei Verletzungen oder Operationen am Zentralnervensystem, Augen- und/oder Ohrenoperationen.
• bei Blutungen im Gehirn, im Augeninneren oder aktuellen, aktiven Blutungen in anderen Organen.
• bei Blutungen in der Lunge, aktive Tuberkulose.
• bei schweren Störungen der Blutgerinnung sowie bei Erkrankungen, die mit einer erhöhten Blutungsneigung einhergehen, z.B. Mangel an Gerinnungsfaktoren, schwere Leber-, Nieren- oder Bauchspeicheldrüsenerkrankungen, stark verminderte Blutplättchenzahl, übermäßig starke Menstruationsblutung.
• bei Erkrankungen mit Verdacht auf eine Funktionsstörung des Gefäßsystems, z.B. Magen- und/oder Darmgeschwüre, unkontrollierter schwerer Bluthochdruck, mit Blutung einhergehender Schlaganfall, krankhafte Ausbuchtungen an der Hirnarterienwand, Erkrankungen der Augennetzhaut, Glaskörperblutungen, Entzündung der Herzinnenhaut (mit oder ohne Sepsis), drohende Fehlgeburt.

Fragmin sollte nicht angewendet werden,

• wenn Sie Nieren- und Harnleitersteine haben.
• bei chronischem Alkoholismus wegen der möglichen erhöhten Blutungsneigung.

Warnhinweise und Vorsichtsmaßnahmen

Stellen Sie sicher, dass Ihr Arzt vor der Anwendung von Fragmin weiß,

• wenn bei Ihnen der Verdacht auf einen bösartigen Tumor mit Blutungsneigung besteht.
• wenn bei Ihnen eine Leber- oder Nierenfunktionsstörung besteht oder wenn Sie ein Magen/Zwölffingerdarmgeschwür in der Krankengeschichte haben.
• wenn bei Ihnen ein Mangel an Blutplättchen oder eine Störung der Blutplättchenfunktion besteht oder wenn Sie an nicht ausreichend behandeltem Bluthochdruck oder an einer Netzhauterkrankung infolge von Bluthochdruck oder Diabetes mellitus leiden.
• wenn Sie gleichzeitig mit Arzneimitteln behandelt werden, die den Serum-Kalium-Spiegel erhöhen, oder ein Risikopatient sind (z.B. bei Diabetes mellitus, stoffwechselbedingter Übersäuerung des Blutes, eingeschränkter Nierenfunktion oder chronischem Nierenversagen) wird Ihr Arzt die Serum-Kaliumwerte kontrollieren.
• wenn Sie gleichzeitig mit oralen gerinnungshemmenden Arzneimitteln (wie z.B. Marcoumar) und/oder mit Acetylsalicylsäure (z.B. Aspirin) behandelt werden (siehe „Anwendung von Fragmin zusammen mit anderen Arzneimitteln“).
• Informieren Sie Ihren Arzt, wenn Sie an anderen Krankheiten leiden, eine Heparinallergie oder andere Allergien haben, eine chronische oder akute Hämodialyse („Blutwäsche“) erhalten oder andere Medikamente nehmen.
• Informieren Sie Ihren Arzt, wenn Sie vermuten, schwanger zu sein.
• Wenn bei Ihnen eine Operation mit Kreuzstich (Epidural- oder Spinalanästhesie) geplant ist, sollten Sie sofort Ihren Arzt informieren wenn Sie danach eine der folgenden Beschwerden bei sich feststellen: Rückenschmerzen, sensorische oder motorische Ausfälle (Gefühllosigkeit und Schwäche in den unteren Gliedmaßen) sowie Darm- oder Blasenfunktionsstörungen.
• Zur Anwendung von Fragmin bei der Vorbeugung von Klappenthrombosen bei Patienten mit künstlichen Herzklappen liegen keine umfangreichen Erfahrungen vor. Die Anwendung von Fragmin kann daher für diesen Zweck nicht empfohlen werden.
• Erste Anzeichen von Nebenwirkungen, insbesondere Blutungen, sollten Sie sofort Ihrem Arzt melden. Eine höhere Blutungsneigung durch dieses niedermolekulare Heparin kann bei Patienten über 80 Jahre auftreten.
• Besondere Vorsicht ist in den ersten 36 Stunden nach der Geburt geboten.
• Wenn Sie erhöhten Blutdruck haben, muss er laufend kontrolliert werden.
• Die vom Arzt angeordneten regelmäßigen Kontrollen der Blutplättchen sind unbedingt einzuhalten. Bei starkem Absinken der Blutplättchenzahl wird Ihr Arzt die Behandlung abbrechen und Sie darüber informieren, ob Sie zu einem späteren Zeitpunkt eine weitere Behandlung mit Fragmin oder anderen Heparinen erhalten dürfen.

