Complied with the help of:
Julie Johnson, PharmD Student
McWhorter School of Pharmacy
Samford University
Birmingham, AL

ANAFRANIL (clomipramine HCl)	ANZEMET (dolasetron mesylate)	BAYCOL (cerivastatin Na)	CAVERJECT (alprostadil)
CORDARONE (amiodarone HCl)	COSOPT (dorzolamide HCl/ timolol maleate)	DILATRATE-SR (isosorbide dinitrate)	HABITROL (nicotine transdermal)
LAMISIL (terbinafine HCl)	LESCOL (fluvastatin Na)	LOESTRIN & LOESTRIN FE (norethindrone acetate/ ethinyl estradiol/ + ferrous fumarate in FE)	MAXIPIME (cefepime HCl)
MEPRON (atovaquone)	MODICON-28 (norethindrone/ ethinyl estradiol)	MONOKET (isosorbide mononitrate)	NITROLINGUAL (nitroglycerin)
ORTHO-NOVUM 1/35 (norethindrone/ ethinyl estradiol)	PREVACID (lansoprazole)	QUELICIN (succinylcholine chloride)	SORBITRATE (isosorbide dinitrate)
VISIPAQUE (iodixanol)	WELLBUTRIN SR (bupropion HCl)	ZYPREXA (olanzapine)

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PRECAUTIONS:

Drug Interactions: Drugs Metabolized by P4502D6: First paragraph revised beginning with 7th sentence (new text in italics) -

"While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, fluvoxamine, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. Fluvoxamine has also been shown to inhibit P450 1A2, an isoform also involved in TCA metabolism. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Conconmitant use of agents in the tricyclic antidepressant["s" deleted] class (which includes Anafranil) with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these drugs is withdrawn from co-therapy, an increased does of tricyclic antidepressant agent may be required. It is desirable to monitor TCA plasma levels whenever ["a TCA" deleted] an agent of the tricyclic antidepressant class (including Anafranil) is going to be co-administered with another drug known to be an inhibitor of P45 2D6 (and/or P450 1A2)."

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PRECAUTIONS:

General: Text added at end of subsection as new 2nd paragraph -

"Cross hypersensitivity reactions have been reported in patients who received other selective 5-HT₃ receptor antagonists. These reactions have not been seen with dolasetron mesylate."

ADVERSE REACTIONS:

Cardiovascular: Text added at end of subsection as new 3rd paragraph -

"Furthermore, severe hypotension, bradycardia and syncope have been reported immediately or closely following IV administration."

Vascular (Extracardiac): Subsection revised (new text in italics) -

Local pain or burning on IV administration;rarely - peripheral ischemia, thrombophlebitis/phlebitis."

OVERDOSAGE:

First sentence revised (new text in italics) -

"A 59-year-old man with metastatic melanoma and no known pre-existing cardiac conditions developed severe hypotension and dizziness 40 minutes after receiving a 15 minute intravenous infusion of 1000 mg (13 mg/kg) of dolasetron mesylate."

WARNINGS:

Skeletal Muscle: Subsection revised (new text in italics) -

"Rare cases of rhabdomyolysis (some with acute renal failure secondary to myoglobinuria) have been reported with cerivastatin and other ["HMG CoA reductase inhibitors" deleted] drugs in this class."

PRECAUTIONS:

Other Concomitant Therapy: Subsection deleted -

"Although specific interaction studies were not performed, in clinical studies, cerivastatin sodium was used concomitantly with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium-channel blockers, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) without evidence of clinically significant adverse interactions."

ADVERSE REACTIONS:

Post-Marketing Adverse Event Reports (new subsection):

"The following events have been reported since market introduction. While these events were temporally associated with the use of Baycol, a causal relationship to the use of Baycol cannot be readily determined due to the spontaneous nature of reporting of medical events, and the lack of controls: hepatitis, myositis, rhabdomyolysis, some with associated renal failure (most cases involved concomitant gemfibrozil), urticaria, angioedema, visual disturbance, blurred vision."

