Download PLR Article Directory Arizona: June 2012

Wednesday, 27 June 2012

Flagyl 375 Capsules

metronidazole

Dosage Form: capsule
FLAGYL® 375

metronidazole capsules

To reduce the development of drug-resistant bacteria and maintain the effectiveness of FLAGYL® 375 and other antibacterial drugs, FLAGYL 375 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Warning

Metronidazole has been shown to be carcinogenic in mice and rats. (See PRECAUTIONS.) Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the INDICATIONS AND USAGE section below.

Flagyl 375 Capsules Description

Metronidazole is an oral synthetic antiprotozoal and antibacterial agent, 2-methyl-5-nitroimidazole-1-ethanol, which has the following structural formula:

Flagyl 375 Capsules contain 375 mg of metronidazole USP. Inactive ingredients include corn starch, magnesium stearate, gelatin, black iron oxide, titanium dioxide, FD&C Green No. 3, and D&C Yellow No. 10.

Flagyl 375 Capsules - Clinical Pharmacology

Disposition of metronidazole in the body is similar for both oral and intravenous dosage forms, with an average elimination half-life in healthy humans of 8 hours.

The major route of elimination of metronidazole and its metabolites is via the urine (60% to 80% of the dose), with fecal excretion accounting for 6% to 15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation [1-(β-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid] and glucuronide conjugation, with unchanged metronidazole accounting for approximately 20% of the total. Renal clearance of metronidazole is approximately 10 mL/min/1.73 m2.

Metronidazole is the major component appearing in the plasma, with lesser quantities of the 2-hydroxymethyl metabolite also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria and in vitro trichomonacidal activity.

Metronidazole appears in cerebrospinal fluid, saliva, and human milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.

Flagyl 375 Capsules have been shown to have a rate and extent of absorption similar to metronidazole tablets (FLAGYL) and were bioequivalent at an equal single dose of 750 mg. In a study conducted with 23 adult healthy female volunteers, oral administration of two 375-mg FLAGYL capsules under fasted conditions produced a mean (±1 SD) peak plasma concentration (Cmax) of 21.4 (±2.8) mcg/mL with a mean Tmax of 1.6 (± 0.7) hours and a mean area under the plasma concentration-time curve (AUC) of 223 (±44) mcg∙hr/mL. In the same study, three 250-mg FLAGYL tablets produced a mean Cmax of 20.4 (± 3.8) mcg/mL with a mean Tmax of 1.4 (± 0.4) hours and a mean AUC of 218 (± 50) mcg∙hr/mL.

Administration of Flagyl 375 Capsules with food does not affect the extent of absorption of metronidazole; however, the presence of food results in a lower Cmax and a delayed Tmax compared to fasted conditions. In a study of 14 healthy adult female volunteers, administration of Flagyl 375 Capsules under fasting conditions produced a mean Cmax of 10.9 (± 1.5) mcg/mL, a mean Tmax of 1.5 (± 1.4) hours, and a mean AUC of 110 (± 34) mcg∙hr/mL compared to a mean Cmax of 8.6 (± 1.6) mcg/mL, a mean Tmax of 4.2 (± 1.7) hours, and a mean AUC of 99 (± 14) mcg∙hr/mL under fed conditions.

Decreased renal function does not alter the single-dose pharmacokinetics of metronidazole. However, plasma clearance of metronidazole is decreased in patients with decreased liver function.

Microbiology

Metronidazole exerts antimicrobial effects in an anaerobic environment by the following possible mechanism: Once metronidazole enters the organism, the drug is reduced by intracellular electron transport proteins. Because of this alteration to the metronidazole molecule, a concentration gradient is maintained, which promotes the drug's intracellular transport. Presumably, free radicals are formed which, in turn, react with cellular components resulting in death of the microorganism.

Metronidazole has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive anaerobes:

Clostridium species

Eubacterium species

Peptococcus niger

Peptostreptococcus species

Gram-negative anaerobes:

Bacteroides

fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B.vulgatus)

Fusobacterium species

Protozoal parasites:

Entamoeba histolytica

Trichomonas vaginalis

The following in vitro data are available, but their clinical significance is unknown:

Metronidazole exhibits in vitro minimum inhibitory concentrations (MICs) of 8 µg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of metronidazole in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Gram-negative anaerobes:

Bacteroides fragilis group (B. caccae, B. uniformis)

Prevotella species (P. bivia, P. buccae, P. disiens); Metronidazole is active against most obligate anaerobes, but does not possess any clinically relevant activity against facultative anaerobes or obligate aerobes.

Susceptibility Tests

Dilution techniques

Quantitative methods that are used to determine minimum inhibitory concentrations provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. For anaerobic bacteria, the susceptibility to metronidazole can be determined by the reference agar dilution method or by alternate standardized test methods1. The MIC values obtained should be interpreted according to the following criteria:

MIC (µg/mL)	Interpretation
≤ 8	Susceptible (S)
16	Intermediate (I)
≥ 32	Resistant (R)

For protozoal parasites: Standardized tests do not exist for use in clinical microbiology laboratories.

A report of "Susceptible" indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in the blood. A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. Standard metronidazole powder should provide the following MIC values:

Microorganism	MIC (µg/mL)
Bacteroides fragilis	0.25–1.0
ATCC 25285
Bacteroides thetaiotaomicron	0.5–2.0
ATCC 29741

Indications and Usage for Flagyl 375 Capsules

Symptomatic Trichomoniasis. Flagyl 375 Capsules are indicated for the treatment of symptomatic trichomoniasis in females and males when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures).

Asymptomatic Trichomoniasis. Flagyl 375 Capsules are indicated in the treatment of asymptomatic females when the organism is associated with endocervicitis, cervicitis, or cervical erosion. Since there is evidence that presence of the trichomonad can interfere with accurate assessment of abnormal cytological smears, additional smears should be performed after eradication of the parasite.

Treatment of Asymptomatic Consorts. T. vaginalis infection is a venereal disease. Therefore, asymptomatic sexual partners of treated patients should be treated simultaneously if the organism has been found to be present, in order to prevent reinfection of the partner. The decision as to whether to treat an asymptomatic male partner who has a negative culture or one for whom no culture has been attempted is an individual one. In making this decision, it should be noted that there is evidence that a woman may become reinfected if her consort is not treated. Also, since there can be considerable difficulty in isolating the organism from the asymptomatic male carrier, negative smears and cultures cannot be relied upon in this regard. In any event, the consort should be treated with metronidazole in cases of reinfection.

Amebiasis. Flagyl 375 Capsules are indicated in the treatment of acute intestinal amebiasis (amebic dysentery) and amebic liver abscess.

In amebic liver abscess, metronidazole therapy does not obviate the need for aspiration or drainage of pus.

Anaerobic Bacterial Infections. Flagyl 375 Capsules are indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with metronidazole therapy. In a mixed aerobic and anaerobic infection, antimicrobials appropriate for the treatment of the aerobic infection should be used in addition to Flagyl 375 Capsules.

In the treatment of most serious anaerobic infections, intravenous metronidazole is usually administered initially. This may be followed by oral therapy with Flagyl 375 Capsules at the discretion of the physician.