• Nach längerer Anwendung von Heparin könnte ein Risiko für eine Verminderung der Knochenmasse (Osteoporose) bestehen. Dies wurde zwar mit Dalteparin bisher nicht beobachtet, kann aber nicht ausgeschlossen werden.
• Fragen Sie Ihren Arzt über Nutzen und Risiko einer Vorbeugung von Reisethrombose, die auch bei stundenlangem Auto- oder Busfahren auftreten kann.
  Falls Sie zu den Personen mit mäßigem Risiko gehören (über 40 Jahre alt sind, eine bekannte Thromboseneigung in der Familie oder eine chronische Funktionsstörung der Venen haben, schwanger sind, die Pille nehmen, übergewichtig sind), genügen in der Regel allgemeine Vorbeugungsmaßnahmen. Hinweise dazu lesen Sie am Ende der Gebrauchsinformation.
  Für Patienten mit hohem Risiko (z.B. Thrombose oder Lungenembolie in der Krankengeschichte, Ruhigstellung eines Beines (Gips) oder knapp zurückliegende Operation/Eingriff mit hohem Thromboserisiko), wird Ihnen Ihr Arzt zusätzlich eine Anwendung von niedermolekularem Heparin empfehlen.

Kinder und Jugendliche

Dosierungsempfehlungen bei Kindern basieren auf klinischen Erfahrungen. Aus klinischen Studien liegen nur begrenzte Daten vor, die Ihrem Arzt bei der Abschätzung der Dosierung von Fragmin helfen könnten.

Anwendung von Fragmin zusammen mit anderen Arzneimitteln

Informieren Sie Ihren Arzt oder Apotheker wenn Sie andere Arzneimittel einnehmen/anwenden, kürzlich andere Arzneimittel eingenommen/angewendet haben oder beabsichtigen andere Arzneimittel einzunehmen/anzuwenden.

Wie bei der Verwendung von hochmolekularem Heparin, sind folgende Wechselwirkungen mit anderen Arzneimitteln nicht auszuschließen:

Wirkungsverstärkung durch bestimmte schmerzstillende und entzündungshemmende Arzneimittel (z.B. Aspirin), gerinnungshemmende Arzneimittel, Rheumapräparate (Phenylbutazon, Indomethacin), andere gerinnungshemmende Mittel (z.B. Marcoumar), die Blutgefäße erweiternde Mittel (Dipyridamol), Plasmaersatzmittel (Dextrane), Arzneimittel gegen erhöhten Harnsäurespiegel bei Gicht (Sulfinpyrazon, Probenecid), intravenös verabreichte Arzneimittel für die Entwässerung (Etacrynsäure), intravenös verabreichte Antibiotika (Penicillin) und Arzneimittel gegen Tumorerkrankungen. Wirkungsabschwächung durch die Einnahme von Arzneimittel gegen Allergien (Antihistaminika), bestimmte intravenös verabreichte Arzneimittel gegen Herzerkrankungen (Nitroglycerininfusion), digitalishaltige Herzmedikamente, bestimmte Antibiotika (Tetracycline), Vitamin-C Präparate und Nikotinmissbrauch.

Wirkungsabschwächung von Chinin und bestimmten Arzneimitteln gegen Depressionen (trizyklischen Antidepressiva).

Eine gleichzeitige Behandlung mit Arzneimitteln, die den Serum-Kaliumspiegel erhöhen, soll nur mit besonders sorgfältiger ärztlicher Überwachung erfolgen (siehe „Warnhinweise und Vorsichtsmaßnahmen“).

Patienten mit instabilen Koronargefäßerkrankungen (z.B. instabile Angina pectoris, Non-Q-wave Myokardinfarkt) sollten oral Acetylsalicylsäure in niedriger Dosierung erhalten, sofern nicht kontraindiziert.

Schwangerschaft, Stillzeit und Zeugungs-/Gebärfähigkeit

Wenn Sie schwanger sind oder stillen, oder wenn Sie vermuten, schwanger zu sein oder beabsichtigen, schwanger zu werden, fragen Sie vor der Anwendung dieses Arzneimittels Ihren Arzt oder Apotheker um Rat.

Umfassende Erfahrungen bei schwangeren Frauen lassen kein Fehlbildungsrisiko erkennen. Fragmin kann während der Schwangerschaft angewendet werden, Ihr Arzt wird allerdings den Nutzen für Sie gegen das Risiko für das ungeborene Kind abwägen und entscheiden, ob Sie mit Fragmin behandelt werden dürfen.

Im Vergleich zu unfraktioniertem Heparin wurde über eine geringere Blutungsneigung und ein geringeres Knochenbruchrisiko bei Osteoporose (Verminderung der Knochenmasse) berichtet.

In Untersuchungen an Tieren ergab sich kein Hinweis auf eine Schädigung des Fötus.

Wenn Sie mit gerinnungshemmenden Arzneimitteln behandelt werden, dürfen Sie während der Geburt auf keinen Fall eine Betäubung im Rückenmark (Kreuzstich) bekommen. Bei der Behandlung von Patienten mit erhöhtem Blutungsrisiko, wie etwa bei Frauen während der letzten Phase der Schwangerschaft, ist erhöhte Vorsicht geboten.

Bei schwangeren Frauen mit künstlichen Herzklappen unter Anwendung von gerinnungshemmenden Höchstdosen von niedermolekularem Heparin wurde über ein Versagen der Therapie berichtet. Die Anwendung von Fragmin bei schwangeren Frauen mit künstlichen Herzklappen wurde nicht ausreichend untersucht.

