Summary Of Safety-Related Drug Labeling
Changes Approved By FDA Center for Drug
Evaluation and Research (CDER)
December 2001

(Posted: 1/18/2002)

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ALDARA (imiquimod) Cream
[December 8, 2001: 3M Pharmaceuticals]

CLINICAL PHARMACOLOGY

Pharmacodynamics

Imiquimod has no direct antiviral activity in cell culture. A study in 22 patients with genital/perianal warts comparing imiquimod and vehicle shows that imiquimod induces mRNA encoding cytokines including interferon-a at the treatment site. In addition HPVL1 mRNA and HPV DNA are significantly decreased following treatment. However, the clinical relevance of these findings is unknown.

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ALPHAGAN (brimonidine tartrate)
Ophthalmic Solution 0.5%, 0.2% & 0.15%
[December 20, 2001: Allergan]

PRECAUTIONS

Pediatric Use:

In a well-controlled clinical study conducted in pediatric glaucoma patients (ages 2 to 7 years) the most commonly observed adverse events with brimonidine tartrate ophthalmic solution 0.2% dosed three times daily were somnolence (50% - 83% in patients ages 2 to 6 years) and decreased alertness. In pediatric patients 7 years of age or older (>20kg), somnolence appears to occur less frequently (25%). Approximately 16% of patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence.

The safety and effectiveness of ALPHAGAN have not been studied in pediatric patients below the age of 2 years. ALPHAGAN is not recommended for use in pediatric patients under the age of 2 years.

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ATIVAN (lorazepam) Injection
[December 12, 2001: Wyeth-Ayerst]

PRECAUTIONS

Geriatric Use:

Clinical studies of Ativan generally were not adequate to determine whether subjects aged 65 and over respond differently than younger subjects, however, age over 65 may be associated with a greater incidence of central nervous system depression and more respiratory depression (see WARNINGS-Preanesthetic Use, PRECAUTIONS-General and ADVERSE REACTIONS-Preanesthetic).

Age does not appear to have a clinically significant effect on lorazepam kinetics (see CLINICAL PHARMACOLOGY).

Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered. Greater sensitivity (e.g., sedation ) of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range (see DOSAGE AND ADMINISTRATION").

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CORDARONE (amiodarone HCl) Tablets
[December 18, 2001: Wyeth]

[Other labeling changes not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/jul01.htm#cordar

[Other safety related information regarding Cordarone I.V. from 2001: http://www.fda.gov/medwatch/safety/2001/safety01.htm#cordar ]

ADVERSE REACTIONS:

In postmarketing surveillance, hepatitis, cholestatic hepatitis, cirrhosis, epididymitis, vasculitis, pseudotumor cerebri, thrombocytopenia, angioedema, bronchiolitis obliterans organizing pneumonia (possibly fatal), pleuritis, pancreatitis, toxic epidermal necrolysis, myopathy, hemolytic anemia, aplastic anemia, pancytopenia, and neutropenia also have been reported in patients receiving Cordarone.

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CUTIVATE (fluticasone propionate) Ointment
[December 9, 2001: GlaxoSmithKline]

Extensive changes to CLINICAL PHARMACOLOGY and some revisions to PRECAUTIONS sections. Contact the company for a copy of the new labeling/package insert.

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FLUDARA (fludarabine phosphate) Injection
[December 3, 2001: Berlex]

CLINICAL PHARMACOLOGY

Second paragraph, second sentence revised:

After the five daily doses of 25 mg 2-fluoro-ara-AMP/m ² to cancer patients infused over 30 minutes, 2-fluoro-ara-A concentrations show a moderate accumulation. During a 5-day treatment schedule, 2-fluoro-ara-A plasma trough levels increased by a factor of about 2. The terminal half-life of 2-fluoro-ara-A was estimated as approximately 20 hours.

SPECIAL POPULATIONS

Patients with Renal Impairment

The total body clearance of the principal metabolite 2-fluoro-ara-A correlated with the creatinine clearance, indicating the importance of the renal excretion pathway for the elimination of the drug. Renal clearance represents approximately 40% of the total body clearance. Patients with moderate renal impairment (17-41 mL/min/m ² ) receiving 20% reduced Fludara dose had a similar exposure (AUC; 21 versus 20 nM · h/mL) compared to patients with normal renal function receiving recommended dose. The mean total body clearance was 172 mL/min for normal and 124 mL/min for patients with moderately impaired renal function.

WARNINGS

Third paragraph added:

Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported. The duration of clinically significant cytopenia in the reported cases has ranged from approximately 2 months to approximately 1 year. These episodes have occurred both in previously treated or untreated patients.

