Labeling provides for revisions to the text printed on the Accutane Prescription Pak which is updated to reflect the approved System to Manage Accutane Related Tetratogenicity (S.M.A.R.T.) program.

For a copy of the Accutane Prescription Pak and complete package insert, go to the following links:

Labeling provides for addition of a new indication, prevention of postmenopausal osteoporosis. Contact the company for a copy of the new labeling/package insert.

Streptococcus pneumoniae ^b from non-meningitis sources.

(Amoxicillin powder should be used to determine susceptibility.)

RECOMMENDED RANGES FOR AMOXACILLIN/CLAVULANIC ACID SUSCEPTIBILITY TESTING

For Streptococcus pneumoniae^b from non-meningitis sources: Isolates should be tested using amoxicillin/clavulanic acid and the following criteria should be used:

^b These interpretive standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.

First sentence moved from HOW SUPPLIED Section.

USE OF FILTERS OTHER THAN THE SPECIFIC TYPE INCLUDED IN THIS PACKAGE WITH EACH AMPOULE IS NOT RECOMMENDED.

DO NOT USE POLYCARBONATE SYRINGES WITH BUSULFEX.

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CERUMENEX (triethanolamine polypeptide oleate-condensate)
Otic Solution

New subheadings (Absorption, Distribution, Metabolism, Excretion and Special Populations) were added to this section and existing information was reorganized under the new subheadings.

Third sentence in the second paragraph added:

Microbiology subsection was extensively revised.

Susceptibility Tests
Dilution Techniques:

c
This interpretive standard is applicable only to agar dilution test with GC agar base and 1% defined growth supplement.

c
This zone diameter standard is applicable only to disk diffusion tests with GC agar base and 1% defined growth supplement.

First bullet revised:

¨ that ciprofloxacin may be taken with or without meals and to drink fluids liberally. As with other quinolones, concurrent administration of ciprofloxacin with magnesium/aluminum antacids, or sucralfate, Videx (didanosine) chewable/buffered tablets or pediatric powder, or with other products containing calcium, iron or zinc should be avoided. These products Ciprofloxacin may be taken two hours after or six hours before ciprofloxacin. before or six hours after taking these products. Ciprofloxacin should not be taken concurrently with milk or yogurt alone dairy products (like milk or with yogurt) or calcium-fortified juices alone since absorption of ciprofloxacin may be significantly reduced. Dietary calcium as part of a meal, however, does not significantly affect ciprofloxacin absorption; however, ciprofloxacin may be taken with a meal that contains these products.

Reproduction studies have been performed in rats and mice using oral doses up to 100 mg/kg (0.6 and 0.3 times the maximum daily human dose based upon body surface area, respectively) and have revealed no evidence of harm to the fetus due to ciprofloxacin. In rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, but no teratogenicity was observed at either dose. After intravenous administration of doses up to 20 mg/kg, no maternal toxicity was produced in the rabbit, and no embryotoxicity or teratogenicity was observed. There are, however, no adequate and well-controlled studies in pregnant women. Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (See WARNINGS.)

Nursing Mothers:

The following sentence was deleted after the list of additional events:

The following paragraph was deleted (was the fourth paragraph in this section):

The following paragraph was added to replace the table of adverse events that previously existed:

agitation, agranulocytosis, albuminuria, anaphylactic reactions, anosmia, candiduria, cholesterol elevation (serum), confusion, constipation, delirium, dyspepsia, dysphagia, erythema multiforme, exfoliative dermatitis, flatulence, glucose elevation (blood), hemolytic anemia, hepatic necrosis, hypotension (postural), jaundice, methemoglobinemia, myalgia, myasthenia gravis (possible exacerbation), myoclonus, nystagmus, pancreatitis, phenytoin alteration (serum), potassium elevation (serum), prothrombin time prolongation, pseudomembranous colitis (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.), psychosis (toxic), renal calculi, Stevens-Johnson syndrome, taste loss, tendinitis, tendon rupture, toxic epidermal necrolysis, triglyceride elevation (serum), vaginal candidiasis, and vasculitis (See PRECAUTIONS.)