Dalteparin-Natrium geht in geringen Mengen in die Muttermilch über, jedoch erscheint ein gerinnungshemmender Effekt auf den Säugling unwahrscheinlich.

Ein Risiko für das gestillte Kind kann nicht ausgeschlossen werden. Die Entscheidung darüber, ob ab- oder weitergestillt bzw. ob die Behandlung mit Fragmin fort- oder abgesetzt wird, wird Ihr Arzt unter Abwägung der Vorteile des Stillens für das Kind bzw. der Fragmin-Therapie für die Mutter treffen.

Die bislang vorliegenden klinischen Daten liefern keine Hinweise darauf, dass Dalteparin-Natrium die Fruchtbarkeit beeinträchtigt.

Verkehrstüchtigkeit und Fähigkeit zum Bedienen von Maschinen

Fragmin hat keinen Einfluss auf die Verkehrstüchtigkeit und die Fähigkeit zum Bedienen von Maschinen.

Wenden Sie dieses Arzneimittel immer genau nach Absprache mit Ihrem Arzt oder Apotheker an. Fragen Sie bei Ihrem Arzt oder Apotheker nach, wenn Sie sich nicht sicher sind.

Sie dürfen die Injektion ausschließlich unter die Haut (subkutan) verabreichen.

Entfernen Sie die Luftblase in der Spritze nicht, denn sie gewährleistet eine vollständige Entleerung der Kanüle.

Formen Sie mit zwei Fingern eine Hautfalte an der vorderen oder seitlichen Bauchwand. Führen Sie die Nadel senkrecht bis zum Glaskolben in die Bauchfalte ein. Injizieren Sie langsam den gesamten Spritzeninhalt und lockern Sie die Hautfalte während der Injektion nicht. Nadel vorsichtig herausziehen. Falls Ihre Fertigspritze mit einer Nadelschutzklemme als Schutzvorrichtung ausgestattet ist, müssen Sie die Schutzvorrichtung vor der Verwendung der Spritze weit genug (ca. 60 bis 80 Grad) wegklappen. Hinweise dazu finden Sie im Abschnitt „Wie Fragmin aussieht und Inhalt der Packung“.

Verwenden Sie nur klare farblose bis gelbliche Lösungen.

Die Dosierung und Dauer der Behandlung wird von Ihrem Arzt sorgfältig auf Sie abgestimmt. Im Allgemeinen werden folgende Dosierungen empfohlen:

A. Vorbeugung von Thrombosen (Blutgerinnsel)

Patienten mit mäßigem Risiko

Am Operationstag: 2 Stunden vor der Operation 2500 IE Fragmin subkutan (= 1 Fertigspritze Fragmin 2500 IE).

An den Tagen nach der Operation: einmal täglich morgens 2500 IE Fragmin s.c. (= 1 Fertigspritze Fragmin 2500 IE).

Patienten mit erhöhtem Risiko (wie z.B. bei Hüftgelenksersatz, in der Onkologie)

Am Operationstag: 2 Stunden vor der Operation und 12 Stunden nach der Operation jeweils 2500 IE Fragmin subkutan (= 1 Fertigspritze Fragmin 2500 IE).

An den Tagen nach der Operation: einmal täglich morgens 5000 IE Fragmin subkutan.

Andernfalls kann Fragmin 5000 IE subkutan am Abend vor dem Eingriff und an den folgenden Abenden verabreicht werden.

Dauer der Anwendung: Bis zur vollen Wiederherstellung der Beweglichkeit, üblicherweise zwischen 7 und 10 Tagen.

Verlängerte Vorbeugung, z.B. in der Orthopädie (bei Hüftgelenksersatz)

Die Behandlung mit Fragmin wird nach der Operation für 5 Wochen fortgesetzt, wobei eines der folgenden Behandlungsregime eingesetzt werden sollte:

Zeitpunkt der ersten Fragmin-Gabe	Fragmin-Dosis (subkutan)
10 - 14 Stunden vor der Operation	innerhalb von 2 Stunden vor der Operation	4 - 8 Stunden nach der Operation	postoperative Behandlung
Behandlungsbeginn vor der Operation (am Operationstag)		2500 IE	2500 IE	5000 IE täglich
Behandlungsbeginn vor der Operation (am Abend vor der Operation)	5000 IE		5000 IE	5000 IE täglich
Behandlungsbeginn nach der Operation			2500 IE	5000 IE täglich

B. Behandlung tiefer Venenthrombosen

(Blutgerinnsel in den tief liegenden Venen) sowie langfristige Vorbeugung des Wiederauftretens venöser Thrombosen und/oder Lungenembolien (Blutgerinnsel in den Lungengefäßen) bei Krebspatienten

B-1 Venöse thromboembolische Prozesse

Dosierungsempfehlungen

200 IE/kg KG s.c. einmal täglich.

Die Einzeldosis soll 18000 IE nicht übersteigen.

