‫בטיחות)‬
‫מידע בטיחות)‬
‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
‫תאריך _________‪ 9‬ספטמבר‪_______2009 ,‬‬
‫שם תכשיר באנגלית_‪DILANTIN‬‬
‫מספר רישום ‪___ 123 70 24017‬‬
‫שם בעל הרישום __‪PFIZER PHARMACEUTICALS ISRAEL LTD‬‬
‫השינויים המבוקשים על רקע צהוב‬
‫לצרכן‬
‫בעלון לצרכן‬
‫בעלון‬
‫פרטים על השינוי‪/‬ים המבוקש‪/‬ים‬
‫טקסט נוכחי‬
‫פרק בעלון‬
‫אין להשתמש אם‬
‫ידועה לך רגישות‬
‫לאחד ממרכיבי‬
‫התרופה‬
‫מתי אין להשתמש‬
‫בתרופה?‬
‫אין להשתמש‬
‫בתרופה מבלי‬
‫להיוועץ ברופא לפני‬
‫התחלת הטיפול‪:‬‬
‫אזהרות‪:‬‬
‫תגובות בין תרופתיות‬
‫תופעות לוואי‬
‫המחייבות התייחסות‬
‫מיוחדת‪:‬‬
‫טקסט חדש‬
‫אין להשתמש אם ידועה לך רגישות לאחד‬
‫ממרכיבי התרופה או לתרופות ממשפחת‬
‫ההידנטואין‪.‬‬
‫אם הינך סובל‪/‬ת או סבלת בעבר מליקוי‬
‫בתפקוד‪ :‬מערכת החיסון‪ ,‬סכרת‪ ,‬חווית בעבר‬
‫תופעות של רגישות יתר לתרופות נוגדות‬
‫פרכוסים ‪Anticonvulsant Hypersensitivity‬‬
‫)‪Syndrome (AHS‬‬
‫בטיפול ממושך בתרופה יש לערוך בדיקת‬
‫צפיפות עצם ורמות ויטמין ‪ D‬באופן תקופתי‪.‬‬
‫טניפוזיד‪ ,‬חומצה פולית‬
‫תנועות לא רצוניות של העיניים‪ ,‬הפרעה בחוש‬
‫הטעם‪ ,‬שיעור יתר‪ ,‬מחלת פיירוני‪,‬‬
‫שוק אנפילקטי‪ ,‬קשיי נשימה עד אובדן הכרה‬
‫)דווח במתן בהזרקה או במינון יתר) ‪ :‬הפסק את‬
‫הטיפול ופנה לרופא מיד‬
‫רופא‬
‫בעלון ללרופא‬
‫בעלון‬
‫פרטים על השינוי‪/‬ים המבוקש‪/‬ים‬
‫פרק בעלון‬
‫‪CONTRA‬‬‫‪INDICATIONS‬‬
‫‪Special‬‬
‫‪warnings and‬‬
‫‪precautions‬‬
‫טקסט נוכחי‬
‫‪Dilantin is‬‬
‫‪contraindicated‬‬
‫‪in those‬‬
‫‪patients with a‬‬
‫‪history of‬‬
‫‪hypersensitivity‬‬
‫‪to phenytoin or‬‬
‫‪other‬‬
‫‪hydantoins.‬‬
‫טקסט חדש‬
‫‪Dilantin is contraindicated in those patients with a history of‬‬
‫‪hypersensitivity to phenytoin or other hydantoins, or the inactive‬‬
‫‪ingredients of this preparation.‬‬
‫‪Anticonvulsant Hypersensitivity Syndrome (AHS) is a rare drug‬‬
‫‪induced, multiorgan syndrome which is potentially fatal and occurs‬‬
‫‪in some patients taking anticonvulsant medication. It is‬‬
‫‪53268‬‬
characterized by fever, rash, lymphadenopathy, and other
multiorgan pathologies, often hepatic. The mechanism is unknown.
The interval between first drug exposure and symptoms is usually 24 weeks but has been reported in individuals receiving
anticonvulsants for 3 or more months.
for use
Patients at higher risk for developing AHS include black patients,
patients who have a family history of or who have experienced this
syndrome in the past, and immuno-suppressed patients. The
syndrome is more severe in previously sensitized individuals. If a
patient is diagnosed with AHS, discontinue the phenytoin and
provide appropriate supportive measures.