PRECAUTIONS

General

Third paragraph revised:

The total body clearance of 2-fluoro-ara-A has been shown to be directly correlated with creatinine clearance. Patients with moderate impairment of renal function (creatinine clearance 30-70 mL/min/1.73 m ² ) should have Fludara dose reduced by 20% and be monitored closely. Fludara is not recommended for patients with severely impaired renal function (creatinine clearance less than 30 mL/min/1.73 m ² .

Mutagenesis: Fludarabine phosphate was not mutagenic to bacteria (Ames test) or mammalian cells (HGRPT assay in Chinese hamster ovary cells) either in the presence or absence of metabolic activation. Fludarabine phosphate was clostogenic in vitro to Chinese hamster ovary cells (chromosome aberrations in the presence of metabolic activation and induced sister chromatid exchanges both with and without metabolic activation). In addition, fludarabine phosphate was clastogenic in vivo (mouse micronucleus assay) but was not mutagenic to germ cells (dominant lethal test in male mice).

ADVERSE REACTIONS

Pulmonary System

Second paragraph added:

In post-marketing experience, cases of severe pulmonary toxicity have been observed with Fludara use which resulted in ARDS, respiratory distress, pulmonary hemorrhage, pulmonary fibrosis, and respiratory failure. After an infectious origin has been excluded, some patients experienced symptom improvement with corticosteroids.

Hematopoietic Systems

First paragraph, second to the last sentence -

Myelosuppression may be severe, cumulative, and may affect multiple cell lines.

Second paragraph added:

Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in postmarketing surveillance. The duration of clinically significant cytopenia in the reported cases has ranged from approximately 2 months to approximately 1 year. These episodes have occurred both in previously treated or untreated patients.

DOSAGE AND ADMINISTRATION

Renal Insufficiency:

Patients with moderate impairment of renal function (creatinine clearance 30-70 mL/min/1.73m ² ) should have a 20% dose reduction of FLUDARA FOR INJECTION. FLUDARA FOR INJECTION should not be administered to patients with severely impaired renal function (creatinine clearance less than 30 mL/min/1.73m ² ).

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LEVAQUIN (levofloxacin) Tablets & Injection
[December 18, 2001: ORTHO-McNEIL]

WARNINGS

Second sentence added to the last paragraph concerning tendon rupture as follows:

Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly.

PRECAUTIONS

General

The following paragraph concerning QTc prolongation was revised to read:

Some quinolones, including levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. During post-marketing surveillance, rare cases of torsades de pointes have been reported in patients taking levofloxacin. These reports generally involved patients who had other with concurrent medical conditions and the relationship to levofloxacin has not been established. Among drugs known to cause prolongation of the QT interval, the or concomitant medications that may have been contributory. The risk of arrhythmias may be reduced by avoiding use in the presence of concurrent use with other drugs that prolong the QT interval including hypokalemia, significant bradycardia, or concurrent treatment with class Ia or class III antiarrhythmic agents; in addition, use of levofloxacin in the presence of risk factors for torsades de pointes such as hypokalemia, significant bradycardia, and cardiomyopathy should be avoided.

Carcinogenesis, Mutagenesis, Impairment of Fertility

The following sentences were added to the first paragraph to read:

Levofloxacin did not shorten the time to tumor development of UV-induced skin tumors in hairless albino (Skh-1) mice at any levofloxacin dose level and was therefore not photo-carcinogenic under conditions of this study. Dermal levofloxacin concentrations in the hairless mice ranged from 25 to 42 µg/g at the highest levofloxacin dose level (300 mg/kg/day) used in the photo-carcinogenicity study. By comparison, dermal levofloxacin concentrations in human subjects receiving 750 mg of levofloxacin averaged approximately 11.8 µg/g at Cmax.

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LOTENSIN HCT
(benazepril HCl/hydrochlorothiazide) Tablets
&
LOTENSIN (benazepril HCl) Tablets
[December 14, 2001: Novartis]

PRECAUTIONS

Geriatric Use [Lotensin HCT]

Of the total number of patients who received Lotensin HCT in U.S. clinical studies of Lotensin HCT, 19% were 65 or older while about 1.5% were 75 or older. Overall differences in effectiveness or safety were not observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Benazepril and benazeprilat are substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Geriatric Use [Lotensin]

Of the total number of patients who received benazepril in U.S. clinical studies of Lotensin, 18% were 65 or older while 2% were 75 or older. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Benazepril and benazeprilat are substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

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MS Contin (morphine sulfate controlled-release) Tablets
[December 18, 2001: Purdue Frederick]

[Other labeling information not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/feb01.htm#mscont ]

WARNINGS:

Other

Although extremely rare, cases of anaphylaxis have been reported.