Für die Fertigspritzen kann die Dosierung entsprechend der Tabelle angepasst werden:

Gewicht (kg)	Dosis	Fertigspritzen
46 – 56 57 – 68 69 – 82 > 83	10000 IE 12500 IE 15000 IE 18000 IE	0,4 ml 0,5 ml 0,6 ml 0,72 ml

Bei Patienten mit erhöhtem Blutungsrisiko bzw. schwerwiegendem Krankheitsbild (z.B. Pulmonalembolie) wird eine Dosis von 100 IE/kg KG s.c. zweimal täglich empfohlen.

Eine Überwachung der Behandlung ist im Allgemeinen nicht erforderlich, kann aber mit einem funktionellen Anti-Faktor Xa-Test durchgeführt werden. Die Blutproben für die Bestimmung sollten 3 - 4 Stunden nach der s.c. Injektion genommen werden, da zu diesem Zeitpunkt die Plasmaspiegel maximal sind. Die Anti-Faktor Xa-Spiegel im Plasma sollen zwischen 0,5 - 1,0 IE/ml liegen.

Dauer der Behandlung

Im Regelfall beträgt die Behandlungsdauer mit Fragmin 5 - 10 Tage. Bei Übergang auf eine gerinnungshemmende Behandlung mit oralen Präparaten soll die gleichzeitige Gabe von Fragmin und oralem Gerinnungshemmer so lange durchgeführt werden, bis die Laborwerte (INR bzw. Prothrombinzeit/Quick-Wert) im Normbereich liegen.

B-2 Langfristige Vorbeugung des Wiederauftretens von Thromboembolien bei Krebspatienten

1. Behandlungsmonat

In den ersten 30 Tagen der Behandlung 200 IE/kg Körpergewicht s.c. einmal täglich (die Anwendung von Fragmin 25000 IE/1 ml Durchstichflasche wird empfohlen). Die maximale Tagesdosis von 18000 IE sollte nicht überschritten werden.

Folgemonate (2 bis 6)

Die empfohlene Dosierung beträgt etwa 150 IE/kg KG s.c. einmal täglich mittels Fertigspritzen. Die Tagesdosierungen sind in der folgenden Liste angeführt.

Körpergewicht (kg)	Fragmin-Dosis (IE)
< 56	7500
57 - 68	10000
69 - 82	12500
83 - 98	15000
>99	18000

Empfohlene Dosierungsreduktionen bei durch Chemotherapie verursachter Thrombozytopenie

Bei einer Thrombozytenanzahl unter 50000/mm³ sollte die Behandlung mit Fragmin so lange unterbrochen werden, bis die Werte sich erholt haben.

Wenn die Thrombozytenzahl zwischen 50000 und 100000/mm3 liegt, sollte die Anfangsdosierung, abhängig vom Körpergewicht der Patienten, um 17% bis 33% reduziert werden (Tabelle 1). Wenn die Werte sich erholt haben und die Thrombozytenzahl wieder über 100000/mm3 liegt, kann die Behandlung mit der vollen Dosierung fortgesetzt werden.

Tabelle 1

Dosisreduktion von Fragmin bei Thrombozytenwerten zwischen 50000 - 100000/mm3

Körpergewicht (kg)	Anfangsdosierung (IE)	Reduzierte Dosierung (IE)	Durchschnittliche Reduktion in %
< 56	7500	5000	33
57 - 68	10000	7500	25
69 - 82	12500	10000	20
83 - 98	15000	12500	17
>99	18000	15000	17

IE = Internationale Einheit

C. Thrombose-Vorbeugung bei Patienten mit eingeschränkter Beweglichkeit

Die empfohlene Dosierung bei Patienten mit anhaltender eingeschränkter Beweglichkeit beträgt 5000 IE Fragmin subkutan (unter die Haut gespritzt), einmal täglich, in der Regel 12 bis 14 Tage lang oder länger. Eine Überwachung der gerinnungshemmenden Wirkung ist in der Regel nicht erforderlich.

D. Vorbeugung von Reisethrombose

2 - 4 Stunden vor Reiseantritt Fragmin 5000 IE/Tag (= 1 Fertigspritze Fragmin 5000 IE). Eine Thrombosevorbeugung am Reisetag ist nur bei Personen mit einer Vorgeschichte von thromboembolischen Ereignissen oder bei Anhäufung von Risikofaktoren angezeigt (siehe „Warnhinweise und Vorsichtsmaßnahmen“).

Der aktuelle Stand des Wissens ist jeweils zu berücksichtigen.

E. Behandlung instabiler Erkrankungen der Herzkranzgefäße (z.B. instabile Angina pectoris, Non- Q-wave-Herzmuskelinfarkt)

120 IE/kg KG subkutan zweimal täglich. Die maximale Dosis beträgt 10000 IE/12 Stunden. Als Behandlungsdauer werden 5 - 8 Tage empfohlen.