INTRA-ABDOMINAL INFECTIONS, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species including the B. fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus), Clostridium species, Eubacterium species, Peptococcus niger, or Peptostreptococcus species.

SKIN AND SKIN STRUCTURE INFECTIONS caused by Bacteroides species including the B. fragilis group, Clostridium species, Peptococcus niger, Peptostreptococcus species, or Fusobacterium species.

GYNECOLOGIC INFECTIONS, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection, caused by Bacteroides species including the B. fragilis group, Clostridium species, Peptococcus niger, or Peptostreptococcus species.

BACTERIAL SEPTICEMIA caused by Bacteroides species including the B. fragilis group or Clostridium species.

BONE AND JOINT INFECTIONS (as adjunctive therapy) caused by Bacteroides species including the B. fragilis group.

CENTRAL NERVOUS SYSTEM (CNS) INFECTIONS, including meningitis and brain abscess, caused by Bacteroides species including the B. fragilis group.

LOWER RESPIRATORY TRACT INFECTIONS, including pneumonia, empyema, and lung abscess, caused by Bacteroides species including the B. fragilis group.

ENDOCARDITIS caused by Bacteroides species including the B. fragilis group.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of FLAGYL 375 and other antibacterial drugs, FLAGYL 375 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Contraindications

Flagyl 375 Capsules are contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.

In patients with trichomoniasis, Flagyl 375 Capsules are contraindicated during the first trimester of pregnancy. (See PRECAUTIONS.)

Warnings

Central and Peripheral Nervous System Effects

Convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with metronidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of metronidazole therapy. Metronidazole should be administered with caution to patients with central nervous system diseases.

Precautions

General

Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously.

Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with metronidazole and requires treatment with a candidacidal agent.

Prescribing FLAGYL 375 in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for patients

Alcoholic beverages should be avoided while taking Flagyl 375 Capsules and for at least three days afterward. (See PRECAUTIONS-Drug interactions.)

Patients should be counseled that antibacterial drugs including FLAGYL 375 should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When FLAGYL 375 is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by FLAGYL 375 or other antibacterial drugs in the future.

Laboratory tests

Metronidazole is a nitroimidazole and should be used with caution in patients with evidence of, or history of, blood dyscrasia. A mild leukopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to metronidazole have been observed in clinical studies. Total and differential leukocyte counts are recommended before and after therapy for trichomoniasis and amebiasis, especially if a second course of therapy is necessary, and before and after therapy for anaerobic infections.

Drug interactions

Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. This possible drug interaction should be considered when metronidazole is prescribed for patients on this type of anticoagulant therapy.

The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.

The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole. In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Serum lithium and serum creatinine levels should be obtained several days after beginning metronidazole to detect any increase that may precede clinical symptoms of lithium intoxication.

Alcoholic beverages should not be consumed during metronidazole therapy and for at least three days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.

Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last 2 weeks.

Drug/Laboratory test interactions

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD+

Carcinogenesis, mutagenesis, impairment of fertility

Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic, oral administration in mice and rats, but similar studies in the hamster gave negative results.

Prominent among the effects in the mouse was the promotion of pulmonary tumorigenesis. This has been observed in all six reported studies in that species, including one study in which the animals were dosed on an intermittent schedule (administration during every fourth week only). At very high dose levels (approximately 1500 mg/m2 which is approximately 3 times the most frequently recommended human dose for a 50 kg adult based on mg/m2), there was a statistically significant increase in the incidence of malignant liver tumors in males. Also, the published results of one of the mouse studies indicate an increase in the incidence of malignant lymphomas as well as pulmonary neoplasms associated with lifetime feeding of the drug. All these effects are statistically significant.

Several long-term, oral-dosing studies in the rat have been completed. There were statistically significant increases in the incidence of various neoplasms, particularly in mammary and hepatic tumors, among female rats administered metronidazole over those noted in the concurrent female control groups.

Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative.

Metronidazole has shown mutagenic activity in a number of in vitro assay systems. In vivo studies have failed to demonstrate a potential for genetic damage.

Fertility studies have been performed in mice at doses up to six times the maximum recommended human dose based on mg/m2 and have revealed no evidence of impaired fertility.

Pregnancy

Teratogenic effects: Pregnancy Category B

Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Reproduction studies have been performed in rats at doses up to five times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to metronidazole. No fetotoxicity was observed when metronidazole was administered orally to pregnant mice at 60 mg/m2/day, which is approximately 10% of the human dose when expressed as mg/m2. However, in a single small study in which the drug was administered intraperitoneally, some intrauterine deaths were observed. The relationship of these findings to the drug is unknown. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed. (See CONTRAINDICATIONS.)

Metronidazole use in the second and third trimesters of pregnancy should be restricted to those patients for whom alternative treatment has been inadequate. Use of metronidazole in the first trimester should be carefully evaluated because metronidazole crosses the placental barrier and its effects on human fetal organogenesis are not known. (See above.)

Nursing mothers

Because of the potential for tumorigenicity shown for metronidazole in mouse and rat studies, 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. Metronidazole is secreted in human milk in concentrations similar to those found in plasma.

Geriatric use

Decreased renal function does not alter the single-dose pharmacokinetics of metronidazole. However, plasma clearance of metronidazole is decreased in patients with decreased liver function. Therefore, in elderly patients, monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

Pediatric use

Safety and effectiveness in pediatric patients have not been established, except in the treatment of amebiasis.

Adverse Reactions

The following reactions have also been reported during treatment with metronidazole:

Central Nervous System: The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of metronidazole, patients should be specifically warned about these reactions and should be told to stop the drug and report immediately to their physicians if any neurologic symptoms occur. In addition, patients have reported dizziness, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia. (See WARNINGS.)

Gastrointestinal: The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea reported by about 12% of patients, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; and abdominal cramping. Constipation has also been reported.

A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy. Rare cases of pancreatitis, which generally abated on withdrawal of the drug, have been reported.

Hematopoietic: Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.

Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings.

Hypersensitivity: Urticaria, erythematous rash, Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever.

Renal: Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance.

Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling "serum sickness." If patients receiving metronidazole drink alcoholic beverages, they may experience abdominal distress, nausea, vomiting, flushing, or headache. A modification of the taste of alcoholic beverages has also been reported.

Patients with Crohn's disease are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn's disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established. Crohn's disease is not an approved indication for Flagyl 375 Capsules.

Overdosage

Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported include nausea, vomiting, and ataxia.

Oral metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to 10.4 g every other day.

Treatment

There is no specific antidote for metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.

Flagyl 375 Capsules Dosage and Administration

In elderly patients, the pharmacokinetics of metronidazole may be altered, and, therefore, monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

Trichomoniasis

In the Female

Seven-day course of treatment—375 mg two times daily for seven consecutive days.

A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain treatment. Pregnant patients should not be treated during the first trimester. (See CONTRAINDICATIONS and PRECAUTIONS.)

When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and that the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leukocyte counts should be made before and after re-treatments.

In the Male

Treatment should be individualized as it is for the female.

Amebiasis

Adults

For acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days.

For amebic liver abscess: 750 mg orally three times daily for 5 to 10 days.

Pediatric patients: 35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days.

Anaerobic Bacterial Infections

In the treatment of most serious anaerobic infections, intravenous metronidazole is usually administered initially.

The usual adult oral dosage is 7.5 mg/kg every 6 hours. A maximum of 4 g should not be exceeded during a 24-hour period.

The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.

The dose of metronidazole should not be specifically reduced in anuric patients because accumulated metabolites may be rapidly removed by dialysis.

How is Flagyl 375 Capsules Supplied

Flagyl 375 Capsules have an iron gray opaque body imprinted with 375 mg and a light green opaque cap imprinted with FLAGYL, supplied as:

NDC Number Size

0025-1942-50 Bottle of 50

Storage and Stability

Store at controlled room temperature 15–25°C (59–77°F). Dispense in a well-closed container with a child-resistant closure.

REFERENCES

1.: National Committee for Clinical Laboratory Standards, Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria – Third Edition. Approved Standard NCCLS Document M11-A3, Vol. 13, No. 26, NCCLS, Villanova, PA, December, 1993.
2.: Ralph ED, Kirby WMM. Bioassay of metronidazole with either anaerobic or aerobic incubation, J. Infect. Dis. 1975; 132 (Nov): 587–591 or Gulaid et al. Determination of metronidazole and its major metabolites in biological fluids by high pressure liquid chromatography, Br. J. Clin. Pharmacol. 1978; 6:430–432.

Rx only

LAB-0163-7.0

April 2010

PRINCIPAL DISPLAY PANEL - 50 Capsule Bottle Label

NDC 0025-1942-50

50 Capsules

Rx only

Flagyl® 375

metronidazole

capsules

375 mg

Pfizer

Distributed by

G.D. Searle LLC

Division of Pfizer Inc, NY, NY 10017

FLAGYL
metronidazole capsule

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	0025-1942
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
metronidazole (metronidazole)	metronidazole	375 mg

Inactive Ingredients
Ingredient Name	Strength
starch, corn
magnesium stearate
gelatin
ferrosoferric oxide
titanium dioxide
FD&C Green No. 3
D&C Yellow No. 10

Product Characteristics
Color	GRAY (iron gray opaque) , GREEN (light green opaque)	Score	no score
Shape	CAPSULE	Size	19mm
Flavor		Imprint Code	FLAGYL;375;mg
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	0025-1942-50	50 CAPSULE In 1 BOTTLE	None
2	0025-1942-34	100 CAPSULE In 1 BOX, UNIT-DOSE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA020334	05/03/1995

Labeler - G.D. Searle LLC (829077085)

Establishment
Name	Address	ID/FEI	Operations
Pfizer Pharmaceuticals LLC		193684656	MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Farchemia S.R.L.		438743601	API MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Warner Lambert Company LLC		001344506	ANALYSIS

Revised: 02/2011G.D. Searle LLC

More Flagyl 375 Capsules resources

Flagyl 375 Capsules Side Effects (in more detail)
Flagyl 375 Capsules Dosage
Flagyl 375 Capsules Use in Pregnancy & Breastfeeding
Drug Images
Flagyl 375 Capsules Drug Interactions
Flagyl 375 Capsules Support Group
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Compare Flagyl 375 Capsules with other medications

Amebiasis
Aspiration Pneumonia
Bacteremia
Bacterial Infection
Bone infection
Clostridial Infection
Crohn's Disease, Acute
Crohn's Disease, Maintenance
Deep Neck Infection
Dental Abscess
Diverticulitis
Dracunculiasis
Endocarditis
Giardiasis
Helicobacter Pylori Infection
Intraabdominal Infection
Joint Infection
Meningitis
Pelvic Inflammatory Disease
Peritonitis
Pneumonia
Pseudomembranous Colitis
Skin Infection
Surgical Prophylaxis
Trichomoniasis

Saturday, 23 June 2012

Boots Dual Action Athlete's Foot Spray

Boots Dual Action Athlete’s Foot Spray

(Tolnaftate)

Effectively treats athlete’s foot

Relieves skin irritation

Fast drying

150 ml e

Read all of this label for full instructions.

What this medicine is for

An anti-fungal spray for the treatment and prevention of athlete’s foot. Also effective for other skin conditions where tenderness and sweating cause skin irritation, such as dhobie itch (groin ringworm), prickly heat.

Before you use this medicine

Do not use:

If you are allergic to any of the ingredients

You can use this medicine if you are pregnant or breastfeeding.

How to use this medicine

Shake well before use. Hold the can 15 cm (6 inches) from the skin before spraying.

Wash and thoroughly dry the affected area

Spray the affected area liberally

If suffering from athlete’s foot, spray the socks and inside of shoes with powder as well

Adults and children of 2 years and over:

Apply morning and night.

Continue treatment for at least one week after the condition has cleared up, to stop it coming back.

For use on the skin only.

Avoid contact with eyes.

Do not use on children under 2 years, unless your doctor tells you to.

If symptoms worsen talk to your doctor.

If symptoms do not go away within 10 days, talk to your doctor.

Possible side effects

Most people will not have problems, but some may get some.

If you get any of these stop using the spray and see a doctor:

Skin irritation

Contact dermatitis (redness and swelling of the skin)

If you notice any side effect not listed here, please tell your pharmacist or doctor.

Do not store above 25°C.

Keep all medicines out of the sight and reach of children.

Use by the date on the base of can.

Active ingredients

This spray powder contains Tolnaftate 1% w/w.

Also contains: dimethyl ether, denatured alcohol, talc, disteardimonium hectorite.

PL 00014/0520

Text prepared 8/07

Manufactured for the Marketing Authorisation holder

The Boots Company PLC

Nottingham

NG2 3AA

ColepCCL UK Limited

Atkinson’s Way

Foxhills Industrial Park

Scunthorpe

North Lincolnshire

DN15 8QJ

Caution: Pressurised container. Protect from sunlight and do not expose to temperatures exceeding 50°C. Do not pierce or burn even when empty. Do not use in confined areas. Do not use near or place on painted or polished surfaces. Avoid inhalation.

EXTREMELY FLAMMABLE

SOLVENT ABUSE CAN KILL INSTANTLY

210

Do not spray on or near naked flame or any incandescent material.

Keep away from sources of ignition. No smoking.

If you need more advice ask your pharmacist.

BTC29774 vA 14/04/08

Atgam

equine thymocyte immune globulin

Dosage Form: injection, solution
Atgam®

(lymphocyte immune globulin,

anti-thymocyte globulin [equine] sterile solution)

For Intravenous Use Only

Warning

Only physicians experienced in immunosuppressive therapy in the treatment of renal transplant or aplastic anemia patients should use Atgam.

Patients receiving Atgam should be treated in facilities equipped and staffed with adequate laboratory and supportive medical resources.

Atgam Description

Atgam Sterile Solution contains lymphocyte immune globulin, anti-thymocyte globulin [equine]. It is the purified, concentrated, and sterile gamma globulin, primarily monomeric IgG, from hyperimmune serum of horses immunized with human thymus lymphocytes. Atgam is a transparent to slightly opalescent aqueous protein solution. It may appear colorless to faintly pink or brown and is nearly odorless. It may develop a slight granular or flaky deposit during storage. (For information about in-line filters, see Infusion Instructions in the DOSAGE AND ADMINISTRATION SECTION.)

Before release for clinical use, each lot of Atgam is tested to assure its ability to inhibit rosette formation between human peripheral lymphocytes and sheep red blood cells in vitro. In each lot, antibody activity against human red blood cells and platelets is also measured and determined to be within acceptable limits. Only lots that test negative for antihuman serum protein antibody, antiglomerular basement membrane antibody and pyrogens are released.

Each milliliter of Atgam contains 50 mg of horse gamma globulin stabilized in 0.3 molar glycine to a pH of approximately 6.8.

CLINICAL AND ANIMAL PHARMACOLOGY

Atgam Sterile Solution is a lymphocyte-selective immunosuppressant as is demonstrated by its ability to reduce the number of circulating, thymus-dependent lymphocytes that form rosettes with sheep erythrocytes. This antilymphocytic effect is believed to reflect an alteration of the function of the T lymphocytes, which are responsible in part for cell-mediated immunity and are involved in humoral immunity. In addition to its antilymphocytic activity, Atgam contains low concentrations of antibodies against other formed elements of the blood. In rhesus and cynomolgus monkeys, Atgam reduces lymphocytes in the thymus-dependent areas of the spleen and lymph nodes. It also decreases the circulating sheep-erythrocyte-rosetting lymphocytes that can be detected, but ordinarily Atgam does not cause severe lymphopenia.

In general, when Atgam is given with other immunosuppressive therapy, such as antimetabolites and corticosteroids, the patient's own antibody response to horse gamma globulin is minimal. In a small clinical study, Atgam administered with other immunosuppressive therapy and measured as horse IgG had a serum half-life of 5.7±3 days.

Indications and Usage for Atgam

Renal Transplantation

Atgam Sterile Solution is indicated for the management of allograft rejection in renal transplant patients. When administered with conventional therapy at the time of rejection, it increases the frequency of resolution of the acute rejection episode. The drug has also been administered as an adjunct to other immunosuppressive therapy to delay the onset of the first rejection episode. Data accumulated to date have not consistently demonstrated improvement in functional graft survival associated with therapy to delay the onset of the first rejection episode.

Aplastic Anemia

Atgam is indicated for the treatment of moderate to severe aplastic anemia in patients who are unsuitable for bone marrow transplantation.

When administered with a regimen of supportive care, Atgam may induce partial or complete hematologic remission. In a controlled trial, patients receiving Atgam showed a statistically significantly higher improvement rate compared with standard supportive care at 3 months. Improvement was defined in terms of sustained increase in peripheral blood counts and reduced transfusion needs.

Clinical trials conducted at two centers evaluated the 1-year survival rate for patients with severe and moderate to severe aplastic anemia. Seventy-four of the 83 patients enrolled were evaluable based on response to treatment. The treatment groups studied consisted of 1) Atgam and supportive care, 2) Atgam administered following 3 months of supportive care alone, 3) Atgam, mismatched marrow infusion, androgens, and supportive care, or 4) Atgam, androgens, and supportive care. There were no statistically significant differences between the treatment groups. The 1-year survival rate for the pooled treatment groups was 69#. These survival results can be compared with a historical survival rate of about 25# for patients receiving standard supportive care alone.

The usefulness of Atgam has not been demonstrated in patients with aplastic anemia who are suitable candidates for bone marrow transplantation or in patients with aplastic anemia secondary to neoplastic disease, storage disease, myelofibrosis, Fanconi's syndrome, or in patients known to have been exposed to myelotoxic agents or radiation.

To date, safety and efficacy have not been established in circumstances other than renal transplantation and aplastic anemia.

Skin Testing

Before the first infusion of Atgam, Pharmacia &Upjohn Company strongly recommends that patients be tested with an intradermal injection of 0.1 mL of a 1:1,000 dilution (5 µg horse IgG) of Atgam in sodium chloride injection, USP and a contralateral sodium chloride injection control. Use only freshly diluted Atgam for skin testing. The patient, and specifically the skin test, should be observed every 15 to 20 minutes over the first hour after intradermal injection. A local reaction of 10 mm or greater with a wheal or erythema, or both, with or without pseudopod formation and itching or a marked local swelling should be considered a positive test. Note: The predictive value of this test has not been proved clinically. Allergic reactions such as anaphylaxis have occurred in patients whose skin test is negative. In the presence of a locally positive skin test to Atgam, serious consideration to alternative forms of therapy should be given. The risk to benefit ratio must be carefully weighed. If therapy with Atgam is deemed appropriate following a locally positive skin test, treatment should be administered in a setting where intensive life support facilities are immediately available and with a physician familiar with the treatment of potentially life threatening allergic reactions in attendance.

A systemic reaction such as a generalized rash, tachycardia, dyspnea, hypotension, or anaphylaxis precludes any additional administration of Atgam.

SEE WARNINGS, PRECAUTIONS, AND ADVERSE REACTIONS.

Contraindications

Do not administer Atgam Sterile Solution to a patient who has had a severe systemic reaction during prior administration of Atgam or any other equine gamma globulin preparation.

Warnings

Only physicians experienced in immunosuppressive therapy in the treatment of renal transplant or aplastic anemia patients should use Atgam.

Patients receiving Atgam should be treated in facilities equipped and staffed with adequate laboratory and supportive medical resources.

Precise methods of determining the potency of Atgam have not been established, thus activity may potentially vary from lot to lot.

Discontinue treatment with Atgam if any of the following occurs:

Symptoms of anaphylaxis (See ADVERSE REACTIONS)

Severe and unremitting thrombocytopenia in renal transplant patients

Severe and unremitting leukopenia in renal transplant patients

Because this product is made using equine and human blood components, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Precautions

General

Because Atgam Sterile Solution is an immunosuppressive agent ordinarily given with corticosteroids and antimetabolites, watch patients carefully for signs of leukopenia, thrombocytopenia, or concurrent infection. Several studies have suggested an increase in the incidence of cytomegalovirus infection in patients receiving Atgam(1). In one study it has been found that it may be possible to reduce this risk by decreasing the dosage of other immunosuppressive agents administered concomitantly with Atgam. If infection occurs, institute appropriate adjunctive therapy promptly. On the basis of the clinical circumstances, a physician should decide whether or not therapy with Atgam will continue.

The safety and effectiveness of Atgam have been demonstrated only in renal transplant patients who received concomitant immunosuppressive therapy and in patients with aplastic anemia.

Dilution of Atgam in dextrose injection, USP, is not recommended, as low salt concentrations may result in precipitation. The use of highly acidic infusion solutions is also not recommended because of possible physical instability over time.

Drug Interactions

When the dose of corticosteroids and other immunosuppressants is being reduced, some previously masked reactions to Atgam may appear. Under these circumstances, observe patients especially carefully during therapy with Atgam.

Pregnancy

Pregnancy category C

Atgam has not been evaluated in either pregnant or lactating women. Animal reproduction studies have not been conducted with Atgam. It is also not known whether Atgam can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Administration of Atgam to pregnant women is not recommended and should be considered only under exceptional circumstances.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious advers e reactions in nursing infants from Atgam Sterile Solution, caution should be exercised when Atgam is administered to a nursing woman.

Pediatric Use

Experience with children has been limited. Atgam has been administered safely to a small number of pediatric renal allograft recipients and pediatric aplastic anemia patients at dosage levels comparable to those in adults.

Adverse Reactions

Renal Transplantation

The primary clinical experience with Atgam Sterile Solution has been in renal allograft patients who were also receiving concurrent standard immunosuppressive therapy (azathioprine, corticosteroids). In controlled trials, investigators frequently reported the following adverse reactions: fever in 1 patient in 3; chills in 1 patient in 7; leukopenia in 1 patient in 7; thrombocytopenia in 1 patient in 9; and dermatologic reactions, such as rash, pruritus, urticaria, wheal, and flare, in 1 patient in 8. The following reactions were reported in more than 1# but less than 5# of the patients: arthralgia; chest or back pain, or both; clotted A/V fistula; diarrhea; dyspnea; headache; hypotension; nausea or vomiting, or both; night sweats; pain at the infusion site; peripheral thrombophlebitis; and stomatitis.

Reactions reported in less than 1# of the patients in the controlled trials were anaphylaxis, dizziness, weakness or faintness, edema, herpes simplex reactivation, hiccoughs or epigastric pain, hyperglycemia, hypertension, iliac vein obstruction, laryngospasm, localized infection, lymphadenopathy, malaise, myalgia, paresthesia, possible serum sickness, pulmonary edema, renal artery thrombosis, seizures, systemic infection, tachycardia, toxic epidermal necrosis, and wound dehiscence.

Aplastic Anemia

In premarketing clinical trials with Atgam in the treatment of aplastic anemia, patients were also being concurrently managed with support therapy (transfusions, steroids, antibiotics, antihistamines).

In these trials most patients experienced fever and skin reactions. Other frequently reported adverse reactions were chills, 1 patient in 2; arthralgia, 1 patient in 2; headache, 1 patient in 6; myalgia, 1 patient in 10; nausea, 1 patient in 15; chest pain, 1 patient in 15 and phlebitis, 1 patient in 20.

The following reactions were reported by at least one patient and less than 5# of the total patients: diaphoresis, joint stiffness, periorbital edema, aches, edema, muscle ache, vomiting, agitation/lethargy, listlessness, light-headedness, seizures, diarrhea, bradycardia, myocarditis, cardiac irregularity, hepatosplenomegaly, possible encephalitis or post viral encephalopathy, hypotension, congestive heart failure, hypertension, burning soles/palms, foot sole pain, lymphadenopathy, post-cervical lymphadenopathy, tender lymph nodes, bilateral pleural effusion, respiratory distress, anaphylactic reaction, and proteinuria.

In other support studies in patients with aplastic anemia and other hematologic abnormalities who have received Atgam, abnormal tests of liver function (SGOT, SGPT, alkaline phosphatase) and renal function (serum creatinine) have been observed. In some trials, clinical and laboratory findings of serum sickness were seen in a majority of patients.

Postmarketing Experience

During approximately 5 years of post approval marketing experience, the frequency of adverse reactions in voluntarily reported cases is as follows: fever 51#; chills 16#; thrombocytopenia 30#; leukopenia 14#; rashes 27#; systemic infection 13#. Events reported in 5# to 10# of reported cases include abnormal renal function tests; serum sickness-like symptoms; dyspnea/apnea; arthralgia; chest, back, or flank pain; diarrhea and nausea and/or vomiting. Events reported with a frequency of less than 5# include: hypertension, Herpes Simplex infection, pain, swelling or redness at infusion site, eosinophilia, headache, myalgias, or leg pains, hypotension, anaphylaxis, tachycardia, edema, localized infection, malaise, seizures, GI bleeding or perforation, deep vein thrombosis, sore mouth/throat, hyperglycemia, acute renal failure, abnormal liver function tests, confusion or disorientation, cough, neutropenia or granulocytopenia, anemia, thrombophlebitis, dizziness, epigastric or stomach pain, lymphadenopathy, pulmonary edema or congestive heart failure, abdominal pain, nosebleed, vasculitis, aplasia or pancytopenia, abnormal involuntary movement or tremor, rigidity, sweating, laryngospasm/edema, hemolysis or hemolytic anemia, viral hepatitis, faintness, enlarged or ruptured kidney, paresthesias, and renal artery thrombosis.

The recommended management for some of the adverse reactions that could occur with treatment with Atgam follows:

Anaphylaxis is uncommon but serious and may occur at any time during therapy with Atgam. Stop infusion of Atgam immediately; administer 0.3 mL aqueous epinephrine (1:1,000 solution) intramuscularly. Administer steroids; assist respiration; and provide other resuscitative measures. DO NOT resume therapy with Atgam.

Hemolysis can usually be detected only in the laboratory. Clinically significant hemolysis has been reported rarely. Appropriate treatment of hemolysis may include transfusion of erythrocytes; if necessary, administer intravenous mannitol, furosemide, sodium bicarbonate, and fluids. Severe and unremitting hemolysis may require discontinuation of therapy with Atgam.

Thrombocytopenia is usually transient in renal transplant patients; platelet counts generally return to adequate levels without discontinuing therapy with Atgam. Platelet transfusions may be necessary in patients with aplastic anemia. (See PRECAUTIONS, WARNINGS, and DOSAGE AND ADMINISTRATION.)

Respiratory distress may indicate an anaphylactoid reaction. Discontinue infusion of Atgam. If distress persists, administer an antihistamine, epinephrine, corticosteroids, or some combination of the three.

Pain in chest, flank, or back may indicate anaphylaxis or hemolysis. Treatment is that indicated above for those conditions.

Hypotension may indicate anaphylaxis. Stop infusion of Atgam and stabilize blood pressure with pressors if necessary.

Chills and fever occur frequently in patients receiving Atgam. Atgam may release endogenous leukocyte pyrogens. Prophylactic and/or therapeutic administration of antihistamines, antipyretics, or corticosteroids generally controls this reaction.

Chemical phlebitis can be caused by infusion of Atgam through peripheral veins. This can often be avoided by administering the infusion solution into a high-flow vein. A subcutaneous arterialized vein produced by a Brescia fistula is also a useful administration site.

Itching and erythema probably result from the effect of Atgam on blood elements. Antihistamines generally control the symptoms.

Serum sickness-like symptoms in aplastic anemia patients have been treated with oral or IV corticosteroids. Resolution of symptoms has generally been prompt and long-term sequelae have not been observed. Prophylactic administration of corticosteroids may decrease the frequency of this reaction.

Overdosage

Because of its mode of action and because it is a biologic substance, the maximal tolerated dose of Atgam Sterile Solution would be expected to vary from patient to patient. To date, the largest single daily dose administered to a patient, a renal transplant recipient, was 7,000 mg administered at a concentration of approximately 10 mg/mL Sodium Chloride Injection, USP, approximately seven times the recommended total dose and infusion concentration. In this patient, administration of Atgam was not associated with any signs of acute intoxication.

The greatest number of doses (10 to 20 mg/kg/dose) that can be administered to a single patient has not yet been determined. Some renal transplant patients have received up to 50 doses in 4 months, and others have received 28-day courses of 21 doses followed by as many as three more courses for the treatment of acute rejection. The incidence of toxicologic manifestations did not increase with any of these regimens.

Atgam Dosage and Administration

Renal Allograft Recipients

Adult renal allograft patients have received Atgam Sterile Solution at the dosage of 10 to 30 mg/kg of body weight daily. The few children studied received 5 to 25 mg/kg daily. Atgam has been used to delay the onset of the first rejection episode(2–5) and at the time of the first rejectionepisode.(6–10) Most patients who received Atgam for the treatment of acute rejection had not received it starting at the time of transplantation.

Usually, Atgam is used concomitantly with azathioprine and corticosteroids, which are commonly used to suppress the immune response. Exercise caution during repeat courses of Atgam; carefully observe patients for signs of allergic reactions.

Delaying the Onset of Allograft Rejection: Give a fixed dose of 15 mg/kg daily for 14 days, then every other day for 14 days for a total of 21 doses in 28 days. Administer the first dose within 24 hours before or after the transplant.

Treatment of Rejection: The first dose of Atgam can be delayed until the diagnosis of the first rejection episode. The recommended dose is 10 to 15 mg/kg daily for 14 days. Additional alternate-day therapy up to a total of 21 doses can be given.

Aplastic Anemia

The recommended dosage regimen is 10 to 20 mg/kg daily for 8 to 14 days. Additional alternate-day therapy up to a total of 21 doses can be administered. (11–13) Because thrombocytopenia can be associated with the administration of Atgam, patients receiving it for the treatment of aplastic anemia may need prophylactic platelet transfusions to maintain platelets at clinically acceptable levels.

Preparation of Solution

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. However, because Atgam is a gamma globulin product, it can be transparent to slightly opalescent, colorless to faintly pink or brown, and may develop a slight granular or flaky deposit during storage. Atgam (diluted or undiluted) should not be shaken because excessive foaming and/or denaturation of the protein may occur.

Dilute Atgam for intravenous infusion in an inverted bottle of sterile vehicle so the undiluted Atgam does not contact the air inside. Add the total daily dose of Atgam to the sterile vehicle (see Compatibility and Stability). The concentration should not exceed 4 mg of Atgam per mL. The diluted solution should be gently rotated or swirled to effect thorough mixing.

Administration

The diluted Atgam should be allowed to reach room temperature before infusion. Atgam is appropriately administered into a vascular shunt, arterial venous fistula, or a high-flow central vein through an in-line filter with a pore size of 0.2 to 1.0 micron. The in-line filter should be used with all infusions of Atgam to prevent the administration of any insoluble material that may develop in the product during storage. The use of high-flow veins will minimize the occurrence of phlebitis and thrombosis. Do not infuse a dose of Atgam in less than 4 hours. Always keep appropriate resuscitation equipment at the patient's bedside while Atgam is being administered. Observe the patient continuously for possible allergic reactions throughout the infusions (See ADVERSE REACTIONS).

Compatibility and Stability

Atgam, once diluted, has been shown to be physically and chemically stable for up to 24 hours at concentrations of up to 4 mg per mL in the following diluents: 0.9# sodium chloride injection, 5# dextrose and 0.225# sodium chloride injection, and 5# dextrose and 0.45# sodium chloride injection.

Adding Atgam to dextrose injection is not recommended, as low salt concentrations can cause precipitation. Highly acidic infusion solutions can also contribute to physical instability over time. It is recommended that diluted Atgam be stored in a refrigerator if it is prepared prior to the time of infusion. Even if it is stored in a refrigerator, the total time in dilution should not exceed 24 hours (including infusion time).

How is Atgam Supplied

Atgam Sterile Solution, containing 50 mg of horse gamma globulin/mL, is supplied as follows:

5 – 5 mL ampoules NDC 0009-7224-02

STORAGE

Store in a refrigerator at 2° to 8°C (36° to 46°F). DO NOT FREEZE.

Rx only

Animal Toxicology

During the development of Atgam Sterile Solution, aliquots of the various clinical lots were infused intravenously in either Macaca mulatta or Macaca irus monkeys. The dosage used was 100 mg/kg on day 0, 200 mg/kg on day 2, and 400 mg/kg on day 4. A 3-week observation period followed.

Many of the changes observed could have been anticipated on the basis of the antilymphocytic activity of Atgam. They are decreased peripheral blood lymphocytes and increased total leukocyte and neutrophil counts occurring within 24 hours after infusion, decreased thymus size with involution or atrophy, or both, and decreased lymphocyte populations in the thymus-dependent areas of the spleen and lymph nodes. The atrophy was particularly common in the animals receiving the higher doses. In animals receiving either dosage regimen, packed cell volume, total erythrocyte counts, and hemoglobin concentrations have decreased and reticulocytes and nucleated erythrocytes have increased enough to be classified as anemia. An occasional animal death believed to have resulted from anemia has occurred. Transient decreases in blood platelet counts have also occurred. Thrombus formation occurred frequently along the routes of infusion, ie, the saphenous and femoral veins. However, the incidence of thrombi has dropped since in-line filters have been used during infusion. In these animals, definitive evidence of DIC (disseminated intravascular coagulation) has not been observed.

REFERENCES

Rubin RH, Cosimi AB, Hirsch MS, Herrin JT: Effects of antithymocyte globulin on cytomegalovirus infection in renal transplant recipients. Transplantation. 1981; 31(2):143–145.

Cosimi AB, Wortis HH, Delmonico FL, Russell PS: Randomized clinical trial of antithymocyte globulin in cadaver renal allograft recipients: importance of T cell monitoring. Surgery. 1976; 80: 155–163.

Wechter WJ, Brodie JA, Morrell RM, Rafi M, Schultz JR: Antithymocyte globulin (Atgam) in renal allograft recipients. Transplantation. 1979; 28(4):294–302.

Kountz SL, Butt KHM, Rao TKS, Zielinski CM, Rafi M, Schultz JR: Antithymocyte globulin (ATG) dosage and graft survival in renal transplantation. Transplant. Proc. 1977; 9:1023–1025.

Butt KMH, Zielinski CM, Parsa I, Elberg AJ, Wechter WJ, Kountz SL: Trends in immunosuppression for kidney transplantation. Kidney Int. 1978; 13(Suppl 8): S95–S98.

Filo RS, Smith EJ, Leapman SB: Reversal of acute renal allograft rejection with adjunctive ATG therapy. Transplant. Proc. 1981; 13(1): 482–490.

Nowygrod R, Appel G, Hardy M: Use of ATG for reversal of acute allograft rejection. Transplant. Proc. 1981; 13(1): 469–472.

Hardy MA, Nowygrod R, Elberg A, Appel G: Use of ATG in treatment of steroid-resistant rejection. Transplantation. 1980; 29:162–164.

Shield CH, Cosimi AB, Tolkoff-Rubin N, Rubin R, Herrin J, Russell PS: Use of antithymocyte globulin for reversal of acute allograft rejection. Transplantation. 1979; 28(6): 461–464.

Cosimi AB: The clinical value of antilymphocyte antibodies. Transplant. Proc. 1981; 13(1): 462–468.

Cosimi AB, Peters C, Harmon D, Ellman L: Treatment of severe aplastic anemia with a prolonged course of antithymocyte globulin. Transplant. Proc. 1982; 14:761–764.

Champlin R, Ho W, Gale R: Antithymocyte globulin treatment in patients with aplastic anemia. N Engl J Med. 1983; 308(3):113–118.

Doney K, Dahlberg S, Monroe D et al: Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: The effect of HLA-haploidentical marrow infusion. Blood. 1984; 63(2):342–348.

LAB-0019-2.0

November 2005

PRINCIPAL DISPLAY PANEL - 250 mg Ampule Label

250 mg protein

NDC 0009-7224-01

Rx only

5 mL

Atgam®

lymphocyte immune globulin,

anti-thymocyte globulin (equine)

50 mg/mL For I.V. use only

DOSAGE AND USE: See accompanying prescribing

information. U.S. License No. 1216.

ATTENTION—May contain particles; this is

normal. Use 0.2µ to 1.0µ in-line filter. See insert.

Distributed by Pharmacia & Upjohn Co

Division of Pfizer Inc, NY, NY 10017

11099900

LOT / EXP

Atgam
equine thymocyte immune globulin injection, solution

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	0009-7224
Route of Administration	INTRAVENOUS	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
EQUINE THYMOCYTE IMMUNE GLOBULIN (EQUINE THYMOCYTE IMMUNE GLOBULIN)	EQUINE THYMOCYTE IMMUNE GLOBULIN	50 mg in 1 mL

Inactive Ingredients
Ingredient Name	Strength
No Inactive Ingredients Found

Product Characteristics
Color		Score
Shape		Size
Flavor		Imprint Code
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	0009-7224-02	5 AMPULE In 1 CARTON	contains a AMPULE
1		5 mL In 1 AMPULE	This package is contained within the CARTON (0009-7224-02)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA103676	11/17/1981

Labeler - Pharmacia and Upjohn Company (829076566)

Establishment
Name	Address	ID/FEI	Operations
Pharmacia and Upjohn Company		829076566	MANUFACTURE

Revised: 04/2010Pharmacia and Upjohn Company

More Atgam resources

Atgam Side Effects (in more detail)
Atgam Dosage
Atgam Use in Pregnancy & Breastfeeding
Atgam Drug Interactions
Atgam Support Group
0 Reviews for Atgam - Add your own review/rating

Atgam MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Atgam with other medications

Aplastic Anemia
Renal Transplant

Thursday, 21 June 2012

Nadostine Topical

Generic Name: nystatin (Topical route)

nye-STAT-in

Commonly used brand name(s)

In the U.S.

Mycostatin

Nystop

Pedi-Dri

In Canada

Mycostatin Cream

Mycostatin Ointment

Mycostatin Powder

Nadostine

Nilstat Topical Cream

Nilstat Topical Ointment

Nyaderm Cream

Nyaderm Ointment

Available Dosage Forms:

Powder

Cream

Ointment

Therapeutic Class: Antifungal

Chemical Class: Polyene

Uses For Nadostine

Nystatin belongs to the group of medicines called antifungals. Topical nystatin is used to treat some types of fungus infections of the skin.

Nystatin is available in the U.S. only with your doctor's prescription.

Before Using Nadostine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Although there is no specific information comparing use of topical nystatin in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of topical nystatin in the elderly with use in other age groups.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of nystatin

This section provides information on the proper use of a number of products that contain nystatin. It may not be specific to Nadostine. Please read with care.

Topical nystatin should not be used in the eyes.

Apply enough nystatin to cover the affected area.

For patients using the powder form of this medicine on the feet:

Sprinkle the powder between the toes, on the feet, and in socks and shoes.

The use of any kind of occlusive dressing (airtight covering, such as kitchen plastic wrap) over this medicine may increase the chance of irritation. Therefore, do not bandage, wrap, or apply any occlusive dressing over this medicine unless directed to do so by your doctor. When using this medicine on the diaper area of children, avoid tight-fitting diapers and plastic pants.

To help clear up your infection completely, keep using this medicine for the full time of treatment, even if your condition has improved. Do not miss any doses.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For topical dosage forms (cream or ointment):
- For fungus infections:
  - Adults and children—Apply to the affected area(s) of the skin two times a day.

For topical dosage form (powder):
- For fungus infections:
  - Adults and children—Apply to the affected area(s) of the skin two or three times a day.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Nadostine Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

Skin irritation not present before use of this medicine

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

Compare Nadostine Topical with other medications

Cutaneous Candidiasis
Vaginal Yeast Infection

Auranofin

Pronunciation: or-RAIN-oh-fin
Generic Name: Auranofin
Brand Name: Ridaura

Auranofin contains gold, which can build up in the blood and become toxic. Report any symptom suggesting toxicity (rash, mouth sores, persistent diarrhea, indigestion, metallic taste, unusual bleeding or bruising, itching, blood in the urine, fainting) to your health care provider immediately.

Auranofin is used for:

Managing rheumatoid arthritis in patients who do not respond to or are intolerant of other medicines.

Auranofin is an antirheumatic agent. The way Auranofin works is not fully understood.

Do NOT use Auranofin if:

you are allergic to any ingredient in Auranofin

you have a history of blood and bone marrow disorders or disease

you have inflammation and peeling of the skin, scar tissue on the lungs, or serious bowel inflammation

you are taking penicillamine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Auranofin:

Some medical conditions may interact with Auranofin. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have small red spots under the skin, unusual bleeding or bruising, eczema, liver disease, kidney problems, lupus, yellowing of the skin or eyes, inflammation of the skin or mouth, blood circulation problems, chronic arthritis accompanied by dry mouth/eyes, itching, skin rash, or colitis

if you are receiving radiation therapy or are debilitated

Some MEDICINES MAY INTERACT with Auranofin. Tell your health care provider if you are taking any other medicines, especially any of the following:

Penicillamine because the risk of serious blood or kidney problems may be increased

This may not be a complete list of all interactions that may occur. Ask your health care provider if Auranofin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Auranofin:

Use Auranofin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Auranofin may be taken with or without food.

Auranofin comes with an additional patient leaflet. Read it carefully and reread it each time you get Auranofin refilled.

If you miss a dose of Auranofin, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Auranofin.

Important safety information:

Three to six months may pass before you feel the full effect of Auranofin. Do not stop taking Auranofin without checking with your doctor.

Auranofin may cause increased sensitivity to the sun. Avoid exposure to the sun, sunlamps, or tanning booths until you know how you react to Auranofin. Use a sunscreen or wear protective clothing if you must be outside for a prolonged period.

