ATROVENT (ipratropium bromide) - BIAXIN (clarithromycin) - FLONASE (fluticasone propionate) - IMITREX (sumatriptan succinate) - NOR-QD (norethindrone) - PRECOSE (acarbose) - PROCANBID (procainamide HCl) - SPORANOX (itraconazole) - XANAX - (alprazolam)

PRECAUTIONS:

Information for Patients: Regarding spraying of aerosol into the eyes, precipitation or worsening of narrow-angle glaucoma or eye pain have been added to temporary blurring of vision as possible consequences. Further, if recommended dosage does not provide relief or symptoms become worse, immediate medical attention should be sought, and other inhaled drugs, unless prescribed, should not be used while taking Atrovent Inhalation Aerosol (see Illustrated Patient's Instructions for Use).

HOW SUPPLIED:

The following information has been added after the storage information:

"Keep out of children's reach. Shake well before using. Patients should be reminded to read and follow the accompanying `"Patient's Instructions for Use,"' which should be dispensed with the product. As with most inhaled canisters, the therapeutic effect of this medication may decrease when the canister is cold.

"Warning: Discard the canister after you have used the labeled number of inhalations. The correct amount of medication in each inhalation cannot be assured after this point."

Additional Changes (Canister):

Warnings to: avoid spraying in eyes; not exceed prescribed dose; use with Atrovent adapter only; store between 59F (15C) and 86F (30C).

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CONTRAINDICATIONS:

Prior statement regarding contraindication of clarithromycin in patients receiving terfenadine has been revised: Concomitant administration of clarithromycin with cisapride, pimozide or terfenadine is contraindicated, as there have been post-marketing reports of drug interactions resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) when clarithromycin and/or erythromycin are co-administered with cisapride, pimozide or terfenadine. The cardiac arrhythmias are most likely due to inhibition of hepatic metabolism of these drugs by erythromycin and clarithromycin; fatalities have been reported.

PRECAUTIONS:

Drug Interactions: Prior statement regarding use of clarithromycin in patients receiving terfenadine has been revised to indicate that concomitant administration of clarithromycin with terfenadine is contraindicated (see CONTRAINDICATIONS).

Statement added denoting that there have been reports of an interaction between erythromycin and astemizole resulting in QT prolongation and torsades de pointes, with concomitant administration of erythromycin and astemizole contraindicated. As clarithromycin is also metabolized by cytochrome P450, concomitant administration with astemizole is not recommended.

Tacrolimus added to list of drugs metabolized by cytochrome P450 system for which there have been reports of interactions with erythromycin and/or clarithromycin.

ADVERSE REACTIONS:

Post-Marketing Experience: Tongue discoloration added to list of other spontaneously reported adverse events.

Statement added that there have been reports of tooth discoloration in patients treated with Biaxin, and that tooth discoloration is usually reversible with professional dental cleaning.

Anxiety and psychosis added to list of transient CNS events that have been reported during post- marketing surveillance, and notation that these events usually resolve with discontinuation of the drug no longer specifies such resolution as occurring quickly (italics denotes eliminated word).

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ADVERSE REACTIONS:

Postmarketing Experience: Angioedema, pruritis, urticaria, wheezing, dyspnea, and anaphylaxis/anaphylactoid reactions added to prior list of hypersensitivity reactions; in addition, bronchospasm no longer noted to be rarely (italics denotes eliminated word) reported, and hypersensitivity reactions now noted to be severe in rare instances.

Statement added that alteration or loss of sense of taste and/or smell and, rarely, nasal septal perforation have been reported during postmarketing experience.

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PRECAUTIONS:

Information for Patients: Subsection changed to the following: "With the autoinjector, the needle penetrates approximately 1/4 of an inch (5 to 6 mm). Since the injection is intended to be given subcutaneously, intramuscular or intravascular delivery should be avoided. Patients should be directed to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle. See PATIENT INFORMATION at the end of this labeling for the text of the separate leaflet provided for patients."

ADVERSE REACTIONS:

Postmarketing Experience: Paragraph focusing on skin/tissue adverse reactions revised, with induration and swelling added to described adverse reactions following subcutaneous administration of sumatriptan that have been reported.

DOSAGE AND ADMINISTRATION:

Revised to include information outlined above in PRECAUTIONS, Information for Patients.

PATIENT INFORMATION:

Information for the Consumer: How to Use Imitrex Injection: Changes made in first two paragraphs:

Paragraph 1: In addition to prior instructions to be followed before using the autoinjector, consumers are now instructed to check with their doctor on acceptable injection sites.

Paragraph 2: As before, the usual dose for adults is a single injection given just below the skin, with following clause ", in an area that has an adequate fatty tissue layer." removed.

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There has been a complete revision of the physician package insert and patient labeling to reflect the progestin oral contraceptive guideline published by the Division of Metabolic and Endocrine Drug Products, Center for Drug Evaluation and Research, FDA. For a copy of the guideline, contact Ms. Christina Kish of the Division of Reproductive and Urologic Drug Products at (301) 827-4260 or available here as a Text Version; contact the manufacturer for the complete labeling/package insert.

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DOSAGE AND ADMINISTRATION:

Initial Dosage: In addition to prior instructions as to recommended starting dosage, there is new notation that some patients may benefit from a more gradual dose titration to minimize gastrointestinal effects; this may achieved by starting treatment at 25 mg once per day and subsequently increasing administration frequency to reach 25 mg t.i.d.