Bei Patienten, die vor einem chirurgischen Eingriff an Herzkranzgefäßen stehen (z.B. Bypass-Operation), wird eine Verabreichung von Fragmin bis zum Tag der Operation empfohlen (PTCA oder CABG). Nach anfänglicher Stabilisierung für 5 - 7 Tage mit einer körpergewichtsadaptierten Dosis von zweimal täglich

120 IE/kg/KG wird Fragmin in einer fixen Dosis von 5000 IE (Frauen < 80 kg und Männer < 70 kg) oder 7500 IE (Frauen 80 kg und Männer 70 kg) zweimal täglich gegeben. Der gesamte Behandlungszeitraum sollte 45 Tage nicht überschreiten.

Eine gleichzeitige Behandlung mit Acetylsalicylsäure in niedriger Dosierung wird empfohlen.

Der Dosisbereich lag in den durchgeführten klinischen Studien zwischen 75 und 325 mg entsprechend der örtlichen Spitalsroutine.

Spezielle Dosierungshinweise

Patienten mit Nierenfunktionsstörung

Wenn Sie eine schwere Nierenfunktionsstörung haben, wird Ihr Arzt die Fragmin-Dosis auf der Basis spezieller Gerinnungstests (Anti-Faktor Xa Spiegel) so anpassen, dass die bestmögliche gerinnungshemmende Wirkung beim kleinstmöglichen Blutungsrisiko sichergestellt werden kann.

Patienten mit Leberfunktionsstörung

Eine Dosisanpassung ist nicht erforderlich.

Ältere Patienten

Bei älteren Patienten ist keine Dosisanpassung erforderlich, sofern die Nierenfunktion nicht eingeschränkt ist.

Anwendung bei Kindern und Jugendlichen

Die Dosis orientiert sich am Alter und Körpergewicht des Kindes. Jüngere Kinder können dabei pro kg Körpergewicht geringfügig höhere Fragmin-Dosierungen benötigen als Erwachsene. Ihr Arzt wird die richtige Dosis festlegen. Während der Behandlung werden Blutproben durch medizinisches Fachpersonal abgenommen, um die Wirkung von Fragmin zu kontrollieren.

Wenn Sie weitere Fragen zur Anwendung dieses Arzneimittels haben, wenden Sie sich an Ihren Arzt oder Apotheker.

Wie alle Arzneimittel kann auch dieses Arzneimittel Nebenwirkungen haben, die aber nicht bei jedem auftreten müssen.

In Abhängigkeit von der Dosierung und häufiger bei Patienten mit zusätzlichen Risikofaktoren können vermehrt Blutungen auftreten, insbesondere aus Haut, Schleimhaut, Wunden, Magen-Darm-Trakt und im Bereich der Harn- und Geschlechtsorgane. Die meisten Blutungen sind leichter Art. Schwere Blutungen wurden ebenfalls beschrieben, diese können in Einzelfällen tödlich verlaufen. Die am häufigsten berichtete Nebenwirkung ist ein Bluterguss (Hämatom) an der Injektionsstelle.

Zur Einteilung der Häufigkeit von Nebenwirkungen werden die folgenden Kategorien angewendet:

Häufig: 1 bis 10 Behandelte von 100

Gelegentlich: 1 bis 10 Behandelte von 1000 Selten: 1 bis 10 Behandelte von 10000

Sehr selten: Weniger als 1 Behandelter von 10000

Nicht bekannt: Häufigkeit auf Grundlage der verfügbaren Daten nicht abschätzbar

Erkrankungen des Blutes und Lymphsystems

Häufig: Leichte vorübergehende Verringerung der Blutplättchenzahl (Thrombozytopenie) zu Beginn der Behandlung. Komplikationen kommen in diesen Fällen im Allgemeinen nicht vor und die Behandlung kann fortgeführt werden.

Nicht bekannt: Allergisch bedingte schwere Thrombozytopenie, welche mit arteriellen und venösen Thrombosen verbunden sein kann und die blutgerinnungshemmende Wirkung von Heparin vermindern kann. Wenn bei Ihnen diese Form der Verringerung der Blutplättchenzahl auftritt, dürfen Sie auch in Zukunft nie mehr mit einem heparinhaltigen Präparat behandelt werden (siehe „Fragmin darf nicht angewendet werden, ...“).

Erkrankungen des Immunsystems

Gelegentlich: Überempfindlichkeit gegenüber Dalteparin-Natrium. Sehr selten: In Einzelfällen wurde ein allergischer Schock beobachtet.

Nicht bekannt: Allergische Reaktionen. Allergische Erscheinungen umfassen Anzeichen wie Übelkeit, Kopfschmerzen, Temperaturanstieg, Gliederschmerzen, Schnupfen, Tränenfluss, Nesselausschlag, Erbrechen, Jucken, Atemnot, Bronchialkrampf und Blutdruckabfall.

Stoffwechsel- und Ernährungsstörungen

Selten: Unterfunktion der Nebenniere mit erhöhten Kalium- und verminderten Natriumkonzentrationen im Serum, Austrocknung und Kollaps, besonders bei Patienten mit eingeschränkter Nierenfunktion und Diabetes mellitus (siehe „Warnhinweise und Vorsichtsmaßnahmen“).

Erkrankungen des Nervensystems

Nicht bekannt: Blutungen im Schädel (können in Einzelfällen tödlich verlaufen).

Gefäßerkrankungen

Häufig: Blutungen.

