METRONIDAZOLE tablet

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

Nopērc to tagad

Produkta apraksts Produkta apraksts (SPC)

23-12-2020

Aktīvā sastāvdaļa:
METRONIDAZOLE (UNII: 140QMO216E) (METRONIDAZOLE - UNII:140QMO216E)
Pieejams no:
Denton Pharma, Inc. dba Northwind Pharmaceuticals
Ievadīšanas:
ORAL
Receptes veids:
PRESCRIPTION DRUG
Ārstēšanas norādes:
Metronidazole tablets, USP are indicated for the treatment of T. vaginalis infection in females and males when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures). Metronidazole tablets, USP are indicated in the treatment of asymptomatic T. vaginalis infection in 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. 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 mak
Produktu pārskats:
Metronidazole Tablets USP, 500 mg are white to off-white, modified oval shape tablets with “I” on one side and “125” on the other side. Bottles of 30 NDC 70934-801-30 Bottles of 21 NDC 70934-801-21 Bottles of 14 NDC 70934-801-14
Autorizācija statuss:
Abbreviated New Drug Application
Autorizācija numurs:
70934-801-14, 70934-801-21, 70934-801-30

Izlasiet visu dokumentu

METRONIDAZOLE- metronidazole tablet

Denton Pharma, Inc. dba Northwind Pharmaceuticals

----------

Metronidazole Tablets, USP Rx Only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of metronidazole

tablets, USP and other antibacterial drugs, metronidazole tablets, USP 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.

DESCRIPTION

Metronidazole tablets USP, 250 mg or 500 mg is an oral formulation of the synthetic nitroimidazole

antimicrobial, 2-methyl-5-nitro-1H-imidazole-1-ethanol, which has the following structural formula:

Metronidazole tablets, USP contain 250 mg or 500 mg of metronidazole. Inactive ingredients include

colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, and stearic

acid.

CLINICAL PHARMACOLOGY

Abs orption

Disposition of metronidazole in the body is similar for both oral and intravenous dosage forms.

Following oral administration, metronidazole is well absorbed, with peak plasma concentrations

occurring between one and two hours after administration.

Plasma concentrations of metronidazole are proportional to the administered dose. Oral administration

of 250 mg, 500 mg, or 2,000 mg produced peak plasma concentrations of 6 mcg/mL, 12 mcg/ mL, and

40 mcg/mL, respectively. Studies reveal no significant bioavailability differences between males and

females; however, because of weight differences, the resulting plasma levels in males are generally

lower.

Dis tribution

Metronidazole is the major component appearing in the plasma, with lesser quantities of metabolites also

being present. Less than 20% of the circulating metronidazole is bound to plasma proteins.

Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentrations similar to those

found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from

hepatic abscesses.

Metabolis m/Excretion

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. Both the parent compound and the

hydroxyl metabolite possess in vitro antimicrobial activity.

Renal clearance of metronidazole is approximately 10 mL/min/1.73 m2. The average elimination half-

life of metronidazole in healthy subjects is eight hours.

Renal Impairment

Decreased renal function does not alter the single-dose pharmacokinetics of metronidazole.

Subjects with end-stage renal disease (ESRD; CLCR= 8.1±9.1 mL/min) and who received a single

intravenous infusion of metronidazole 500 mg had no significant change in metronidazole

pharmacokinetics but had 2-fold higher Cmax of hydroxy-metronidazole and 5-fold higher Cmax of

metronidazole acetate, compared to healthy subjects with normal renal function (CLCR= 126±16

mL/min). Thus, on account of the potential accumulation of metronidazole metabolites in ESRD patients,

monitoring for metronidazole associated adverse events is recommended (see PRECAUTIONS).

Effect of Dialysis

Following a single intravenous infusion or oral dose of metronidazole 500 mg, the clearance of

metronidazole was investigated in ESRD subjects undergoing hemodialysis or continuous ambulatory

peritoneal dialysis (CAPD). A hemodialysis session lasting for 4 to 8 hours removed 40% to 65% of

the administered metronidazole dose, depending on the type of dialyzer membrane used and the duration

of the dialysis session. If the administration of metronidazole cannot be separated from the dialysis

session, supplementation of metronidazole dose following hemodialysis should be considered (see

DOSAGE AND ADMINISTRATION). A peritoneal dialysis session lasting for 7.5 hours removed

approximately 10% of the administered metronidazole dose. No adjustment in metronidazole dose is

needed in ESRD patients undergoing CAPD.