PATIENT INSTRUCTIONS:

Preparing and injecting Caverject: Third paragraph revised (new text in italics) -

"Follow these instructions exactly to prepare and inject a sterile dose of CAVERJECT. A dose may be administered manually as described in the 'Inject Your Dose of Caverject' section below, or with the use of an autoinjector (PenInject 2.25 AutoInjector)which is available separately. If you choose to use the PenInject 2.25 Autoinjector, see the pamphlet provided with it for instructions on loading, using, and maintaining this device."

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WARNINGS"

Mortality: Second paragraph deleted -

"The applicability of these results to other populations (e.g., those without recent myocardial infarctions) or to Cordarone-treated patients is uncertain. While definitive controlled trials with Codarone are in progress, pooled analysis of small controlled studies in patients with structural heart disease (including post-myocardial infarction) have not shown excess mortality in the Cordarone-treated population."

Replaced with the following text -

"Cordarone therapy was evaluated in two multi-centered, randomized, double-blind, placebo-controlled trials involving 1202 (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial; CAMIAT) and 1486 (European Myocardial Infarction Amiodarone Trial; EMIAT) post-MI patients followed for up to 2 years. Patients in CAMIAT qualified with ventricular arrhythmias, and those randomized to amiodarone received weight- and response-adjusted doses of 200 to 400 mg/day. Patients in EMIAT qualified with ejection fraction <40%, and those randomized to amiodarone received fixed doses of 200 mg/day. Both studies had weeks-long loading dose schedules. Intent-to-treat all-cause mortality results were as follows:"

	Placebo		Amiodarone		Relative Risk
	N	Deaths	N	Deaths		95% CI
EMIAT	743	102	743	103	0.99	0.76-1.31
CAMIAT	596	68	606	57	0.88	0.58-1.16

"These data are consistent with the results of a pooled analysis of smaller, controlled studies involving patients with structural heart disease (including myocardial infarction)."

Pregnancy: Pregnancy Category D: Subsection deleted

Neonatal Hypo- or Hyperthyroidism: Text added as last paragraph of subsection -

"In pregnant rats and rabbits, amiodarone HCl in doses of 25 mg/kg/day (approximately 0.4 and 0.9 times, respectively, the maximum recommended human maintenance dose*)had no adverse effects on the fetus. In the rabbit, 75 mg/kg/day (approximately 2.7 times the maximum recommended human maintenance dose*) caused abortions in greater than 90% of the animals. In the rat, doses of 50 mg/kg/day or more were associated with slight displacement of the testes and an increased incidence of incomplete ossification of some skull and digital boones; at 100 mg/kg/day or more, fetal body weights were reduced; at 200 mg/kg/day, there was an increased incidence of fetal resorption. (These doses in the rat are approximately 0.8, 1.6, and 3.2 times the maximum recommended human maintenance dose.*) Adverse effects on fetal growth and survival also were noted in one of two strains of mice at a dose of 5 mg/kg/day (approximately 0.04 times the maximum recommended human maintenance dose*). * 600 mg in a 50 kg patient (doses compared on a body surface area basis)."

PRECAUTIONS:

Surgery: Volatile Anesthetic Agents (new subsection): "Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated inhalational anesthetics."

Drug Interactions:Volatile Anesthetic Agents (new subsection): (See "PRECAUTIONS, Surgery, Volatile Anesthetic Agents.")

Carcinogenesis, Mutagenesis, Impairment of Fertility: Subsection revised and reorganized (new text in italics) -

"["Cordarone" deleted] Amiodarone HCl ["caused" deleted] was associated with a statistically significant, dose-related increase in the incidence of thyroid tumors (follicular adenoma and/or carcinoma) in rats. The incidence of thyroid tumors was greater than control even at the lowest dose level tested, i.e., 5mg/kg/day (approximately ["equal to 1/2 the highest" deleted] 0.08 times the maximum recommended human maintenance dose ^*).

"Mutagenicity studies (Ames, micronucleus, and lysogenic tests) with Cordarone were negative.

