The detailed view includes drug products with safety labeling changes to the CONTRAINDICATIONS, BOXED WARNING, WARNINGS, PRECAUTIONS, or ADVERSE REACTIONS sections. The prescribing information may be accessed by clicking on the drug name.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Bextra (valdecoxib) Tablets

(click product name to read prescribing information)

BOXED WARNING

• Serious Skin Reactions

WARNINGS

• Coronary Artery Bypass Graft Surgery

PRECAUTIONS

• Information for Patients

ADVERSE REACTIONS

• Postmarketing Experience
  • Gastrointestinal
    • Pancreatitis

Bextra is contraindicated for the treatment of post-operative pain immediately following coronary artery bypass graft (CABG) surgery and should not be used in this setting. 

BOXED WARNING

Serious skin reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) have been reported in patients receiving Bextra. Some of these reactions have resulted in death.  

Patients appear to be at higher risk for these events within the first two weeks of treatment, but these may occur at any time during treatment.  

The reported rate of these serious skin events appears to be greater for Bextra as compared to other COX-2 agents.  

Bextra should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

WARNINGS

Patients treated with Bextra for pain following coronary artery bypass graft surgery have a higher risk for cardiovascular/thromboembolic events, deep surgical infections or sternal wound complications. Bextra is therefore contraindicated for the treatment of postoperative pain following CABG surgery.

(click product name to read prescribing information)

PRECAUTIONS

• Initial Paragraph
• Nursing Mothers

ADVERSE REACTIONS

• Clinical Adverse Experience

Canasa 500 mg and 1000 mg suppositories are contraindicated in patients who have demonstrated hypersensitivity to mesalamine (5-aminosalicylic acid) or to the suppository vehicle [saturated vegetable fatty acid esters (Hard Fat, NF)], or to salicylates (including aspirin).

Cosmegen (dactinomycin for injection)

(click product name to read prescribing information)

PRECAUTIONS

• General

ADVERSE REACTIONS

• Gastrointestinal

Hypersensitivity to any component of this product.....

Depo-Provera Contraceptive Injection (medroxyprogesterone acetate injectable suspension)

(click product name to read prescribing information)

BOXED WARNING

WARNINGS

• Loss of Bone Mineral Density

PRECAUTIONS

• Pediatric Use

ADVERSE REACTIONS

• Postmarketing Experience

Significant liver disease

BOXED WARNING

Women who use Depo-Provera Contraceptive Injection may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. 

It is unknown if use of Depo-Provera Contraceptive Injection during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. 

Depo-Provera Contraceptive Injection should be used as a long-term birth control method (longer than two years) only if other birth control methods are inadequate.

WARNINGS

Use of Depo-Provera CI reduces serum estrogen levels and is associated with significant loss of bone mineral density (BMD) as bone metabolism accommodates to a lower estrogen level. This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion...... (See prescribing information.)

Naprosyn (naproxen tablets) 

EC-Naprosyn (naproxen delayed -release tablets) 

Anaprox/Anaprox DS (naproxen sodium) Tablets 

(click product name to read prescribing information)

WARNINGS

• Gastrointestinal (GI) Effects
• Anaphylactoid Reactions
• Advanced Renal Disease
• Pregnancy

PRECAUTIONS

• General
• Hepatic Effects
• Renal Effects
• Hematologic Effects
• Fluid Retention and Edema
• Preexisting Asthma
• Information for Patients
• Laboratory Tests
• Drug Interactions
  • Aspirin
  • Methotrexate
  • ACE-inhibitors
  • Furosemide
  • Lithium
  • Warfarin
• Other Information Concerning Drug Interactions
• Pregnancy
  • Teratogenic Effects
    • Pregnancy Category C
• Labor and Delivery
• Nursing Mothers
• Pediatric Use
• Geriatric Use

ADVERSE REACTIONS

• In patients taking NSAIDs, the following adverse experiences have also been reported in approximately 1 to 10% of patients
  • Gastrointestinal (GI) Experiences
  • General
  • Dermatologic
• In patients taking NSAIDs, the following adverse experiences have also been reported in <1% of patients
  • Body as a Whole
  • Cardiovascular
  • Gastrointestinal
  • Hemic and Lymphatic
  • Metabolic and Nutritional 
  • Nervous System
  • Respiratory
  • Dermatologic
  • Special Senses
  • Urogenital

CONTRAINDICATIONS

......It is also contraindicated in patients in whom aspirin or other nonsteroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis, and nasal polyps. Both types of reactions have the potential of being fatal..... Therefore, careful questioning of patients for such things as asthma, nasal polyps, urticaria, and hypotension associated with nonsteroidal anti-inflammatory drugs before starting therapy is important. In addition, if such symptoms occur during therapy, treatment should be discontinued.

WARNINGS

Extensive revisions to the WARNINGS/Gastrointestinal (GI) Effects section.  (See prescribing information.)

Anaphylactoid Reactions: As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to naproxen. Naproxen should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Advanced Renal Disease: In cases with advanced kidney disease, treatment with naproxen is not recommended. If NSAID therapy, however, must be initiated, close monitoring of the patient’s kidney function is advisable.

Pregnancy:  In late pregnancy, as with other NSAIDs, naproxen should be avoided because it may cause premature closure of the ductus arteriosus.

Norditropin Cartridges (somatropin [rDNA origin] injection)

(click product name to read prescribing information)

PRECAUTIONS

• General
• Pediatric Patients
• Adult Patients
• Laboratory Tests
• Drug Interactions
• Geriatric use
• Information for Patients

ADVERSE REACTIONS

• Growth Hormone Deficient Pediatric Patients
• Growth Hormone Deficient Adult Patients

Norditropin is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients.

In general, somatropin is contraindicated in the presence of active neoplasia. Any preexisting neoplasia should be inactive and its treatment complete prior to instituting therapy with Norditropin. Norditropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Norditropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial space-occupying lesion. Available information suggests that the rate of tumor recurrence is not increased by growth hormone therapy.....

.....Norditropin is contraindicated in patients with proliferative or preproliferative diabetic retinopathy.....

.....Norditropin should not be used for growth promotion in pediatric patients with closed epiphyses.

Phenergan (promethazine HCl) Tablets and Suppositories

(click product name to read prescribing information)

WARNINGS

• Initial Statement (enclosed in box)
• Use in Pediatric Patients

PRECAUTIONS

• Pediatric Use

CONTRAINDICATIONS

Phenergan Tablets and Suppositories are contraindicated for use in pediatric patients less than two years of age.....

WARNINGS

Phenergan should not be used in pediatric patients less than two years of age because of the potential for fatal respiratory depression...... (See prescribing information.)

.....Respiratory depression and apnea, sometimes associated with death, are strongly associated with promethazine products and are not directly related to individualized weight-based dosing, which might otherwise permit safe administration.....

(click product name to read prescribing information)

CONTRAINDICATIONS

WARNINGS

PRECAUTIONS

• General

  • Renal Disease

  • Prostatic Hypertrophy

  • Use of Anticholinergetic Drugs

• Information for the Patient

• Drug Interactions

  • Anticholinergics

  • Potassium Chloride

• Carcinogenesis, Mutagenesis, Impairment of Fertility

• Pregnancy

  • Teratogenic Effects

  • Nonteratogenic Effects

• Nursing Mothers

• Pediatric Use

ADVERSE REACTIONS

• Xerostomia
• Photophobia
• Dilation of the Pupil
• Cycloplegia
• Anaphylactic/Anaphylactoid Reactions
• Hypersensitivity
• Pruritus
• Dry Skin
• Post-marketing Experience
  • Heart Block
  • Prolonged QTc Interval

Known hypersensitivity to glycopyrrolate or any of its inactive ingredients.....

WARNINGS

.....In addition, in the presence of fever, high environmental temperature and/or during physical exercise, heat prostration can occur with use of anticholinergic agents including glycopyrrolate (due to decreased sweating), particularly in children and the elderly.

The closure system contains dry natural rubber that may cause hypersensitivity reactions when handled by or when the product is injected in persons with known or possible latex sensitivity.

Saizen (somatropin [rDNA origin] for injection)

(click product name to read prescribing information)

WARNINGS

PRECAUTIONS

• General
  • Intracranial hypertension
  • Pediatric Patients
  • Drug Interactions
    • Cytochrome P450 3A4

ADVERSE REACTIONS

• Growth Hormone Deficient Pediatric Patients
• Growth Hormone Deficient Adult Patients

CONTRAINDICATIONS

Saizen is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients.....

....Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment. Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Saizen is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

WARNINGS

.....There have been reports of fatalities after initiating therapy with growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females ........ (See prescribing information.)

Striant (testosterone buccal system) mucoadhesive

(click product name to read prescribing information)

Tracleer (bosentan) Tablets

(click product name to read prescribing information)

• Pregnancy Category X

• Drug Interactions

  • Hormonal Contraceptives, Including Oral, Injectable, Transdermal, and Implantable Contraceptives

ADVERSE REACTIONS

• Post-marketing Experience

  • Hypersensitivity, Rash

CONTRAINDICATIONS

Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective in patients receiving Tracleer.

It has been demonstrated that hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives may not be reliable in the presence of Tracleer and should not be used as the sole contraceptive method in patients receiving Tracleer.

Brand (Generic) Name

Summary of Changes to Contraindications and Warnings

Altace (ramipril) Capsules

(click product name to read prescribing information)

• Hepatic Failure

ADVERSE REACTIONS

• Gastrointestinal
• Post-Marketing Experience

Rarely, ACE inhibitors, including Altace, have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death....

(click product name to read prescribing information)

PRECAUTIONS

• Information for Patients

.....Alcohol based gels are flammable. Avoid fire, flame or smoking until the gel has dried.

Levaquin (levofloxacin) Tablets, Oral Solution and Injection 

Levaquin (levofloxacin in 5% dextrose) Injection

(click product name to read prescribing information)

PRECAUTIONS

• Information for Patients

PATIENT PACKAGE INSERT

.....In immature rats and dogs, the oral and intravenous administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight bearing joints and other signs of arthropathy in immature animals of various species. The relevance of these findings to the clinical use of levofloxacin is unknown.....

