Ceclor (Cefaclor)

CECLOR®

Lilly

Cefaclor

Antibiotic

Action And Clinical Pharmacology: Like other b-lactam antibiotics, cefaclor owes its antibacterial activity to its ability to bind to and inhibit the action of certain bacterial cell wall synthetic enzymes, the penicillin-binding proteins.

Cefaclor is well absorbed after oral administration to fed and fasted subjects. Following doses of 250 mg, 500 mg and 1 g to fasted subjects, average peak serum levels of approximately 7, 13 and 23 mg/L respectively were obtained within 0.5 to 1 hour. Total absorption is the same whether the drug is given before or after meals. However, when it is taken after food, the peak concentration achieved is 50 to 75% of that observed when the drug is administered to fasted subjects and is delayed by 0.8 to 1 hour. Approximately 25% of cefaclor is bound to human plasma.

Within 8 hours 60 to 85% of the drug is excreted unchanged in the urine, the greater portion being excreted within the first 2 hours. During this 8-hour period, peak urine concentrations following the 250 mg, 500 mg and 1 g doses were approximately 600, 900 and 1 900 mg/L respectively.

The serum half-life in normal subjects is 0.6 to 0.9 hours. In patients with reduced renal function, the serum half-life of cefaclor is slightly prolonged. In those with complete absence of renal function, the plasma half-life of the intact molecule is 2.3 to 2.8 hours. Excretion pathways in patients with markedly impaired renal function have not been determined. Hemodialysis shortens the half-life by 25 to 30%.

Probenecid administered with a 500 mg dose of cefaclor increased the peak serum concentration only slightly, from 12.4 to 13.9 mg/L, and urine levels were predictably diminished. The mean half-life among 5 fasted volunteers with normal renal function was 0.8 hour, and probenecid significantly prolonged the half-life to a mean of 1.3 hours.

Indications And Clinical Uses: May be used in the treatment of the following infections caused by S. pyogenes and S. pneumoniae, Staphylococci, (including coagulase-positive, coagulase-negative, and penicillinase producing strains), E. coli, P. mirabilis, K. pneumoniae, H. influenzae, including ampicillin resistant strains: otitis media; lower respiratory tract infections, including pneumonia, bronchitis, and pulmonary complications resulting from cystic fibrosis; upper respiratory tract infections, including pharyngitis and tonsillitis; skin and soft tissue infections; urinary tract infections. Appropriate culture and susceptibility studies should be performed.

Contra-Indications: Hypersensitivity to the cephalosporin antibiotics.

Manufacturers’ Warnings In Clinical States: Before therapy with cefaclor is instituted, careful inquiry should be made concerning previous hypersensitivity reactions to cefaclor, cephalosporins, penicillins or other drugs. If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross-hypersensitivity, including anaphylaxis, among b-lactam antibiotics has been clearly documented.

Antibiotics including cefaclor should be administered with caution, and then only when absolutely necessary, to any patient who has demonstrated some form of allergy, particularly to drugs.

As is the case with all new drugs, patients should be followed carefully so that adverse reactions or unusual manifestations of drug idiosyncrasy may be detected. If an allergic reaction to cefaclor occurs, the drug should be discontinued and the patient treated with the usual agents (e.g., epinephrine, antihistamines, pressor amines or corticosteroids).

Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics, including cefaclor; therefore, it is important to consider its diagnosis in patients who develop diarrhea in association with the use of antibiotics. Such colitis may range in severity from mild to life-threatening. Treatment with broad-spectrum antibiotics 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. Mild cases of pseudomembranous colitis usually respond to drug discontinuance alone. In moderate to severe cases, management should include sigmoidoscopy, appropriate bacteriologic studies, and fluid, electrolyte, and protein supplementation. When the colitis does not improve after the drug has been discontinued, or when it is severe, oral vancomycin is the drug of choice for antibiotic-associated pseudomembranous colitis produced by C. difficile. Other causes of colitis should be ruled out.

Precautions: If an allergic reaction to cefaclor occurs, the drug should be discontinued and the patient treated appropriately.

Pregnancy: The safety of cefaclor in the treatment of infections during pregnancy has not been established. Reproduction studies in rats have revealed no evidence of impaired fertility.

Lactation: Small amounts of cefaclor, up to 0.21 mg/L, have been detected in mother’s milk following administration of single 500 mg doses. The effect on nursing infants is not known. Caution should be exercised when cefaclor is administered to a nursing woman.