ADVERSE REACTIONS:

Less Frequently Observed Reactions

Gastrointestinal: Dry mouth, biliary tract spasm, laryngospasm, anorexia, diarrhea, cramps, taste alteration, constipation, ileus, intestinal obstruction

Other: Antidiuretic effect, paresthesia, muscle tremor, blurred vision, nystagmus, diplopia, miosis, anaphylaxis

OVERDOSAGE: Acute overdosage with morphine is manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes bradycardia, hypotension and death.

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OCUDOSE (timolol maleate)
Ophthalmic Solution 0.25% and 0.5%
[December 7, 2001: Merck]

PRECAUTIONS

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

HYPERSENSITIVITY

Signs and symptoms of systemic allergic reactions including anaphylaxis, angioedema, urticaria, and localized and generalized rash.

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PAXIL (paroxetine HCl) Tablets
[December 14, 2001:GlaxoSmithKline]

[Other labeling information not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/feb01.htm#paxil , http://www.fda.gov/medwatch/safety/2000/sep00.htm#paxil , http://www.fda.gov/medwatch/SAFETY/2001/apr01.htm#paxil]

Labeling provides for the use of Paxil(paroxetine hydrochloride) Tablets for the treatment of posttraumatic stress disorder as a new indication. Contact the company for a copy of the new labeling/package insert.

Safety information on discontinuation of treatment with Paxil is also included in the new labeling.

PRECAUTIONS

General

Discontinuation of Treatment with Paxil: Recent clinical trials supporting the various approved indications for employed a taper phase regimen, rather than an abrupt discontinuation of treatment. The taper phase regimen used in GAD and PTSD clinical trials involved an incremental decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, patients were continued on this dose for 1 week before treatment was stopped.

With this regimen in those studies,the following adverse events were reported at an incidence of 2% or greater for Paxil and were at least twice that reported for placebo: abnormal dreams (2.3% vs 0.5%), paresthesia (2.0% vs 0.4%), and dizziness (7.1% vs 1.5%). In the majority of patients, these events were mild to moderate and were self-limiting and did not require medical intervention.

During Paxil marketing, there have been spontaneous reports of similar adverse events, which may have no causal relationship to the drug, upon the discontinuation of Paxil (particularly when abrupt), including the following: dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), agitation, anxiety, nausea, and sweating. These events are generally self-limiting. Similar events have been reported for other selective serotonin reuptake inhibitors.

Patients should be monitored for these symptoms when discontinuing treatment, regardless of the indication for which Paxil is being prescribed. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate (see DOSAGE and ADMINISTRATION).

DOSAGE AND ADMINISTRATION

Discontinuation of Treatment with Paxil: Symptoms associated with discontinuation of Paxil have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment, regardless of the indication for which Paxil is being prescribed. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

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PRAVACHOL (pravastatin sodium) Tablets
[December 18, 2001: Bristol-Myers Squibb]

[Other labeling information not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/jun01.htm#pravac ]

Labeling provides for the use of a new dosage strength (80 mg) and dosing regimen (80 mg once per day) of Pravachol (pravastatin sodium) tablets. Contact the company for a copy of the new labeling/package insert.

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PROPECIA (finasteride) Tablets
[December 8, 2001: Merck]

CLINICAL PHARMACOLOGY

Clinical Studies

Study in Women

In a study involving 137 postmenopausal women with androgenetic alopecia who were treated with PROPECIA (n=67) or placebo (n=70) for 12 months, effectiveness could not be demonstrated. There was no improvement in hair counts, patient self-assessment, investigator assessment, or ratings of standardized photographs in the women treated with PROPECIA when compared with the placebo group (see INDICATIONS AND USAGE).

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PULMICOR TURBUHALER (budesonide) Inhalation Powder
[December 31, 2001: AstraZeneca]

New labeling provides for changes to the Pregnancy subsection of the Precautions section related to a change in the pregnancy category from "C" to "B".

PRECAUTIONS

Pregnancy

Teratogenic Effects: Pregnancy Category B: As with other glucocorticoids, budesonide produced fetal loss, decreased pup weight, and skeletal abnormalities at subcutaneous doses of 25 mcg/kg/day in rabbits (approximately 1/3 the maximum recommended daily inhalation dose in adults on a mcg/m ² basis) and 500 mcg/kg/day in rats (approximately 3 times the maximum recommended daily inhalation dose in adults on a mcg/m ² basis).