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ADVERSE REACTIONS:

Gastrointestinal System: Sentence "Hepatomegaly with increased serum aminotransferase activity has been reported after a single oral dose." has been deleted.

Elevated Liver Enzymes (new subsection): "Elevations of transaminase with and without elevations of alkaline phosphatase and bilirubin have been reported in patients taking oral procainamide. Some patients have had clinical symptoms (eg, malaise, right upper quadrant pain). Deaths from liver failure have been reported."

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BOXED WARNING:

Prior warning regarding contraindication of itraconazole with terfenadine, astemizole, and cisapride has been revised to the following general statement: Coadministration of terfenadine, astemizole, and cisapride with Sporanox (itraconazole) Capsules is contraindicated. Sporanox is a potent inhibitor of the cytochrome P450 3A enzyme system and may raise plasma concentrations of drugs metabolized by this pathway. Serious cardiovascular events, including death, ventricular tachycardia, and torsades de pointes have occurred in patients taking itraconazole concomitantly with terfenadine or cisapride, which are metabolized by the cytochrome P450 3A system. See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS: Drug Interactions for more information.

CONTRAINDICATIONS:

Prior statements regarding contraindication of itraconazole with terfenadine, astemizole, cisapride, oral triazolam, and oral midazolam have been revised to the following general statement: Coadministration of Sporanox (itraconazole) Capsules with certain drugs metabolized by the P450 3A enzyme system may result in increased plasma concentrations of those drugs leading to potentially serious and/or life-threatening adverse events. Terfenadine, astemizole, oral triazolam, oral midazolam, and cisapride are specifically contraindicated with Sporanox. HMG-CoA reductase inhibitors metabolized by this system (e.g., lovastatin and simvastatin) should also be discontinued during Sporanox therapy (See PRECAUTIONS: Drug Interactions).

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WARNINGS:

Dependence and withdrawal reactions, including seizures: Regarding risk of dependence and its severity, in notation regarding spontaneous reporting system (replacing "post-marketing surveillance") data, long periods now defined as more than 12 (rather than "8-12", as before) weeks. Followed by new statement: "However, in a controlled post-marketing discontinuation study of panic disorder patients, the duration of treatment (three months compared to six months) had no effect on the ability of patients to taper to zero dose. In contrast, patients treated with doses of Xanax greater than 4 mg/day had more difficulty tapering to zero dose than those treated with less than 4 mg/day."

The importance of dose and the risks of Xanax as a treatment for panic disorder: Prior statement that patients' ability to completely discontinue Xanax after long-term therapy has not been reliably determined has been replaced by "In a controlled post-marketing discontinuation study of panic disorder patients, the duration of treatment (three months compared to six months) had no effect on the ability of patients to taper to zero dose."

PRECAUTIONS:

Information for Patients: For all users of Xanax: First reference to "higher doses" replaced by doses greater than 4 mg/day.

Additional advice for panic disorder patients: Phrases "the high doses (above 4 mg per day) ", "high doses for long intervals", and "high doses" replaced by doses greater than 4 mg/day.

Prior statement that patients' ability to completely discontinue Xanax after long-term therapy has not been reliably determined has been replaced by "In a controlled post-marketing discontinuation study of panic disorder patients, the patients treated with doses of Xanax greater than 4 mg/day had more difficulty tapering to zero dose than patients treated with less than 4 mg/day."

ADVERSE REACTIONS:

In paragraph regarding discontinuation of Xanax, the following has been added after statement that some patients may benefit from (replacing "require") an even slower dosage reduction than the suggested maximum of 0.5 mg every three days: " In a controlled post-marketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome."

In paragraph regarding panic disorder and major depressive disorders, "the higher doses of Xanax" has been replaced by doses of Xanax greater than 4 mg/day.

DRUG ABUSE AND DEPENDENCE:

In paragraph regarding psychological dependence, "higher doses" has been replaced by doses greater than 4 mg/day.

DOSAGE AND ADMINISTRATION:

In first paragraph, "higher doses" has been replaced by doses greater than 4 mg/day.

Panic disorder: In first paragraph, "maximum" has been removed from before Xanax in dosages of greater than 7 mg/day.

In second paragraph, statement that "However, in the absence of systematic studies evaluating the dose response relationship, the dosing regimen for the administration of Xanax to patients with panic disorder must be based on generic principles." has been removed.

In second paragraph, the following statement has been added before the prior statement cautioning against abrupt discontinuation: "For patients receiving doses greater 4 mg/day, periodic reassessment and consideration of dosage reduction is advised. In a controlled post-marketing dose-response study, patients treated with doses of Xanax greater than 4 mg/day for three months were able to taper to 50% of their total maintenance dose without apparent loss of clinical benefit."

The following regimen is one that follows the principles outlined above: In first paragraph, "the higher dose levels" has been replaced by dose levels greater than 4 mg/day.

In third paragraph, statement that "Although no experimental studies have been conducted to assess the comparative benefits of various discontinuation regimens, a possible approach is to reduce the dose by no more than 0.5 mg every three days, with the understanding that some patients may require an even more gradual discontinuation." has been replaced by " In a controlled post-marketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. It is suggested that the dose be reduced by no more than 0.5 mg every three days, with the understanding that some patients may benefit from an even more gradual discontinuation."

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