Amoxicillin k clav

Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin-class antibiotics, but the significance of these findings is unknown.

Hepatic dysfunction, including hepatitis and cholestatic jaundice, [see CONTRAINDICATIONS ], increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with AUGMENTIN or AUGMENTIN XR. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment.

The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes.

The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued.

The hepatic dysfunction, which may be severe, is usually reversible.

Deaths have been reported [see CONTRAINDICATIONS , WARNINGS AND PRECAUTIONS ].

Renal: Interstitial nephritis, hematuria, and crystalluria have been reported [see OVERDOSAGE ]. Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins.

These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

There have been reports of increased prothrombin time in patients receiving AUGMENTIN and anticoagulant therapy concomitantly. Central Nervous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, headache, insomnia, and reversible hyperactivity have been reported rarely. Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported.

Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with AUGMENTIN XR may result in increased and prolonged blood levels of amoxicillin. Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants.

Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

The concurrent administration of allopurinol and amoxicillin substantially increases the incidence of rashes in patients receiving both drugs as compared to patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients. In controlled clinical trials of AUGMENTIN XR, 25 patients received concomitant allopurinol and AUGMENTIN XR. However, this sample size is too small to allow for any conclusions to be drawn regarding the risk of rashes with concomitant AUGMENTIN XR and allopurinol use.

AUGMENTIN XR may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

High urine concentrations of amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST®, Benedict's Solution, or Fehling's Solution. Since this effect may also occur with AUGMENTIN, it is recommended

that

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving AUGMENTIN XR.

These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with AUGMENTIN XR, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.

If an allergic reaction occurs, AUGMENTIN XR should be discontinued and appropriate therapy instituted.

AUGMENTIN XR should be used

with

Hepatic toxicity associated with the use of amoxicillin/clavulanate potassium is usually reversible. Deaths have been reported (fewer than 1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications [see CONTRAINDICATIONS and ADVERSE REACTIONS ].

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AUGMENTIN XR, and may range in severity from mild diarrhea to fatal colitis.

Treatment with antibacterial agents alters the normal flora of amoxicillin clav 875 mg the colon leading to overgrowth of C. difficile produces toxins A and B which contribute to the development of CDAD. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use.

Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.

Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, AUGMENTIN XR should not be administered to patients with mononucleosis.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy.

If superinfections occur (usually involving Pseudomonas spp.

or Candida spp.), the drug should be discontinued and/or appropriate therapy instituted. Prescribing AUGMENTIN XR in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION) Nonclinical Toxicology.

Carcinogenesis, Mutagenesis, Impairment Of Fertility. Long-term studies in animals have not been performed to evaluate carcinogenic potential.

The mutagenic potential of AUGMENTIN was investigated in vitro with amoxicillin 125 mg price an Ames test, a human lymphocyte cytogenetic assay, a yeast test, and a mouse lymphoma forward mutation assay, and in vivo with mouse micronucleus tests and a dominant lethal test.

All were negative apart from the in vitro mouse lymphoma assay, where weak activity was found at very high, cytotoxic concentrations. AUGMENTIN at oral doses of up to 1,200 mg/kg/day (1.9 times the maximum human dose of amoxicillin and 15 times the maximum human dose of clavulanate based on body surface area) was found to have no effect on fertility and reproductive performance in rats dosed with a 2:1 ratio formulation of amoxicillin:clavulanate. Reproduction studies performed in pregnant rats and mice given AUGMENTIN at oral doses up to 1,200 mg/kg/day revealed no evidence of harm to the fetus due to AUGMENTIN. In terms of body surface area, the doses in rats were 1.6 times the maximum human oral dose of amoxicillin and 13 times the maximum human dose for clavulanate. For mice, these doses were 0.9 and 7.4 times the maximum human oral dose of amoxicillin and clavulanate, respectively.

There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions.

However, it is not known whether the use of AUGMENTIN XR in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.

