(Posted: 11/6/2001)
Additions: Color green and underlined: text
addition example
Deletions: Color red and strikethrough: text
deletion example
[Other labeling changes not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/mar01.htm#aggras]
WARNINGS:
First paragraph, last sentence added -
Fatal bleeding events have been reported (see ADVERSE REACTIONS).
Second paragraph revised:
AGGRASTAT should be used with caution in patients with platelet count <150,000/mm3, in patients with hemorrhagic retinopathy, and in chronic hemodialysis patients.
PRECAUTIONS/Bleeding Precautions/Laboratory Monitoring
First paragraph, the following sentence has been inserted between the first and second sentences:
In patients who have previously received GP IIb/IIIa receptor antagonists, consideration should be given to earlier monitoring of platelet count.
The following text has been added at the beginning of the second paragraph:
In addition, the activated partial thromboplastin (APTT) should be determined before treatment and the anticoagulant effects of heparin should be carefully monitored by repeated determinations of APTT and the dose should be adjusted accordingly (see also DOSAGE AND ADMINISTRATION). Potentially life-threatening bleeding may occur especially when heparin is administered with other products affecting hemostasis, such as GP IIb/IIIa receptor antagonists.
ADVERSE REACTIONS/Allergic Reactions/Readministration :
No patients in the clinical database developed anaphylaxis and/or hives requiring discontinuation of the infusion of tirofiban (see also Post-Marketing Experience, Hypersensitivity). No information is available regarding the development of antibodies to tirofiban; very few patients received tirofiban twice.
Although no patients in the clinical trial database developed anaphylaxis and/or hives requiring discontinuation of the infusion of tirofiban, anaphylaxis has been reported in post-marketing experience (see also Post-Marketing Experience, Hypersensitivity ). No information is available regarding the development of antibodies to tirofiban.
ADVERSE REACTIONS/Laboratory Findings:
The following text was added as the last sentence:
Platelet decreases have been observed in patients with no prior history of thrombocytopenia upon readministration of GP IIb/IIIa receptor antagonists.
ADVERSE REACTIONS/Post-Marketing Experience:
The following additional adverse reactions have been reported in post-marketing experience:
Hypersensitivity: Rash and/or hives
Severe allergic reactions including anaphylactic reactions.
The reported cases have occurred during the first day of tirofiban infusion,
during initial treatment, and during readministration of tirofiban. Some cases
have been associated with severe thrombocytopenia (platelet counts<10,000/mm3).
The following sentence has been added, in bold, immediately preceding the dosing chart in the DOSING AND ADMINISTRATION section:
AGGRASTAT Injection must first be diluted to the same strength as AGGRASTAT Injection Premixed, as noted under Directions for Use.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
AndroGel (testosterone
gel)
[September 5, 2001: Unimed]
DESCRIPTION
A daily application of AndroGel® 5 G, 7.5 G, or 10 G delivers
contains 50 mg,
75 mg, or 100 mg of testosterone, respectively,
per day, to be applied
daily to the skin's surface.
Pharmacokinetics
Absorption
…The skin serves as a reservoir for the sustained release
of testosterone into the systemic circulation. Approximately
10% of the testosterone dose applied on the skin surface from AndroGel is absorbed
into systemic circulation. Therefore, 5 G and 10 G of AndroGel systemically
delivers 5 mg and 10 mg of testosterone, respectively.
In a study with the
10 G dose of AndroGel
(to deliver 100 mg testosterone),
all patients showed an increase in serum testosterone within 30 minutes, and
eight of nine patients had a serum testosterone concentration within normal
range by 4 hours after the initial application. …
DOSAGE AND ADMINISTRATION
The recommended starting dose of AndroGel 1% is 5 G (to deliver 50 mg of testosterone) delivering 5 mg of testosterone systemically, applied once daily (preferably in the morning) to clean, dry, intact skin of the upper arms and/or abdomen.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
ASENDIN (amoxapine) Tablets
[September 25, 2001:Wyeth-Ayerst]
ADVERSE REACTIONS
The first and last paragraph of the section -
The phrase "but not reported to date with
ASENDIN" removed.
OVERDOSE
The first paragraph in the subsection Signs and Symptoms -
"Fatal overdoses with amoxapine have occurred" added.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
AVAPRO (irbesartan) Tablets
& AVALIDE (irbesartan and hydrochlorothiazide)
Tablets
[September 26, 2001: Bristol-Myers Squibb]
[Other labeling changes not appearing in 2001 PDR:
http://www.fda.gov/medwatch/SAFETY/2001/may01.htm#avapro
http://www.fda.gov/medwatch/safety/2000/sep00.htm#avapro
PRECAUTIONS: Geriatric Use
Avapro
Of the 1965 subjects in controlled clinical studies of AVAPRO (irbesartan) for hypertension, 15% were age 65 and over, but few were over age 75. No striking differences in antihypertensive effect or in adverse events appear to be present in this database, but there were insufficient numbers of aged subjects to enable detection of less than striking differences. Greater or lesser sensitivity of some older individuals cannot be ruled out. (see Pharmacokinetics, Special Populations, and Clinical Studies).
Avalide
Clinical studies of AVALIDE did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
DANTRIUM (dantrolene sodium) Injection
[September 28, 2001: Procter & Gamble Pharmaceuticals]
PRECAUTIONS: Geriatric Use:
Clinical studies of Dantrium Intravenous did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience had not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
DETROL LA
(tolterodine tartrate) Capsules
[September 21, 2001: Pharmacia & Upjohn]
[Other labeling changes not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/apr01.htm#detrol]
[Not appearing in 2000 PDR]
PRECAUTIONS:
Addition of two additional adverse events in the Information for Patient subsection, to read as follows: Patients should be informed that antimuscarinic agents such as Detrol LA may produce the following effect: blurred vision, dizziness, or drowsiness.
ADVERSE EVENTS:
Postmarketing Surveillance [Not appearing in 2000 PDR]
The following events have been reported in association with tolterodine use in clinical practice: anaphylactoid reactions, tachycardia, and peripheral edema.
[Not appearing in 2000-2001 PDR] Because these spontaneously reported events are from the worldwide postmarketing experience, the frequency of events and the role of tolterodine in their causation cannot be reliably determined.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
FORADIL (formoterol fumarate) Inhalation
Powder
[September 29, 2001: Novartis]
Labeling provides for the use of Foradil (formoterol fumarate inhalation powder) Aerolizer for the long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with Chronic Obstructive Pulmonary Disease including chronic bronchitis and emphysema. Contact the company for a copy of the new labeling/package insert.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
ISOPTIN SR (verapamil HCl) Tablets
[September 28, 2001: Abbott]
PRECAUTIONS:
Drug Interactions
Cytochrome inducers/inhibitors: In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Clinically significant interactions have been reported with inhibitors of CYP3A4 (eg, erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (eg, rifampin) have caused a lowering of plasma levels of verapamil; therefore, patients should be monitored for drug interactions.
Aspirin: In a few reported cases, coadministration of verapamil with aspirin has led to increased bleeding times greater than observed with aspirin alone.
Grapefruit juice: The intake of grapefruit juice may increase drug levels of verapamil.
General
First sentence of the third paragraph revised -
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne’s muscular dystrophy, prolongs recovery from the neuromuscular blocking agent vecuronium, and causes a worsening of myasthenia gravis.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
ISORDIL (isosorbide dinitrate)
Sublingual Tablets
[September 16, 2001: Wyeth-Ayerst]
&
ISORDIL Titradose (isosorbide dinitrate) Tablets
[September 16, 2001: Wyeth-Ayerst]
PRECAUTIONS:
Geriatric Use
Clinical studies of Isordil (isosorbide dinitrate) Sublingual [or] Titradose did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
LESCOL Capsule &
LESCOL XL (fluvastatin sodium) Extended Release Tablet
[September 25, 2001: Novartis]
INDICATIONS AND USAGE
New table:
After the LDL-C goal has been achieved, if the TG is still >200 mg/dL, non-HDL-C (total-C minus HDL-C) becomes a secondary target of therapy. Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
LEXXEL (enalapril maleate/felodipine)
Tablets
[September 18, 2001: AstraZeneca] PRECAUTIONS: Drug Interactions
CYP3A4 Inhibitors – Co-administration of CYP3A4 inhibitors (eg, ketoconazole, itraconalzole, erythromycin, grapefruit juice, cimetidine) with felodipine may lead to several-fold increases in the plasma levels of felodipine, either due to an increase in bioavailability or due to a decrease in metabolism. These increases in concentration may lead to increased effects, (lower blood pressure and increased heart rate). These effects have been observed with co-administration of itraconazole (a potent CYP3A4 inhibitor). Caution should be used when CYP3A4 inhibitors are co-administered with felodipine. A conservative approach to dosing felodipine should be taken. The following non-specific interactions have been reported:
Itraconazole – Co-administration of another extended release formulation of felodipine with itraconazole resulted in approximately 8-fold increase in the AUC, more than 6-fold increase in the Cmax and 2-fold prolongation in the half-life of felodipine.
