Augmentin XR

Name: Augmentin XR

Augmentin XR 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 immediately if any of the following side effects occur:

Less common
  • Hives or welts
  • itching
  • itching of the vagina or genital area
  • pain during sexual intercourse
  • redness of the skin
  • skin rash
  • thick, white vaginal discharge with no odor or with a mild odor
Rare
  • Bloody or cloudy urine
  • fever
  • greatly decreased frequency of urination or amount of urine
  • seizures
  • swelling of the feet or lower legs
Incidence not known
  • Abdominal or stomach cramps or tenderness
  • back, leg, or stomach pains
  • black, hairy tongue
  • black, tarry stools
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • bloating
  • blood in the stools
  • bloody nose
  • chest pain
  • chills
  • clay-colored stools
  • cough or hoarseness
  • cracks in the skin
  • dark urine
  • diarrhea
  • diarrhea, watery and severe, which may also be bloody
  • difficulty with breathing
  • difficulty with moving
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • fever with or without chills
  • general body swelling
  • general feeling of tiredness or weakness
  • headache
  • heavier menstrual periods
  • increased thirst
  • joint or muscle pain
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • light-colored stools
  • loss of appetite
  • loss of heat from the body
  • lower back or side pain
  • muscle stiffness
  • nausea or vomiting
  • pain
  • pain, swelling, or redness in the joints
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • rash
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • red, swollen skin
  • scaly skin
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swollen glands
  • tightness in the chest
  • troubled breathing with exertion
  • unpleasant breath odor
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight loss
  • upper right abdominal or stomach pain
  • vomiting of blood
  • white patches in the mouth or throat or on the tongue
  • white patches with diaper rash
  • yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose
  • Abdominal or stomach pain
  • cloudy urine
  • diarrhea
  • greatly decreased frequency of urination or amount of urine
  • sleepiness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Rare
  • Anxiety
  • dry mouth
  • hyperventilation
  • irregular heartbeats
  • irritability
  • restlessness
  • shaking
  • sleeplessness
  • tooth discoloration
  • trouble sitting still
  • trouble with sleeping
Incidence not known
  • Burning feeling in the chest or stomach
  • indigestion
  • redness, swelling, or soreness of the tongue
  • stomach upset
  • swelling or inflammation of the mouth

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.

Drug Interactions

Probenecid

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with Augmentin XR may result in increased and prolonged blood levels of amoxicillin. Coadministration of probenecid is not recommended.

Oral Anticoagulants

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.

Allopurinol

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. No rashes were reported in these patients. 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.

Oral Contraceptives

In common with other broad-spectrum antibiotics, Augmentin XR may reduce the efficacy of oral contraceptives.

Effects on Laboratory Tests

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 glucose tests based on enzymatic glucose oxidase reactions be used. Following administration of amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.

Use in specific populations

Pregnancy

Teratogenic Effects: Pregnancy Category B. 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.

Labor and Delivery

Oral ampicillin is poorly absorbed during labor. 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 risk of necrotizing enterocolitis in neonates.

Nursing Mothers

Amoxicillin has been shown to be excreted in human milk; therefore, caution should be exercised when Augmentin XR is administered to a nursing woman.

Pediatric Use

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 (12.2)].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.

Geriatric Use

Of the total number of subjects in clinical studies of Augmentin XR, 18.4% were 65 years or older and 7.2% 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.

Renal Impairment

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 < 30 mL/min and in hemodialysis patients [see Contraindications (4)].

Hepatic Impairment

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals [see Warnings and Precautions (5.3)].

Augmentin XR Description

Augmentin XR (amoxicillin and clavulanate potassium) extended release tablet for oral use is an antibacterial combination consisting of the semisynthetic antibacterial amoxicillin (present as amoxicillin trihydrate and amoxicillin sodium) and the β-lactamase inhibitor clavulanate potassium (the potassium salt of clavulanic acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus 6‑aminopenicillanic acid. The amoxicillin trihydrate molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.45. Chemically, amoxicillin trihydrate is (2S,5R,6R)-6-[(R)-(-)-2-Amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate and may be represented structurally as:

The amoxicillin sodium molecular formula is C16H18N3NaO5S, and the molecular weight is 387.39. Chemically, amoxicillin sodium is [2 -[2α,5α,6β(S*)]]-6-[[Amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid monosodium salt and may be represented structurally as:

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula is C8H8KNO5, and the molecular weight is 237.25. Chemically, clavulanate potassium is potassium (Z)-(2R,5R)-3-(2-hydroxy ethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate, and may be represented structurally as:

Inactive Ingredients: Citric acid, colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, titanium dioxide, and xanthan gum.

