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CLAVULIN®
SmithKline Beecham
Amoxicillin - Clavulanate Potassium
Antibiotic - b-Lactamase Inhibitor
 
Action And Clinical Pharmacology: Amoxicillin exerts a bactericidal action against sensitive organisms during the stage of active multiplication through the inhibition of the biosynthesis of bacterial cell wall mucopeptides. Clavulanic acid inhibits specific b-lactamases of some microorganisms and allows amoxicillin to inhibit amoxicillin (ampicillin) resistant organisms which produce clavulanic acid sensitive b-lactamases. tag_IndicationsIndications

Indications And Clinical Uses: For the treatment of the following infections when caused by Clavulin-susceptible strains of the designated bacteria: Upper respiratory tract infections when caused by b-lactamase producing strains of S. aureus. Sinusitis when caused by b-lactamase producing strains of H. influenzae or M. (B.) catarrhalis. Otitis media when caused by b-lactamase producing strains of H. influenzae or M. (B.) catarrhalis.

Lower respiratory tract infections when caused by b-lactamase producing strains of H. influenzae, K. pneumoniae, S. aureus or M. (B.) catarrhalis. Skin and soft tissue infections when caused by b-lactamase producing strains of S. aureus. Urinary tract infections when caused by b-lactamase producing strains of E. coli, P. mirabilis or Klebsiella species.

While Clavulin is indicated only for the conditions listed above, infections caused by ampicillin (amoxicillin) susceptible organisms are also amenable to Clavulin treatment due to its amoxicillin content. Furthermore, mixed infections caused by organisms susceptible to ampicillin (amoxicillin) and b-lactamase producing organisms susceptible to Clavulin should not require the addition of another antibiotic.

Appropriate culture and susceptibility studies should be performed to identify the causative organism(s) and determine the susceptibility to Clavulin. However, when there is reason to believe an infection may involve any of the b-lactamase producing organisms listed above, therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies. Once these results are known, therapy should be adjusted if appropriate.

Contra-Indications: In patients with a history of hypersensitivity to the penicillin, clavam, or cephalosporin group of b-lactams.

In patients where infectious mononucleosis is either suspected or confirmed.

In patients with a previous history of Clavulin-associated jaundice/hepatic dysfunction.

Manufacturers' Warnings In Clinical States: Serious and occasionally fatal hypersensitivity reactions (anaphylaxis and angioedema) have been reported in patients on penicillin therapy. Although these reactions are more frequent following parenteral therapy, they have occurred in patients receiving penicillins orally. These reactions are most apt to occur in individuals with a history of sensitivity to multiple allergens. There have been reports of individuals with a history of cephalosporin hypersensitivity who have experienced severe reactions when treated with penicillins. Before initiating therapy with Clavulin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, clavams, or other allergens.

If an allergic reaction occurs the administration of Clavulin should be discontinued and appropriate therapy should be instituted. Serious anaphylactoid reactions require immediate emergency treatment with epinephrine. Oxygen, i.v. steroids, and airway management, including intubation, should also be used as indicated.

Clavulin should be used with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of Clavulin is usually reversible. On rare occasions, deaths have been reported (less 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 Effects, Liver).

Precautions: Periodic assessment of renal, hepatic, and hematopoietic function should be made during prolonged therapy.

Clavulin is excreted mostly by the kidney. There is insufficient data to make specific dosage recommendations for patients with renal dysfunction. However, either a reduction in dose level or an extension in dose interval in proportion to the degree of loss of renal function will be needed.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfection should occur (usually involving Aerobacter, Pseudomonas, or Candida), the administration of Clavulin should be discontinued and appropriate therapy instituted.

The occurrence of a morbilliform rash following the use of ampicillin in patients with infectious mononucleosis is well documented. This reaction has also been reported following the use of amoxicillin. A similar reaction would also be expected with Clavulin.

In common with other broad-spectrum antibiotics, Clavulin may reduce the efficacy of oral contraceptives and patients should therfore be advised accordingly.

Pregnancy: The safety of Clavulin in the treatment of infections during human pregnancy is unknown. As with all medicines, use should be avoided during pregnancy, especially during the first trimester, unless the anticipated benefit justifies the potential risk to the fetus.

Lactation: Penicillins (including ampicillin) have been shown to be excreted in human breast milk. It is not known whether clavulanic acid is excreted in breast milk. Caution should be exercised if Clavulin is to be administered to a nursing mother.

Adverse Reactions: Gastrointestinal: nausea, vomiting, diarrhea, abdominal cramps, flatulence, constipation, anorexia, colic pain, acid stomach, intestinal candidiasis and pseudomembranous colitis. If gastrointestinal reactions are evident, they may be reduced by taking Clavulin at the start of the meal. The incidence of gastrointestinal side effects tends to be proportional to dose and tends to be greater in children than in adults.

Hypersensitivity: erythematous maculopapular rash, urticaria, anaphylaxis, and pruritus. A morbilliform rash in patients with mononucleosis. Rarely erythema multiforme and Stevens-Johnson syndrome have been reported. Other reactions including angioedema, toxic epidermal necrolysis and exfoliative dermatitis, as in the case of other beta lactam antibiotics, have been seen rarely. Interstitial nephritis can occur rarely.

