Return to Quick Reference

ADVERSE REACTIONS:

Last paragraph, revised (new text in italics) -

"There have been rare postmarketing reports of mechanical upper gastrointestinal tract obstruction in patients taking Claritin-D 24 Hour Extended Release Tablets. In ["most" deleted] many of these cases, patients have had a history of difficulty in swallowing tablets or have had known upper gastrointestinal narrowing or abnormal esophageal peristalsis."

Return to Quick Reference

PRECAUTIONS:

Addition of new second paragraph -

"Nuclear medicine procedures involving withdrawal and reinjection of blood have the potential for transmission of blood borne pathogens. Procedures should be implemented to avoid administration errors and viral contamination of personnel during blood product labeling. A system of checks similar to the ones used for administering blood transfusions should be routine."

Return to Quick Reference

CONTRAINDICATIONS:

Second paragraph revised (new text in italics) -

"Cognex is contraindicated in patients previously treated with Cognex who developed treatment-associated jaundice ["confirmed by elevated total bilirubin greater than 3.0 mg/dL" deleted] ; a serum bilirubin > 3 mg/dL; and/or those exhibiting clinical signs or symptoms of hypersensitivity (eg, rash or fever) in association with ALT/SGPT elevations."

WARNINGS:

Gastrointestinal disease and Dysfunction: First paragraph revised (new text in italics) -

Cognex is an inhibitor of cholinesterase and may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients are at increased risk for developing ulcers ["- eg," deleted]. Those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) ["-" deleted] should be monitored closely for symptoms of active or occult gastrointestinal ["bleeding" deleted] disease.

Liver Injury: In third paragraph, "8000 patients" changed to "12,000 patients".

Controlled Clinical Trials, Treatment IND and Post Marketing Experience: Clinically evident liver toxicity: "8000 patients" changed to "12,000 patients"> Monitoring of Liver function and the Management of the patient who develops transaminase elevations: Blood chemistries: Subsection revised (new text in italics) -

"Serum transaminase levels (specifically ALT/SGPT) should be monitored every other week ["for at least the first 16 weeks" deleted] from at least week 4 to week 16 following initiation of ["Cognex" deleted] treatment, after which monitoring may be decreased to ["monthly for 2 months and" deleted] every 3 months ["thereafter" deleted]. For patients who develop ALT/SGPT elevations greater than two times the upper limit of normal, the dose and monitoring regimen should be modified as described in Table 4 (see DOSAGE AND ADMINISTRATION)."

PRECAUTIONS:

Hematology: Third paragraph - "8000 patients" changed to "12,000 patients".

ADVERSE REACTIONS:

Table 3: Title revised (new text in italics) -

"Adverse Events Occurring in at Least 2% of Patients Receiving Cognex ["Using the Recommended Regimen for Dose Introduction and Titration" deleted] at a Starting Dose of 40 mg/day with Titration in 40 mg/day Increments Every 6 Weeks in Controlled Clinical Trials"

Postintroduction Reports: Subsection revised (new text in italics) -

"Voluntary reports of adverse events temporally associated with Cognex that have been received since market introduction, that are not listed above, and that may have no causal relationship with the drug include the following: falling, pancreatitis, perforated ["duodenal" deleted] peptic ulcer."

DOSAGE AND ADMINISTRATION:

Initiation of Treatment: Second sentence revised (new text in italics) -

"This dose should be maintained for a minimum of ["6" deleted] 4 weeks with every-other-week monitoring of transaminase levels beginning 4 weeks after initiation of treatment."

Dose Titration: Subsection revised (new text in italics) -

"Following ["6" deleted] 4 weeks of treatment at 40 mg/day (10 mg QID), the dose of Cognex should then be increased to 80 mg/day (20 mg QID), providing there are no significant transaminase elevations and the patient is tolerating treatment. Patients should be titrated to higher doses (120 and 160 mg/day, in divided doses on a QID schedule) at ["6" deleted] 4-week intervals on the basis of tolerance."

Dose Adjustment: First sentence revised (new text in italics) -

"Serum ALT/SGPT should be monitored every other week from at least ["the first 16 weeks" deleted] week 4 to week 16 following initiation of ["Cognex" deleted] treatment, after which monitoring may be decreased to ["monthly for every 2 months and" deleted] every 3 months ["thereafter" deleted]."

Return to Quick Reference

PRECAUTIONS:

Pediatric Use (new subsection): "Safety and effectiveness in pediatric patients have not been established."

DOSAGE AND ADMINISTRATION:

For children: Entire subsection deleted.

