MedWatch - January 2006 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- January 2006

The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, or ADVERSE REACTIONS sections. Deletions or editorial revisions made to these sections are not included in this summary. The prescribing information may be accessed by clicking on the drug name.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Anaprox /Anaprox DS (naproxen sodium tablets) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Ansaid (flurbiprofen tablets, USP) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Arthrotec (diclofenac sodium/misoprostol) Tablets (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Cataflam (diclofenac potassium immediate-release tablets) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Clinoril (sulindac) Tablets (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Daypro (oxaprozin) Caplets (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Daypro Alta (oxaprozin potassium) Tablets (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Depacon (valproate sodium injection) (click product name to read prescribing information)	BOXED WARNING Teratogenicity PRECAUTIONS Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use General Multi-organ Hypersensitivity Reaction Information for Patients Drug Interactions Drugs for Which a Potentially Important Valproate Interaction Has Been Observed Topiramate	BOXED WARNING .....This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is contemplated. See WARNINGS, Information for Patients.

Depakene (valproic acid capsules and syrup) (click product name to read prescribing information)	BOXED WARNING Teratogenicity PRECAUTIONS Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use General Multi-organ Hypersensitivity Reaction Information for Patients Drug Interactions Drugs for Which a Potentially Important Valproate Interaction Has Been Observed Topiramate PATIENT PACKAGE INSERT	BOXED WARNING .....This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is contemplated. See WARNINGS, Information for Patients. An Information Sheet describes the teratogenic potential of Valproate is available for patients.

Depakote (divalproex sodium coated particles in capsules) Sprinkle Capsules (click product name to read prescribing information)	BOXED WARNING Teratogenicity PRECAUTIONS Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use General Multi-organ Hypersensitivity Reaction Information for Patients Drug Interactions Drugs for Which a Potentially Important Valproate Interaction Has Been Observed Topiramate PATIENT PACKAGE INSERT	BOXED WARNING .....This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is contemplated. See WARNINGS, Information for Patients. An Information Sheet describes the teratogenic potential of Valproate is available for patients.

Dolobid (diflunisal) Tablets (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Elidel (pimecrolimus) Cream 1% (click product name to read prescribing information)	BOXED WARNING (located in the WARNINGS section) Long-term Safety of Topical Calcineurin Inhibitors Has Not Been Established WARNINGS MEDICATION GUIDE	BOXED WARNING Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including Elidel Cream. Therefore: • Continuous long-term use of topical calcineurin inhibitors, including Elidel Cream, in any age group should be avoided, and application limited to areas of involvement with atopic dermatitis. • Elidel Cream is not indicated for use in children less than 2 years of age. WARNINGS Prolonged systemic use of calcineurin inhibitors for sustained immunosuppression in animal studies and transplant patients following systemic administration has been associated with an increased risk of infections, lymphomas, and skin malignancies. These risks are associated with the intensity and duration of immunosuppression..... For additional details, see MedWatch 1/20/06 Safety Alert.

Feldene (piroxicam) Capsules (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertitlity Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Indocin (indomethacin) Capsules, Oral Suspension, and Suppositories (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Lodine (etodolac capsules and tablets) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertitlity Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Lodine XL (etodolac extended-release tablets) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertitlity Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Motrin (ibuprofen) Suspension 100 mg/5 mL (click product name to read prescribing information)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Pregnancy Teratogenic Effects - Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached prescribing information. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. For additional details, see MedWatch 6/15/05 Safety Alert.

Motrin (ibuprofen tablets, USP) (click product name to read prescribing information)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin-type Anticoagulants Pregnancy Teratogenic Effects: Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached prescribing information. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. For additional details, see MedWatch 6/15/05 Safety Alert.

Nalfon (fenoprofen calcium capsules, USP) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Naprelan (naproxen sodium) Controlled-Release Tablets (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Naprosyn (naproxen tablets) Naprosyn (naproxen suspension) EC-Naprosyn (naproxen delayed-release tablets) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Nimotop (nimodipine) Capsules For Oral Use (click product name to read prescribing information)	BOXED WARNING WARNINGS Death due to inadvertent intravenous administration PRECAUTIONS General: Blood Pressure Death Bradycardia	BOXED WARNING Do not administer Nimotop intravenously or by other parenteral routes. Deaths and serious, life threatening adverse events have occurred when the contents of Nimotop Capsules have been injected parenterally. WARNINGS Do not administer Nimotop intravenously or by other parenteral routes. Deaths and serious, life threatening adverse events, including cardiac arrest, cardiovascular collapse, hypotension, and bradycardia, have occurred when the contents of Nimotop Capsules have been injected parenterally. For additional details, see MedWatch 2/15/06 Safety Alert.

Orudis (ketoprofen) Capsules Oruvail (ketoprofen) Extended-Release Capsules) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Ponstel (mefenamic acid capsules, USP) (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease Anaphylactoid Reactions Skin Reactions Pregnancy PRECAUTIONS General Hepatic Effects Hematological Effects Preexisting Asthma Information for Patients Laboratory Tests Drug Interactions ACE-inhibitors Aspirin Diuretics Lithium Methotrexate Warfarin Drug/Laboratory Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects. Pregnancy Category C Nonteratogenic Effects Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use MEDICATION GUIDE	Please see attached labeling template. This labeling supplement is in response to the Agency’s June 15, 2005 letter to all sponsors of nonsteroidal anti-inflammatory drugs (NSAIDs) to revise the labeling of all NSAIDs to provide more specific information for practitioners, patients, family members and caregivers about potential risks of CV (cardiovascular) and GI (gastrointestinal) adverse effects for patients taking NSAIDs. Additionally, the label was revised to include a description of early symptoms associated with Stevens-Johnson Syndrome. The labeling template includes the recommended general changes and not the specific approved product labeling. For additional details, see MedWatch 6/15/05 Safety Alert.

Protopic (tacrolimus) Ointment, 0.03% and 0.1% (click product name to read prescribing information)	BOXED WARNING (located in the WARNINGS section) Long-term Safety of Topical Calcineurin Inhibitors Has Not Been Established WARNINGS MEDICATION GUIDE	BOXED WARNING Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including Protopic Cream. Therefore: • Continuous long-term use of topical calcineurin inhibitors, including Protopic Ointment, in any age group should be avoided, and application limited to areas of involvement with atopic dermatitis. • Protopic Ointment is not indicated for use in children less than 2 years of age. Only 0.03% Protopic Ointment is indicated for use in children 2-15 years of age. WARNINGS Prolonged systemic use of calcineurin inhibitors for sustained immunosuppression in animal studies and transplant patients following systemic administration has been associated with an increased risk of infections, lymphomas, and skin malignancies. These risks are associated with the intensity and duration of immunosuppression..... For additional details, see MedWatch 1/20/06 Safety Alert.

Relafen (nabumetone) Tablets (click product name to read labeling template)	BOXED WARNING Cardiovascular Risk Gastrointestinal Risk CONTRAINDICATIONS WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Hypertension Congestive Heart Failure and Edema Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation Renal Effects Advanced Renal Disease