Komposition:
Wird bei der Behandlung verwendet:
Medizinisch geprüft von Oliinyk Elizabeth Ivanovna, Apotheke Zuletzt aktualisiert am 26.06.2023
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NAPROSYN-Tabletten, EC-NAPROSYN und ANAPROX DS sind angezeigt für:
die Linderung der Anzeichen und Symptome von:
- rheumatoide Arthritis
- Arthrose
- Spondylitis ankylosans
- Polyartikuläre juvenile idiopathische Arthritis
NAPROSYN-Tabletten und ANAPROX DS sind ebenfalls angegeben für:
die Linderung von Anzeichen und Symptomen von:
- Sehnenentzündung
- Schleimbeutelentzündung
- akute Gicht
die Verwaltung von:
- Schmerzen
- primäre Dysmenorrhoe
Erwachsene:
Behandlung von rheumatoider Arthritis, Arthrose (degenerative Arthritis), Spondylitis ankylosans, akuter Gicht, akuten Erkrankungen des Bewegungsapparates und Dysmenorrhoe.
Kinder:
Juvenile rheumatoide Arthritis
Prexan-Tabletten sind zur Behandlung von:
- rheumatoide Arthritis (RA)
- Arthrose (OA)
- Spondylitis ankylosans (AS)
- Sehnenentzündung, Schleimbeutelentzündung
- akute Gicht
- primäre Dysmenorrhoe (PD)
- die Linderung von leichten bis mittelschweren Schmerzen
.
Prexan Tablets, EC-Prexan und ANAPROX DS sind angezeigt für:
die Linderung der Anzeichen und Symptome von:
- rheumatoide Arthritis
- Arthrose
- Spondylitis ankylosans
- Polyartikuläre juvenile idiopathische Arthritis
Prexan Tablets und ANAPROX DS sind ebenfalls angezeigt für:
die Linderung von Anzeichen und Symptomen von:
- Sehnenentzündung
- Schleimbeutelentzündung
- akute Gicht
die Verwaltung von:
- Schmerzen
- primäre Dysmenorrhoe
General Dosing Instructions
Carefully consider the potential benefits and risks of NAPROSYN Tablets, EC-NAPROSYN and ANAPROX DS and other treatment options before deciding to use NAPROSYN Tablets, EC-NAPROSYN and ANAPROX DS. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
After observing the response to initial therapy with NAPROSYN Tablets, EC-NAPROSYN or ANAPROX DS, the dose and frequency should be adjusted to suit an individual patient's needs.
To maintain the integrity of the enteric coating, the EC-NAPROSYN tablet should not be broken, crushed or chewed during ingestion.
Naproxen-containing products such as NAPROSYN, EC-NAPROSYN and ANAPROX DS, and other naproxen products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.
Rheumatoid Arthritis, Osteoarthritis And Ankylosing Spondylitis
The recommended dosages of NAPROSYN Tablets, ANAPROX DS, and EC-NAPROSYN are shown in Table 1.
Table 1: Recommended dosages for NAPROSYN Tablets, ANAPROX DS, and EC-NAPROSYN
| NAPROSYN | 250 mg (one half tablet) 500 mg | twice daily |
| ANAPROX DS | 275 mg (one half tablet) 550 mg (naproxen 500 mg with 50 mg sodium) | twice daily |
| EC-NAPROSYN | 375 mg | twice daily |
| or 500 mg | twice daily |
During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.
The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response.
In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk.
Polyarticular Juvenile Idiopathic Arthritis
Naproxen solid-oral dosage forms may not allow for the flexible dose titration needed in pediatric patients with polyarticular juvenile idiopathic arthritis. A liquid formulation may be more appropriate for weight-based dosing and due to the need for dose flexibility in children.
In pediatric patients, doses of 5 mg/kg/day produced plasma levels of naproxen similar to those seen in adults taking 500 mg of naproxen. The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses. Dosing with NAPROSYN Tablets is not appropriate for children weighing less than 50 kilograms.
Management Of Pain, Primary Dysmenorrhea, And Acute Tendonitis And Bursitis
The recommended starting dose of ANAPROX DS (naproxen sodium) tablets is 550 mg followed by 550 mg every 12 hours or 275 mg (one half of a 550 mg tablet) every 6 to 8 hours as required. The initial total daily dose should not exceed 1375 mg (two and one-half tablets) of naproxen sodium. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen is more rapidly absorbed, ANAPROX DS is recommended for the management of acute painful conditions when prompt onset of pain relief is desired. NAPROSYN Tablets may also be used. The recommended starting dose of NAPROSYN Tablets is 500 mg followed by 250 mg (one half of a 500 mg NAPROSYN tablet) every 6-8 hours as required.. The total daily dose should not exceed 1250 mg of naproxen.
EC-NAPROSYN is not recommended for initial treatment of acute pain because absorption of naproxen is delayed compared to other naproxen-containing products.