Hepatic Impairment

Following a single intravenous infusion of 500 mg metronidazole, the mean AUC24 of metronidazole

was higher by 114% in patients with severe (Child-Pugh C) hepatic impairment, and by 54% and 53% in

patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment, respectively,

compared to healthy control subjects. There were no significant changes in the AUC24 of hydroxyl-

metronidazole in these hepatically impaired patients. A reduction in metronidazole dosage by 50% is

recommended in patients with severe (Child-Pugh C) hepatic impairment (see DOSAGE AND

ADMINISTRATION). No dosage adjustment is needed for patients with mild to moderate hepatic

impairment. Patients with mild to moderate hepatic impairment should be monitored for metronidazole

associated adverse events (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Geriatric Patients

Following a single 500 mg oral or IV dose of metronidazole, subjects >70 years old with no apparent

renal or hepatic dysfunction had a 40% to 80% higher mean AUC of hydroxy-metronidazole (active

metabolite), with no apparent increase in the mean AUC of metronidazole (parent compound), compared

to young healthy controls <40 years old. In geriatric patients, monitoring for metronidazole associated

adverse events is recommended (see PRECAUTIONS).

Pediatric Patients

In one study, newborn infants appeared to demonstrate diminished capacity to eliminate metronidazole.

The elimination half-life, measured during the first 3 days of life, was inversely related to gestational

age. In infants whose gestational ages were between 28 and 40 weeks, the corresponding elimination

half-lives ranged from 109 to 22.5 hours.

Microbiology

Mechanism of Action

Metronidazole, a nitroimidazole, exerts antibacterial effects in an anaerobic environment against most

obligate anaerobes. Once metronidazole enters the organism by passive diffusion and activated in the

cytoplasm of susceptible anaerobic bacteria, it is reduced; this process includes intracellular electron

transport proteins such as ferredoxin, transfer of an electron to the nitro group of the metronidazole, and

formation of a short-lived nitroso free radical. Because of this alteration of the metronidazole

molecule, a concentration gradient is created and maintained which promotes the drug’s intracellular

transport. The reduced form of metronidazole and free radicals can interact with DNA leading to

inhibition of DNA synthesis and DNA degradation leading to death of the bacteria. The precise

mechanism of action of metronidazole is unclear.

Resistance

A potential for development of resistance exists against metronidazole.

Resistance may be due to multiple mechanisms that include decreased uptake of the drug, altered

reduction efficiency, overexpression of the efflux pumps, inactivation of the drug, and/or increased

DNA damage repair.

Metronidazole does not possess any clinically relevant activity against facultative anaerobes or obligate

aerobes.

Antimicrobial Activity

Metronidazole has been shown to be active against most isolates of the following bacteria both in vitro

and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive anaerobes

Clostridium species

Eubacterium species

Peptococcus species

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 minimal inhibitory concentrations (MIC’s) of 8 mcg/mL or less against

most (≥ 90%) isolates of the following bacteria; however, the safety and effectiveness of

metronidazole in treating clinical infections due to these bacteria 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)

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods

and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

INDICATIONS AND USAGE

Symptomatic Trichomoniasis

Metronidazole tablets, USP are indicated for the treatment of T. vaginalis infection in females and males

when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet

smears and/or cultures).

undefined

Metronidazole tablets, USP are indicated in the treatment of asymptomatic T. vaginalis infection in

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 Sexual Partners

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 sexual

partner 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 sexual partner should be treated with metronidazole tablets, USP in cases of reinfection.

Amebias is

Metronidazole tablets, USP are indicated in the treatment of acute intestinal amebiasis (amebic

dysentery) and amebic liver abscess.

In amebic liver abscess, metronidazole tablets, USP therapy does not obviate the need for aspiration or

drainage of pus.

Anaerobic Bacterial Infections

Metronidazole tablets, USP are indicated in the treatment of serious infections caused by susceptible

anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with

metronidazole tablets, USP therapy. In a mixed aerobic and anaerobic infection, antimicrobials

appropriate for the treatment of the aerobic infection should be used in addition to metronidazole

tablets, USP.

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 species, and

Peptostreptococcus species.

SKIN AND SKIN STRUCTURE INFECTIONS caused by Bacteroides species including the B. fragilis

group, Clostridium species, Peptococcus species, Peptostreptococcus species, and 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 species, Peptostreptococcus species, and Fusobacterium species.

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

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 metronidazole

tablets, USP and other antibacterial drugs, metronidazole tablets, USP 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

Hypers ens itivity

Metronidazole tablets, USP are contraindicated in patients with a prior history of hypersensitivity to

metronidazole or other nitroimidazole derivatives.

In patients with trichomoniasis, metronidazole tablets, USP are contraindicated during the first trimester

of pregnancy (see PRECAUTIONS).

Psychotic Reaction with Disulfiram

Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using

disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within

the last two weeks (see PRECAUTIONS, Drug Interactions).

Psychotic Reaction with Disulfiram

Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using

disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within

the last two weeks (see PRECAUTIONS, Drug Interactions).