The following information was added to the beginning of this section:

CIPRO Oral Suspension is supplied in 5% (5g ciprofloxacin in 100 mL) and 10% (10g ciprofloxacin in 100 mL) strengths. The drug product is composed of two components (microcapsules and diluent) which must be combined prior to dispensing.

The following sentences were added to this section:

CIPRO Oral Suspension should not be administered through feeding tubes due to its physical characteristics.

Instruct the patient to shake CIPRO Oral Suspension vigorously each time before use for approximately 15 seconds and not to chew the microcapsules.

New subheadings (Absorption, Distribution, Metabolism, Excretion and Special Populations) were added to this section and existing information was reorganized under the new subheadings.

Drug Interactions:
Drug-drug Interactions:
The potential for pharmacokinetic drug interactions between ciprofloxacin and theophylline, caffeine, cyclosporins, phenytoin, sulfonylurea, glyburide, metronidazole, warfarin, probenecid, and piperacillin sodium has been evaluated. (See PRECAUTIONS: Drug Interactions.)

Lower Respiratory Infections caused by Escherichia coli, Klebsiella pneumoniae subspecies pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, or Streptococcus pneumoniae.

Also, Moraxella catarrhalis for the treatment of acute exacerbations of chronic bronchitis.

The table of demographics information for Empirical Therapy for Febrile Neutropenic Patients was deleted.

Second bullet revised:

The following two statements were moved from the CLINICAL PHARMACOLOGY section and added to the Drug Interactions subsection:

" The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs were given concomitantly."

"Following infusion of 400 mg I.V. ciprofloxacin every eight hours in combination with 50 mg /kg I.V. piperacillin sodium every four hours, mean serum ciprofloxacin concentrations were 3.02 mg/mL ½ hour and 1.18 m g/mL between 6-8 hours after the end of infusion."

At the end of the Drug Interactions subsection the following statement was deleted to be consistent with other quinolone labeling:

There are no adequate and well-controlled studies in pregnant women. An expert review of published data on experiences with ciprofloxacin use during pregnancy by TERIS – the Teratogen Information System - concluded that therapeutic doses during pregnancy

are unlikely to pose a substantial teratogenic risk (quantity and quality of data=fair), but the data are insufficient to state that there is no risk.⁷

A controlled prospective observational study followed 200 women exposed to fluoroquinolones-(52.5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation.⁸ In utero exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. The reported rates of major congenital malformations were 2.2% for the fluoroquinolone group and 2.6% for the control group (background incidence of major malformations is 1-5%). Rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups and there were no clinically significant musculoskelatal dysfunctions up to one year of age in the ciprofloxacin exposed children. Another prospective follow-up study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester exposures). ⁹ There were 70 ciprofloxacin exposures, all within the first trimester. The malformation rates among live-born babies exposed to ciprofloxacin and to fluoroquinolones overall were both within background incidence ranges. No specific patterns of congenital abnormalities were found. The study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin. No differences in the rates of prematurity, spontaneous abortions, or birth weight were seen in women exposed to ciprofloxacin during pregnancy.^7,8 However, these small postmarketing epidemiology studies, of which most experience is from short term, first trimester exposure, are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses. Ciprofloxacin should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother (see WARNINGS).

Nursing Mothers - second sentence added:

Some text moved or reformatted from table to paragraph within the section.

DOSAGE AND ADMINISTRATION section was extensively revised.

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Other adverse reactions that have been reported with the individual components are listed below:

Dorzolamide —

Timolol (ocular administration) —

INSTRUCTIONS FOR USE

The first two paragraphs revised (providing for an alternative starting dose of 160 mg):

E. E. S. Granules, EryPed Drops
Ery Ped 200 and EryPed 400 (erythromycin ethylsuccinate) Oral Suspension
EryPed (erythromycin ethylsuccinate) Chewable Tablets
PCE (erythromycin particles) Tablets

General: 3rd paragraph:

Ergotamine/dihydroergotamine: Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.

Labeling provides for labeling changes, specifically modification of labeling text to more clearly state that these agents are indicated for the treatment of schizophrenia. Contact the company for a copy of the new labeling/package insert.

