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Each tablet contains: Amoxicillin (as trihydrate) 500 mg, Clavulanic Acid (as Potassium clavunate) 125 mg.
CO-AMOXICLAV is an antibacterial combination consisting of semisynthetic antibiotic amoxicillin and β-lactamase inhibitor, potassium clavulanate (the potassium salt of clavulanic acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. Clavulanic acid is a β-lactam structurally related to the penicillins and possess the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. It is particularly active against the clinically important plasmid mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins.

Susceptible strains: Staphylococcus aureus*, Staphylococcus epidermidis*, Streptococcus pyogenes (group A β-hemolytic), Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Bacillus anthracis, Listeria monocytogenes, Clostridium spp., Peptococcus spp., Peptostreptococcus spp., Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella species*, Salmonella spp.*, Bordetella pertussis, Yersinia enterocolitica*, Brucella spp., Neisseria meningitidis, Neisseria gonorrhoeae*, Moraxella catarrhalis*, Hemophilus influenzae*, Hemophilus ducreyi*, Pasteurella multocida, Campylobacter jejuni, Vibrio cholerae, Bacteroides (including Bacteroides fragilis*).
(*β-lactamase and non β-lactamase producing)
Indications: Acute & chronic bronchitis, lobar and bronchial pneumonia, empyema, pulmonary abscess, tonsillitis, sinusitis, otitis media; Cystitis, urethritis, pyelonephritis; Septic abortion, puerperal sepsis, pelvic inflammatory disease, chancroid, gonorrhea; Furunculus and abscess, cellulitis, wound infection; Peritonitis; Myelitis; Sepsis, intra-abdominal sepsis; Dental infections (except injection): Infection after operation (in case of injection).

Adult and pediatric patient over 12 years or weighting 40 kg or more: 375mg tablet every 8 hours. For more severe infections and infections respiratory tract, the dose may be one 625mg tablet or two 375mg tablets every 8 hours. For dental infections, the dose should be one 375mg tablet every 8 hours for 5 days.
For renal dysfunction, fluctuate depend on creatinine clearance rate.
Patients with impaired renal function: Adjust the dose by creatinine clearance as follows: (See table.)

Click on icon to see table/diagram/image

Symptoms: The problems of overdose are seldom occurred but when it occurs, gastrointestinal symptoms (stomach & abdominal pain, diarrhea, vomiting, etc.), imbalance of body fluids and electrolytes, and in some cases, rashes, hyperactivity disease, drowsiness, might be observed.
In case of amoxicillin overdose, it has been rarely reported that interstitial nephritis was observed due to oliguric renal failure. The symptoms of renal failure has been reversibly recovered when the administration of the drug was stopped. Patients with renal failure have maintained high blood concentrations of drug because of decreased renal clearance rates of amoxicillin and potassium clavulanate.
In case of penicillin overdose, epileptic convulsion might occur. Patients receiving penicillin have often shown anaphylactic shock, although it is not a symptom due to poisoning. It is rare but acute and can be fatal. It might be generally appeared within 30 minutes of drug administration. All possible treatments should be performed immediately to normalize the blood circulation.
Other allergic reactions such as skin reactions, bleeding, and pancytopenia can be occurred.
Treatments: Stop the medication immediately if it occurred and treatments should be performed depending on the symptoms while balancing the water-electrolyte equilibrium. This drug can be eliminated by hemodialysis. If the overdose 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 (in case of oral preparations).
In the presence of convulsion due to overdose, diazepam is used to tranquilize the condition.

Do not give this medicine to the following patients: Patients with a history of hypersensitivity or allergic reactions (including shock) to any ingredient of this medicine or β-lactam (penicillin, cephem) drugs (concerns for cross-resistance for β-lactam drugs).
Patients with accompanying infection of virus diseases such as infectious mononucleosis and lymphocytic leukemia (possible increase of eruption or rashes).
Patients with a history of amoxicillin/clavulanate potassium-associated or penicillin-associated jaundice or hepatic dysfunction (possible recurrence).

Patients with severe hepatic dysfunction (the hepatic dysfunction may be aggravated).
Patients with moderate or severe renal disorder (to be used with proper intervals because the blood concentrations is maintained longer than patients without renal disorder).
Patients who or whose patients or siblings is/are susceptible to such allergic symptoms as bronchial asthma, rashes, urticaria, etc.
Patients with poor oral intakes, parenteral nutrition, elderly, or poor general condition (possible vitamin K deficiency).
Patients with gastro-intestinal diseases with vomiting or diarrhea (no guarantee to sufficient drug absorption) (in case of oral medication).
Because this drug contains potassium, patients who have to restrict potassium should consider its contents.
Also, patients who have to restrict sodium should consider its content if high-dose parenteral administration is required (in case of injections).
General Precautions: It is desirable to use this drug for the minimum period of time that is required for the treatment by confirming the sensitivity to prevent the expression of drug-resistant bacteria.
Serious and occasionally hypersensitivity (anaphylactic) reactions and angioedema have been reported in patients on penicillin therapy. These reactions are more likely to occur in patients with the history of hypersensitivity to penicillins or multiple allergens. It occurs more often in parenteral therapy but it also occurs in oral therapy.
Treatment should be directed to the careful monitoring and the maintenance of sedate condition, because anaphylactic shock can occur although it is rare. After the administration, the patient should be maintained with stable condition and carefully observed. When serious anaphylactic reaction occurs, emergency treatment such as epinephrine should be quickly performed. Perform treatments as instructed by doctors such as catheterization, oxygen supply, intravenous injection of corticoids, and securing the airway.
Almost all antibiotics including this drug have been reported as causing moderate to severe pseudomembranous colitis. Thus, it is important to observe and diagnose patients with continuous diarrhea among patients who have received antibiotics including this drug. The intestinal flora can be changed due to the use of antibiotics and causes the overgrowth of clostridia. According to some studies, toxins produced by Clostridium difficile is the major cause of antibiotic-associated colitis. If diagnosed as having pseudomembranous colitis, the treatment should be initiated. Mild pseudomembranous colitis can be recovered by stopping the drug. Moderate to severe cases should be treated with fluids, electrolytes, and protein supplementation, and then treated with clinically effective antibiotics against Clostridium difficile.
Sometimes the excessive proliferation of insusceptible bacteria can be observed with prolonged drug use. Thus it should be carefully observed when used more than 14 days.
Changes in liver function tests have been observed in some patients receiving this drug. The clinical significance of these changes is uncertain but Co-amoxiclav should be used with caution in patients with signs of hepatic dysfunction. Cholestatic jaundice which may be severe but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for 6 weeks after the treatment has ceased.
Because most of this drug is excreted through the kidney, the dosage of this drug should be controlled in patients with more than medium degree of renal dysfunction (see Dosage & Administration for recommended dosing for patients with impaired renal function).
Because erythematous eruption is related to infectious mononucleosis that is developed due to the use of amoxicillin, the use of this drug should be avoided when infectious mononucleosis is concerned.
When symptoms such as urticaria, skin rash, and serum diseases occur, stop the medication and consult the medication and take proper actions.
This drug has low toxicity among penicillins antibiotics, but regular observations on renal function, hepatic function, and hematopoiesis are necessary in case of prolonged administration.
An inquiry is necessary to confirm the medical history of hypersensitivity reactions to penicillins, cephalosporins, or other allergens before starting the treatment with this drug.
Store reconstituted suspension under refrigeration and use within 7 days (in case of dry syrup products).
Use in Children: Administration to Infants (In Case of Oral Medication): The safety for premature babies and infants (less than 2 months of age) has not been established (in case of syrup preparation). The safety or young children has not been established (few experiences) (in case of tablets).
Use in Elderly: Take precautions when administer to the elderly by checking the condition of patients and the dosage and intervals.
Adverse reactions can be easily developed due to decreased physiological functions.
Hemorrhage can be occurred due to vitamin K deficiency.