Prolonged use of cefaclor may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If super-infection occurs during therapy, administration of cefaclor should cease and appropriate measures should be taken.

Positive direct Coombs’ tests have been reported during treatment with cephalosporin antibiotics. In hematologic studies or in transfusion cross matching procedures, when antiglobulin tests are performed on the minor side or in Coombs’ testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs’ test may be due to the drug.

Cefaclor should be administered with caution in the presence of markedly impaired renal function. Since the half-life of cefaclor in anuria is 2.3 to 2.8 hours, dosage adjustments for patients with moderate or severe renal impairment are not usually required. Clinical experience with cefaclor under such conditions is limited; therefore, careful clinical observation and laboratory studies should be made.

In patients treated with cefaclor, a false-positive reaction for glucose in the urine may occur with Benedict’s or Fehling’s solution or with Clinitest tablets but not with Tes-Tape.

Drug Interactions: There have been rare reports of increased prothrombin time with or without clinical bleeding in patients receiving cefaclor and warfarin concomitantly.

As with many other b-lactam antibiotics, the renal excretion of cefaclor is inhibited by probenecid.

Adverse Reactions: During clinical trials in 8 346 patients (4 626 adults and 3 720 children under the age of 16) treated with cefaclor, the adverse reactions listed below were observed. The majority of these adverse reactions were mild and transient. The incidence rates were less than 1 in 100 (less than 1%), except as otherwise noted.

Gastrointestinal: The most frequent side effect has been diarrhea (1.5%). It was rarely severe enough to warrant cessation of therapy. Nausea, vomiting and dyspepsia have been reported. As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported. Colitis, including rare instances of pseudomembranous colitis, has been reported in conjunction with or after therapy has stopped.

Hypersensitivity: Allergic reactions, such as urticaria and morbilliform eruptions 1%, have been observed, as have pruritus, rash and positive Coombs’ tests. These reactions usually subsided upon discontinuation of the drug. Eosinophilia (2%), genital pruritus or vaginitis, and rarely, thrombocytopenia or reversible interstitial nephritis have also occurred.

Cases of serum sickness-like reactions have been reported. In contrast to classic serum sickness, signs and symptoms of serum sickness-like reactions involving cefaclor appear to be primarily confined to findings including erythema multiforme or other skin manifestations accompanied by arthritis/arthralgia, with or without fever. Serum sickness-like reactions are apparently due to hypersensitivity and more often occur during or following a second (or subsequent) course of therapy with cefaclor. Such reactions have been reported more frequently in children than in adults with an overall occurrence ranging from 1 in 200 (0.5%) in one focused trial to 2 in 8 346 (0.024%) in overall clinical trials (with an incidence in children in clinical trials of 0.055%) to 1 in 38 000 (0.003%) in spontaneous event reports. Signs and symptoms usually occur a few days after initiation of therapy and subside within a few days after cessation of therapy; occasionally these reactions have resulted in hospitalization, usually of short duration (median hospitalization=2 to 3 days, based on postmarketing surveillance studies). In those requiring hospitalization, the symptoms have ranged from mild to severe at the time of admission with more of the severe reactions occurring in children. Antihistamines and glucocorticoids appear to enhance resolution of the signs and symptoms. No serious sequelae have been reported.

More severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema and anaphylaxis have been reported rarely. Anaphylaxis may be more common in patients with a history of penicillin allergy.

CNS: Rarely, reversible hyperactivity, nervousness, insomnia, confusion, hypertonia, headache, dizziness, or somnolence have been reported.

Genitourinary: Vaginal moniliasis and vaginitis have been reported with cefaclor (1%).

Other: Transitory abnormalities in clinical laboratory test results have been reported. Although they were of uncertain etiology, they are listed here to serve as alerting information for the physician.

Hepatic: Slight elevations of AST, ALT, or alkaline phosphatase values have been reported.

Hematopoietic: Transient lymphocytosis, leukopenia, eosinophilia and, rarely, hemolytic anemia, aplastic anemia, agranulocytosis, and reversible neutropenia of possible clinical significance were observed.

There have been rare reports of increased prothrombin time with or without clinical bleeding in patients receiving cefaclor and warfarin concomitantly.

Renal: Slight and transient elevations in BUN or serum creatinine or abnormal urinalysis have been observed with cefaclor.

