Clavulin

In common with other broad spectrum antibiotics, amoxicillin-clavulanate may reduce the efficacy of combined oral contraceptives by altering the gut-flora to result in lower estrogen reabsorption. Concomitant use of probenecid is not recommended, and may result in increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.

CLAVULIN is excreted mostly by the kidney. There are 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.

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.

Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of CLAVULIN should be modified in pediatric patients younger than 12 weeks (3 months) (see Dosage, Children).

In infants 12 weeks (3 months) of age or older and in children, b.i.d. use of the CLAVULIN 200 and 400 mg formulations is recommended because of a significantly reduced incidence of diarrhea with the b.i.d. regimen (see Adverse Effects).

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

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

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including CLAVULIN, and has ranged in severity from mild to life-threatening; therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by C. difficile is one primary cause of “antibiotic-associated colitis.” After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.

CLAVULIN suspensions, which contain aspartame, should be used with caution in patients with phenylketonuria.

In a single study in women with preterm, premature rupture of the fetal membranes (pPROM), it was reported that prophylactic treatment with CLAVULIN may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided in pregnancy, unless considered essential by the physician.

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 xanthan gum. Bottles of 100 and 150 mL.

Each white oval film-coated 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 4000, polyethylene glycol 6000, sodium starch glycolate and titanium dioxide. Bottles of 100.

Each white, capsule-shaped tablet contains: amoxicillin 875 mg as the trihydrate and clavulanic acid 125 mg as the potassium salt (in a ratio of 7:1). Nonmedicinal ingredients: colloidal silica, dimethicone 500, hydroxypropyl methylcellulose (methocel E5), hydroxypropyl methylcellulose (methocel E15), magnesium stearate, microcrystalline cellulose, polyethylene glycol 4000, polyethylene glycol 6000, sodium starch glycolate and titanium dioxide. Bottles of 60.

Each white oval film-coated 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 4000, polyethylene glycol 6000, sodium starch glycolate and titanium dioxide. Bottles of 100.

Each 5 mL of reconstituted suspension contains: amoxicillin 400 mg as the trihydrate and clavulanic acid 57 mg as the potassium salt (in a ratio of 7:1). Nonmedicinal ingredients: aspartame, colloidal silica, flavors (golden syrup dry, orange dry 1, orange dry 2, raspberry dry), hydroxypropyl methylcellulose, silicon dioxide, succinic acid and xanthan gum. Bottles of 70 mL.

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 xanthan gum. Bottles of 100 and 150 mL.

Each 5 mL of reconstituted suspension contains amoxicillin 200 mg as the trihydrate and clavulanic acid 28.5 mg as the potassium salt (in a ratio of 7:1). Nonmedicinal ingredients: aspartame, colloidal silica, flavors (golden syrup dry, orange dry 1, orange dry 2, raspberry dry), hydroxypropyl methylcellulose, silicon dioxide, succinic acid and xanthan gum. Bottles of 70 mL.

vaginitis, headache, bad taste, dizziness, malaise, glossitis, black hairy tongue and stomatitis. Tooth discoloration has been reported very rarely in children and less frequently in adults. Good oral hygiene may help to prevent tooth discoloration as it can often be removed by brushing.

nausea, vomiting, diarrhea, abdominal cramps, flatulence, constipation, anorexia, colic pain, acid stomach, mucocutaneous candidiasis, intestinal candidiasis, antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) have been reported rarely. 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.

A US-Canadian clinical trial compared a 10-day CLAVULIN b.i.d. regimen (45/6.4 mg/kg/day q12h) with a 10-day CLAVULIN t.i.d. regimen (40/10 mg/kg/day q8h) in 575 patients with acute otitis media, aged 2 months to 12 years. The incidence of diarrhea was significantly lower in patients who received the b.i.d. regimen compared to patients who received the t.i.d. regimen (9.6% vs 26.7%; p<0.001). Significantly fewer patients who received the b.i.d. regimen withdrew due to diarrhea compared to patients receiving the t.i.d. regimen (2.8% vs 7.6%; p=0.009). The incidence of related/possibly related diaper rash was also lower in patients who received the b.i.d. regimen compared to patients who received the t.i.d. regimen (3.1% vs 6.6%; p=0.054).

Data from 2 pivotal studies in 1191 patients treated for either lower respiratory tract infections or complicated urinary tract infections compared a regimen of 875 mg CLAVULIN tablets every 12 hours with 500 mg CLAVULIN tablets dosed every 8 hours.

The most frequently reported adverse event was diarrhea; incidence rates were similar (14.9% and 14.3% respectively) for the 875 mg every 12 hours and 500 mg every 8 hours dosing regimens. However, there was a statistically significant difference in rates of moderate/severe diarrhea between the regimens: 3.4% for 875 mg every 12 hours dosing vs 5.9% for the 500 mg every 8 hours dosing.

Convulsions may occur with impaired renal function or in those receiving high doses.

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/or ALT have been noted in patients treated with ampicillin class antibiotics. The significance of these findings is unknown.

Erythematous maculopapular rash, urticaria, anaphylaxis, hypersensitivity vasculitis 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, and acute generalized exanthematous pustulosis (AGEP) as in the case of other β-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, CLAVULIN should be discontinued, unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to CLAVULIN therapy.

Very rare: crystalluria (see Overdose).

As with other β-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.

Many patients have been asymptomatic following overdosage or have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Warnings for use).

In the case of overdosage, discontinue CLAVULIN, treat symptomatically, and institute supportive measures as required. If gastrointestinal symptoms and disturbance of the fluid and electrolyte balances are evident, they may be treated symptomatically. CLAVULIN can be removed from the circulation by hemodialysis. 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 centre suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying. Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin. 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.

Reconstitute powder for oral suspension with purified water.

Shake vigorously.

Oral Suspensions: Store powder in a dry place at room temperature (15 to 25°C). Use the powder only if its appearance is white to off-white.

The reconstituted CLAVULIN-125F and CLAVULIN-250F oral suspension should be stored under refrigeration and should be used within 10 days.

The reconstituted CLAVULIN-200 and CLAVULIN-400 oral suspension should be stored under refrigeration and should be used within 7 days.

Keep bottle tightly closed at all times.

Tablets: Store in a dry place at room temperature (15 to 25°C).

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

The usual adult dose is 1 CLAVULIN 500 mg tablet every 12 hours or 1 CLAVULIN 250 mg tablet every 8 hours. For more severe infections and infections of the lower respiratory tract, the dose should be 1 CLAVULIN 875 mg tablet every 12 hours or 1 CLAVULIN 500 mg tablet every 8 hours.

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