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CLINICAL PHARMACOLOGY,

Clinical Studies: the last paragraph deleted.

INDICATIONS AND USAGE the presentation of the updated NCEP treatment Guidelines table was updated accordingly with the supplemental request letter of August 17, 2001.

NCEP Treatment Guidelines: LDL-C Goals And Cutpoints for Therapeutic Lifestyle Changes and Drug Therapy in Different Risk Categories

Third paragraph:

[Labeling changes not appearing in 2001 PDR]

What are the possible side effects of MAXALT? - has been revised for consistency to reflect the changes to the package insert.

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Third paragraph revised:

Although the glucocorticoid activity of MEGACE Oral Suspension has not been fully evaluated, evidence of adrenal suppression has been observed. Clinical cases of new onset diabetes, exacerbation of pre-existing diabetes, and Cushing's syndrome have been reported in association with the use of MEGACE. Cases of clinically apparent adrenal insufficiency have also been reported in association with MEGACE. The possibility of adrenal suppression should be considered in any patient taking or withdrawing from chronic MEGACE therapy who presents with symptoms of adrenal insufficiency such as hypotension, nausea, vomiting, dizziness, or weakness. Laboratory evaluation for adrenal insufficiency and replacement stress doses of a rapidly acting glucocorticoid may be indicated for such patients. Failure to recognize inhibition of the hypothalmic-pituitary-adrenal axis may result in death.

Replaced with:

After a single dose, the bioavailability (C_max and AUC) of methylphenidate in 26 healthy adults was unaffected by sprinkling the capsule contents on applesauce as compared to the intact capsule. This finding demonstrates that a 20 mg METADATE CD Capsule, when opened and sprinkled on one tablespoon of applesauce, is bioequivalent to the intact capsule.

There is no experience with the use of METADATE CD in patients with renal insufficiency. After oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of ritalinic acid. Since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of METADATE CD.

There is no experience with the use of METADATE CD in patients with hepatic insufficiency.

Clinical Studies - Addition of data including updated "Effect on Hair Count" chart obtained from a five year extension study. Contact the company for a copy of the new labeling/package insert.

PROTONIX (pantoprazole sodium) Delayed-Release Tablets

Labeling provides for the use of Protonix Delayed-Release Tablets for pathological hypersecretory conditions including Zollinger-Ellison Syndrome. Contact the company for a copy of the new labeling/package insert.

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Labeling provides for the use of Remeron (mirtazapine) tablets in maintaining a response in patients with major depressive disorder. Contact the company for a copy of the new labeling/package insert.

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Labeling provides for the addition of a patient package insert (PPI) to the Sporanox Capsule label. Contact the company for a copy of the new labeling/package insert.

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[April 1, 2002: Novartis]

Labeling provides for the use of VIDEX(didanosine) Buffered Tablets, VIDEX(didanosine) Buffered Powder for Oral Solution, and VIDEX(didanosine) Pediatric Powder in pediatric patients from two weeks to eight months of age. Contact the company for a copy of the new labeling/package insert.

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For the full, highlighted revised label and patient package insert, including other safety related information, go to the following link:

Extensive labeling changes include:

Labeling changes in the Clinical Pharmacology; Clinical Studies, include (Rheumatoid Arthritis and VIOXX GI Clinical Outcomes Research (VIGOR study) pharmacokinetic data in patients with moderate hepatic insufficiency, drug interaction with theophylline, drug interaction with methotrexate.

Clinical Pharmacology and Precautions include inclusion of post-marketing adverse reactions and post-marketing experience of concurrent administration of clinical doses of Vioxx with lithium.

Indications and Usage provides for relief of the signs and symptoms of rheumatoid arthritis in adults.

Labeling changes to Warnings; Precautions, include Cardiovascular Effects and Adverse Reactions sections, including post-marketing adverse reactions and post-marketing experience of hypersensitivity vasculitis and hyperkalemia, hepatic failure, bronchospasm, toxic epidermal necrolysis, and anaphylactic reaction.

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VISUDYNE therapy is indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis.