NECLORAL 750 mg Модифицированные Таблетки

Содержание инструкции

1. NECLORAL 750 mg modified-release tablets
2. NECLORAL “250 mg/5 ml – Granulato per sospensione orale”

NECLORAL 750 mg modified-release tablets

Cefaclor monohydrate
Equivalent medicinal product
COMPOSITION
Each tablet contains:

Active ingredient:
Cefaclor monohydrate equivalent to Cefaclor 750 mg

Excipients:hydroxypropylmethylcellulose, mannitol, povidone, magnesium stearate, colloidal silica, propylene glycol, titanium dioxide.

PHARMACEUTICAL FORM AND CONTENT
Modified-release tablets in packs of 6 tablets.

PHARMACOTHERAPEUTIC CATEGORY
Oral antibiotic, belonging to the class of cephalosporins.

MARKETING AUTHORISATION HOLDER
NEW RESEARCH srl
Via della Tenuta di Torrenova n° 142 - 00133 Rome

MANUFACTURER AND FINAL CONTROLLER
FACTA FARMACEUTICI S.p.A.
Via Laurentina Km 24,730 - 00040 Pomezia (Rome)

THERAPEUTIC INDICATIONS
NECLORAL 750 mg modified-release tablets is indicated for the treatment of the more severe forms of the following infections:

• acute bronchitis and exacerbation of chronic bronchitis;
• pharyngitis and tonsillitis;
• skin and soft tissue infections;
• uncomplicated lower urinary tract infections.

CONTRAINDICATIONS
Hypersensitivity to the active ingredient or to any of the excipients and to other cephalosporins or penicillins.

PRECAUTIONS FOR USE
There have been patients who have experienced severe reactions (including anaphylaxis) following the administration of penicillins or cephalosporins including Cefaclor, IgE-mediated reactions that usually manifest at the skin, gastrointestinal, respiratory and cardiovascular levels.
Symptoms may include: severe and sudden hypotension, acceleration and slowing of the heartbeat, unusual fatigue or weakness, anxiety, agitation, dizziness, loss of consciousness, difficulty breathing or swallowing, generalized itching especially on the soles of the feet and palms of the hands, urticaria with or without angioedema (swollen and itchy skin areas located more frequently on the extremities, external genitalia and face, especially in the region of the eyes and lips), redness of the skin especially around the ears, cyanosis, profuse sweating, nausea, vomiting, cramp-like abdominal pain, diarrhea.
Before initiating therapy with NECLORAL, careful investigation should be carried out to determine if the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs.
If an allergic reaction to NECLORAL occurs, discontinue administration of the drug.
Treatment with broad-spectrum antibiotics, including NECLORAL, alters the normal flora of the colon and leads to an increase in the number of clostridia. Various studies have shown that a toxin produced by Clostridium difficile is the main cause of severe diarrhea associated with antibiotic therapy, including pseudomembranous colitis. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during therapy with these antibiotics.
As with other antibiotics, during treatment with NECLORAL, the possible emergence of resistant microorganisms should be considered, which may lead to a superinfection for which appropriate measures must be taken.

Use in neonates
Efficacy and tolerability in children have not been well established.

INTERACTIONS
The extent of NECLORAL absorption decreases if antacids containing magnesium hydroxide or aluminum are administered within one hour of taking the antibiotic, while H2-blockers do not alter the rate and extent of NECLORAL absorption.
Similarly to other beta-lactams, the renal excretion of NECLORAL is inhibited by the administration of probenecid; no other significant interactions with drugs have been observed during clinical studies.

SPECIAL WARNINGS
The medicine is not contraindicated for subjects affected by celiac disease

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

Effects on ability to drive and operate machinery
NECLORAL does not affect the ability to drive and operate machinery.

Keep out of the reach and sight of children.