Reproduction studies in animals with orally and parenterally administered this drug have shown no teratogenic effects. There are, however, no adequate and well-controlled studies in pregnant women. Therefore, this drug should be given to pregnant women only if the potential benefits justifies the potential risk, and should not be used during the first trimester.
During the period of lactation, trace amount of penicillin antibiotics (including ampicillin) may be transferred to breast milk.
The administration of this drug to nursing mothers can cause some risks in infants such as diarrhea, mucosal colonisation with fungus, and hypersensitivity reactions (skin rashes, etc.) Thus, when abnormal reactions occur, stop the medication.

Gastrointestinal: Diarrhea, pseudomembranous colitis, indigestion, stomatitis, rarely gastritis, glossitis, black hairy tongue, and occasionally nausea, vomiting, loss of appetite, abdominal pain, abdominal distention, constipation, colonalgia, gastric hyperacidity, loose stools and dry mouth have been reported. Candidiasis and antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) has been reported rarely. It is less occurred after parenteral administration (in case of injections). Severe colitis along with bloody stool can be occurred, thus regular check-up or observation is necessary and if abdominal pain and frequent diarrhea occurred, stop the medication and take proper actions. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal side effects occur with oral administration, they may be reduced by taking Co-amoxiclav tablet at the start of meals. As with other antibiotics the incidence of gastrointestinal side effects may be raised in children under two years. In clinical trials, however, only 4% of children under 2 years were withdrawn from treatment.
Liver: Moderate rises in AST, ALT, ALP, LDH, and serum bilirubin have been reported occasionally. Hepatitis and cholestatic jaundice have been reported rarely. These symptoms have been reported more frequently in this drug than other penicillin drugs and more commonly in adults, elderly patients (in particular, over 60), or males. Signs and symptoms of adverse reactions can be occurred during the treatment but can be reported later at 6 weeks after cessation of treatment. Hepatic reactions are usually reversible but very rare deaths have been reported. These deaths have been generally related to patients with prolonged serious illness or co-administration of other drugs. Abnormal hepatic reactions have been mainly reported in males and the elderly, which were increased in case of prolonged treatment of more than 14 days. Histologic observation on liver biopsy has shown cholestatic, hepatocellular, or combination of both changes. In particular, it has been reported in young children in rare cases. The period of drug administration should be properly examined depending on indications and should not be exceeded 14 days without examination.
Hypersensitivity: Rarely, itch and erythema multiforme exudativum, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, and acute generalized exanthematous pustulosis (AGEP) have been reported. These skin reactions can be controlled by antihistamines or systemic corticosteroids if necessary. If rashes are developed, stop the medication and follow the doctors' instruction. As with other β-lactam antibiotics, angioedema, anaphylaxis, serum sickness-like syndrome [serum sickness-like III type hypersensitivity (immune complex disease) is characterized by fever, rashes (particularly skin rash around the mouth, urticaria, urticaria rash), arthralgia, edema, and lymphadenopathy]. Hypersensitivity angitis, acute generalized exanthematous pustulosis (AGEP), dyspnea with bronchospasm, laryngeal edema, and decreased blood pressure that causes anaphylactic shock.
Hematology: As with other β-lactam antibiotics, reversible leucopenia (including neutropenia and agranulocytosis), reversible thrombocytopenia and haemolytic anemia, thrombocytopenic purpura, eosinophilia, leukemia, agranulocytosis and lymphocytopenia have been reported rarely. Slight thrombocytosis and myelosuppression have been rarely reported. Also, the extension of bleeding time and prothrombin time has been reported rarely.
Genitourinary: In addition to mucocutaneous candidiasis, vaginal itch, soreness, or discharge can be increased.
CNS: Adverse reactions to the CNS are very rare but possible. These reactions include dysesthesia, anxiety, behavioral changes, confusion, drowsiness, insomnia, reversible hyperactivity, dizziness, rarely headaches and convulsions. Convulsions may occur with impaired renal function or at high dose therapy doses.
Renal: Serious renal dysfunction such as acute renal failure, interstitial nephritis, and related hematuria can be rarely possible. Thus, close observation including regular check-up is necessary and if abnormality is recognized, stop the medication and take proper action.
Superinfection: Rare occurrence of stomatitis and candidiasis. When these symptoms occur, stop the medications and take proper actions.
Vitamin deficiencies: Vitamin K deficiencies (hypoprothrombinemia, bleeding tendency, etc.) and vitamin B complex deficiencies (glossitis, stomatitis, loss of appetite, neuritis, etc.) are rarely possible.
Others: Superficial tooth discoloration has been reported in young children and rarely in adults, mostly with the suspension. However, it can usually be removed by brushing and good oral hygiene can prevent the discoloration of teeth (in case of syrups). Also, dysgeusia and malaise have been rarely reported.