Acute Gout
The recommended starting dose is 750 mg (one and one-half tablets) of NAPROSYN Tablets followed by 250 mg (one-half tablet) every 8 hours until the attack has subsided. ANAPROX DS may also be used at a starting dose of 825 mg (one and one-half tablets) followed by 275 mg (one-half tablet) every 8 hours. EC-NAPROSYN is not recommended because of the delay in absorption.
Non-Interchangeability With Other Formulations Of Naproxen
Different dose strengths and formulations (e.g., tablets, suspension) of naproxen are not interchangeable. This difference should be taken into consideration when changing strengths or formulations.
For oral administration
Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
To be taken preferably with or after food
Rheumatic Disorders (Adults):
500mg to 1g taken in 2 doses at 12-hour intervals or alternatively, as a single administration. In the following cases a loading dose of 750mg or 1g per day for the acute phase is recommended:
a) In patients reporting severe night-time pain/or morning stiffness.
b) In patients being switched to Naprosyn from a high dose of another anti-rheumatic compound.
c) In osteoarthrosis where pain is the predominant symptom.
Children (over 5 years) : A dose of 10mg per kg body weight daily in two divided doses has been used in children over 5 years of age with juvenile rheumatoid arthritis.
Acute Gout (Adults): In acute gout an initial dose of 750 mg followed by 250mg every 8 hours until attack has passed; has been suggested.
Child: Not recommended in children under 16 years.
Musculoskeletal Disorders and Dysmenorrhoea (Adults); 500mg may be given initially followed by 250mg every 6 to 8 hours as required. Maximum daily dose after first day is 1250mg daily.
Child: Not recommended in children under 16 years.
The lowest recommended dose should be used especially in the elderly to reduce the risk of adverse reactions.
Elderly: Studies indicate that although total plasma concentration of Prexan is unchanged, the unbound plasma fraction of Prexan is increased in the elderly.
Renal/hepatic impairment: A lower dose should be considered in patients with renal or hepatic impairment. Naprosyn is contraindicated in patients with baseline creatinine clearance less than 30 ml/minute because accumulation of Prexan metabolites has been seen in patients with severe renal failure or those on dialysis.
Treatment should be reviewed at regular intervals and discontinued if no benefit is seen or intolerance occurs.
General Dosing Instructions
Carefully consider the potential benefits and risks of Prexan and other treatment options before deciding to use Prexan. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
After observing the response to initial therapy with Prexan, the dose and frequency should be adjusted to suit an individual patient's needs.
Rheumatoid Arthritis, Osteoarthritis, And Ankylosing Spondylitis
The recommended starting dose of Prexan Tablets in adults is two Prexan 375 mg tablets (750 mg) once daily, one Prexan 750 mg (750 mg) once daily, or two Prexan 500 mg tablets (1,000 mg) once daily. Patients already taking naproxen 250 mg, 375 mg, or 500 mg twice daily (morning and evening) may have their total daily dose replaced with Prexan Tablets as a single daily dose.
During long-term administration, the dose of Prexan Tablets may be adjusted up or down depending on the clinical response of the patient. In patients who tolerate lower doses of Prexan Tablets well, the dose may be increased to two Prexan 750 mg tablets (1,500 mg), or three Prexan 500 mg tablets (1,500 mg) once daily for limited periods when a higher level of anti-inflammatory/analgesic activity is required. When treating patients, especially at the higher dose levels, the physician should observe sufficient increased clinical benefit to offset the potential increased risk. The lowest effective dose should be sought and used in every patient. Symptomatic improvement in arthritis usually begins within one week; however, treatment for two weeks may be required to achieve a therapeutic benefit.
Management Of Pain, Primary Dysmenorrhea, And Acute Tendinitis and Bursitis
The recommended starting dose is two Prexan 500 mg tablets (1,000 mg) once daily. For patients requiring greater analgesic benefit, two Prexan 750 mg tablets (1,500 mg) or three Prexan 500 mg tablets (1,500 mg) may be used for a limited period. Thereafter, the total daily dose should not exceed two Prexan 500 mg tablets (1,000 mg).
Acute Gout
The recommended dose on the first day is two to three Prexan 500 mg tablets (1,000 to 1,500 mg) once daily, followed by two Prexan 500 mg tablets (1,000 mg) once daily, until the attack has subsided.
Dosage Adjustments In Patients With Hepatic Impairment
A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients. Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly it is prudent to use the lowest effective dose.
General Dosing Instructions
Carefully consider the potential benefits and risks of Prexan Tablets, EC-Prexan and ANAPROX DS and other treatment options before deciding to use Prexan Tablets, EC-Prexan and ANAPROX DS. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
After observing the response to initial therapy with Prexan Tablets, EC-Prexan or ANAPROX DS, the dose and frequency should be adjusted to suit an individual patient's needs.
To maintain the integrity of the enteric coating, the EC-Prexan tablet should not be broken, crushed or chewed during ingestion.
Naproxen-containing products such as Prexan, EC-Prexan and ANAPROX DS, and other naproxen products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.
Rheumatoid Arthritis, Osteoarthritis And Ankylosing Spondylitis
The recommended dosages of Prexan Tablets, ANAPROX DS, and EC-Prexan are shown in Table 1.