DOSAGE, ADMINISTRATION AND DURATION OF TREATMENT
NECLORAL is administered orally and can be taken independently of meals.
However, concomitant intake of food increases the absorption of NECLORAL (see Pharmacokinetics).
The tablets must be taken whole, and therefore not broken, crushed or chewed.
The following dosage regimens are recommended:

• Pharyngitis, tonsillitis and skin and soft tissue infections: 750 mg 2 times a day.
• Uncomplicated lower urinary tract infections: 750 mg 2 times a day.
• Bronchitis: 750 mg 2 times a day. In the treatment of infections caused by S. pyogenes (group A streptococci) therapy with NECLORAL should be continued for up to 10 days.

Instructions for use
NECLORAL is administered orally and can be taken independently of meals. The tablets must be taken whole, and therefore not broken, crushed or chewed.

OVERDOSE
Signs and symptoms. Toxic symptoms resulting from NECLORAL overdose may include nausea, vomiting, gastric disturbances and diarrhea.
Treatment. In addition to general measures that may be required, intestinal absorption may be reduced by emesis, gastric lavage or administration of activated charcoal.
Forced diuresis, peritoneal dialysis, hemodialysis or hemoperfusion have not been shown to be beneficial in accelerating the elimination of NECLORAL.

UNDESIRABLE EFFECTS
After oral administration of NECLORAL in clinical studies, a low number of side effects (with an incidence rate generally less than 1%) was observed, most of which were mild and transient.

Gastrointestinal manifestations:diarrhea, nausea, vomiting and dyspepsia.

Allergic manifestations:skin rash, urticaria and pruritus have been reported. In controlled clinical studies, in 3,272 patients treated with NECLORAL, a serum sickness-like reaction (0.03%) was found, characterized by the appearance of erythema multiforme, skin rash and other skin manifestations accompanied by arthritis/arthralgia, with or without fever. These manifestations occur more often during or after a treatment cycle with Cefaclor and have been observed more frequently in children than in adults. Signs and symptoms usually appear a few days after the start of therapy and disappear a few days after the end of treatment. Antihistamines and corticosteroids promote healing. No serious complications have been observed.

Lymphatic and circulatory system:eosinophilia.

Genitourinary system:vaginal candidiasis and vaginitis.
The following adverse events, whose causal relationship with the drug is however uncertain, have been observed in patients treated with NECLORAL: headache, dizziness, drowsiness, transient increases in transaminases and alkaline phosphatase, transient azotemia and creatininemia, transient thrombocytopenia, leukopenia, lymphocytosis, neutropenia and urine test abnormalities.
In patients treated with Cefaclor, the following have been observed: erythema multiforme, fever, anaphylaxis (more frequent in patients with a history of penicillin allergy), Stevens-Johnson syndrome, positive direct Coombs test, genital itching, toxic epidermal necrolysis, reversible interstitial nephritis, altered liver function including cholestasis, increased prothrombin time in patients receiving Cefaclor and warfarin concurrently, reversible hyperactivity, nervousness, insomnia, confusion, hypertonia, aplastic anemia, agranulocytosis and hemolytic anemia.
Treatment with broad-spectrum antibiotics can alter the intestinal bacterial flora, sometimes leading to manifestations of pseudomembranous colitis.
Anaphylactoid reactions may be represented by isolated manifestations, including angioedema, asthenia, edema (both facial and of the limbs), dyspnea, paresthesia, syncope and vasodilation.
Report any adverse effects not listed in this leaflet to your doctor or pharmacist.

SHELF LIFE AND STORAGE
ATTENTION: DO NOT USE THE MEDICINE AFTER THE EXPIRY DATE INDICATED ON THE PACKAGING.

SPECIAL STORAGE PRECAUTIONS
Store at a temperature not exceeding 25°C.

PHARMACEUTICAL PRODUCT
21 April 2007

NECLORAL “250 mg/5 ml – Granulato per sospensione orale”

Cefacloro monoidrato
Medicinale equivalente
COMPOSITION
5 ml of suspension contains:

Active ingredient
Cefacloro monohydrate equivalent to Cefacloro 250 mg

Excipients:
Dimethicone, Polysaccharide gum, Starch 10 mg, Erythrosine E127 aluminum lake, Strawberry aroma,
Sodium lauryl sulfate, Methylcellulose, Sucrose.