Nicht bekannt: Blutdruckabfall, verlangsamter Herzschlag, Blutungen in verschiedenen Bereichen (können in Einzelfällen tödlich verlaufen), Gehirnblutungen (können in Einzelfällen tödlich verlaufen), in Einzelfällen kann eine mit Taubheitsgefühl verbundene Verengung der Blutgefäße, bei Männern auch eine schmerzhafte Dauererektion ohne sexuelle Erregung auftreten.

Erkrankungen des Magen-Darm-Trakts

Nicht bekannt: Blut im Stuhl, Blutungen im hinteren Bauchfell (können in Einzelfällen tödlich verlaufen).

Leber- und Gallenerkrankungen

Häufig: Vorübergehender Anstieg der Leberwerte, der sich nach Absetzen der Behandlung meist wieder normalisiert und klinisch nicht von Bedeutung ist.

Erkrankungen der Haut und des Unterhautzellgewebes

Selten: Untergang von Hautarealen (Hautnekrose), vorübergehender Haarausfall.

Nicht bekannt: Ausschlag, Blutungen, kleine, punktförmige Blutungen der Haut oder Schleimhäute.

Skelettmuskulatur, Bindegewebs und Knochenerkrankungen

Nicht bekannt: Nach längerer Anwendung von Heparin könnte ein Risiko für eine Verminderung der Knochenmasse (Osteoporose) bestehen. Dies wurde zwar mit Dalteparin bisher nicht beobachtet, kann aber nicht ausgeschlossen werden.

Erkrankungen der Nieren und Harnwege

Nicht bekannt: Blutungen im Bereich der Harn- und Geschlechtsorgane.

Allgemeine Beschwerden und Beschwerden am Verabreichungsort

Häufig: Kleinere Blutergüsse und Schmerzen an der Injektionsstelle.

Gelegentlich: Hautreaktionen an der Injektionsstelle (Verhärtungen, Rötungen, allergische Reaktionen und Verfärbungen).

Selten: Blutungen an der Injektionsstelle.

Untersuchungen

Nicht bekannt: Erhöhung der Thyroxinwerte und Kaliumretention, Verfälschung von HDL-Cholesterin und Blutzuckerwerten sowie der Ergebnisse des Bromsulphtalein-Tests.

Verletzungen, Vergiftungen und durch Eingriffe bedingte Kompliaktionen

Nicht bekannt: Blutergüsse im Bereich der Wirbelsäule bzw. des Rückenmarks.

Zusätzliche Nebenwirkungen bei Kindern und Jugendlichen

Es wird erwartet, dass die Nebenwirkungen bei Kindern denen bei Erwachsenen entsprechen. Über die möglichen Nebenwirkungen einer Langzeitanwendung bei Kindern liegen nur wenige Informationen vor.

Meldung von Nebenwirkungen

Wenn Sie Nebenwirkungen bemerken, wenden Sie sich an Ihren Arzt oder Apotheker. Dies gilt auch für Nebenwirkungen, die nicht in dieser Packungsbeilage angegeben sind.

Sie können Nebenwirkungen auch direkt über das nationale Meldesystem anzeigen: Bundesamt für Sicherheit im Gesundheitswesen

Traisengasse 5 1200 WIEN ÖSTERREICH

Fax: + 43 (0) 50 555 36207 Website: http://www.basg.gv.at/

Indem Sie Nebenwirkungen melden, können Sie dazu beitragen, dass mehr Informationen über die Sicherheit dieses Arzneimittels zur Verfügung gestellt werden.

Nicht über Raumtemperatur (25°C) lagern.

Bewahren Sie dieses Arzneimittel für Kinder unzugänglich auf.

Sie dürfen dieses Arzneimittel nach dem auf dem Etikett und dem Umkarton nach „Verwendbar bis“ angegebenen Verfalldatum nicht mehr verwenden. Das Verfalldatum bezieht sich auf den letzten Tag des angegebenen Monats.

Entsorgen Sie Arzneimittel nicht im Abwasser oder Haushaltsabfall. Fragen Sie Ihren Apotheker, wie das Arzneimittel zu entsorgen ist, wenn Sie es nicht mehr verwenden. Sie tragen damit zum Schutz der Umwelt bei.

Was Fragmin enthält

• Der Wirkstoff ist Dalteparin-Natrium. 1 Fertigspritze zu 0,2 ml enthält:

Dalteparin-Natrium

5000 IE Anti-Faktor Xa* (ca. 2500 IE aPTT)

(mittleres Molekulargewicht 5600 - 6400)

• Der sonstige Bestandteil ist: Wasser für Injektionszwecke.

*) Die aPTT ist ein Maß für die gerinnungshemmende Wirkung, während die Anti-Xa-Aktivität die antithrombotische Wirkung widerspiegelt.

Wie Fragmin aussieht und Inhalt der Packung

Fertigspritzen ohne Nadelschutzklemme

Injektionslösung in einer Einzeldosis Fertigspritze (Typ I Glas) mit einer latexfreien Nadelschutzkappe, einem Gummistopfen und einem Kolben.