Table 1: Recommended dosages for Prexan Tablets, ANAPROX DS, and EC-Prexan
| Prexan | 250 mg (one half tablet) 500 mg | twice daily |
| ANAPROX DS | 275 mg (one half tablet) 550 mg (naproxen 500 mg with 50 mg sodium) | twice daily |
| EC-Prexan | 375 mg | twice daily |
| or 500 mg | twice daily |
During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.
The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response.
In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk.
Polyarticular Juvenile Idiopathic Arthritis
Naproxen solid-oral dosage forms may not allow for the flexible dose titration needed in pediatric patients with polyarticular juvenile idiopathic arthritis. A liquid formulation may be more appropriate for weight-based dosing and due to the need for dose flexibility in children.
In pediatric patients, doses of 5 mg/kg/day produced plasma levels of naproxen similar to those seen in adults taking 500 mg of naproxen. The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses. Dosing with Prexan Tablets is not appropriate for children weighing less than 50 kilograms.
Management Of Pain, Primary Dysmenorrhea, And Acute Tendonitis And Bursitis
The recommended starting dose of ANAPROX DS (naproxen sodium) tablets is 550 mg followed by 550 mg every 12 hours or 275 mg (one half of a 550 mg tablet) every 6 to 8 hours as required. The initial total daily dose should not exceed 1375 mg (two and one-half tablets) of naproxen sodium. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen is more rapidly absorbed, ANAPROX DS is recommended for the management of acute painful conditions when prompt onset of pain relief is desired. Prexan Tablets may also be used. The recommended starting dose of Prexan Tablets is 500 mg followed by 250 mg (one half of a 500 mg Prexan tablet) every 6-8 hours as required.. The total daily dose should not exceed 1250 mg of naproxen.
EC-Prexan is not recommended for initial treatment of acute pain because absorption of naproxen is delayed compared to other naproxen-containing products.
Acute Gout
The recommended starting dose is 750 mg (one and one-half tablets) of Prexan Tablets followed by 250 mg (one-half tablet) every 8 hours until the attack has subsided. ANAPROX DS may also be used at a starting dose of 825 mg (one and one-half tablets) followed by 275 mg (one-half tablet) every 8 hours. EC-Prexan is not recommended because of the delay in absorption.
Non-Interchangeability With Other Formulations Of Naproxen
Different dose strengths and formulations (e.g., tablets, suspension) of naproxen are not interchangeable. This difference should be taken into consideration when changing strengths or formulations.
NAPROSYN-Tabletten, EC-NAPROSYN und ANAPROX DS sind bei folgenden Patienten kontraindiziert:
- Bekannte Überempfindlichkeit (z.anaphylaktische Reaktionen und schwerwiegende Hautreaktionen) auf Naproxen oder Komponenten des Arzneimittels
- Vorgeschichte von Asthma, Urtikaria oder anderen allergischen Reaktionen nach Einnahme von Aspirin oder anderen NSAIDs. Bei solchen Patienten wurden schwere, manchmal tödliche anaphylaktische Reaktionen auf NSAIDs berichtet
- Bei der Einstellung der CABG-Operation (Coronary Artery Bypass Transplant)
- Überempfindlichkeit gegen einen der Bestandteile.
- Da das Potenzial für Kreuzempfindlichkeitsreaktionen besteht, ist Prexan bei Patienten kontraindiziert, die zuvor Überempfindlichkeitsreaktionen gezeigt haben (z. Asthma, Rhinitis, Nasenpolypen, Angioödeme oder Urtikaria) als Reaktion auf Ibuprofen, Aspirin oder andere nichtsteroidale entzündungshemmende Arzneimittel. Diese Reaktionen können tödlich sein. Bei solchen Patienten wurden schwere anaphylaktische Reaktionen auf Prexan berichtet.
- - Besondere Warnhinweise und Vorsichtsmaßnahmen für den Gebrauch).
- )
- Eine Vorgeschichte von gastrointestinalen Blutungen oder Perforationen im Zusammenhang mit früheren NSAIDs-Therapien. Aktive oder Vorgeschichte von Magengeschwüren / oder aktiven gastrointestinalen Blutungen (zwei oder mehr verschiedene Episoden nachgewiesener Geschwüre oder Blutungen).
- Im Prinzip darf Prexan nicht bei Patienten mit Magen-Darm-Geschwüren, kongestiver Gastritis oder atrophischer Gastritis, gastrointestinalen Blutungen oder anderen Blutungen wie zerebrovaskulären Blutungen angewendet werden.
- Hämorrhoiden oder Veranlagung für rektale Blutungen.