Erythromycin – Co-administration of felodipine (PLENDIL) with erythromycin resultedn in approximately 2.5-fold increase in the AUC and Cmax, and about 2-fold prolongation in the half-life of felodipine.
Grapefruit juice – Co-administration of felodipine with grapefruit juice resulted in more than 2-fold increase in the AUC and Cmax, but no prolongation in the half-life of felodipine.
Cimetidine – In healthy
subjects, pharmacokinetic studies showed an approximately 50% increase
in the area under the plasma concentration time curve (AUC) as well as the Cmax
of felodipine when given concomitantly with cimetidine. It is anticipated that
a clinically significant interaction may occur in some hypertensive patients.
Cimetidine – Co-administration of felodipine with cimetidine (a non-specific CYP-450 inhibitor) resulted in an increase of approximately 50% in the AUC and the Cmax of felodipine.
ADVERSE REACTIONS:
Felodipine as an Extended-Release Formulation
Skin: Angioedema, contusion, erythema, urticaria, leukocytoclastic vasculitis
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
Lupron Depot
(leuprolide acetate) Injection
[September 21, 2001: TAP Pharmaceuticals]
Labeling provides for the use of Lupron Depot-3 Month 11.25 mg with norethindrone acetate 5 mg daily for initial management of endometriosis and for management of recurrence of symptoms. Duration of initial treatment or retreatment should be limited to 6 months.
Labeling provides for the use of Lupron Depot® 3.75 mg monthly with norethindrone acetate 5 mg daily for initial management of endometriosis and for management of recurrence of symptoms. Duration of initial treatment or retreatment should be limited to 6 months.
Contact the company for a copy of the new package inserts/labeling.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
LUVOX (fluvoxamine
maleate) Tablets
[September 6, 2001: Solvay]
[Other labeling changes not appearing in 2001PDR: http://www.fda.gov/medwatch/safety/2000/sep00.htm#luvox , http://www.fda.gov/medwatch/safety/2000/aug00.htm#luvox , http://www.fda.gov/medwatch/safety/2000/jun00.htm#luvox ]
WARNINGS-Other Potentially Important Drug Interactions
Mexiletine
The effect of steady state fluvoxamine (50 mg BID for 7 days) on the single dose pharmacokinetics of mexiletine (200 mg) was evaluated in 6 healthy Japanese males. The clearance of mexiletine was reduced by 38% following co-administration with fluvoxamine compared to mexiletine alone. If fluvoxamine and mexiletine are co-administered, serum mexiletine levels should be monitored.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
MIDAMOR (amiloride HCl) Tablets &
MODURETIC (amiloride HCl/ hydrochlorothiazide) Tablets
[September 18, 2001: Merck]
WARNINGS/Hyperkalemia and
PRECAUTIONS/Drug Interactions/Amiloride HCl
"cyclosporine or tacrolimus" has been added to the list of agents that may increase the risk of hyperkalemia when administered with amiloride HCl.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
RETROVIR (zidovudine)
Injection
[September 12, 2001: GlaxoSmithKline]
[Other labeling changes not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/mar01.htm#retrov ]
PRECAUTIONS:
Geriatric Use: Clinical studies of RETROVIR did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
SEROSTIM (somatropin) Injection
[September 6, 2001: Serono]
[Other safety related information not appearing in the 2001 PDR: http://www.fda.gov/medwatch/safety/2001/safety01.htm#serost , http://www.fda.gov/medwatch/safety/2000/jul00.htm#serost ]
DOSAGE AND ADMINISTRATION:
Labeling revised to state that reconstitution may be done with 0.5 to 1.0 mL sterile water for injection.
"Reconstitute each vial of Serostim 4 mg, 5 mg, or 6 mg with 0.5 – 1.0 mL sterile water for injection."
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
THALOMID (thalidomide) Tablets
[September 9, 2001:
Celgene]
PRESCRIBERS
[The following revision included throughout labeling.]
Two reliable forms of contraception must be used simultaneously unless continuous
abstinence from reproductive heterosexual
sexual intercourse contact
is the chosen method.
Before starting treatment
Male Patients: Because thalidomide is present in the
semen of patients receiving the drug, males receiving thalidomide must always
use a latex condom during any sexual contact with women of childbearing potential.
MALE PATIENTS
Fourth and fifth bullets revised:
CLINICAL PHARMACOLOGY
Pharmacokinetics and Drug Metabolism
Distribution
It is not known whether thalidomide is present in the ejaculate of males. The extent of plasma protein binding of thalidomide is unknown.
In human blood plasma, the geometric mean plasma protein binding was 55% and 66%, respectively, for (+)-(R)- and (-)-(S)-thalidomide.8 In a pharmacokinetic study of thalidomide in HIV-seropositive adult male subjects receiving thalidomide 100 mg/day, thalidomide was detectable in the semen.
CONTRAINDICATIONS
Next-to-the-last paragraph added -
Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential.
WARNINGS
Birth defects
Because it is not known whether or not thalidomide
is present in the ejaculate of males receiving the drug, males receiving thalidomide
must always use a latex condom when engaging in sexual activity with women of
childbearing potential.
Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential.
PRECAUTIONS
Stevens-Johnson Syndrome and Toxic Epidermal
Necrolysis:
Serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, which may be fatal, have been reported.
Seizures:
Although not reported from pre-marketing controlled clinical trials, seizures, including grand mal convulsions, have been reported during post-approval use of THALOMID (thalidomide) in clinical practice. Because these events are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. Most patients had disorders that may have predisposed them to seizure activity, and it is not currently known whether thalidomide has any epileptogenic influence. During therapy with thalidomide, patients with a history of seizures or with other risk factors for the development of seizures should be monitored closely for clinical changes that could precipitate acute seizure activity.
Pregnancy
Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential.
ADVERSE REACTIONS
Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential.
STORAGE AND DISPENSING
DRUG MUST ONLY BE DISPENSED IN NO MORE THAN A 1-MONTH SUPPLY AND ONLY ON PRESENTATION OF A NEW PRESCRIPTION WRITTEN WITHIN THE PREVIOUS 7 DAYS. SPECIFIC INFORMED CONSENT (copy attached as part of this package insert) AND COMPLIANCE WITH THE MANDATORY PATIENT REGISTRY AND SURVEY ARE REQUIRED FOR ALL PATIENTS (MALE AND FEMALE) PRIOR TO DISPENSING BY THE PHARMACIST.
BEFORE DISPENSING THALOMID (thalidomide), YOU MUST ACTIVATE THE AUTHORIZATION NUMBER ON EVERY PRESCRIPTION BY CALLING THE CELGENE CUSTOMER CARE CENTER AT 1-888-4-CELGENE (1-888-423-5436) AND OBTAINING A CONFIRMATION NUMBER. YOU MUST ALSO WRITE THE CONFIRMATION NUMBER ON THE PRESCRIPTION. YOU SHOULD ACCEPT A PRESCRIPTION ONLY IF IT HAS BEEN ISSUED WITHIN THE PREVIOUS 7 DAYS (TELEPHONE PRESCRIPTIONS ARE NOT PERMITTED); DISPENSE NO MORE THAN A 4-WEEK (28- DAY) SUPPLY, WITH NO AUTOMATIC REFILLS; DISPENSE BLISTER PACKS INTACT (CAPSULES CANNOT BE REPACKAGED); DISPENSE SUBSEQUENT PRESCRIPTIONS ONLY IF FEWER THAN 7 DAYS OF THERAPY REMAIN ON THE PREVIOUS PRESCRIPTION; AND EDUCATE ALL STAFF PHARMACISTS ABOUT THE DISPENSING PROCEDURE FOR THALOMID (thalidomide).
Important Information and Warnings for All Patients Taking THALOMID (thalidomide)
WARNING: SERIOUS SEVERE,
LIFE-THREATENING HUMAN BIRTH DEFECTS.
CONSENT FOR WOMEN
CONSENT FOR MEN
Extensively revised:
|
All Patients
|
|
Female Patients of Childbearing Potential
At least one highly effective method AND One additional effective method
If she misses her menstrual period, or experiences unusual menstrual bleeding If she stops using birth control If she thinks FOR ANY REASON that she may be pregnant The patient understands that if her doctor is not available, she can call 1-888-668-2528 for information on emergency contraception. |
|||
|
Female Patients Not of Childbearing Potential
|
|||
|
Male Patients
If he has had unprotected sexual contact with a woman who can become pregnant. If he thinks FOR ANY REASON, that his sexual partner may be pregnant. The patient understands that if his doctor is not available, he can call 1-888-668-2528 for information on emergency contraception.