Note: Urticaria, other skin rashes, and serum sickness-like reactions may be controlled with antihistamines and if necessary systemic corticosteroids. Whenever such reactions occur, discontinue therapy unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to Clavulin therapy.

Liver: Transient hepatitis and cholestatic jaundice have been reported rarely. These events have been noted with other penicillins and cephalosporins. The hepatic events associated with Clavulin may be severe, and occur predominantly in adult and elderly patients. Signs and symptoms usually occur during or shortly after treatment, but in some cases may not become apparent until several weeks after treatment has ceased. The hepatic events are usually reversible. However, in extremely rare circumstances, deaths have been reported. These have almost always been cases associated with serious underlying disease or concomitant medications. Moderate rises in AST, alkaline phosphatase, lactic dehydrogenase and ALT have been noted in patients treated with ampicillin class antibiotics. The significance of these findings is unknown.

Hemic and Lymphatic Systems: As with other beta-lactams, anemia, hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, lymphocytopenia, basophilia, slight increase in platelets, neutropenia and agranulocytosis have been reported rarely during therapy with the penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Prolongation of bleeding time and prothrombin time have also been reported rarely.

Other: vaginitis, headache, bad taste, dizziness, malaise, glossitis, black hairy tongue, and stomatitis.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: There has been no reported overdosage. If a large overdose is consumed, the patient should be kept under observation and appropriate treatment undertaken as considered necessary. tag_DosageDosage

Dosage And Administration: The absorption of Clavulin is optimized when taken at the start of a meal.

Adults: Note: Since both Clavulin-250 and Clavulin-500F contain the same amount of clavulanic acid (125 mg as the potassium salt) 2 tablets Clavulin-250 are not equivalent to 1 tablet Clavulin-500F. Therefore, 2 tablets Clavulin-250 should not be substituted for 1 tablet Clavulin-500F. See Table I.

Each 25 mg of Clavulin oral suspension is equivalent to 0.80 mL of reconstituted Clavulin-125F and 0.40 mL of reconstituted Clavulin-250F.

20 mL of reconstituted Clavulin-125F oral suspension or 10 mL of reconstituted Clavulin-250F oral suspension are equivalent to 1 Clavulin-500F tablet. There is no equivalency between Clavulin oral suspensions and the Clavulin-250 tablet because of the different ratio of amoxicillin: clavulanic acid.

A calibrated dropper should be used to measure the appropriate volume for dosing.

The normal duration of treatment is 7 to 10 days. However, in general, treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days treatment for any infection caused by b-hemolytic streptococci to prevent the occurrence of acute rheumatic fever or glomerulonephritis.

Reconstitution: Reconstitute with purified water: Clavulin-125F Powder for Oral Suspension: The approximate average concentration after reconstitution is 125 mg of amoxicillin (as the trihydrate) and 31.25 mg of clavulanic acid (as the potassium salt) per 5 mL. See Table IV.

Stability and Storage: Store powder in a dry place at room temperature. Use the powder only if its appearance is white to off-white. The reconstituted suspension should be stored under refrigeration and should be used within 10 days. Keep bottle tightly closed at all times.

Availability And Storage: Suspension: Clavulin-125F: Each 5 mL of reconstituted suspension contains: amoxicillin 125 mg as the trihydrate and clavulanic acid 31.25 mg as the potassium salt (in a ratio of 4:1). Nonmedicinal ingredients: aspartame, colloidal silica, flavors (golden syrup dry, orange dry 1, orange dry 2, raspberry dry), hydroxypropyl methylcellulose, silicon dioxide, succinic acid and xantham gum. Bottles of 100 and 150 mL.

Clavulin-250F: Each 5 mL of reconstituted suspension contains: amoxicillin 250 mg as the trihydrate and clavulanic acid 62.5 mg as the potassium salt (in a ratio of 4:1). Nonmedicinal ingredients: aspartame, colloidal silica, flavors (golden syrup dry, orange dry 1, orange dry 2, raspberry dry), hydroxypropyl methylcellulose, silicon dioxide, succinic acid and xantham gum. Bottles of 100 and 150 mL.

Tablets: Clavulin-250: Each white oval tablet contains: amoxicillin 250 mg as the trihydrate and clavulanic acid 125 mg as the potassium salt (in a ratio of 2:1). Nonmedicinal ingredients: colloidal silica, dimethicone 500, hydroxypropyl methylcellulose (methocel E5), hydroxypropyl methylcellulose (methocel E15), magnesium stearate, microcrystalline cellulose, polyethylene glycol 4 000, polyethylene glycol 6 000, sodium starch glycollate and titanium dioxide. Bottles of 100.

Clavulin-500F: Each white oval tablet contains: amoxicillin 500 mg as the trihydrate and clavulanic acid 125 mg as the potassium salt (in a ratio of 4:1). Nonmedicinal ingredients: colloidal silica, dimethicone 500, hydroxypropyl methylcellulose (methocel E5), hydroxypropyl methylcellulose (methocel E15), magnesium stearate, microcrystalline cellulose, polyethylene glycol 4 000, polyethylene glycol 6 000, sodium starch glycollate and titanium dioxide. Bottles of 30 and 100.

Clavulin Discs: Each disc is impregnated with: amoxicillin 20 µg as trihydrate and clavulanic acid 10 µg as the potassium salt (in a ratio of 2:1). Cartridges of 50 susceptibility discs. (Shown in Product Recognition Section)