Clorazer

NAME OF THE MEDICINAL PRODUCT
CLORAZER 750 mg modified-release tablets
Cefaclor

COMPOSITION
Each tablet contains:
Active substance: cefaclor monohydrate equivalent to cefaclor 750 mg
Excipients:
Mannitol, methylhydroxypropylcellulose, hydroxypropylcellulose, methacrylic acid copolymer,
stearic acid, magnesium stearate, blue dye mixture, propylene glycol.

PHARMACEUTICAL FORM
Modified-release 750 mg tablets for oral use.

THERAPEUTIC CATEGORY
CLORAZER is a broad-spectrum oral antibiotic belonging to the cephalosporin class.

MARKETING AUTHORISATION HOLDER
Biomed Pharma S.r.l.,
Via Colla 6/3,
17014 Cairo Montenotte (SV)

MANUFACTURED AND CONTROLLED BY
FACTA FARMACEUTICI S.p.A.
Via Laurentina Km 24.730 - 00040 Pomezia (RM)

THERAPEUTIC INDICATIONS
CLORAZER is indicated for the treatment of the following infections caused by susceptible organisms:
Acute bronchitis and acute exacerbation of chronic bronchitis.
Pharyngitis and tonsillitis.
Uncomplicated lower urinary tract infections.
Skin and soft tissue infections.

CONTRAINDICATIONS
Hypersensitivity to cefaclor or to cephalosporin antibiotics, or to any of the other components.

PRECAUTIONS FOR USE
Severe reactions (including anaphylaxis) have occurred in patients following administration of penicillins or cephalosporins, including cefaclor. These IgE-mediated reactions usually manifest as cutaneous, gastrointestinal, respiratory, or cardiovascular symptoms. Symptoms may include: severe and sudden hypotension, tachycardia or bradycardia, unusual fatigue or weakness, anxiety, agitation, dizziness, loss of consciousness, breathing or swallowing difficulties, generalized pruritus (especially on the soles of the feet and palms of the hands), urticaria with or without angioedema (swollen and itchy skin areas, most frequently affecting extremities, external genitalia, and face, particularly around the eyes and lips), facial flushing, cyanosis, profuse sweating, nausea, vomiting, cramp-like abdominal pain, and diarrhea.

Before initiating therapy with CLORAZER, carefully investigate whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs. If an allergic reaction to CLORAZER occurs, discontinue the drug immediately.

Treatment with broad-spectrum antibiotics, including CLORAZER, alters the normal colonic flora and leads to overgrowth of clostridia. Several studies have shown that a toxin produced by Clostridium difficile is the primary cause of severe antibiotic-associated diarrhea, including pseudomembranous colitis. Pseudomembranous colitis has been reported with the use of broad-spectrum antibiotics (including macrolides, semisynthetic penicillins, and cephalosporins); therefore, this diagnosis must be considered in patients who develop diarrhea during or after antibiotic therapy.

Mild cases of colitis usually resolve upon discontinuation of the drug. Moderate to severe cases require appropriate therapeutic measures, including appropriate bacteriological investigations and administration of fluids, electrolytes, and proteins.

If colitis does not improve after discontinuation of the drug or if symptoms are not severe, oral vancomycin is the treatment of choice.

As with other antibiotics, the possibility of emergence of resistant microorganisms during treatment with CLORAZER must be considered, which may lead to superinfection requiring appropriate management.

INTERACTIONS
The extent of absorption of CLORAZER decreases if antacids containing magnesium or aluminium hydroxide are administered within one hour of the antibiotic. H2-receptor antagonists do not alter the rate or extent of CLORAZER absorption.

Like other beta-lactam antibiotics, renal excretion of cefaclor (and presumably CLORAZER) is inhibited by probenecid (an antigout drug that enhances uric acid elimination). No other significant drug interactions have been observed in clinical studies.

SPECIAL WARNINGS
CLORAZER has no effect on the ability to drive or use machinery.

Carcinogenesis, mutagenesis, impairment of fertility
No studies have been conducted in animals to evaluate the potential carcinogenic or mutagenic effects of CLORAZER.
Reproduction studies have not revealed any evidence of impaired fertility.

Use in pregnancy and during breastfeeding
There are no specific, well-controlled studies in pregnant women, and since animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
The use of CLORAZER during labor and delivery has not been studied; therefore, the drug should be administered only if clearly necessary.
The effects of CLORAZER on the nursing infant are unknown. The drug should be used with caution during breastfeeding.

Use in children
The efficacy and tolerability of CLORAZER in children have not been well established.

DOSAGE, ADMINISTRATION AND DURATION
CLORAZER is administered orally and may be taken independently of meals. However, concomitant food intake increases the absorption of CLORAZER. Tablets must be swallowed whole and must not be split, crushed, or chewed.