Toxic hepatitis and liver damage have been reported and may, in
rare cases, be fatal. Cases of acute hepatotoxicity, including
infrequent cases of acute hepatic failure, have been reported with
phenytoin. These incidents have been associated with a
hypersensitivity syndrome characterized by fever, skin eruptions,
and lymphadenopathy, and usually occur within the first 2 months of
treatment. Other common manifestations include arthralgias, rash,
jaundice, hepatomegaly, elevated serum transaminase levels,
leukocytosis, and eosinophilia. The clinical course of acute
phenytoin hepatotoxicity ranges from prompt recovery to fatal
outcomes. In these patients with acute hepatotoxicity, phenytoin
should be immediately discontinued and not re-administered.
Integumentary Effect - Published literature has suggested that there
may be an increased, although still rare, risk of hypersensitivity
reactions, including skin rash, SJS, TEN, hepatotoxicity, and
Anticonvulsant Hypersensitivity Syndrome in black patients.
Studies in patients of Chinese ancestry have found a strong
association between the risk of developing SJS/TEN and the
presence of HLA-B*1502, an inherited allelic variant of the HLA B
gene, in patients using another carbamazepine. Limited evidence
suggests that HLA-B*1502 may be a risk factor for the development
of SJS/TEN in patients of Asian ancestry taking drugs associated
with SJS/TEN, including phenytoin. Consideration should be given
to avoiding use of drugs associated with SJS/TEN, including
phenytoin, in HLA-B*1502 positive patients when alternative
therapies are otherwise equally available.
Literature reports suggest that the combination of phenytoin, cranial
irradiation and the gradual reduction of corticosteroids may be
associated with the development of erythema multiforme, and/or
Stevens-Johnson syndrome, and/or toxic epidermal necrolysis.
Musculoskeletal Effect
Phenytoin and other anticonvulsants that have been shown to
induce the CYP450 enzyme are thought to affect bone mineral
metabolism indirectly by increasing the metabolism of Vitamin D3.
This may lead to Vitamin D deficiency and heightened risk of
osteomalacia, bone fractures, osteoporosis, hypocalcemia, and
hypophosphatemia in chronically treated epileptic patients.
Drug classes which may potentially increase phenytoin serum
levels:
Analgesic / Anti-inflammatory agents: azapropazone
53268
Interaction
Antibacterial agents: erythromycin
Anticonvulsants: felbamate
Antifungal agents: amphotericin B , fluconazole , ketoconazole,
miconazole , itraconazole
Benzodiazepines /Psychotropic agents: viloxazine
Calcium channel blockers / Cardiovascular agents: diltiazem,
nifedipine
Proton pump inhibitors: omeprazole
Serotonin re-uptake inhibitors: fluvoxamine, sertraline
with other
medicinal
products and
other forms of
interaction
Drugs which may decrease phenytoin plasma levels:
Anticonvulsants: vigabatrin
Bronchodilators: theophylline
Hyperglycemic agents: diazoxide
Drugs whose blood levels and/or effects may be altered by
phenytoin:
Antibacterial agents: praziquantel
Anticonvulsants: lamotrigine
Antifungal agents: azoles
Antineoplastic agents: teniposide
Calcium channel blockers / Cardiovascular agents: nicardipine,
nimodipine, verapamil
Neuromuscular blocking agents: alcuronium, pancuronium
vecuronium
Opioid analgesics: methadone
Oral hypoglycemic agents: chlorpropamide, glyburide
Psychotropic agents / Antidepressants: clozapine, Sertraline
Patients should be advised not to drive a car or operate potentially
dangerous machinery until it is known that this medication does not
affect their ability to engage in these activities.
Effects on
ability to drive
and use
machines
Body as a Whole: Anaphylactoid reaction and anaphylaxis.
Special Senses: Taste perversion.
Post-marketing Experience: Musculoskeletal System: Bone
fractures and osteomalacia have been associated with long-term
(10 years) use of phenytoin by patients with chronic epilepsy.
Osteoporosis and other disorders of bone metabolism such as
hypocalcemia, hypophophatemia and decreased levels of Vitamin D
metabolites have also been reported.
53268
Undesirable
effects