"In a study in which amiodarone HCl was administered to male and female rats, beginning 9 weeks prior to mating, ["Cordarone" deleted] reduced fertility ["of male and female rats" deleted] was observed at a dose level of 90 mg/kg/day (["8 X highest" deleted] approximately 1.4 times the maximum recommended human maintenance dose^*).

"* 600 mg in a 50 kg patient (dose compared on a body surface area basis)"

Pregnancy: Pregnancy Category D: Subsection revised (new text in italics)

"See 'WARNINGS, Neonatal Hypo- or Hyperthyroidism.' "

ADVERSE REACTIONS:

Dorzolamide: Skin/Mucous Membranes: (subsection name changed from "Skin"): Subsection revised (new text in italics) -

"Contact dermatitis, throat irritation "

Timolol (ocular administration): Cardiovascular: "edema" added

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PRECAUTIONS:

Geriatric Use (new subsection): "Clinical studies of dopamine injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy."

DOSAGE AND ADMINISTRATION:

Rate of Administration:Text added as new third paragraph -

"When discontinuing the infusion, it may be necessary to gradually decrease the dose of dopamine HCl while expanding the blood volume with IV fluids to prevent the development of marked hypotension."

CLINICAL PHARMACOLOGY:

Clinical Studies: New paragraph inserted after the fifth sentence of the first paragraph -

"In a fourth placebo-controlled, double-blind trial (N=893) of non-depressed, chronic cigarette smokers, smoking at least 15 cigarettes per day, both Habitrol and Zyban, given alone as well as in combination, were shown to be more effective than placebo as an aid to smoking cessation when used in combination with behavioral support. (See Zyban label for important warnings and precautions.)"

Text added at end of subsection -

"The fourth study was a comparative trial conducted at four clinical centers. Four treatments were evaluated: Zyban 300 mg/day, Habitrol starting at 21 mg/day, combination of Zyban 300 mg/day plus Habitrol starting at 21 mg/day, and placebo. Patients were treated for 9 weeks. Treatment with Zyban was initiated at 150 mg/day while the patient was still smoking and was increased after 3 days to 300 mg/day given as 150 mg twice daily. Habitrol 21 mg/day was added to treatment with Zyban after approximately 1 week when the patient reached the target quit date. During weeks 8 and 9 of the study, Habitrol was tapered to 14 and 7 mg, respectively. Quitting, defined as total abstinence during weeks 4 through 7, was determined by patient daily diaries and verified by expired air carbon monoxide levels.

"In this study, patients treated with either Habitrol or Zyban achieved greater 4-week abstinence rates than patients treated with placebo. In addition, patients treated with the combination of Habitrol and Zyban achieved significantly higher 4-week abstinence rates than patients treated with Habitrol alone.

"Habitrol, Zyban, and combination treatment were all more effective than placebo in helping patients maintain abstinence through week 10 of the study. The treatment combination of Habitrol and Zyban displayed the highest rates of continuous abstinence throughout the study compared to placebo and Habitrol alone; however the quit rates for the combination were not significantly higher (p<0.05) than for Zyban alone.

"The comparison between Zyban, Habitrol, and combination treatment in this study have not been replicated, and therefore should not be interpreted as demonstrating the superiority of any of the active treatment arms over any other.

"Quit rates for Habitrol-treated patients and placebo-treated patients fell within the range of quit rates presented above. Quit rates in clinical trials are influenced by the population selected. Quit rates in an unselected population may be lower than the above rates."

PRECAUTIONS:

Allergic Reactions: Text added as new last paragraph in subsection -

"Patients receiving combination treatment with Habitrol and Zyban should also be made aware of risk of allergic reactions related to Zyban. (See Zyban label for important warnings and precautions.)"