The following dosage regimens are recommended:

• Pharyngitis, tonsillitis, and skin and soft tissue infections: 375 mg twice daily.
• Uncomplicated lower urinary tract infections: 375 mg twice daily.
• Bronchitis: 375 mg twice daily. Higher doses (750 mg twice daily) may be required for more severe infections. In the treatment of infections caused by S. pyogenes (group A streptococci), therapy with CLORAZER should be continued for up to 10 days.

OVERDOSE
Signs and symptoms: may include nausea, vomiting, epigastric distress, and diarrhea; the severity of gastrointestinal symptoms and diarrhea is dose-related. If other symptoms are present, they are likely secondary to a pre-existing condition, an allergic reaction, or another toxic state.

Treatment: in managing overdose, consider the possibility of multiple drug ingestion, drug interactions, or unusual pharmacokinetics in the patient. Ensure adequate respiratory ventilation and perfusion. Carefully monitor and maintain within acceptable limits vital signs (heart rate and blood pressure), blood gas analysis, serum electrolytes, etc.

Intestinal absorption of drugs may be reduced by administering activated charcoal, which in many cases is more effective than induced emesis or gastric lavage; thus, activated charcoal should be considered as an alternative or additional treatment to gastric emptying. Repeated administration of activated charcoal may enhance elimination of other absorbed drugs.

Protect the patient's airway when performing gastric emptying or administering activated charcoal.

It is not known whether forced diuresis, peritoneal dialysis, hemodialysis, or hemoperfusion with charcoal would be beneficial in the treatment of CLORAZER overdose.

FOR FURTHER INFORMATION ON THE USE OF THIS MEDICINE,
CONSULT YOUR DOCTOR OR PHARMACIST.

UNDESIRABLE EFFECTS
Adverse reactions considered related to CLORAZER treatment include the following:

Allergic manifestations: hypersensitivity reactions (1.5%) have been observed, including morbilliform rashes (1%); pruritus, urticaria, and positive Coombs test occur in fewer than 1 in 200 treated patients. Generalized reactions known as "serum-sickness-like" reactions have also been reported, characterized by erythema multiforme, skin eruptions, and other cutaneous manifestations, often accompanied by arthritis and/or arthralgia (inflammatory or painful joint disorders), with or without fever. "Serum-sickness-like" reactions occur more frequently during or after a course of cefaclor therapy, and more commonly in children than in adults. Signs and symptoms appear a few days after starting treatment and resolve a few days after discontinuation. Antihistamines and corticosteroids facilitate recovery. No severe complications have been observed. More severe hypersensitivity reactions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis) have been reported rarely.

Gastrointestinal manifestations: may occur in approximately 2.5% of patients, sometimes with diarrhea. Pseudomembranous colitis may occur during or after antibiotic treatment. Nausea and vomiting are rarely observed. Transient hepatitis and cholestatic jaundice have been rarely reported with some penicillins and other cephalosporins.

Other manifestations: angioedema (abnormal fluid retention in tissues of allergic origin), eosinophilia, genital pruritus, vaginal moniliasis, vaginitis, and, rarely, thrombocytopenia and reversible interstitial nephritis. Cases of hemolytic anemia have been reported following treatment with cephalosporins.

Effects for which a causal relationship to treatment is uncertain:

CNS: rarely, reversible hyperactivity, restlessness, insomnia, mental confusion, hypertonia (increased muscle tone), hallucinations, sense of instability and staggering, drowsiness.

Digestive system: mild increases in transaminase levels (SGOT and SGPT) or alkaline phosphatase.

Hemolymphatic system: transient lymphocytosis, leukopenia, and, rarely, hemolytic anemia, aplastic anemia, agranulocytosis, and reversible neutropenia. Rare cases of increased prothrombin time, with or without clinical consequences (e.g., bleeding), have been reported in patients receiving cefaclor and sodium warfarin (an antithrombotic agent) concomitantly.

Genitourinary system: slight increases in blood urea nitrogen, serum creatinine, and abnormalities in urine analysis.

Following the instructions in this leaflet reduces the risk of adverse effects.

IF ANY ADVERSE EFFECTS OCCUR – EVEN IF DIFFERENT FROM THOSE DESCRIBED – THE PATIENT IS ADVISED TO INFORM THEIR DOCTOR OR PHARMACIST.

Expiry date: see the date on the packaging.
This date refers to the product stored in its original, unopened packaging under recommended conditions.
WARNING: DO NOT USE THE MEDICINE AFTER THE EXPIRY DATE INDICATED ON THE PACKAGING.
KEEP THE MEDICINE OUT OF THE SIGHT AND REACH OF CHILDREN.