(click product name to read prescribing information)

PRECAUTIONS

• Information for Patients

Tabloid (thioguanine) Tablets

(click product name to read prescribing information)

ADVERSE REACTIONS

• Hepatic Effects

.....Thioguanine is not recommended for maintenance therapy or similar long term continuous treatment due to the high risk of liver toxicity associated with vascular endothelial damage. This liver toxicity has been observed in a high proportion of children receiving thioguanine as part of maintenance therapy for acute lymphoblastic leukaemia and in other conditions associated with continuous use of thioguanine. This liver toxicity is particularly prevalent in males..... (See prescribing information.)

(click product name to read prescribing information)

• Clinical Worsening and Suicide Risk

PRECAUTIONS

• Information for Patients

Arava (leflunomide) Tablets

(click product name to read prescribing information)

• Respiratory
  • Interstitial Lung Disease
• Geriatric Use

ADVERSE REACTIONS

• Respiratory System

Augmentin ES-600 (amoxicillin/clavulanate potassium) Powder for Oral Suspension

(click product name to read prescribing information)

PRECAUTIONS

• General
• Information for  the Patient

(click product name to read prescribing information)

• Carcinogenesis, Mutagenesis, Impairment of Fertility

• Pregnancy

Iressa (gefitinib tablets)

(click product name to read prescribing information)

• Drug Interactions
  • Vinorelbine

ADVERSE REACTIONS

• Interstitial Lung Disease
  • Hemorrhage
    • Epistaxis 
    • Hematuria

Keflex (cephalexin, USP) Pulvules

(click product name to read prescribing information)

• Pediatric Use

Lexiva (fosamprenavir calcium) Tablets

(click product name to read prescribing information)

• Hepatic Impairment and Toxicity

Miostat (carbachol intraocular solution, USP) 0.01%

(click product name to read prescribing information)

• Initial Statement

(click product name to read prescribing information)

• Drug Interactions 
  • Warfarin

ADVERSE REACTIONS

• Postmarketing Reports

Rifampin Capsules

(click product name to read prescribing information)

PRECAUTIONS

• General
• Information for Patients

(click product name to read prescribing information)

• Nursing Mothers
• Geriatric Use

ADVERSE REACTIONS

• Skin Rash

Timentin (sterile ticarcillin disodium/clavulanate potassium) for Intravenous Administration

(click product name to read prescribing information)

PRECAUTIONS

• General
• Information for Patients

Zofran (ondansetron hydrochloride) Injection, Premixed

(click product name to read prescribing information)

• Drug Interactions
  • CYP3A4, CYP2D6, CYP1A2
  • Phenytoin, Carbamazepine, and Rifampicin
  • Tramadol

Zofran (ondansetron hydrochloride) Tablets and Oral Solution

Zofran ODT (ondansetron hydrochloride) Orally Disintegrating Tablets

(click product name to read prescribing information)

• Drug Interactions
  • CYP3A4, CYP2D6, CYP1A2
  • Phenytoin, Carbamazepine, and Rifampicin
  • Tramadol

Benicar (olmesartan medoxomil) Tablets

(click product name to read prescribing information)

• Angioedema
• Post-marketing Experience
  • Angioedema and Rhabdomyolysis

(click product name to read prescribing information)

• Olmesartan Medoxomil-Hydrochlorothiazide
  • Angioedema
• Post-marketing Experience
  • Angioedema and Rhabdomyolysis

Cordarone (amiodarone HCl) Intravenous

(click product name to read prescribing information)

• Postmarketing Reports
  
  • Toxic Epidermal Necrolysis 
  • Hallucination
  • Confusional State
  • Disorientation
  • Delirium

Cordarone (amiodarone HCl)  Tablets

(click product name to read prescribing information)

• Postmarketing Reports

  • Toxic Epidermal Necrolysis 

  • Hallucination 

  • Confusional State

  • Disorientation

  • Delirium

Eloxatin (oxaliplatin for injection)

(click product name to read prescribing information)

• Combination Adjuvant Therapy with Eloxatin and Infusional 5-FU/LV in Patients with Stage II or III Colon Cancer
• Postmarketing Experience
  • Liver and Gastrointestinal System Disorders
    • Colitis (including Clostridium difficile diarrhea)
  • Red Blood Cell Disorders
    • Immuno-allergic hemolytic anemia

Malarone (atovaquone and proguanil hydrochloride) Tablets

Malarone (atovaquone and proguanil hydrochloride) Pediatric Tablets

(click product name to read prescribing information)

• Post-marketing Experience Adverse Reactions
  • Skin
  • Central Nervous System

Protonix I.V. (pantoprazole sodium) for Injection

(click product name to read prescribing information)

• Postmarketing Reports

(click product name to read prescribing information)

• Post-Marketing Experience for All Indications

FDA/CDER/OCD/Safety Policy and Communication Staff
Web page last revised by jlw January 24, 2005