Return to Quick Reference

INDICATION:

Section revised (new text in italics) -

"Fastin is indicated ["in the management of exogenous obesity" deleted] as a short-term (a few weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity for patients with an initial body mass index > or = 30 kg/m², or > or = 27 kg/m² in the presence of other risk factors (e.g., hypertension, diabetes, hyperlipidemia).

"Below is a chart of Body Mass Index (BMI) based on various heights and weights.

"BMI is calculated by taking the patient's weight, in kilograms (kg), divided by the patient's height, in meters (m) squared. Metric conversions are as follows: pounds divided by 2.2 = kg; inches x 0.0254 = meters.

"

BODY MASS INDEX (BMI), kg/m2 Height (feet, inches)
Weight (pounds)	5'0"	5'3"	5'6"	5'9"	6'0"	6'3"
140	27	25	23	21	19	18
150	29	27	24	22	20	19
160	31	28	26	24	22	20
170	33	30	28	25	23	21
180	35	32	29	27	25	23
190	37	34	31	28	26	24
200	39	36	32	30	27	25
210	41	37	34	31	29	26
220	43	39	36	33	30	28
230	45	41	37	34	31	29
240	47	43	39	36	33	30
250	49	44	40	37	34	31

"The limited usefulness of agents of this class (see ACTIONS) should be measured against possible risk factors inherent in their use such as those described below."

WARNINGS

Addition of three paragraphs to beginning of section -

"Fastin capsules are indicated only as short-term monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with phentermine and any other drug products for weight loss, including selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine), have not been established. Therefore, coadministration of these drug products for weight loss is not recommended.

"Primary Pulmonary Hypertension (PPH) - a rare, frequently fatal disease of the lungs - has been reported to occur in patients receiving a combination of phentermine with fenfluramine or dexfenfluramine. The possibility of an association between PPH and the use of phentermine alone cannot be ruled out; there have been rare cases of PPH in patients who reportedly have taken phentermine alone. The initial symptom of PPH is usually dyspnea. Other initial symptoms include: angina pectoris, syncope or lower extremity edema. Patients should be advised to report immediately any deterioration in exercise tolerance. Treatment should be discontinued in patients who develop new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema.

"Valvular Heart Disease: Serious regurgitant cardiac valvular disease, primarily affecting the mitral, aortic and/or tricuspid valves, has been reported in otherwise healthy persons who had taken a combination of phentermine with fenfluramine or dexfenfluramine for weight loss. The etiology of these valvulopathies has not been established and their course in individuals after the drugs are stopped is not known. There have been no reported cases to date of this valvular condition occurring with the use of phentermine alone."

Usage in Pregnancy: and Usage in Children: subsections deleted (see PRECAUTIONS below).

PRECAUTIONS:

Addition of new text to the end of the section -

"Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies have not been performed with Fastin (phentermine hydrochloride) to determine the potential for carcinogenesis, mutagenesis or impairment of fertility.

"Pregnancy - Teratogenic Effect: Pregnancy Category C. Animal reproduction studies have not been conducted with Fastin. It is also not known whether Fastin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Fastin should be given to a pregnant woman only if clearly needed.

"Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

"Pediatric Use: Safety and effectiveness in children have not been established."

ADVERSE REACTIONS:

Cardiovascular: Subsection revised (new text in italics) -

"Primary pulmonary hypertension and/or regurgitant cardiac valvular disease (see WARNINGS) , palpitation tachycardia, elevation of blood pressure."

Return to Quick Reference

CLINICAL PHARMACOLOGY:

Absorption: First paragraph, last sentence revised (new text in italics) -

"The systemic bioavailability of fluticasone propionate inhalation aerosol in healthy volunteers averaged about 30% of the dose delivered from the actuator."

ADVERSE REACTIONS:

Observed During Clinical Practice (new subsection):

"In addition to adverse events reported from clinical trials, the following events have been identified during postapproval use of fluticasone propionate in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, causal connection to fluticasone propionate, or a combination of these factors.

"Ear, Nose, and Throat: Throat soreness and irritation, hoarseness, laryngitis, aphonia.

"Endocrine and Metabolic: Cushingoid features, growth velocity reduction in children/adolescents, weight gain, hyperglycemia.

"Psychiatry: Restlessness, agitation, aggression, depression.

"Respiratory: Paradoxical bronchospasm, asthma exacerbation, dyspnea, wheeze, chest tightness, bronchospasm, cough.

"Skin: Pruritus, contusions, ecchymoses.

OVERDOSAGE:

Deletion of first sentence - "There are no data available on the effects of acute or chronic overdosage with Flovent Inhalation Aerosol."