2, 5, 10 Fertigspritzen zu 0,2 ml

Fertigspritzen mit Nadelschutzklemme

Injektionslösung in einer Einzeldosis Fertigspritze (Typ I Glas) mit einer latexfreien Nadelschutzkappe, einem Gummistopfen, einem Kolben und einer Nadelschutzklemme.

2, 5, 10 Fertigspritzen zu 0,2 ml mit Sicherheitssystem (Nadelschutzklemme)

Spritzanleitung

Die Fertigspritze ist mit einem Sicherheitssystem (Nadelschutzklemme) ausgestattet, das nach der Injektion aktiviert werden muss. So kann das Risiko von Nadelstichverletzungen reduziert werden. Die Nadelschutzklemme (orange) ist am Glaszylinder der Fertigspritze befestigt.

Die Fertigspritze vor Injektion.

1. Nadelschutzkappe (grau)
2. Nadelschutzklemme (orange)
3. Glaszylinder

Den Kolben nicht vor Injektion betätigen. Die vorhandene Luftblase dient zur vollständigen

Entleerung der Spritze und sollte daher nicht entfernt werden.

1. Deckfolie vollständig abziehen. Fertigspritze nicht durch die Deckfolie drücken.

2. Fertigspritze vorsichtig entnehmen.

3. Nadelschutzklemme weit genug (ca. 60 bis 80 Grad) wegklappen.

4. Graue Nadelschutzkappe gerade abziehen. Eventuell vorhandene Tropfen an der Nadelspitze vorsichtig abschütteln (nicht abstreifen).

5. Hautfalte bilden: Dazu die vorgesehene Einstichstelle mit Daumen und Zeigefinger anheben (nicht pressen). Fertigspritze senkrecht zur Hautfalte ansetzen, die Nadel vollständig einstechen. Gesamten Inhalt der Fertigspritze langsam injizieren. Nadel vorsichtig herausziehen. Ein Pflaster ist in der Regel nicht erforderlich. An der Einstichstelle kann sich später eventuell ein kleiner Bluterguss bilden.

Nadel aktiv sichern: Nadelschutzklemme mit einer Hand gegen eine feste Oberfläche drücken. Um mehr als 45 Grad biegen, bis ein „Klick“ zu hören ist.

ACHTUNG: Nadelschutzklemme niemals mit dem Finger umbiegen!

Pharmazeutischer Unternehmer und Hersteller

Pharmazeutischer Unternehmer: Pfizer Corporation Austria Ges.m.b.H., Wien

Hersteller: Catalent France Limoges S.A.S., Limoges, Frankreich

Pfizer Manufacturing Belgium NV, Puurs, Belgien

Z.Nr.: 1-18733

Diese Packungsbeilage wurde zuletzt überarbeitet im Mai 2014.

Reisethrombose – vermeidbar mit rechtzeitiger Prophylaxe

Die Gefahr einer Reisethrombose bei Langstreckenflügen oder bei langen Busfahrten kann durch einfache Vorsichtsmaßnahmen minimiert werden.

Das Sitzen mit abgewinkelten Beinen, ohne Bewegung, führt, auch bei Menschen mit gesunden Venen, nach einigen Stunden zu einer Beinschwellung. Der Grund ist ein Versacken des Blutes in den Beinen und darauffolgend eine Drucksteigerung in den Venen, welche sich erweitern.

Als besondere Risikofaktoren für eine Reisethrombose gelten:

• langes Sitzen (länger als fünf Stunden)
• Alter über 40
• Venenerkrankungen, Herzschwäche, Schwangerschaft, Pille, Übergewicht
• vorangegangene Thrombosen oder Embolien, Gipsverband an den unteren Extremitäten, nach größeren Operationen (vor allem orthopädischen), Gerinnungsstörung, Krebserkrankungen
• Beim Fliegen wird das Risiko, an einer Reisethrombose zu erkranken, durch die extrem trockene Luft (führt zum Eindicken des Blutes) und durch das Konsumieren von alkoholischen Getränken (Gefäße erweitern sich) und eventuelle Einnahme von Schlafmitteln erhöht.

Wenn Sie zu den Patienten mit niedrigem oder mäßigem Risiko gehören, können Sie mit folgenden Vorsichtsmaßnahmen die Gefahr einer Reisethrombose weitgehend reduzieren:

• die Beine regelmäßig bewegen
• die Schuhe ausziehen und einmal pro Stunde die Zehen bewegen, die Füße kreisen lassen oder im Sprunggelenk wippen
• immer wieder aufstehen und herumzugehen
• die Rückenlehne jede Stunde zurückstellen, damit man sich durchstrecken kann
• reichlich Flüssigkeit zu sich nehmen (kein Alkohol)
• Zurückhaltung bei der Einnahme von Schlaf- und Beruhigungsmitteln
• bei schmerzenden und geschwollenen Beinen erfrischt ein nasses Tuch oder ein kühlender Spray
• Personen mit mittlerem Risiko sollten während Langstreckenflügen Stützstrümpfe der Kompressionsklasse 1 bis 2 tragen.