LAB TESTS, including complete blood cell counts, may be performed to monitor your progress. Be sure to keep all doctor and lab appointments.

Auranofin is not recommended for use in CHILDREN. Safety and effectiveness have not been confirmed.

PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Auranofin during pregnancy. It is unknown if Auranofin is excreted in breast milk. Do not breast-feed while taking Auranofin.

Possible side effects of Auranofin:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Abdominal pain; constipation; diarrhea; gas; inflammation of the eye, mouth, or skin; itching; loose stools; nausea; stomach pain; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bleeding disorder; blood in the urine; fainting; indigestion; itching; metallic taste; mouth sores; peeling skin; persistent diarrhea; purple blotches or other unusual skin spots; rash; shortness of breath; sore throat; unusual bleeding or bruising; unusual weakness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Auranofin side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include diarrhea; fever; nausea; skin disorders (hives and severe itching); vomiting.

Proper storage of Auranofin:

Store Auranofin at room temperature, between 59 and 86 degrees F (15 and 30 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Auranofin out of the reach of children and away from pets.

General information:

If you have any questions about Auranofin, please talk with your doctor, pharmacist, or other health care provider.

Auranofin is to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Auranofin. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Auranofin resources

Auranofin Side Effects (in more detail)
Auranofin Use in Pregnancy & Breastfeeding
Auranofin Drug Interactions
Auranofin Support Group
2 Reviews for Auranofin - Add your own review/rating

Auranofin Professional Patient Advice (Wolters Kluwer)

auranofin Concise Consumer Information (Cerner Multum)

Ridaura Prescribing Information (FDA)

Ridaura Advanced Consumer (Micromedex) - Includes Dosage Information

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Tuesday, 19 June 2012

A200 Maximum Strength Topical

Generic Name: pyrethrum extract and piperonyl butoxide (Topical route)

pye-REE-thrum EX-trackt, PIP-er-oh-nil byoo-TOX-ide

Commonly used brand name(s)

In the U.S.

A200 Maximum Strength

A200 Time-Tested Formula

Lice-X

Licide

Medi-Lice Maximum Strength

Pronto Maximum Strength

Pyrinex

Pyrinyl

Tisit

Available Dosage Forms:

Gel/Jelly

Liquid

Shampoo

Foam

Therapeutic Class: Pediculicide

Chemical Class: Pyrethrums

Uses For A200 Maximum Strength

Medicine containing pyrethrins is used to treat head, body, and pubic lice infections. This medicine is absorbed by the lice and destroys them by acting on their nervous systems. It does not affect humans in this way. The piperonyl butoxide is included to make the pyrethrins more effective in killing the lice. This combination medicine is known as a pediculicide.

This medicine is available without a prescription.

Before Using A200 Maximum Strength

Allergies

Pediatric

Although there is no specific information comparing use of pyrethrins and piperonyl butoxide combination in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of pyrethrins and piperonyl butoxide combination medicine in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Interactions with Food/Tobacco/Alcohol

Proper Use of pyrethrum extract and piperonyl butoxide

This section provides information on the proper use of a number of products that contain pyrethrum extract and piperonyl butoxide. It may not be specific to A200 Maximum Strength. Please read with care.

Pyrethrins and piperonyl butoxide combination medicine usually comes with patient directions. Read them carefully before using this medicine.

Use this medicine only as directed. Do not use more of it and do not use it more often than recommended on the label. To do so may increase the chance of absorption through the skin and the chance of side effects.

Keep pyrethrins and piperonyl butoxide combination medicine away from the mouth and do not inhale it. This medicine is harmful if swallowed or inhaled.

To lessen the chance of inhaling this medicine, apply it in a well-ventilated room (for example, one with free flowing air or with a fan turned on).

Keep this medicine away from the eyes and other mucous membranes, such as the inside of the nose, mouth, or vagina, because it may cause irritation. If you accidentally get some in your eyes, flush them thoroughly with water at once.

Do not apply this medicine to the eyelashes or eyebrows . If they become infected with lice, check with your doctor.

To use the gel or solution form of this medicine:

Apply enough medicine to thoroughly wet the dry hair and scalp or skin. Allow the medicine to remain on the affected areas for exactly 10 minutes.

Then, thoroughly wash the affected areas with warm water and soap or regular shampoo. Rinse thoroughly and dry with a clean towel.

To use the shampoo form of this medicine:

Apply enough medicine to thoroughly wet the dry hair and scalp or skin. Allow the medicine to remain on the affected areas for exactly 10 minutes.

Then use a small amount of water and work shampoo into the hair and scalp or skin until a lather forms. Rinse thoroughly and dry with a clean towel.

After rinsing and drying, use a nit removal comb (special fine-toothed comb, usually included with this medicine) to remove the dead lice and eggs (nits) from hair.

Immediately after using this medicine, wash your hands to remove any medicine that may be on them.

This medicine should be used again in 7 to 10 days after the first treatment in order to kill any newly hatched lice.

Lice can easily move from one person to another by close body contact. This can happen also by direct contact with such things as clothing, hats, scarves, bedding, towels, washcloths, hairbrushes and combs, or the hair of infected persons. Therefore, all members of your household should be examined for lice and receive treatment if they are found to be infected.

To use this medicine for pubic (crab) lice:

Your sexual partner may also need to be treated, since the infection may spread to persons in close contact. If your partner is not being treated or if you have any questions about this, check with your doctor.

Dosing

For topical dosage forms (gel, solution shampoo, and topical solution):
- For head, body, or pubic lice:
  - Adults and children—Use one time, then repeat one time in seven to ten days.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using A200 Maximum Strength

To prevent reinfection or spreading of the infection to other people, good health habits are also required. These include the following:

For head lice
- Machine wash all clothing (including hats, scarves, and coats), bedding, towels, and washcloths in very hot water and dry them by using the hot cycle of a dryer for at least 20 minutes. Clothing or bedding that cannot be washed should be dry-cleaned or sealed in a plastic bag for 2 weeks.
- Shampoo all wigs and hairpieces.
- Wash all hairbrushes and combs in very hot soapy water (above 130 °F) for 5 to 10 minutes and do not share them with other people.
- Clean the house or room by thoroughly vacuuming upholstered furniture, rugs, and floors.

For body lice
- Machine wash all clothing, bedding, towels, and washcloths in very hot water and dry them by using the hot cycle of a dryer for at least 20 minutes. Clothing or bedding that cannot be washed should be dry-cleaned or sealed in a plastic bag for 2 weeks.
- Clean the house or room by thoroughly vacuuming upholstered furniture, rugs, and floors.

For pubic lice
- Machine wash all clothing (especially underwear), bedding, towels, and washcloths in very hot water and dry them by using the hot cycle of a dryer for at least 20 minutes. Clothing or bedding that cannot be washed should be dry-cleaned or sealed in a plastic bag for 2 weeks.
- Scrub toilet seats frequently.

A200 Maximum Strength Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

Less common or rare

Skin irritation not present before use of this medicine

skin rash or infection

sneezing (sudden attacks of)

stuffy or runny nose

wheezing or difficulty in breathing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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