Sentence moved to beginning of section - "Chronic overdosage may result in signs/symptoms of hypercorticism (see PRECAUTIONS)."

Return to Quick Reference

Return to Quick Reference

Return to Quick Reference

PRECAUTIONS:

Addition of new paragraph -

"Nuclear medicine procedures involving withdrawal and reinjection of blood have the potential for transmission of blood borne pathogens. Procedures should be implemented to avoid administration errors and viral contamination of personnel during blood product labeling. A system of checks similar to the ones used for administering blood transfusions should be routine."

Return to Quick Reference

Return to Quick Reference

Return to Quick Reference

CLINICAL PHARMACOLOGY:

Pharmacokinetics and Drug Metabolism: Absorption: Third sentence revised (new text in italics) -

"The absolute bioavailability of atorvastatin (parent drug) is approximately ["12%" deleted] 14% and the systemic availability of HMG-Coa reductase inhibitory activity is approximately 30%."

Distribution: First sentence revised (new text in italics) -

"Mean volume of distribution of atorvastatin is approximately ["565" deleted] 381 liters."

[Other changes within past 12 months: May97]

Return to Quick Reference

N.B. Ketoconazole 1% Shampoo OTC has the dandruff indication now.

Return to Quick Reference

[Other changes not appearing in 1997 PDR: Sep96, Jan97, Mar97]

CLINICAL PHARMACOLOGY:

Pharmacokinetics: Special Populations: Drug-Drug Interactions: Table 2 "Effects on AUC and C_max of Coadministration of Ritonavir With Other Drugs" revised - the following text was added to the "Effect of Co-Administered Drug" section.

Drug	Ritonavir Dosage	n	AUC % (95 CI)	Cmax % (95 CI)
Alprazolam 1 mg single dose	500 mg q 12h 10 days	12	¯ 12% (-5, 30%)	¯ 16% (5, 27%)
Saquinavir 400 mg bid steady-state3	400 mg bid steady-state	7	­ 17-fold (9, 31X)	­ 14-fold (7, 28X)
3 Comparison to a standard saquinavir 600 mg tid regimen (n=114)

INDICATIONS AND USAGE:

First sentence revised (new text in italics) -

"Norvir is indicated in combination with ["nucleoside analogues" deleted] other antiretroviral agents or as monotherapy for the treatment of HIV-infection ["when therapy is warranted" deleted]."

CONTRAINDICATIONS:

Third paragraph, first sentence revised -

"Ritonavir co-administration is also expected to produce large increases in these highly metabolized sedatives and hypnotics: ["alprazolam," deleted] clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, and zolpidem."

WARNINGS:

New text added at end of section -

"New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during postmarketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established."

PRECAUTIONS:

Drug Interactions: Effects on co-administered drugs: Saquinavir: Subsection revised (new text in italics) -

"Ritonavir extensively inhibits the metabolism of saquinavir resulting in greatly increased saquinavir plasma concentrations. ["Co-administration of ritonavir 400 or 600 mg bid regimens produced greater than 20-fold increases in steady-state dose-normalized saquinavir concentrations in healthy subjects. The appropriate doses for this combination, with respect to activity and safety, have not been established." deleted] Following approximately 4 weeks of a combination regimen of saquinavir (400 or 600 mg bid) and ritonavir (400 or 600 mg bid) in HIV-infected patients, saquinavir AUC values were at least 17-fold greater than historical AUC values patients who received saquinavir 600 mg tid without ritonavir. When used in combination therapy for up to 24 weeks, doses greater than 400 mg bid of either ritonavir or saquinavir were associated with an increase in adverse events."

Table 3 "Predicted Effects on Drugs Co-administered with Ritonavir, Contraindicated Medications are Listed in Column 1 (see PRECAUTIONS, Drug Interactions for Clinical Pharmacology Study Results)": Table revised to delete "alprazolam" from the Sedative/hypnotics column.

ADVERSE REACTIONS:

Post-Marketing Experience: First paragraph, second sentence deleted -

"Hyperglycemia has been reported in individuals with and without a known history of diabetes."

DOSAGE AND ADMINISTRATION:

Pediatric Patients: First and last sentences - "nucleoside analogue(s)" changed to "other antiretroviral agents".

Return to Quick Reference

Return to Quick Reference

CLINICAL PHARMACOLOGY:

Special Populations (new subsection): "Pharmacokinetic and pharmacodynamic studies have not been systematically conducted to determine the optimal dose and optimal imaging time in patients with abnormal renal function or renal failure, in the elderly, or in pediatric patients with immature renal function."