Each tablet of Augmentin XR contains approximately 13 mg of potassium and 30 mg of sodium.

Patient Counseling Information

17.1 Information for Patients

Counsel patients to take Augmentin XR every 12 hours with a meal or snack to reduce the possibility of gastrointestinal upset. If diarrhea develops and is severe or lasts more than 2 or 3 days, call your doctor.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Patients should be counseled that antibacterial drugs, including Augmentin XR, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Augmentin XR 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 Augmentin XR or other antibacterial drugs in the future. Discard any unused medicine.

Augmentin XR and AUGMENTIN are registered trademarks of GlaxoSmithKline and are licensed to Dr. Reddy's Laboratories Inc.

MAALOX is a registered trademark of Novartis Consumer Health, Inc.

CLINITEST is a registered trademark of Miles, Inc. 

Manufactured by:

Dr. Reddy's Laboratories Tennessee LLC,

Bristol, TN 37620

For Healthcare Professionals

Applies to amoxicillin / clavulanate: oral powder for reconstitution, oral tablet, oral tablet chewable, oral tablet extended release

General

In general, side effects have been classified as mild and transient. Less than 3% of patients in clinical trials discontinued treatment due to side effects. The most frequent adverse reactions associated with immediate-release formulations have included diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%), and vaginitis (1%). Extended-release tablets have been most frequently associated with diarrhea (14.5%), vaginal mycosis (3.3%), nausea (2.1%), and loose stools (1.6%).[Ref]

Gastrointestinal

Gastrointestinal side effects have included diarrhea, nausea, abdominal pain, vomiting, indigestion, gastritis, generalized abdominal cramps, stomatitis, glossitis, mucocutaneous candidiasis, enterocolitis, black "hairy" tongue, small intestinal motor disturbances, hemorrhagic colitis, and pseudomembranous colitis. Colitis and Clostridium difficile pseudomembranous colitis have been reported with amoxicillin.[Ref]

Amoxicillin has been associated with hemorrhagic, sometimes inflammatory colitis, which typically affects the ascending colon. In addition, C difficile pseudomembranous colitis should be considered in patients who develop severe or prolonged diarrhea during or following amoxicillin-clavulanate therapy.

The incidence of diarrhea appears to increase with higher doses, and to decrease with twice daily dosing regimens (of immediate release formulations).[Ref]

Hypersensitivity

Hypersensitivity reactions to amoxicillin are more likely in patients with a history of allergy, asthma, hay fever, or urticaria.[Ref]

Hypersensitivity reactions have occurred in up to 10% of patients, and may present as a skin rash, urticaria, pruritus, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens-Johnson syndrome (rarely), acute generalized exanthematous pustulosis, hypersensitivity vasculitis, exfoliative dermatitis, and toxic epidermal necrolysis. Anaphylaxis has been rarely reported (up to 0.2%). Hypersensitivity may play a role in some cases of amoxicillin-clavulanate-induced renal and hepatic toxicity. Urticarial rash, erythematous maculopapular rash, edema, hypotension, fever, eosinophilia, and dyspnea have been associated with hypersensitivity reactions to amoxicillin.[Ref]

Dermatologic

Three out of four patients with infectious mononucleosis and an amoxicillin-associated rash displayed hypersensitivity to amoxicillin and ampicillin by skin tests and lymphocyte transformation tests. Two of these patients had side-chain-specific sensitization.[Ref]

Dermatologic side effects have included rash, fixed drug eruption, bullous pemphigoid, erythema multiforme, Stevens-Johnson syndrome, and exfoliative dermatitis. Amoxicillin rashes occur more frequently in patients with unrecognized infectious mononucleosis. This rash is not necessarily indicative of a lifelong amoxicillin hypersensitivity.[Ref]

Hepatic

Hepatic side effects have included moderate elevations in serum transaminases (ALT and/or AST). Hepatic dysfunction (including cholestatic jaundice and hepatitis, increases in ALT and/or AST, serum bilirubin, and/or alkaline phosphatase) has been reported infrequently. Rare cases of jaundice, ductopenia, cholestatic hepatitis, granulomatous hepatitis, hepatic necrosis, and hepatocellular damage have also been reported. Less than 1 death per approximately 4 million prescriptions has been reported worldwide. Hepatic cholestasis and acute cytolytic hepatitis have been reported with amoxicillin use.[Ref]

In cases of amoxicillin-clavulanate-induced hepatotoxicity, biopsy findings have typically revealed evidence of cholestatic injury. However, hepatocellular and mixed-type (cholestatic and hepatocellular) injury have also been documented. In many instances, hepatotoxicity may be due to a hypersensitivity. Onset of symptoms has been delayed in some patients, with presentation occurring after therapy has been discontinued. Prolonged treatment may increase the risk of hepatotoxicity. Elderly patients may be at increased risk of developing amoxicillin-clavulanate-induced jaundice. Fatalities are rare, but have been reported.

Rechallenge with amoxicillin alone has not been followed by a recurrence of hepatitis. However, rechallenge with amoxicillin-clavulanate has resulted in a relapse of liver injury. Therefore, the clavulanic acid may be the hepatotoxic part of the drug.

In patients with liver disease, frequent monitoring of liver function tests during amoxicillin-clavulanate therapy is recommended.[Ref]

Renal

Renal side effects have rarely included crystalluria, hematuria, acute renal failure, and acute interstitial nephritis, often associated with fever, rash, and eosinophilia.[Ref]

A 45-year-old female developed massive crystalluria, gross hematuria, and acute anuric renal failure after 12 days of intravenous amoxicillin-clavulanate at a dose of 2 g amoxicillin 3 times daily (not available in the United States). The crystals were composed of amoxicillin trihydrate. The renal failure and hematuria resolved over 6 days after discontinuation of the antibiotic.[Ref]

Hematologic

Amoxicillin has been shown to induce hemolytic anemia in rare cases. A case of bone marrow "maturation arrest" resulting in neutropenia and of Henoch-Schonlein purpura syndrome has been associated with amoxicillin-clavulanate.

A patient undergoing dental extraction and receiving warfarin anticoagulation therapy had prolonged bleeding times (PT and INR), and decreased hemoglobin and hematocrit. The bleeding was felt due to vitamin K deficiency as a result of depletion of intrinsic vitamin K-producing gut flora from use of amoxicillin for prophylaxis of subacute bacterial endocarditis.[Ref]

Hematologic side effects associated with penicillins have included thrombocytopenia, anemia, hemolytic anemia, thrombocytopenic purpura, eosinophilia, agranulocytosis, and leukopenia. These are believed to be due to hypersensitivity and are usually reversible when the drug is discontinued. Mild to moderate thrombocytosis has been reported in less than 1% of patients treated with amoxicillin-clavulanate and 3.6% of patients treated with the extended-release tablets. Purpura, pancytopenia, granulocytopenia, medullary aplasia, prolongation of prothrombin time, and transient neutropenia have also been reported.[Ref]

Immunologic

Immunologic side effects associated with amoxicillin have included mucocutaneous candidiasis and vulvovaginal mycotic infection.[Ref]

Nervous system

Nervous system side effects have rarely included agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, headache, insomnia, and reversible hyperactivity. Rare cases of psychosis associated with amoxicillin therapy have been reported, but may have been due to underlying infection or concomitant medication. Rarely, somnolence and aseptic meningitis have been reported with amoxicillin.[Ref]

Genitourinary

Genitourinary side effects have included genital moniliasis (2.1%).[Ref]

Other

Amoxicillin-clavulanate may cause false-positive urine glucose tests in patients using Clinitest(R) tablets. Enzymatic glucose oxidase tests should be used during amoxicillin-clavulanate therapy.[Ref]

Other side effects have rarely included brown, yellow, or gray tooth discoloration, primarily in pediatric patients. Brushing or dental cleaning reduced or eliminated the discoloration in most cases.[Ref]

Respiratory

Respiratory side effects associated with amoxicillin have included cough and rhinorrhea.[Ref]

Some side effects of Augmentin XR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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