Prexan ist bei folgenden Patienten kontraindiziert:
- Bekannte Überempfindlichkeit (z.anaphylaktische Reaktionen und schwerwiegende Hautreaktionen) auf Naproxen oder Komponenten des Arzneimittels
- Vorgeschichte von Asthma, Urtikaria oder anderen allergischen Reaktionen nach Einnahme von Aspirin oder anderen NSAIDs. Bei solchen Patienten wurden schwere, manchmal tödliche anaphylaktische Reaktionen auf NSAIDs berichtet
- Bei der Einstellung der CABG-Operation (Coronary Artery Bypass Transplant)
Prexan-Tabletten, EC-Prexan und ANAPROX DS sind bei folgenden Patienten kontraindiziert:
- Bekannte Überempfindlichkeit (z.anaphylaktische Reaktionen und schwerwiegende Hautreaktionen) auf Naproxen oder Komponenten des Arzneimittels
- Vorgeschichte von Asthma, Urtikaria oder anderen allergischen Reaktionen nach Einnahme von Aspirin oder anderen NSAIDs. Bei solchen Patienten wurden schwere, manchmal tödliche anaphylaktische Reaktionen auf NSAIDs berichtet
- Bei der Einstellung der CABG-Operation (Coronary Artery Bypass Transplant)
Die folgenden Nebenwirkungen werden in anderen Abschnitten der Kennzeichnung ausführlicher erörtert:
- Herz-Kreislauf-Thrombotika
- GI-Blutung, Ulzeration und Perforation
- Hepatotoxizität
- Hypertonie
- Herzinsuffizienz und Ödeme
- Renntoxizität und Hyperkaliämie
- Anaphylaktische Reaktionen
- Schwere Hautreaktionen
- Hämatologische Toxizität
Erfahrung in klinischen Studien
Da klinische Studien unter sehr unterschiedlichen Bedingungen durchgeführt werden, können die in den klinischen Studien eines Arzneimittels beobachteten Nebenwirkungen nicht direkt mit den Raten in den klinischen Studien eines anderen Arzneimittels verglichen werden und spiegeln möglicherweise nicht die in der Praxis beobachteten Raten wider.
Wie bei allen Arzneimitteln dieser Klasse hängt die Häufigkeit und Schwere unerwünschter Ereignisse von mehreren Faktoren ab: der Dosis des Arzneimittels und der Dauer der Behandlung; das Alter, das Geschlecht, die körperliche Verfassung des Patienten; gleichzeitige medizinische Diagnosen oder individuelle Risikofaktoren. Die folgenden Nebenwirkungen werden je nach Häufigkeit und der Möglichkeit eines kausalen Zusammenhangs zwischen dem Drogenkonsum und diesen unerwünschten Ereignissen in drei Teile unterteilt. Bei den als „wahrscheinlich kausaler Zusammenhang“ aufgeführten Reaktionen gibt es mindestens einen Fall für jede Nebenwirkung, in dem Anhaltspunkte dafür vorliegen, dass ein kausaler Zusammenhang zwischen dem Drogenkonsum und dem gemeldeten Ereignis besteht. Die gemeldeten Nebenwirkungen basierten auf den Ergebnissen von zwei doppelblinden kontrollierten klinischen Studien mit einer Dauer von drei Monaten und einer zusätzlichen offenen Verlängerung um neun Monate. Insgesamt 542 Patienten erhielten Prexan-Tabletten entweder in der Doppelblindperiode oder in der neunmonatigen Open-Label-Erweiterung. Von diesen 542 Patienten erhielten 232 Prexan-Tabletten, 167 wurden zunächst mit Naprosyn® behandelt und 143 wurden zunächst mit Placebo behandelt. Nebenwirkungen von Patienten, die Prexan-Tabletten erhielten, werden nach Körpersystemen gezeigt. Die mit Naproxen beobachteten, aber in kontrollierten Studien mit Prexan-Tabletten nicht berichteten Nebenwirkungen sind kursiv geschrieben.
Die häufigsten unerwünschten Ereignisse aus doppelblinden und offenen klinischen Studien waren Kopfschmerzen (15%), gefolgt von Dyspepsie (14%) und Grippesyndrom (10%). Die Inzidenz anderer unerwünschter Ereignisse bei 3% bis 9% der Patienten ist mit einem Sternchen gekennzeichnet.
Diese Reaktionen, die bei weniger als 3% der Patienten auftreten, sind nicht markiert.
Inzidenz größer als 1% (wahrscheinlicher kausaler Zusammenhang)
Körper als Ganzes - Schmerzen (Rücken) *, Schmerzen *, Infektionen *, Fieber, Verletzungen (Unfall), Asthenie, Schmerzbrust, Kopfschmerzen (15%), Grippesyndrom (10%).
Gastrointestinal - Übelkeit *, Durchfall *, Verstopfung *, Bauchschmerzen *, Blähungen, Gastritis, Erbrechen, Dysphagie, Dyspepsie (14%), Sodbrennen *, Stomatitis.
Hämatologisch - Anämie, Ekchymose.
Atemwege - Pharyngitis *, Rhinitis *, Sinusitis *, Bronchitis, Husten erhöht.
Renal - Harnwegsinfektion *, Blasenentzündung.
Dermatologisch - Hautausschlag *, Hautausschläge *, Ekchymosen *, Purpura.