Cardiovascular or Peripheral Diseases: Text added as new last paragraph in subsection -

"Monitoring for treatment-emergent hypertension is recommended in patients receiving the combination of Zyban and Habitrol. In the comparative trial, 6.1% of patients treated with the combination of Zyban and Habitrol had treatment-emergent hypertension compared to 2.5%, 1.6%, and 3.1% of patients treated with Zyban, Habitrol, and placebo, respectively. The majority of these patients had evidence of preexisting hypertension. Three patients (1.2%) treated with the combination of Zyban and Habitrol and one patient (0.4%) treated with Habitrol had study medication discontinued due to hypertension compared to none of the patients treated with Zyban or placebo. (See Zyban label for important warnings and precautions.)"

ADVERSE REACTIONS:

Text added at the end of section -

"The following table enumerates selected treatment-emergent adverse events from the comparative trial that occurred at an incidence of 1% or more and were more common in patients treated with Habitrol, Zyban, or the combination of Habitrol and Zyban compared to those treated with placebo. Reported adverse events were classified using a COSTART-based dictionary."

Treatment-Emergent Adverse Event Incidence in the Comparative Trial*

Adverse Experience (COSTART Term)	ZYBAN 300 mg/day (n=243) %	Habitrol 21 mg/day (n=243) %	ZYBAN and Habitrol (n=244) %	Placebo (n=159) %
Body Abdominal pain Accidental injury Chest pain Neck pain Facial edema	3 2 <1 2 <1	4 2 1 1 0	1 1 3 <1 1	1 1 1 0 0
Cardiovascular Hypertension Palpitations	1 2	<1 0	2 1	0 0
Digestive Nausea Dry mouth Constipation Diarrhea Anorexia Mouth ulcer Thirst	9 10 8 4 3 2 <1	7 4 4 4 1 1 <1	11 9 9 3 5 1 2	4 4 3 1 1 1 0
Musculoskeletal Myalgia Arthralgia	4 5	3 3	5 3	3 2
Nervous system Insomnia Dream abnormality Anxiety Disturbed concentration Dizziness Nervousness Tremor Dysphoria	40 5 8 9 10 4 1 <1	28 18 6 3 2 <1 <1 1	45 13 9 9 8 2 2 2	18 3 5 4 6 2 0 1
Respiratory Rhinitis Increased cough Pharyngitis Sinusitis Dyspnea Epistaxis	12 3 3 2 1 2	11 5 2 2 0 1	9 <1 3 2 2 1	8 1 0 1 1 0
Skin Application site reaction** Rash Pruritus Urticaria	11 4 3 2	17 3 1 0	15 3 5 2	7 2 1 0
Special senses Taste perversion Tinnitus	3 1	1 0	3 <1	2 0

*Selected adverse events with an incidence of at least 1% of patients treated with either Zyban, Habitrol or the combination of Zyban and Habitrol and more frequent than in placebo group.

**Patients randomized to Zyban or placebo received placebo patches.

DOSAGE AND ADMINISTRATION:

Combination Treatment with Habitrol and Zyban (bupropion hydrochloride) Sustained-Release Tablets (new subsection):

"Combination treatment with Habitrol and Zyban may be prescribed for smoking cessation. The prescriber should review the complete prescribing information for both Habitrol and Zyban before using combination treatment. See also CLINICAL STUDIES for methods and dosing used in the Habitrol and Zyban combination trial. Monitoring for treatment-emergent hypertension in patients treated with the combination of Habitrol and Zyban is recommended."

[NOTE: The Patient Package Insert has also been revised to reflect these changes.]

CLINICAL PHARMACOLOGY:

Microbiology: Subsection revised (new text in italics) -

"Terbenafine hydrochloride is a synthetic allylamine derivative. Terbinafine hydrochloride ["exerts its antifungal effect" deleted] is hypothesized to act by inhibiting squalene epoxidase, ["a key enzyme in sterol biosynthesis in fungi" deleted] thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes. ["This action results in a deficiency in ergosterol and a corresponding accumulation of squalene within the fungal cell." deleted]. In vitro, mammalian squalene epoxidase is only inhibited at higher (4000 fold) concentrations than is needed for inhibition of the dermatophyte enzyme. Depending on the concentration of the drug and the fungal species test in vitro, terbinafine hydrochloride may be fungicidal. However, the clinical significance of ["these" deleted] in vitro data is unknown. ["In vitro, mammalian squalene epoxidase is only inhibited at higher (4000-fold) concentrations." deleted].

"Terbinafine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections ["of the nail" deleted] as described in the INDICATIONS AND USAGE section:

"Trichophyton mentagrophytes
Trichophyton rubrum

"["Blood and tissue levels of terbinafine following oral dosing with Lamisil 250 mg QD exceed in vitro MIC's against most strains of the following organisms which can infect the nail; however, the efficacy of terbinafine in treating nail infections due to these organisms has not been studied in controlled clinical trials." deleted]

"The following in vitro data are available, but their clinical significance is unknown. In vitro, terbinafine exhibits satisfactory MIC's against most strains of the following microorganisms; however, the safety and efficacy of terbinafine in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials:

["Microsporum gypseum
Microsporum nanum
Trichophyton verrucosum" deleted]
Candida albicans
Epidermophyton floccusum
Scopulariopsis brevicaulis"

INDICATIONS AND USAGE:

Last sentence revised (new text in italics) -

"(See DOSAGE AND ADMINISTRATION, CLINICAL STUDIES)."

CONTRAINDICATIONS:

Last sentence revised (new text in italics).

"Lamisil (terbinafine hydrochloride tablets) Tablets are contraindicated in individuals with hypersensitivity to terbinafine or to any other ingredients of the formulation."

WARNINGS:

Second sentence revised (new text in italics) -

"Treatment with Lamisil (terbinafine hydrocloride tablets) Tablets should be discontinued if hepatobiliary dysfunction develops (see PRECAUTIONS, ADVERSE REACTIONS)"

PRECAUTIONS:

General:First paragraph, third sentence revised (new text in italics) -

"Hepatic function (hepatic enzyme) tests are recommended in patients administered Lamisil (terbinafine hydrochloride) Tablets for more than six weeks or in those who develop unexplained persistent nausea, anorexia, or fatigue or jaundice, dark urine or pale stools (see WARNINGS)."

Drug Interactions: Third sentence deleted -

"Terbinafine does not affect the clearance of warfarin or warfarin's effect on prothrombin time."

Carcinogenesis, Mutagenesis, Impairment of Fertility: First paragraph, third sentence revised (new text in italics) -

"No increased incidence in liver tumors was noted in female rats at dose levels up to 97 mg/kg/day (["19.4X the MRHD based on BW and" deleted] 4.5X the MRHD based on BSA) or in male or female mice treated orally for 23 months at doses up to 156 mg/kg/day (["31.2X the MRHD based on BW and" deleted] 3.9X the MRHD based on BSA)."

Fourth paragraph revised (new text in italics) -

"The results of a variety of in vitro (mutations in E. coli and Salmonella, DNA repair in rat hepatocytes, mutagenicity in Chinese hamster fibroblasts, chromosome aberration and sister chromatid exchanges in Chinese hamster) and in vivo (chromosome aberration in Chinese hamsters, micronucleus test in mice) genotoxicity tests gave no evidence of a mutagenic or clastogenic potential and demonstrated the absence of tumor-initiating or cell-proliferating activity."

ADVERSE REACTIONS:

Second paragraph revised (new text in italics) -

"Rare adverse events, based on worldwide experience with Lamisil ["(terbinafine hydrochloride tablets) Tablets" deleted], include: symptomatic idiosyncratic hepatobiliary dysfunction (including cholestatic hepatitis and very rarely liver failure)(see WARNINGS and PRECAUTIONS), serious skin reactions (see WARNINGS), severe neutropenia, (see PRECAUTIONS), thrombocytopenia and allergic reactions (including anaphylaxis). ["Rarely" deleted] Uncommonly, Lamisil may cause taste disturbance (including taste loss) which usually recovers within several weeks after discontinuation of the drug."

Text added as last paragraph in section -

"Clinical adverse effects reported spontaneously since the drug was marketed include altered prothrombin time (prolongation and reduction) in patients concomitantly treated with warfarin and Lamisil Tablets and agranulocytosis (very rare)."

PRECAUTIONS:

Drug Interactions: Other Concomitant Therapy: Subsection deleted, text had read-

"Although specific interaction studies were not performed, in clinical studies, fluvastatin sodium was used concomitantly with angiotension-converting enzyme (ACE) inhibitors, beta blockers, calcium-channel blockers, diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) without evidence of clinically significant adverse interactions."

PRECAUTIONS

Pediatric Use (new subsection): "Safety and efficacy of Loestrin have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated."

CLINICAL PHARMACOLOGY:

Special Populations: Pediatric patients (new subsection):

"Cefepime pharmcokinetics have been evaluated in pediatric patients from 2 months to 11 years of age following single and multiple doses on q8h (n=29) and q12h (n=13) schedules. Following a single IV dose, total body clearance and the steady state volume of distribution averaged 3.3 (+/- 1.0) mL/min/kg and 0.3 (+/- 0.1) L/kg, respectively. The urinary recovery of unchanged cefepime was 60.4 (+/- 30.4)% of the administered dose, and the average renal clearance was 2.0 (+/- 1.1) mL/min/kg. There were no significant effects of age or gender (25 male vs. 17 female) on total body clearance or volume of distribution, corrected for body weight. No accumulation was seen when cefepime was given at 50 mg/kg q 12h (n=13), while C_max, AUC, and t_1/2 were increased about 15% at steady state after 50 mg/kg q8h. The exposure to cefepime following a 50 mg/kg IV dose in a pediatric patient is comparable to that in an adult treated with a 2 q IV dose. The absolute bioavailablity of cefepime after an IM dose of 50 mg/kg was 82.3 (+/-15)% in eight patients."

INDICATIONS AND USAGE:

First sentence revised (new text in italics) -

"Maxipime is indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms (see also PRECAUTIONS: Pediatric Use and DOSAGE AND ADMINISTRATION):"

PRECAUTIONS:

Pediatric Use: Existing text -

"The safety and efficacy of Maxipime (cefepime hydrochloride) in pediatric patients below the age of 12 years have not been established. This product is intended for use in patients 12 years of age and older."

deleted and replaced with -

"The safety and effectiveness of cefepime in the treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, pneumonia, and as empiric therapy for febrile neutropenic patients have been established in the age groups 2 months up to 16 years. Use of Maxipime in these age groups is supported by evidence from adequate and well-controlled studies of cefepime in adults with additional pharmacokinetic and safety data from pediatric trials (see CLINICAL PHARMACOLOGY).

"Safety and effectiveness in pediatric patients below the age of 2 months have not been established. There are insufficient clinical data to support the use of Maxipime in pediatric patients under 2 months of age or for the treatment of serious infections in the pediatric population where the suspected or proven pathogen is Haemophilus influenzae type b.

"In those patients in whom meningeal seeding from a distant infection site or in whom meningitis is suspected or documented, an alternate agent with demonstrated clinical efficacy in this setting should be used."

ADVERSE REACTIONS:

Clinical Trials: Text added as last sentence in subsection -

"A similar safety profile was seen in clinical trials of pediatric patients (see PRECAUTIONS: Pediatric Use)."

DOSAGE AND ADMINISTRATION:

First sentence revised (new text in italics) -

"The recommended adult and pediatric dosages and routes of administration are outlined in the following table."

Table 12 "Recommended Dosage Schedule for Maxipime" -

The word "Adults" added before the existing rows of dosage schedules.

Text added as new row in Table 12 -

"Pediatric Patients (2 months up to 16 years)
The maximum dose for pediatric patients should not exceed the recommended adult dose. The usual recommended daily dosage in pediatric patients up to 40 kg in weight for uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, pneumonia, and as empiric therapy for febrile neutropenic patients is 50 mg/kg, administered q 12h (q8h for febrile neutropenic patients), for durations as given above."