PRECAUTIONS:

General: New sentence added at end of second paragraph -

"For elimination of Omniscan in pediatric patients, see the Pediatric Use section."

Pediatric Use: Section revised (new text in italics) -

"The safety and efficacy of Omniscan at a single dose of 0.05 to 0.1 mmol/kg have been established in ["children 2 years of age and older (See INDICATIONS and USAGE and DOSAGE and ADMINISTRATION)" deleted] the pediatric population over 2 years of age. The safety and efficacy for doses greater than 0.1 mmol/kg and ["for" deleted] the clinical benefit of repeated procedures have not been studied in ["children" deleted] pediatric patients. ["The safety and efficacy for children under 2 years of age have not been established." deleted] The use of Omniscan in these age groups is supported by evidence from adequate and well controlled studies of Omniscan in adults, a pediatric study of the MR imaging of the central nervous system and additional safety data obtained in the literature.

"Pharmacokinetics of Omniscan have not been studied in the pediatric population. Literature reports that the glomerular filtration rate of neonates and infants is much less than that of adults. The pharmacokinetics volume of distribution is different as well. The effect of these differences on the elimination and dosing regimen in pediatric patients under 2 years of age has not been studied. Whether the dose administered or optimal imaging times should be adjusted has not been studied.

"However, in the 173 pediatric patients in the central nervous system Omniscan (see the Clinical Trials section) and the 144 pediatric patients in the literature, the adverse events were similar to those reported in adults."

ADVERSE REACTIONS:

Skin and Appendage Disorders: "sweating" changed to "sweating increased"

DOSAGE AND ADMINISTRATION:

CNS (Central Nervous System): Subsection title changed from "Children (2-18 years):" to "Pediatric Patients (2-16 years):"

Body (Intrathoracic [noncardiac], Intra-abdominal, Pelvic, and Retroperitoneal Regions): New subsection title added before existing text - "Adult and Pediatric Patients (2-16 years of age):"

Within this subsection the DOSAGE CHART has been modified to add a column for Pediatric Dosing at 0.05 mmol/kg. See the revised table within new labeling.

Return to Quick Reference

[Other changes in past 12 months: Feb97]

OVERDOSAGE:

Section revised (new text in italics) -

"An 18 month old infant inadvertently received 1600 mg of intravenous pentamidine isethionate which was followed by renal and hepatic function impairment, cardiac arrest and respiratory arrest. The patient recovered from these adverse events, but later died due to an unknown cause."

Return to Quick Reference

CLINICAL PHARMACOLOGY:

Enterochromaffin-like (ECL) Cell Effects: Section revised (new text in italics) -

"In 24-month carcinogenicity studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals (see PRECAUTIONS, Carcinogenesis, Mutagenesis, Impairment of Fertility). ["Hypergastrinemia secondary to prolonged and sustained hypochlorhydria has been postulated to be the mechanism by which ECL cell hyperplasia and gastric carcinoid tumors develop. Omeprazole may also affect other cells in the gastrointestinal tract (e.g. G cells), either directly or by inducing sustained hypochlorhydria, but this possibility has not been extensively studied." deleted] Carcinoid tumors have also been observed in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H₂-receptor antagonists.

"["Human gastric biopsy specimens from about 200 patients treated continuously with omeprazole for an average of over 12 months have not detected ECL cell effects of omeprazole similar to those seen in rats. Longer term data are needed to rule out the possibility of an increased risk for the development of gastric tumors in patients receiving long-term therapy with omeprazole" deleted]

"Human gastric biopsy specimens have been obtained from more than 3000 patients treated with omeprazole in long-term clinical trials. The incidence of ECL cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia has been found in these patients (See also CLINICAL PHARMACOLOGY, Pathogical Hypersecretory Conditions)."

Return to Quick Reference

Return to Quick Reference

Return to Quick Reference

ADVERSE REACTIONS:

Other: Addition of "gynecomastia"

OVERDOSAGE:

Hypotension: Addition of new second paragraph -

"In a few reported cases, overdose with calcium channel blockers has been associated with hypotension and bradycardia, initially refractory to atropine but becoming more responsive to this treatment when the patients received large doses (close to 1 gram/hour for more than 24 hours) of calcium chloride."

Return to Quick Reference

Return to Quick Reference

[Other changes within past 12 months: Jun97]

Return to Quick Reference

CLINICAL PHARMACOLOGY:

Addition of new second paragraph -

"Viroptic is also effective in the treatment of epithelial keratitis that has not responded clinically to the topical administration of idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients found to be resistant to topical vidarabine, Viroptic was also effective."