Stoffwechsel und Ernährung - Peripheres Ödem, Hyperglykämie.
Zentrales Nervensystem - Schwindel, Parästhesie, Schlaflosigkeit, Schläfrigkeit *, Benommenheit.
Herz-Kreislauf - Hypertonie, Ödeme *, Atemnot *, Herzklopfen.
Bewegungsapparat - Krämpfe (Bein), Myalgie, Arthralgie, Gelenkerkrankung, Sehnenstörung.
Besondere Sinne - Tinnitus *, Hörstörungen, Sehstörungen.
Allgemeines - Durst.
Inzidenz weniger als 1% (wahrscheinlicher kausaler Zusammenhang)
Körper als Ganzes - Abszess, Monilie, Nackensteif, Schmerzhals, Bauch vergrößert, Karzinom, Cellulitis, Ödem allgemein, LE-Syndrom, Unwohlsein, Schleimhautstörung, allergische Reaktion, Schmerzbecken.
Gastrointestinal - Anorexie, Cholezystitis, Cholelithiasis, Aufstoßen, GI-Blutung, Rektalblutung, aphthöse Stomatitis, Stomatitis-Geschwür, Geschwürmund, Magengeschwür, Parodontalabszess, Kardiospasmus, Kolitis, Ösophagitis, Gastroenteritis, Rektalstörung, Zahnstörung, Leberfunktionsschmelisse.
Renal - Dysmenorrhoe, Dysurie, Nierenfunktionsstörungen, Nykturie, Prostatastörung, Pyelonephritis, Karzinombrust, Harninkontinenz, Nierenrechnung, Nierenversagen, Menorrhagie, Metrorrhagie, Neoplasma-Brust, Nephrosklerose, Hämaturie, Schmerzniere, Pyurie, Urin abnormal, Harnfrequenz, Harnverhaltung, Uteruskrampf, Vaginitis, glomeruläre Nephritis, Hyperkaliämie, interstitielle Nephritis, nephrotisches Syndrom, Nierenerkrankung, Nierenversagen, Nierenpapillarnekrose.
Hämatologisch - Leukopenie, erhöhte Blutungszeit, Eosinophilie, abnorme RBC, abnorme WBC, Thrombozytopenie, Agranulozytose, Granulozytopenie.
Zentrales Nervensystem - Depressionen, Angstzustände, Hypertonie, Nervosität, Neuralgie, Neuritis, Schwindel, Amnesie, Verwirrung, Koordination, abnorme Diplopie, emotionale Labilität, subdurales Hämatom, Lähmung, Traumanomalien, Konzentrationsunfähigkeit, Muskelschwäche.
Dermatologisch: Angiodermatitis, Herpes simplex, trockene Haut, Schwitzen, Geschwürhaut, Akne, Alopezie, Dermatitis-Kontakt, Ekzem, Herpes zoster, Nagelstörung, Hautnekrose, subkutaner Knoten, Juckreiz, Urtikaria, Neoplasma-Haut, lichtempfindliche Dermatitis, Lichtempfindlichkeitsreaktionen ähnlich porphyria kutane Tarda, Epidermolyse Bullosa.
Besondere Sinne - Amblyopie, Skleritis, Katarakt, Bindehautentzündung, Taub, Ohrstörung, Keratokonjunktivitis, Tränenstörung, Mittelohrentzündung, Schmerzauge.
Herz-Kreislauf - Angina pectoris, Erkrankung der Herzkranzgefäße, Myokardinfarkt, tiefe Thrombophlebitis, Vasodilatation, Gefäßanomalie, Arrhythmie, Bündelzweigblock, abnormales EKG, Herzinsuffizienz, Blutung, Migräne, Aortenstenose, Synkope, Tachykardie, Herzinsuffizienz.
Atemwege - Asthma, Atemnot, Lungenödem, Laryngitis, Lungenerkrankung, Epistaxis, Lungenentzündung, Atemnot, Atemwegserkrankung, eosinophile Pneumonitis.
Bewegungsapparat - Myasthenie, Knochenerkrankung, spontane Knochenfraktur, Fibrotendinitis, Knochenschmerzen, Ptosis, allgemeiner Krampf, Bursitis.
Stoffwechsel und Ernährung - Kreatininanstieg, Glucosurie, Hypercholesterämie, Albuminurie, Alkalose, BUN erhöht, Dehydration, Ödem, Glukosetoleranzabnahme, Hyperurikämie, Hypokaliämie, SGOT-Anstieg, SGPT-Anstieg, Gewichtsabnahme.
Allgemeines - Anaphylaktoide Reaktionen, angioneurotisches Ödem, Menstruationsstörungen, Hypoglykämie, Pyrexie (Schüttelfrost und Fieber).
Inzidenz weniger als 1% (kausale Beziehung unbekannt)
Andere Nebenwirkungen, die auf dem Naproxen-Packungsetikett aufgeführt sind, jedoch von denjenigen, die Prexan-Tabletten erhalten haben, nicht gemeldet wurden, sind kursiv dargestellt. Diese Beobachtungen werden als Warninformationen für den Arzt aufgeführt.
Hämatologisch - Aplastische Anämie, hämolytische Anämie.
Zentrales Nervensystem - Aseptische Meningitis, kognitive Dysfunktion.
Dermatologisch - Epidermale Nekrolyse, Erythema multiforme, Stevens-Johnson-Syndrom.
Gastrointestinal - Nicht-peptische GI-Geschwüre, ulzerative Stomatitis.
Herz-Kreislauf - Vaskulitis.
Die Symptome nach akuten NSAID-Überdosierungen beschränkten sich typischerweise auf Lethargie, Schläfrigkeit, Übelkeit, Erbrechen und epigastrische Schmerzen, die im Allgemeinen mit unterstützender Pflege reversibel waren. Gastrointestinale Blutungen sind aufgetreten. Hypertonie, akutes Nierenversagen, Atemdepression und Koma sind aufgetreten, aber selten.
Bei einigen Patienten traten Anfälle auf, es ist jedoch nicht klar, ob diese arzneimittelbedingt waren oder nicht. Es ist nicht bekannt, welche Dosis des Arzneimittels lebensbedrohlich wäre.
Verwalten Sie Patienten mit symptomatischer und unterstützender Behandlung nach einer NSAID-Überdosierung. Es gibt keine spezifischen Gegenmittel. Die Hämodialyse verringert die Plasmakonzentration von Naproxen aufgrund des hohen Grads seiner Proteinbindung nicht. Betrachten Sie Erbrechen und / oder Aktivkohle (60 bis 100 Gramm bei Erwachsenen, 1 bis 2 Gramm pro kg Körpergewicht bei pädiatrischen Patienten) und / oder osmotisch kathartisch bei symptomatischen Patienten innerhalb von vier Stunden nach der Einnahme oder bei Patienten mit einer großen Überdosierung (5- bis 10-fache empfohlene Dosierung). Zwangsdiurese, Alkalinisierung des Urins, Hämodialyse oder Hämoperfusion sind aufgrund der hohen Proteinbindung möglicherweise nicht nützlich.
Weitere Informationen zur Überdosierungsbehandlung erhalten Sie von einem Giftnotrufzentrum (1-800-2221222).
Prexan hat analgetische, entzündungshemmende und pyretische Wirkungen.
Prexan ist eine nichtsteroidale entzündungshemmende analgetische Verbindung mit antipyretischen Eigenschaften, wie in klassischen Tierversuchssystemen gezeigt wurde. Prexan zeigt seine entzündungshemmende Wirkung auch bei adrenalektomisierten Tieren, was darauf hinweist, dass seine Wirkung nicht durch die Hypophysen-Adrenal-Achse vermittelt wird.
Prexan hemmt die Prostaglandinsynthetase (wie andere NSAIDs). Wie bei anderen NSAIDs ist der genaue Mechanismus seiner entzündungshemmenden Wirkung jedoch nicht bekannt.
Naproxen and naproxen sodium are rapidly and completely absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%. The different dosage forms of NAPROSYN are bioequivalent in terms of extent of absorption (AUC) and peak concentration (Cmax); however, the products do differ in their pattern of absorption. These differences between naproxen products are related to both the chemical form of naproxen used and its formulation. Even with the observed differences in pattern of absorption, the elimination half-life of naproxen is unchanged across products ranging from 12 to 17 hours. Steady-state levels of naproxen are reached in 4 to 5 days, and the degree of naproxen accumulation is consistent with this half-life. This suggests that the differences in pattern of release play only a negligible role in the attainment of steady-state plasma levels.
Absorption
NAPROSYN Tablets/ANAPROX DS: After administration of NAPROSYN Tablets, peak plasma levels are attained in 2 to 4 hours. After oral administration of ANAPROX DS, peak plasma levels are attained in 1 to 2 hours. The difference in rates between the two products is due to the increased aqueous solubility of the sodium salt of naproxen used in ANAPROX DS.
EC-NAPROSYN: EC-NAPROSYN is designed with a pH-sensitive coating to provide a barrier to disintegration in the acidic environment of the stomach and to lose integrity in the more neutral environment of the small intestine. The enteric polymer coating selected for EC-NAPROSYN dissolves above pH 6. When EC-NAPROSYN was given to fasted subjects, peak plasma levels were attained about 4 to 6 hours following the first dose (range: 2 to 12 hours). An in vivo study in man using radiolabeled ECNAPROSYN tablets demonstrated that EC-NAPROSYN dissolves primarily in the small intestine rather than in the stomach, so the absorption of the drug is delayed until the stomach is emptied.
When EC-NAPROSYN and NAPROSYN Tablets were given to fasted subjects (n=24) in a crossover study following 1 week of dosing, differences in time to peak plasma levels (Tmax) were observed, but there were no differences in total absorption as measured by Cmax and AUC:
| EC-NAPROSYN* 500 mg bid | NAPROSYN* 500 mg bid | |
| Cmax (μg/mL) | 94.9 (18%) | 97.4 (13%) |
| Tmax (hours) | 4 (39%) | 1.9 (61%) |
| AUC0-12 hr (μg•hr/mL) | 845 (20%) | 767 (15%) |
| *Mean value (coefficient of variation) |
Antacid Effects
When EC-NAPROSYN was given as a single dose with antacid (54 mEq buffering capacity), the peak plasma levels of naproxen were unchanged, but the time to peak was reduced (mean Tmax fasted 5.6 hours, mean Tmax with antacid 5 hours), although not significantly.
Food Effects
When EC-NAPROSYN was given as a single dose with food, peak plasma levels in most subjects were achieved in about 12 hours (range: 4 to 24 hours). Residence time in the small intestine until disintegration was independent of food intake. The presence of food prolonged the time the tablets remained in the stomach, time to first detectable serum naproxen levels, and time to maximal naproxen levels (Tmax), but did not affect peak naproxen levels (Cmax).
Distribution
Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels naproxen is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day there is less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough Css 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of naproxen, respectively). The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma.
Elimination
Metabolism
Naproxen is extensively metabolized in the liver to 6-0-desmethyl naproxen, and both parent and metabolites do not induce metabolizing enzymes. Both naproxen and 6-0-desmethyl naproxen are further metabolized to their respective acylglucuronide conjugated metabolites.
Excretion
The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen ( < 1%), 6-0-desmethyl naproxen ( < 1%) or their conjugates (66% to 92%). The plasma half-life of the naproxen anion in humans ranges from 12 to 17 hours. The corresponding half-lives of both naproxen's metabolites and conjugates are shorter than 12 hours, and their rates of excretion have been found to coincide closely with the rate of naproxen clearance from the plasma. Small amounts, 3% or less of the administered dose, are excreted in the feces. In patients with renal failure metabolites may accumulate.
Prexan is readily absorbed from the gastro-intestinal tract and peak plasma levels are reached in 2 to 4 hours. Prexan is present in the blood mainly as unchanged drug. It is extensively bound to plasma proteins and has a half-life of about 15 hours. enabling a steady state to be achieved within 3 days of initiation of therapy on a twice daily dose regimen. The degree of absorption is not significantly affected by either foods or most antacids. Excretion is almost entirely via the urine, mainly as conjugated Prexan, with some unchanged drug. Metabolism in children is similar to that in adults. Chronic alcoholic liver disease reduces the total plasma concentration of Prexan but the concentration of unbound Prexan increases. In the elderly, the unbound plasma concentration of Prexan is increased although total plasma concentration is unchanged.About half of the dose is excreted in the urine in 24 hours and about 94% in 5 days largely as the glucuronide.
Although naproxen itself is well absorbed, the sodium salt form is more rapidly absorbed, resulting in higher peak plasma levels for a given dose. Approximately 30% of the total naproxen sodium dose in Prexan Tablets is present in the dosage form as an immediate release component. The remaining naproxen sodium is coated as microparticles to provide sustained release properties. After oral administration, plasma levels of naproxen are detected within 30 minutes of dosing, with peak plasma levels occurring approximately 5 hours after dosing. The observed terminal elimination half-life of naproxen from both immediate release naproxen sodium and Prexan Tablets is approximately 15 hours. Steady state levels of naproxen are achieved in 3 days and the degree of naproxen accumulation in the blood is consistent with this.
Plasma Naproxen Concentrations Mean of 24 Subjects (+/-2SD) (Steady State, Day 5)
Pharmacokinetic Parameters at Steady State Day 5 (Mean of 24 Subjects)
| Parameter (units) | naproxen 500 mg Q12h/5 days (1000 mg) | Prexan 2 x 500 mg tablets (1000 mg) Q24h/5 days | ||||
| Mean | SD | Range | Mean | SD | Range | |
| AUC 0-24 (mcgxh/mL) | 1446 | 168 | 1167 - 1858 | 1448 | 145 | 1173 - 1774 |
| Cmax (mcg/mL) | 95 | 13 | 71 - 117 | 94 | 13 | 74 - 127 |
| Cava (mcg/mL) | 60 | 7 | 49 -77 | 60 | 6 | 49 -74 |
| Cmin (mcg/mL) | 36 | 9 | 13 - 51 | 33 | 7 | 23 -48 |
| Tmax (hrs) | 3 | 1 | 1 -4 | 5 | 2 | 2-10 |
Absorption
Naproxen itself is rapidly and completely absorbed from the GI tract with an in vivo bioavailability of 95%. Based on the pharmacokinetic profile, the absorption phase of Prexan Tablets occurs in the first 4 to 6 hours after administration. This coincides with disintegration of the tablet in the stomach, the transit of the sustained release microparticles through the small intestine and into the proximal large intestine. An in vivo imaging study has been performed in healthy volunteers that confirms rapid disintegration of the tablet matrix and dispersion of the microparticles.
The absorption rate from the sustained release particulate component of Prexan Tablets is slower than that for conventional naproxen sodium tablets. It is this prolongation of drug absorption processes that maintains plasma levels and allows for once daily dosing.
Food Effects
No significant food effects were observed when twenty-four subjects were given a single dose of Prexan Tablets 500 mg either after an overnight fast or 30 minutes after a meal. In common with conventional naproxen and naproxen sodium formulations, food causes a slight decrease in the rate of naproxen absorption following Prexan Tablets administration.
Distribution
Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels, naproxen is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day, there is a less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses. However the concentration of unbound naproxen continues to increase proportionally to dose. Prexan Tablets exhibit similar dose proportional characteristics.
Elimination
Metabolism
Naproxen is extensively metabolized to 6-0-desmethyl naproxen and both parent and metabolites do not induce metabolizing enzymes.
Excretion
The elimination half-life of Prexan Tablets and conventional naproxen is approximately 15 hours. Steady state conditions are attained after 2 to 3 doses of Prexan Tablets. Most of the drug is excreted in the urine, primarily as unchanged naproxen (less than 1%), 6-0-desmethyl naproxen (less than 1%) and their glucuronide or other conjugates (66 to 92%). A small amount (<5%) of the drug is excreted in the feces. The rate of excretion has been found to coincide closely with the rate of clearance from the plasma. In patients with renal failure, metabolites may accumulate.
Naproxen and naproxen sodium are rapidly and completely absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%. The different dosage forms of Prexan are bioequivalent in terms of extent of absorption (AUC) and peak concentration (Cmax); however, the products do differ in their pattern of absorption. These differences between naproxen products are related to both the chemical form of naproxen used and its formulation. Even with the observed differences in pattern of absorption, the elimination half-life of naproxen is unchanged across products ranging from 12 to 17 hours. Steady-state levels of naproxen are reached in 4 to 5 days, and the degree of naproxen accumulation is consistent with this half-life. This suggests that the differences in pattern of release play only a negligible role in the attainment of steady-state plasma levels.
Absorption
Prexan Tablets/ANAPROX DS: After administration of Prexan Tablets, peak plasma levels are attained in 2 to 4 hours. After oral administration of ANAPROX DS, peak plasma levels are attained in 1 to 2 hours. The difference in rates between the two products is due to the increased aqueous solubility of the sodium salt of naproxen used in ANAPROX DS.
EC-Prexan: EC-Prexan is designed with a pH-sensitive coating to provide a barrier to disintegration in the acidic environment of the stomach and to lose integrity in the more neutral environment of the small intestine. The enteric polymer coating selected for EC-Prexan dissolves above pH 6. When EC-Prexan was given to fasted subjects, peak plasma levels were attained about 4 to 6 hours following the first dose (range: 2 to 12 hours). An in vivo study in man using radiolabeled ECPrexan tablets demonstrated that EC-Prexan dissolves primarily in the small intestine rather than in the stomach, so the absorption of the drug is delayed until the stomach is emptied.
When EC-Prexan and Prexan Tablets were given to fasted subjects (n=24) in a crossover study following 1 week of dosing, differences in time to peak plasma levels (Tmax) were observed, but there were no differences in total absorption as measured by Cmax and AUC:
| EC-Prexan* 500 mg bid | Prexan* 500 mg bid | |
| Cmax (μg/mL) | 94.9 (18%) | 97.4 (13%) |
| Tmax (hours) | 4 (39%) | 1.9 (61%) |
| AUC0-12 hr (μg•hr/mL) | 845 (20%) | 767 (15%) |
| *Mean value (coefficient of variation) |
Antacid Effects
When EC-Prexan was given as a single dose with antacid (54 mEq buffering capacity), the peak plasma levels of naproxen were unchanged, but the time to peak was reduced (mean Tmax fasted 5.6 hours, mean Tmax with antacid 5 hours), although not significantly.
Food Effects
When EC-Prexan was given as a single dose with food, peak plasma levels in most subjects were achieved in about 12 hours (range: 4 to 24 hours). Residence time in the small intestine until disintegration was independent of food intake. The presence of food prolonged the time the tablets remained in the stomach, time to first detectable serum naproxen levels, and time to maximal naproxen levels (Tmax), but did not affect peak naproxen levels (Cmax).
Distribution
Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels naproxen is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day there is less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough Css 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of naproxen, respectively). The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma.
Elimination
Metabolism
Naproxen is extensively metabolized in the liver to 6-0-desmethyl naproxen, and both parent and metabolites do not induce metabolizing enzymes. Both naproxen and 6-0-desmethyl naproxen are further metabolized to their respective acylglucuronide conjugated metabolites.
Excretion
The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen ( < 1%), 6-0-desmethyl naproxen ( < 1%) or their conjugates (66% to 92%). The plasma half-life of the naproxen anion in humans ranges from 12 to 17 hours. The corresponding half-lives of both naproxen's metabolites and conjugates are shorter than 12 hours, and their rates of excretion have been found to coincide closely with the rate of naproxen clearance from the plasma. Small amounts, 3% or less of the administered dose, are excreted in the feces. In patients with renal failure metabolites may accumulate.