|
|||
|
Authorization: This information has been read aloud to me in the language of my choice. I understand that if I do not follow all of my doctor’s instructions, I will not be able to receive THALOMID (thalidomide) I now authorize my doctor to begin my treatment with THALOMID (thalidomide). Patient Signature______________________________________Date____________________ I have fully explained to the patient the nature, purpose, and risks of the treatment described above, especially the risks to women of childbearing potential. I have asked the patient if he/she has any questions regarding his/her treatment with THALOMID ® (thalidomide) and have answered those questions to the best of my ability. I will comply with all of my obligations and responsibilities as a prescriber registered under the S.T.E.P.S. ™ restricted distribution program. Prescriber Name (please type): ___________________________________________________ DEA Number:__________________ Social Security Number if PA or NP: _________________ Street Address: ________________________________________________________________ City: ____________________________ State: _____________________ Zip: ______________ Prescriber Signature ____________________________________________________________ |
REFERENCES
8. Eriksson T, Björkman S, Roth B, et al. 1998. Chirality. 10(3): 223-228.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
VERSED (midazolam HCl) Injection
[September 4, 2001: Hoffmann-LaRoche]
[Other labeling changes not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/may01.htm#versed ]
PRECAUTIONS:
In a placebo-controlled study, saquinavir administered as a 1200 mg dose, tid, for 5 days (n=12), a 56% reduction in the clearance of midazolam following a single 0.05 mg/kg IV dose was observed. The half-life was approximately doubled.
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
XELODA (capcitabine) Tablets
[September 7, 2001: Hoffman-LaRoche]
[Other labeling changes not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/apr01.htm#xeloda , http://www.fda.gov/medwatch/safety/2000/mar00.htm#xeloda ]
Labeling provides for the use of Xeloda (capcitabine) Tablets in combination with Taxotere (docetaxel) for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior anthracycline containing chemotherapy. Contact the company for a copy of the new labeling/package insert.
Other safety related labeling changes not included in 2001 PDR:
Boxed Warning:
|
WARNING XELODA Warfarin Interaction: Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly. A clinically important XELODA-Warfarin drug interaction was demonstrated in a clinical pharmacology trial(see CLINICAL PHARMACOLOGY AND PRECAUTIONS). Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. Post-marketing reports have shown clinically significant increases in prothrombin time (PT) and INR in patients who were stabilized on anticoagulants at the time XELODA was introduced. These events occurred within several days and up to several months after initiating XELODA therapy and, in a few cases, within one month after stopping XELODA. These events occurred in patients with and without liver metastases. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy. |
CLINICAL PHARMACOLOGY
Drug-Drug Interactions:
Anticoagulants: In four patients with cancer, chronic administration of capecitabine (1250 mg/ m 2 bid) with a single 20 mg dose of warfarin increased the mean AUC of S-warfarin by 57% and decreased its clearance by 37%. Baseline corrected AUC of INR in these 4 patients increased by 2.8 fold, and the maximum observed mean INR value was increased by 91% (see Box WARNINGS and PRECAUTIONS: Drug-Drug Interactions).
WARNINGS
Coagulopathy: [replaces Coagulopathy: subsection]
See box warning.
PRECAUTIONS
Drug-Drug Interactions:
Anticoagulants: [replaces Coumarin Anticoagulants] Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely with great frequency and the anticoagulant dose should be adjusted accordingly (see BOX WARNINGS and CLINICAL PHARMACOLOGY). Altered coagulation parameters and/or bleeding have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. These events occurred within several days and up to several months after initiating XELODA therapy and, in a few cases, within one month after stopping XELODA. These events occurred in patients with and without liver metastases. In a drug interaction study with single dose warfarin administration, there was a significant increase in the mean AUC of S-warfarin. The maximum observed INR value increased by 91%. This interaction is probably due to an inhibition of cytochrome P450 2C9 by capecitabine and/or its metabolites (see CLINICAL PHARMACOLOGY.)
CYP2C9 substrates: Other than warfarin, no formal drug-drug interaction studies between XELODA and other CYP2C9 substrates have been conducted. Care should be exercised when XELODA is co-administered with CYP2C9 substrates.
Patient Package Insert
[Information for patients taking a blood thinner, revised for emphasis.]
TELL YOUR DOCTOR IF YOU
Return to Quick Reference | MedWatch Home | MedWatch Safety Info | Online MedWatch Report | Contact Medwatch
![[FDA Home Page]](https://webarchive.library.unt.edu/eot2008/20081028093534im_/http://www.fda.gov/icon/iconhome.gif){kind=icon} |
HTML by JLW