Clinical Studies (new subsection): The three paragraphs beginning "During a controlled multicenter clinical trial, ...", "In other clinical studies, ...", and "The clinical efficacy of Viroptic ..." moved from INDICATIONS AND USAGE section.

INDICATIONS AND USAGE:

First paragraph, second and third sentences moved to CLINICAL PHARMACOLOGY as new second paragraph

The remainder of the section moved to CLINICAL PHARMACOLOGY, Clinical Studies.

PRECAUTIONS:

Drug Interactions: Entire subsection deleted.

Pediatric Use (new subsection): "Safety and effectiveness in pediatric patients below six years of age have not been established."

REFERENCES:

Entire section deleted. Citations in other sections of the labeling also deleted.

Return to Quick Reference

Return to Quick Reference

Return to Quick Reference

CLINICAL PHARMACOLOGY:

First paragraph, addition of new third and fourth sentences- "Though frequently found in association with low HDL, elevated plasma triglycerides (TG) has not been established as independent risk factor for coronary heart disease. The independent effect of raising HDL or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined."

Third paragraph next to last sentence revised (new text in italics) -

"In addition, Zocor ["modestly" deleted] reduces VLDL cholesterol and plasma triglycerides (TG) and ["can produce" deleted] increases ["of variable magnitude in" deleted] HDL cholesterol."

Clinical Studies: Second paragraph, last paragraph (new text in italics) -

"Zocor also ["modestly" deleted] decreased triglycerides ["(TRIG)" deleted] (TG) and ["produced" deleted] increased ["of variable magnitude in" deleted] HDL cholesterol (HDL-C)".

INDICATIONS AND USAGE:

Hypercholesterolemia: Entire subsection deleted.

Hyperlipidemia (new subsection): "Zocor is indicated as an adjunct to diet to reduce elevated TOTAL-C, LDL-C, Apo B, and TG levels in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb^**)."

General Recommendations: Last paragraph revised (new text in italics) -

"["Although" deleted] Zocor ["may be useful" deleted] is indicated to reduce elevated LDL cholesterol and triglyceride levels in patients with ["combined hypercholesterolemia and hypertriglyceridemia" deleted] Type IIb hyperlipoproteinemia (where hypercholesterolemia is the major abnormality ["(Type IIb hyperlipoproteinemia)" deleted] ). However, it has not been studied in conditions where the major abnormality is elevation of chylomicrons, VLDL or IDL (i.e., hyperlipoproteinemia Types I, III, IV, or V).^**"

^** Classification of Hyperlipoproteinemias

Return to Quick Reference

[Other changes in past 12 months:Apr97]

Return to Quick Reference

ADVERSE REACTIONS:

Incidence in Placebo-Controlled Trials:Other Adverse Events in Pediatric Patients (new subsection):

"In approximately n=250 pediatric patients treated with Zoloft, the overall profile of adverse events was generally similar to that seen in adult studies, as shown in Tables 1 and 2. However, the following adverse events, not appearing in Tables 1 and 2, were reported at an incidence of at least 2% and occurred at a rate at least twice the placebo rate in a controlled trial (n=187): hyperkinesia, twitching, fever, malaise, purpura, weight decrease, concentration impaired, manic reaction, emotional lability, thinking abnormal, and epistaxis."

Other Events Observed During Postmarketing Experience with Zoloft: Increased coagulation times, bradycardia, AV block, atrial arrhythmias, hypothyroidism, leukopenia, thrombocytopenia, hyperglycemia, and priapism added to the list of adverse events temporally associated with Zoloft that have been received since market introduction, are not otherwise listed, and may have no causal relationship with the drug.

DRUG ABUSE AND DEPENDENCE:

Physical and Psychological Dependence: Subsection revised (new text in italics) -

"In a placebo controlled, double-blind, randomized study of the comparative abuse liability of Zoloft, alprazolam, and d-amphetamine in humans, Zoloft did not produce the positive subjective effects indicative of abuse potential, such as euphoria or drug liking, that were observed with the other two drugs. Premarketing clinical experience with Zoloft did not reveal any tendency for a withdrawal syndrome or any drug-seeking behavior. In animal studies Zoloft does not demonstrate stimulant or barbiturate-like (depressant) abuse potential. As with any CNS active drug, however, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of Zoloft misuse or abuse (e.g. development of tolerance, incrementation of dose, drug-seeking behavior)."

N.B.:The labeling has also been extensively revised to provide clinical data supporting the use of Zoloft in the treatment of obsessive compulsive disorder in the pediatric population.
Contact the company for a copy of the labeling/package insert.

Return to Quick Reference