No teratogenic or embryocidal effects were observed in rats when budesonide was administered by inhalation at doses up to 250 mcg/kg/day (approximately 2 times the maximum recommended daily inhalation dose in adults on a mcg/m ² basis).

Studies of pregnant women, however, have not shown that PULMICORT TURBUHALER increases the risk of abnormalities when administered during pregnancy. The results from a large population-based prospective cohort epidemiological study reviewing data from three Swedish registries covering approximately 99% of the pregnancies from 1995-1997 (i.e., Swedish Medical Birth Registry; Registry of Congenital Malformations; Child Cardiology population rate (3.8 % vs 3.5%, respectively). In addition, after exposure to inhaled budesonide, the number of infants born with orofacial clefts was similar to the expected number in the normal population (4 children vs 3.3, respectively).

These same data were utilized in a second study bringing the total to 2,534 infants whose mothers were exposed to inhaled budesonide. In this study, the rate of congenital malformations among infants whose mothers were exposed to inhaled budesonide during early pregnancy was not different from the rate for all newborn babies during the same period (3.6%).

Despite the animal findings, it would appear that the possibility of fetal harm is remote if the drug is used during pregnancy. Nevertheless, because the studies in humans cannot rule out the possibility of harm, PULMICORT TURBUHALER should be used during pregnancy only if clearly needed.

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REBETRON Combination Therapy
REBETOL (ribavirin) Capsules &
INTRON A (interferon alfa-2b) Injection
[December 28, 2001:Schering]

[Other labeling information not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/feb01.htm#rebetr , http://www.fda.gov/medwatch/SAFETY/2001/mar01.htm#rebetr , http://www.fda.gov/medwatch/SAFETY/2001/oct01.htm#rebetr ]

CLINICAL PHARMACOLOGY

Pharmacokinetics

Special Populations

Pediatric Patients

Multiple-dose pharmacokinetic properties for ribavirin in pediatric patients with chronic hepatitis C between 5 and 16 years of age are summarized in TABLE 2.

PRECAUTIONS

Pediatric use

One hundred twenty-five pediatric patients between three and sixteen years of age with chronic hepatitis C virus infection (median duration 10.7 years) received REBETOL Capsules with INTRON A for up to 48 weeks. The overall sustained response rate cannot be calculated since all patients have not yet completed 24-weeks of off-therapy follow-up.

Injection site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in pediatric patients compared to adult patients. Conversely, pediatric patients experienced less fatigue, dyspepsia, arthralgia, insomnia, irritability, impaired concentration, dyspnea, and pruritis compared to adult patients.

DOSAGE AND ADMINISTRATION

REBETOL may be administered without regard to food, but should be administered in a consistent manner. (See CLINICAL PHARMACOLOGY.)

Pediatrics

Efficacy of REBETOL and INTRON A for pediatric patients has not been established. Based on pharmacokinetic data, the following doses of REBETOL and INTRON A provide similar exposures in pediatric patients as observed in adult patients treated with the approved doses of REBETOL and INTRON A (see TABLE 8).

Under no circumstances should REBETOL capsules be opened, crushed or broken (see Contraindications and Warnings).

An amended version of the Rebetron Combination Therapy Medguide, in the "How should I take REBETRON Combination Therapy?" section was implemented to provide consistency with information contained in the current package insert for Rebetron Combination Therapy.

Contact the company for a copy of the new Medguide.

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SERZONE (nefazodone HCl) Tablets
[December 4, 2001: Bristol-Myers Squibb Company]

[Other labeling changes not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/mar01.htm#serzon, http://www.fda.gov/medwatch/SAFETY/2001/jan01.htm#serzon]

Addition of boxed warning

CONTRAINDICATIONS

SERZONE tablets are contraindicated in patients who were withdrawn from SERZONE because of evidence of liver injury (see Boxed Warning). SERZONE tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone, its ingredients, or other phenylpiperazine antidepressants.

WARNINGS

Hepatotoxicity (See BOXED WARNING)

Cases of life-threatening hepatic failure have been reported in patients treated with SERZONE. The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 – 300,000 patient-years of SERZONE treatment. This represents a rate of about 3-4 times the estimated background rate of liver failure. This rate is an underestimate because of under reporting, and the true risk could be considerably greater than this. A large cohort study of antidepressant users found no cases of liver failure leading to death or transplant among SERZONE users in about 30,000 patient-years of exposure. The spontaneous report data and the cohort study results provide estimates of the upper and lower limits of the risk of liver failure in nefazodone treated patients, but are not capable of providing a precise risk estimate.