PHARMACEUTICAL FORM AND CONTENT
Granulato for oral suspension” – 1 bottle of 100 ml

PHARMACOTHERAPEUTIC CATEGORY
Oral antibiotic, belonging to the class of cephalosporins.

MARKETING AUTHORISATION HOLDER
NEW RESEARCH srl
Via della Tenuta di Torrenova n° 142 - 00133 Roma

MANUFACTURER AND FINAL CONTROLLER
FRANCIA FARMACEUTICI srl
Via Dei Pestagalli n° 7 – 20138 Milano

THERAPEUTIC INDICATIONS
Cefaclor is indicated for the treatment of the following infections caused by susceptible germs:

• infections of the respiratory tract, including pneumonia, bronchitis, exacerbations of chronic bronchi-tis, pharyngitis and tonsillitis;
• otitis media;
• skin and soft tissue infections;
• infections of the urinary tract, including pyelonephritis and cystitis;
• sinusitis;
• gonococcal urethritis.

CONTRAINDICATIONS
Hypersensitivity to the active ingredient or to any of the excipients and to other cephalosporins or penicil-
lins.

PRECAUTIONS FOR USE
There have been patients who have experienced severe reactions (including anaphylaxis) following the
administration of penicillins or cephalosporins including Cefaclor, IgE-mediated reactions that usually
manifest at the skin, gastrointestinal, respiratory and cardiovascular level. The symptoms
may include: severe and sudden hypotension, acceleration and slowing of the heartbeat, unusual fatigue or weakness, anxiety, agitation, dizziness, loss of consciousness, difficulty
breathing or swallowing, generalized itching especially on the soles of the feet and palms of the hands, hives with or without angioedema (swollen and itchy skin areas localized more
frequently to the extremities, external genitalia and face, especially in the region of the eyes and
lips), redness of the skin especially around the ears, cyanosis, profuse sweating, nausea, vomiting, cramp-like abdominal pain, diarrhea.
Before initiating therapy with NECLORAL, careful investigation should be conducted to determine if the patient has
had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs.
If an allergic reaction to NECLORAL occurs, discontinue administration of the drug.
Treatment with broad-spectrum antibiotics, including NECLORAL, alters the normal flora of the colon
and leads to an increase in the number of clostridia. Various studies have shown that a toxin produced
by Clostridium difficile is the main cause of severe diarrhea associated with antibiotic therapy, includ-
ing pseudomembranous colitis. Therefore, it is important to consider this diagnosis in patients who de-
velop diarrhea during therapy with these antibiotics.
As with other antibiotics, during treatment with NECLORAL, the possible emergence of resistant microorganisms should be considered
which may result in a superinfection for which appropriate measures must be taken.

Use in neonates
Efficacy and tolerability in children have not been well established

INTERACTIONS
The extent of absorption of NECLORAL decreases if antacids containing magnesium hydroxide or aluminum are administered within one hour of taking the antibiotic,
while H2-blockers do not alter the rate and extent of NECLORAL absorption.
Similarly to other beta-lactam antibiotics, the renal excretion of NECLORAL is inhibited by the administration of probenecid; no other significant interactions with
drugs were observed during clinical studies.

SPECIAL WARNINGS
The medicine is not contraindicated for subjects affected by celiac disease

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

Effects on ability to drive and operate machinery
NECLORAL has no effects on the ability to drive and operate machinery.

Keep out of the reach and sight of children.

DOSAGE, ADMINISTRATION AND DURATION OF TREATMENT
Cefaclor is administered orally and can be taken independently of meals.

Adults.The normal dosage in adults is 250 mg every 8 hours. Higher doses may be necessary in more severe infections.
The maximum recommended dose is 2 g per day.
For the treatment of acute gonococcal urethritis in both sexes, a single administration of 3 g of Cefaclor is recommended, possibly in association with 1 g of Probenecid.