In addition to the adverse reactions listed above, renal dysfunction and toxic nephropathy have been reported in patients treated with b-lactam antibiotics.

Several b-lactam antibiotics have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Symptoms And Treatment Of Overdose: Symptoms: The toxic symptoms following an overdose of cefaclor may include nausea, vomiting, epigastric distress, and diarrhea. The severity of the epigastric distress and the diarrhea are dose related. If other symptoms are present, it is probable that they are secondary to an underlying disease state, an allergic reaction, or the effects of other intoxication.

Treatment: In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient. Unless 5 times the normal dose of cefaclor has been ingested, gastrointestinal decontamination will not be necessary.

Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal.

Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of cefaclor.

Dosage And Administration: Administered orally, without regard to meals.

Adults: The usual adult dosage is 250 mg every 8 to 12 hours. For more severe infections or those caused by less susceptible organisms, larger doses may be needed. The maximum recommended dosage is 2 g/day, although doses of 4 g/day have been administered safely for 28 days.

For lower respiratory tract infections, the dosage should be administered 3 times daily.

For skin and soft tissue infections the dosage is 250 mg administered 2 or 3 times daily.

Children: The usual recommended daily dosage for children is 20 mg/kg/day in divided doses every 8 to 12 hours. For streptococcal pharyngitis or tonsillitis and soft tissue infections, the total daily dosage may be divided and administered every 12 hours.

In more serious infections, otitis media, and those infections caused by less susceptible organisms, 40 mg/kg/day is recommended, up to 1 g/day.

For otitis media, the total daily dosage may be divided and administered every 12 hours. For lower respiratory tract infections the total daily dosage should be divided and administered 3 times daily.

In the treatment of b-hemolytic streptococcal infections, a therapeutic dosage of cefaclor should be administered for at least 10 days.

Most clinical studies were performed with a duration of therapy between 5 and 14 days.

Directions for Reconstitution of Oral Suspensions: 125 mg: Add 60 mL of water to each 100 mL bottle or 90 mL to each 150 mL bottle in 2 portions. Shake well after each addition.

250 mg: Add 60 mL of water to each 100 mL bottle or 90 mL to each 150 mL bottle in 2 portions. Shake well after each addition.

375 mg: Add 44 mL of water to each 70 mL bottle or 62 mL to each 100 mL bottle in 2 portions. Shake well after each addition.

Availability And Storage: Capsules: 250 mg: Each opaque purple and white capsule contains: cefaclor 250 mg. Nonmedicinal ingredients: cornstarch, FD&C Blue No. 1, FD&C Red No. 3, gelatin, magnesium stearate, silicone and titanium dioxide. Tartrazine-free. Bottles of 100 and 250.

500 mg: Each opaque purple and grey capsule contains: cefaclor 500 mg. Nonmedicinal ingredients: cornstarch, FD&C Blue No. 1, FD&C Red No. 3, gelatin, iron oxide, magnesium stearate, silicone and titanium dioxide. Tartrazine-free. Bottles of 30 and 100.

Oral Suspension: 125 mg: Each 5 mL dose of strawberry-flavored suspension contains: cefaclor 125 mg (25 mg/mL). Nonmedicinal ingredients: artificial strawberry flavor, cornstarch, FD&C Red No. 40, methylcellulose, silicone, sodium lauryl sulfate, sucrose and xantham gum. Energy: 52.9 kJ (12.6 kcal)/5 mL.
250 mg: Each 5 mL dose of strawberry-flavored suspension contains: cefaclor 250 mg (50 mg/mL). Nonmedicinal ingredients: artificial strawberry flavor, cornstarch, FD&C Red No. 40, methylcellulose, silicone, sodium lauryl sulfate, sucrose and xantham gum. Energy: 50.6 kJ (12.1 kcal)/5 mL.
375 mg: Each 5 mL dose of strawberry-flavored suspension contains: cefaclor 375 mg (75 mg/mL). Nonmedicinal ingredients: artificial strawberry flavor, cornstarch, FD&C Red No. 40, methylcellulose, silicone, sodium lauryl sulfate, sucrose and xantham gum. Energy: 47.0 kJ (11.2 kcal)/5 mL.
Store between 15 and 25°C. After reconstitution, oral suspensions must be refrigerated and used within 14 days. Shake well before using. Keep tightly closed.

CECLOR® Lilly Cefaclor Antibiotic

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