Interaction with Alcohol

Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal

cramps, nausea, vomiting, headaches, and flushing. Discontinue consumption of alcohol or products

containing propylene glycol during and for at least three days after therapy with metronidazole (see

PRECAUTIONS, Drug Interactions).

WARNINGS

Central and Peripheral Nervous System Effects

Encephalopathy and peripheral neuropathy

Cases of encephalopathy and peripheral neuropathy (including optic neuropathy) have been reported

with metronidazole.

Encephalopathy has been reported in association with cerebellar toxicity characterized by ataxia,

dizziness, and dysarthria. CNS lesions seen on MRI have been described in reports of encephalopathy.

CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole.

CNS lesions seen on MRI have also been described as reversible.

Peripheral neuropathy, mainly of sensory type has been reported and is characterized by numbness or

paresthesia of an extremity.

Convulsive seizures have been reported in patients treated with metronidazole.

Aseptic meningitis

Cases of aseptic meningitis have been reported with metronidazole. Symptoms can occur within hours

of dose administration and generally resolve after metronidazole therapy is discontinued

The appearance of abnormal neurologic signs and symptoms demands the prompt evaluation of the

benefit/risk ratio of the continuation of therapy (see ADVERSE REACTIONS).

Risk of Hepatotoxicity and Death in Patients with Cockayne Syndrome

Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very

rapid onset after treatment initiation in patients with Cockayne syndrome have been reported with

products containing metronidazole for systemic use. In this population, metronidazole should therefore

be used after careful benefit-risk assessment and only if no alternative treatment is available. Obtain

liver function tests prior to the start of therapy, within the first 2-3 days after initiation of therapy,

frequently during therapy and after end of treatment. Discontinue metronidazole if elevation of liver

function tests occurs, and monitor liver function tests until the baseline values are reached.

Advise patients with Cockayne syndrome to stop taking metronidazole immediately if they experience

any symptoms of potential liver injury, such as abdominal pain, nausea, change in stool color or

jaundice, and to contact their healthcare provider.

PRECAUTIONS

General

Hepatic Impairment

Patients with hepatic impairment metabolize metronidazole slowly, with resultant accumulation of

metronidazole in the plasma. For patients with severe hepatic impairment (Child-Pugh C), a reduced

dose of metronidazole tablets, USP is recommended. For patients with mild to moderate hepatic

impairment, no dosage adjustment is needed but these patients should be monitored for metronidazole

associated adverse events (see CLINICAL PHARMACOLOGY and DOSAGE AND

ADMINISTRATION).

Renal Impairment

Patients with end-stage renal disease may excrete metronidazole and metabolites slowly in the urine,

resulting in significant accumulation of metronidazole metabolites. Monitoring for metronidazole

associated adverse events is recommended (see CLINICAL PHARMACOLOGY).

Fungal Superinfections

Known or previously unrecognized candidiasis may present more prominent symptoms during therapy

with metronidazole tablets, USP and requires treatment with a candidacidal agent.

Use in Patients with Blood Dyscrasias

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.

Drug-Resistant Bacteria and Parasites

Prescribing metronidazole tablets, USP in the absence of a proven or strongly suspected bacterial or

parasitic infection or a prophylactic indication is unlikely to provide benefit to the patient and increases

the risk of the development of drug-resistant bacteria and parasites.

Information for Patients

Interaction with Alcohol

Discontinue consumption of alcoholic beverages or products containing propylene glycol while taking

metronidazole tablets, USP and for at least three days afterward because abdominal cramps, nausea,

vomiting, headaches, and flushing may occur (see CONTRAINDICATIONS and PRECAUTIONS,

Drug Interactions).

Treatment of Bacterial and Parasitic Infections

Patients should be counseled that metronidazole tablets, USP should only be used to treat bacterial and

parasitic infections. Metronidazole tablets, USP does not treat viral infections ( e.g., the common cold).

When metronidazole tablets, USP are 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 metronidazole tablets, USP in the future.

Drug Interactions

Disulfiram

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 two weeks (see CONTRAINDICATIONS).

Alcoholic Beverages

Abdominal cramps, nausea, vomiting, headaches, and flushing may occur if alcoholic beverages or

products containing propylene glycol are consumed during or following metronidazole therapy (see

CONTRAINDICATIONS).

Warfarin and other Oral Anticoagulants

Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral

coumarin anticoagulants, resulting in a prolongation of prothrombin time. When metronidazole tablets,

USP are prescribed for patients on this type of anticoagulant therapy, prothrombin time and INR should

be carefully monitored.

Lithium

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.