Impaired Renal Function: Text added as last paragraph in subsection -

"Data in pediatric patients with impaired renal function are not available; however, since cefepime pharmacokinetics are similar in adults and pediatric patients (see CLINICAL PHARMACOLOGY), changes in dosing regimen similar to those in adults (see Table 13) are recommended for pediatric patients."

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WARNINGS:

Text added as new first paragraph -

"Amplification of the vasodilatory effects of Monoket/Dilatrate-SR by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion."

WARNINGS:

Text added as new first paragraph -

"Amplification of the vasodilatory effects of Nitrolingual by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion."

PRECAUTIONS:

Information for Patients (new subsection): "Physicians should discuss with patients the contraindication of Nitrolingual Spray with concurrent sildenafil (Viagra)."

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PRECAUTIONS:

Information for Patients: First sentence, second paragraph revised (new text in italics) -

"For patients who have difficulty swallowing capsules, Prevacid Delayed-Release Capsules can be opened, and the intact granules contained within can be sprinkled on one tablespoon of either applesauce, Ensure, pudding, cottage cheese or yogurt and swallowed immediately."

DOSAGE AND ADMINISTRATION:

Next to last paragraph, third sentence revised (new text in italics) -

"For patients who have difficulty swallowing capsules, Prevacid Delayed-Release Capsules can be opened, and the intact granules contained within can be sprinkled on one tablespoon of either applesauce, Ensure, pudding, cottage cheese or yogurt and swallowed immediately."

CLINICAL PHARMACOLOGY:

Second paragraph, text added as new third sentence -

"Succinylcholine levels were reported to be below the detection limit of 2 ug/mL after 2.5 minutes of an IV bolus dose of 1 or 2 mg/kg in fourteen (14) anesthetized patients."

PRECAUTIONS:

Pediatric Use (new subsection): "Safety and effectiveness of succinylcholine have been established in pediatric patient age groups, neonate to adolescent. There are rare reports of ventricular dysrhythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients who receive succinylcholine (see BOX WARNING). Many of these pediatric patients were subsequently found to have a skeletal muscle myopathy such as Duchenne's muscular dystrophy whose clinical signs were not obvious. The syndrome often presents as sudden cardiac arrest within minutes after the administration of succinylcholine. These pediatric patients are usually, but not exclusively, males, and most frequently 8 years of age or younger. There have also been reports in adolescents. There may be no signs or symptoms to alert the practitioner to which pediatric patients are at risk. A careful history and physical may identify developmental delays suggestive of a myopathy. A preoperative creatine kinase could identify some but not all pediatric patients at risk. Due to the abrupt onset of this syndrome, routine resuscitative measures are likely to be unsuccessful. Careful monitoring of the electrocardiogram may alert the practitioner to peaked T-waves (an early sign). Administration of intravenous calcium, bicarbonate, and glucose with insulin, with hyperventilation have resulted in successful resuscitation in some of the reported cases. Extraordinary and prolonged resuscitative efforts have been effective in some cases. In addition, in the presence of signs of malignant hyperthermia, appropriate treatment should be initiated concurrently (see WARNINGS). Since it is diffficult to identify which pediatric patients are at risk, it is recommended that the use of succinylcholine in pediatric patients should be reserved for emergency intubation or instances where immediate securing of the airway is necessary, e.g., laryngospasm, difficult airway, full stomach, or for intramuscular use when a suitable vein is inaccessible.

"As in adults, the incidence of bradycardia in pediatric patients is higher following the second dose of succinylcholine. The incidence and severity of bradycardia is higher in pediatric patients than adults. Pre-treatment with anticholinergic agents, e.g., atropine, may reduce the occurrence of bradyarrhythmias."

Geriatric Use (new subsection): "Clinical studies of Quelicin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy."

WARNINGS:

Text added as new first paragraph -

"Amplification of the vasodilatory effects of Sorbitrate by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction has not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion."

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ADVERSE REACTIONS:

Postintroduction Reports (new subsection):

"Adverse events reported since market introduction which were temporally (but not necessarily causally) related to Zyprexa therapy include the following: priapism."