The time to liver injury for the reported liver failure cases resulting in death or transplant generally ranged from 2 weeks to 6 months on SERZONE therapy. Although some reports described dark urine and nonspecific prodromal symptoms (e.g., anorexia, malaise, and gastrointestinal symptoms), other reports did not describe the onset of clear prodromal symptoms prior to the onset of jaundice.

The physician may consider the value of liver function testing. Periodic serum transaminase testing has not been proven to prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery.

Patients should be advised to be alert for signs and symptoms of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they occur. Ongoing clinical assessment of patients should govern physician interventions, including diagnostic evaluations and treatment.

SERZONE should be discontinued if clinical signs or symptoms suggest liver failure (see PRECAUTIONS-Information for Patients). Patients who develop evidence of hepatocellular injury such as increased serum AST or serum ALT levels > 3 times the upper limit of normal, while on SERZONE should be withdrawn from the drug. These patients should be presumed to be at increased risk for liver injury if SERZONE is reintroduced. Accordingly, such patients should not be considered for re-treatment.

PRECAUTIONS-General

Hepatotoxicity (see Boxed Warning)

PRECAUTIONS – Information for Patients:

Hepatotoxicity

Patients should be informed that SERZONE therapy has been associated with liver abnormalities ranging from asymptomatic reversible serum transaminase increases to cases of liver failure resulting in transplant and/or death. At present, there is no way to predict who is likely to develop liver failure. Ordinarily, patients with active liver disease should not be treated with SERZONE. Patients should be advised to be alert for signs of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they occur.

ADVERSE REACTIONS-Postintroduction Clinical Experience

Second paragraph -

Anaphylactic reactions; angioedema; convulsions (including grand mal seizures); galactorrhea; gynecomastia (male); liver necrosis and liver failure, in some cases leading to liver transplantation and/or death (see WARNINGS); …

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TABLOID (thioguanine) Tablets
[December 12, 2001: GlaxoSmithKline]

WARNINGS:

There are individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) who may be unusually sensitive to the myelosuppressive effects of mercaptopurine and prone to developing rapid bone marrow suppression following the initiation of treatment. This problem could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine, or sulphasalazine.

PRECAUTIONS:

Drug Interactions: As there is in vitro evidence that aminosalicylate derivatives (e.g., olsalazine, mesalazine, or sulphasalazine) inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent thioguanine therapy (see WARNINGS).

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TIGAN (trimethobenzamide HCl) Capsules
[December 13, 2001: King Pharmaceuticals]

Labeling provides for the following in response to the Federal Register notice of January 9, 1979, classifying this drug effective for postoperative nausea and vomiting and nausea associated with gastroenteritis: draft labeling, results of bioavailability studies, and updated manufacturing and controls and testing procedures. Contact the company for a copy of the new label/package insert.

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ZESTORETIC (lisinopril/hydrochlorothiazide) Tablets
[December 18, 2001: AstraZeneca]

CONTRAINDICATIONS

First sentence revised:

Zestoretic is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema.

PRECAUTIONS

General

Lisinopril

Aortic Stenosis/Hypertrophic Cardiomyopathy:

As with all vasodilators, lisinopril should be given with caution to patients with obstruction in the outflow tract of the left ventricle.

Drug Interactions Indomethacin has been changed to:

Non-steroidal Anti-inflammatory Agents

In some patients with compromised renal function who are being treated with non-steroidal anti-inflammatory drugs, the co-administration of lisinopril may result in a further deterioration of renal function. These effects are usually reversible. In a study in 36 patients with mild to moderate hypertension where the antihypertensive effects of lisinopril alone were compared to lisinopril given concomitantly with indomethacin, the use of indomethacin was associated with a reduced effect, although the difference between the two regimens was not significant.

OVERDOSAGE

Lisinopril - Third paragraph revised to include the following statement at the end of the paragraph:

(See WARNINGS, Anaphylactoid Reaction During Membrane Exposure.)

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ZITHROMAX (azithromycin) Oral Suspension
[December 14, 2001: Pfizer]

[Other labeling information not appearing in 2001 PDR: http://www.fda.gov/medwatch/SAFETY/2001/feb01.htm#zithro ]

Labeling provides for the use of Zithromax (azithromycin) for Oral Suspension for: acute otitis media with a 1-day dosing regimen and acute otitis media with a 3-day dosing regimen. Contact the company for a copy of the new labeling/package insert.

 

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