In a single study in women with premature rupture of fetal membranes, it was reported that prophylactic treatment with AUGMENTIN may be associated with an increased amoxicillin 500mg prescription risk of necrotizing enterocolitis in neonates. Amoxicillin has been shown to be excreted in human milk; therefore, caution should be exercised when AUGMENTIN XR is administered to a nursing woman. The safety and effectiveness of AUGMENTIN XR have been established for pediatric patients weighing ? 40 kg who are able to swallow tablets. Use of AUGMENTIN XR in these pediatric patients is supported by evidence from adequate and well-controlled trials of adults with acute bacterial sinusitis and community-acquired pneumonia with additional data from a pediatric pharmacokinetic study. A pharmacokinetic study in pediatric patients (7 to 15 years of age and weighing ? 40 kg) was conducted [see CLINICAL PHARMACOLOGY ]. The adverse event profile in 44 pediatric patients who received at least one dose of AUGMENTIN XR was consistent with the established adverse event profile for the product in adults. Of the total number of subjects in clinical studies of AUGMENTIN XR, 18% were 65 years or older and 7% were 75 years or older. No overall differences in safety and effectiveness were observed between these subjects and younger subjects, and other clinical experience has not reported differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney, and the risk of dose dependent toxic reactions to this drug may be greater in patients with impaired renal function.

Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.

The pharmacokinetics of AUGMENTIN XR have not been studied in patients with renal impairment. AUGMENTIN XR is contraindicated in patients with a creatinine clearance of. Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain,

vomiting

If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying 5 .

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.

Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In the case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria.

Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis [see DOSAGE AND ADMINISTRATION ]. AUGMENTIN XR is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins).

Augmentin XR is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with treatment with amoxicillin/clavulanate potassium.

AUGMENTIN XR is contraindicated in patients with severe renal impairment (creatinine clearance. AUGMENTIN XR is an extended-release formulation which provides sustained plasma concentrations of amoxicillin. Amoxicillin systemic exposure achieved with AUGMENTIN XR is amoxicillin for pid similar to that produced by the oral administration of equivalent doses of amoxicillin alone. Amoxicillin and clavulanate potassium are well absorbed from the gastrointestinal tract after oral administration of AUGMENTIN XR. In a study of healthy adult volunteers, the pharmacokinetics of AUGMENTIN XR were compared when administered in a fasted state, at the start of a standardized meal (612 kcal, 89.3 g carb, 24.9 g fat, and 14.0 g protein), or 30 minutes after a high-fat meal.

When the systemic exposure to both amoxicillin and clavulanate is taken into consideration, AUGMENTIN XR is optimally administered at the start of a standardized meal.

Absorption of amoxicillin is decreased in the fasted state.

AUGMENTIN XR is not recommended to be taken with a high-fat

meal

The pharmacokinetics of the components of AUGMENTIN XR following administration of two AUGMENTIN XR tablets at the start of a standardized meal are presented in Table 1.

Table 1: Mean (SD) Pharmacokinetic Parameter for Amoxicillin and Clavulanate Following Oral Administration of Two AUGMENTIN XR Tablets (2,000 mg/125 mg) to Healthy Adult Volunteers (n = 55) Fed a Standardized Meal Parameter (units) Amoxicillin Clavulanate AUC(0-inf) (mcg•hr/mL) 71.6 (16.5) 5.29 (1.55) Cmax (mcg/mL) 17.0 (4.0) 2.05 (0.80) Tmax (hours) a 1.50 (1.00 -6.00) 1.03 (0.75 -3.00) T? (hours) 1.27 (0.20) 1.03 (0.17) a Median (range). The half-life of amoxicillin after the oral administration of AUGMENTIN XR is approximately 1.3 hours, and that of clavulanate is approximately 1.0 hour. Neither component in AUGMENTIN XR is highly protein-bound; clavulanate has been found to be approximately 25% bound to human serum and amoxicillin approximately 18% bound. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of the brain and spinal fluid.

The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues. Clearance of amoxicillin is predominantly renal, with approximately 60% to 80% of the dose being excreted unchanged in urine, whereas clearance of clavulanate has both a renal (30% to 50%) and a non-renal component.

Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanate.

In a study of adults, the pharmacokinetics of amoxicillin and clavulanate were not affected by administration of an antacid (MAALOX®), either simultaneously with or 2 hours after AUGMENTIN XR.