Busulfan

Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an

increased risk for serious busulfan toxicity. Metronidazole should not be administered concomitantly

with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are

available, and concomitant administration with busulfan is medically needed, frequent monitoring of

busulfan plasma concentration should be performed and the busulfan dose should be adjusted

accordingly.

Drugs that Inhibit CYP450 Enzymes

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.

Drugs that Induce CYP450 Enzymes

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.

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 glucose hexokinase. 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+

NADH). Interference is due to the

similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Tumors affecting the liver, lungs, mammary, and lymphatic tissues have been detected in several studies

of metronidazole in rats and mice, but not hamsters.

Pulmonary tumors have been observed in all six reported studies in the mouse, including one study in

which the animals were dosed on an intermittent schedule (administration during every fourth week

only). Malignant liver tumors were increased in male mice treated at approximately 1500 mg/ m2 (similar

to the maximum recommended daily dose, based on body surface area comparisons). Malignant

lymphomas and pulmonary neoplasms were also increased with lifetime feeding of the drug to mice.

Mammary and hepatic tumors were increased among female rats administered oral metronidazole

compared to concurrent controls. Two lifetime tumorigenicity studies in hamsters have been performed

and reported to be negative.

Metronidazole has shown mutagenic activity in in vitro assay systems including the Ames test. Studies in

mammals in vivo have failed to demonstrate a potential for genetic damage.

Metronidazole failed to produce any adverse effects on fertility or testicular function in male rats at

doses up at 400 mg/kg/day (similar to the maximum recommended clinical dose, based on body surface

area comparisons) for 28 days. However, rats treated at the same dose for 6 weeks or longer were

infertile and showed severe degeneration of the seminiferous epithelium in the testes as well as marked

decreases in testicular spermatid counts and epididymal sperm counts. Fertility was restored in most rats

after an eight week, drug-free recovery period.

Pregnancy

Teratogenic Effects

There are no adequate and well controlled studies of metronidazole tablets, USP in pregnant women.

There are published data from case-control studies, cohort studies, and 2 meta-analyses that include

more than 5000 pregnant women who used metronidazole during pregnancy. Many studies included first

trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in

infants exposed to metronidazole in-utero; however, these findings were not confirmed. In addition,

more than ten randomized placebo-controlled clinical trials enrolled more than 5000 pregnant women to

assess the use of antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence

of preterm delivery. Most studies did not show an increased risk for congenital anomalies or other

adverse fetal outcomes following metronidazole exposure during pregnancy. Three studies conducted

to assess the risk of infant cancer following metronidazole exposure during pregnancy did not show an

increased risk; however, the ability of these studies to detect such a signal was limited.

Metronidazole crosses the placental barrier and its effects on the human fetal organogenesis are not

known. Reproduction studies have been performed in rats, rabbits, and mice at doses similar to the

maximum recommended human dose based on body surface area comparisons. There was no evidence

of harm to the fetus due to metronidazole.

Nursing Mothers

Metronidazole is present in human milk at concentrations similar to maternal serum levels, and infant

serum levels can be close to or comparable to infant therapeutic levels. 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. Alternatively, a nursing mother may choose to pump and discard human milk for the duration of

metronidazole therapy, and for 24 hours after therapy ends and feed her infant stored human milk or

formula.

Geriatric Use

In elderly geriatric patients, monitoring for metronidazole associated adverse events is recommended

(see CLINICAL PHARMACOLOGY, PRECAUTIONS). Decreased liver function in geriatric

patients can result in increased concentrations of metronidazole that may necessitate adjustment of

metronidazole dosage (see DOSAGE AND ADMINISTRATION).

Pediatric Use

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

amebiasis.

ADVERSE REACTIONS

The following reactions have 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 headache,

syncope, dizziness, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression,

weakness, and insomnia (see WARNINGS).

Gas trointes tinal

The most common adverse reactions reported have been referable to the gastrointestinal tract,

particularly nausea, sometimes accompanied by headache, anorexia, and occasionally vomiting;

diarrhea; epigastric distress; and abdominal cramping and constipation.

Mouth

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.

Dermatologic

Erythematous rash and pruritus.

Hematopoietic

Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.

Cardiovas cular

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

Hypers ens itivity

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.” Rare cases of pancreatitis, which generally abated on

withdrawal of the drug, have 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 metronidazole tablets, USP.

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 of Overdosage

There is no specific antidote for metronidazole overdose; therefore, management of the patient should

consist of symptomatic and supportive therapy.

DOSAGE AND ADMINISTRATION

Trichomonias is

In the Female

One-day treatment – two grams of metronidazole tablets, USP, given either as a single dose or in two

divided doses of one gram each, given in the same day.

Līdzīgi produkti

Meklēt brīdinājumus, kas saistīti ar šo produktu

Skatīt dokumentu vēsturi

Kopīgojiet šo informāciju