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Die folgenden Informationen sind für Ärzte bzw. medizinisches Fachpersonal bestimmt:

Spezielle Dosierungshinweise

Patienten mit Niereninsuffizienz

In klinischen Studien, die mit Fragmin durchgeführt wurden, ist als Grenze für schwer niereninsuffiziente Patienten ein Serum-Kreatinin von >dem 3fachen des oberen Normwertes festgelegt worden. Aus diesen Studien ging hervor, dass die Fragmin-Dosis bei diesen Patienten so angepasst werden soll, dass eine therapeutische Anti-Faktor Xa-Konzentration von 1 IE/ml (zwischen 0,5 und 1,5 IE/ml) 4 bis 6 Stunden nach Verabreichung erreicht wird. Wenn der Anti-Faktor Xa-Spiegel unter oder über dem therapeutischen Bereich liegt, sollte die Fragmin-Dosis entsprechend nach oben oder unten korrigiert werden. Die Messung des Anti-Faktors Xa sollte nach 3 - 4 Dosierungen erneut vorgenommen und die Dosisanpassung so lange wiederholt werden, bis der therapeutische Bereich erreicht wird.

Patienten mit Leberinsuffizienz

Eine Dosisanpassung ist nicht erforderlich.

Ältere Patienten

Bei älteren Patienten ist keine Dosisanpassung erforderlich, sofern die Nierenfunktion nicht eingeschränkt ist. (siehe Abschnitt 4.4)

Kinder und Jugendliche

Bei Kindern wurden die Sicherheit und Wirksamkeit von Dalteparin-Natrium nicht nachgewiesen. In den Abschnitten 5.1 und 5.2 sind die derzeit vorliegenden Daten aufgeführt. Es können jedoch keine Dosierungsangaben gemacht werden.

Kontrolle des Plasma-Anti-Faktor Xa-Spiegels bei Kindern

Bei bestimmten Patientenpopulationen, wie z.B. bei Kindern, sollte bei Anwendung von Fragmin ca. 4 Stunden nach der Applikation eine Bestimmung des maximalen Plasma-Anti-Faktor Xa-Spiegels erwogen werden. Bei therapeutischer Anwendung mit Einmalgabe sollten die ca. 4 Stunden nach der Applikation gemessenen maximalen Plasma-Anti-Faktor Xa-Spiegel üblicherweise zwischen 0,5 und 1,0 IE/ml liegen. Bei eingeschränkter und instabiler physiologischer Nierenfunktion, wie etwa bei Neugeborenen, wird eine engmaschige Kontrolle der Plasma-Anti-Faktor Xa-Spiegel empfohlen. Bei prophylaktischer Anwendung sollten sich die Plasma-Anti-Faktor Xa-Spiegel üblicherweise zwischen 0,2 und 0,4 IE/ml bewegen.

Wie bei allen Antikoagulanzien besteht auch bei Anwendung von Fragmin die Gefahr systemischer Blutungen. Bei frisch operierten Patienten sollte die Anwendung von Fragmin in hohen Dosen mit erhöhter Vorsicht erfolgen. Nach Behandlungsbeginn sollten die Patienten engmaschig auf Blutungskomplikationen kontrolliert werden. Das kann durch die üblichen Kontrolluntersuchungen bei den Patienten, sorgfältige Beobachtung der Wunddrainage und regelmäßige Bestimmung von Hämoglobin sowie des Plasma-Anti-Faktor Xa-Spiegels erfolgen.

Art der Anwendung

Nur zur subkutanen Injektion.

Die Luftblase in der Spritze nicht entfernen, sie gewährleistet eine vollständige Entleerung der Kanüle. Die Injektion sollte in eine von zwei Fingern geformte Hautfalte der vorderen oder seitlichen Bauchwand erfolgen. Die Nadel senkrecht bis zum Glaskolben in die Bauchfalte einführen. Langsam injizieren. Die Hautfalte darf während der Injektion nicht gelockert werden.

Bei Ausstattung mit einer Nadelschutzklemme als Schutzvorrichtung wird die Spritze nach der Injektion einhändig mit der orangefarbenen Nadelschutzklemme gegen eine feste Oberfläche gedrückt und solange gebogen (um mehr als 45°), bis die Nadel einrastet. Die Nadel ist nun dauerhaft unbrauchbar (siehe Abschnitte 6.5 und 6.6).

Durch diese Schutzvorrichtung wird das Risiko unbeabsichtigter Nadelstichverletzungen reduziert.

• Überdosierung

Inaktivierung von Fragmin im Notfall:

Die gerinnungshemmende Wirkung von Dalteparin kann durch Protamin (1 mg) neutralisiert werden. Während die induzierte Verlängerung der Gerinnungszeit vollständig normalisiert wird, wird die Anti- Faktor Xa-Aktivität nur zu etwa 25 - 50% aufgehoben: 1 mg Protamin hebt die Wirkung von 100 IE (Anti-Faktor Xa) Dalteparin auf.

Protamin sollte jedoch nur in Notfällen eingesetzt werden und eine Überdosierung von Protamin sollte vermieden werden, da Protamin selbst einen gerinnungshemmenden Effekt ausübt.