It is not desirable to use with probenecid at the same time. Probenecid decreases the renal tubular secretion of amoxicillin and thus concurrent use with Co-amoxiclav may result in increased and prolonged blood levels of amoxicillin regardless of clavulanic acid.
Concomitant use of allopurinol and ampicillin can increase the likelihood of allergic skin reactions (rashes) in patients when compared in those receiving ampicillin only. However, it is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients.
Co-administration of disulfiram cannot be recommended.
Prolongation of bleeding time and prothrombin time has been reported in some patients receiving this drug. Thus, more cautious administration of this drug is recommended in case of patients under the anticoagulant therapy.
Patients should aware that it can reduce the efficacy of oral contraceptive by influencing the intestinal flora.
Simultaneous administration of acetyl salicylic acid, phenylbutazone, and large amount of anti-inflammatory agent with penicillin increases the blood concentration.
Co-administration of oral chemotherapy antibiotics including tetracyclines, macrolides, sulfonamides, and chloramphenicols develops antagonism (counteraction).
When used with sulfasalazine at the same time, it decreased the plasma concentration of sulfasalazine.
Amoxicillin decreases the renal clearance rate of methotrexate.
Changes of INR (international normalized ratio): The increased anticoagulant activity has been reported in patients who received anticoagulant with antibiotics including this drug. Infectious diseases (and accompanied by inflammation), age, and general condition of a patient can become risk factors. Although the interaction between this drug and warfarin has not been proved through clinical studies, INR monitoring should be performed and the dose of oral anticoagulants should be properly controlled if necessary. Some kinds of antibiotics, particularly fluoroquinolones, macrolides, cyclines, co-trimoxazole, and some cephalosporins heavily interact with anticoagulants.
The absorption of cardiac glycosides (including digoxin) can be increased in some patients because the use of antibiotics affects the intestinal flora.
Drug Laboratory Interactions: This drug is largely excreted in the urine. High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using Clinitest, Benedict's Solution or Fehling's Solution. Thus, it is not desirable to perform these tests while a patient is receiving this drug. This drug does not influence tes-tape test.
It has been observed that the plasma concentrations of total conjugated estriol, estriol glucoronide, conjugated estrone, and estradiol were temporarily decreased when ampicillin was administered to pregnant women. This result was also observed when amoxicillin and this drug were administered.
It can be influenced in the urobilinogen test.
Clavulanic acid tends to be absorbed on the membrane surface of erythrocytes. If an antibody for the drug exists, the result of the Coombs' test can be positive.
It should be careful for the following tendency when using high concentration of amoxicillin: It interferes with the decision of total protein ratio of serum due to color reaction.

Cautions in Application (In Case of Injection): This drug can be used as intravenous injection or intermittent drip infusion, but not appropriate for intramuscular injection.
Discard any remaining solution.
Because the stability of this drug is decreased in solutions containing glucose, dextran or bicarbonate, do not mix with these solutions. However, it can be administered through infusion cannula for 3-4 minutes.
Do not mix this drug with protein solutions such as blood preparations and other protein hydrolysates preparations (amino acid mixtures), lipid emulsion for intravenous infusion, hydrocortisone succinate, neosynephrine hydrochloride, and mannitol solution (diuresis concentration).
When this drug is prescribed along with aminoglycosides antibiotics, the potency of aminoglycoside antibiotics can be lost and should not be mixed inside the syringe or infusion container.
In case of high dosage, adequate fluid intake and diuresis should be maintained to minimize the risk of crystalluria. When it is existed with high concentration in the urine, amoxicillin, can be precipitated in urethral catheter and thus patency test should be done on a regular basis.

Store at temperatures not exceeding 30°C.

Penicillins

J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

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