Children.The normal daily dosage for children is 20 mg/kg in divided doses every 8 hours.
In more severe infections (such as otitis media), a dosage of 40 mg/kg/day up to a maximum daily dose of 1 g is recommended.

Alternative dosage:in otitis media and pharyngitis, the total daily dose can be administered in divided doses every 12 hours.

MEASURING SPOON AND SYRINGE FOR NECLORAL 250 mg/5 ml

For explanatory purposes, for a daily dose of 40 mg/Kg
(NECLORAL 250 mg/5 ml) --------3 times a day (unit dose)

Alternative administration scheme; in otitis media and pharyngitis, the total daily dose can be administered in divided doses every 12 hours; the amount of reconstituted product must be taken according to the following scheme:
For explanatory purposes, for a daily dose of 40 mg/Kg
(NECLORAL 250 mg/5 ml) ----- 2 times a day (unit dose)

Note:the tables refer to the maximum daily dose of 40 mg/Kg; doses of 20 mg/Kg correspond to half of the values above.

Instructions for preparing the suspension
Shake the bottle well before preparation; then add water to the level indicated by the
arrow on the label, cap and shake the suspension well. Add water again, up to the
level indicated by the arrow, and shake well until a uniform suspension is obtained.

• 1.Before adding water 2.Add water to the shake well the bottle to level indicated by the arrow disperse the powder. on the label

• 3.Close the bottle. 4.Add more water Shake well until the to bring the level suspension becomes homogeneous. below the indicated level.

• 5.Shake again. 5.Use the syringe or measuring spoon for administration

If prepared according to these instructions, 5 ml of suspension will contain Cefacloro monohydrate equivalent to 250 mg of Cefaclor. Shake well before each administration.

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

Treatment:always keep in mind the possibility that the overdose is caused by multiple drugs, by
drug interactions or by the particular pharmacokinetics in the patient.
Gastric lavage is not necessary when the patient has not ingested more than 5 times the normal do-
se of Cefaclor.
The patient should be carefully monitored, in particular checking the state of the airways ensuring
ventilation and perfusion, vital signs (heart rate and blood pressure), blood gas analysis,
serum electrolytes, etc.
Intestinal absorption can be reduced by administering activated charcoal, which, in many cases, is more
effective than induced vomiting or gastric lavage. Repeated administration of activated charcoal can facilitate
the elimination of some drugs that may have been taken. Carefully monitor the patient's airways during gastric emptying and with the use of activated charcoal.
It has not been established that forced diuresis, peritoneal dialysis, hemodialysis or hemoperfusion with
activated charcoal are beneficial to the patient.

UNDESIRABLE EFFECTS

Adverse reactions considered to be related to treatment with Cefaclor are as follows:

Allergic manifestations: hypersensitivity reactions have been observed in 1.5% of patients, including
morbilliform rashes (1%); itching, urticaria and positive Coombs test are observed in less than 1 in 200 treated patients.
Generalized reactions of the "serum sickness-like" type have been reported, characterized by the presence of
erythema multiforme, skin rash and other manifestations affecting the skin, accompanied by arthri-tis/arthralgia (inflammatory or painful joint disorders), with or without fever. "Serum sickness-like" reactions appear to be due to hypersensitivity and occur more
often during and after a course of treatment with Cefaclor and, more frequently, in children than in adults. Signs and symptoms appear a few days after the start of therapy and disappear a few
days after its conclusion. Antihistamines and corticosteroids promote healing. No
serious complications have been observed.
More severe hypersensitivity reactions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis and anaphylaxis) have been rarely observed.

Gastrointestinal manifestations: can occur in approximately 2.5% of patients, also with the
appearance of diarrhea.
Pseudomembranous colitis can be observed during and after antibiotic treatment. Rarely, nausea and vomiting are observed. With some penicillins and other cephalosporins, transient hepatitis and cholestatic jaundice are rarely observed.

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

Effects for which the correlation with treatment is uncertain.

Central Nervous System: rarely reversible hyperactivity, restlessness, insomnia, mental confusion, hypertonia (increased muscle tone), hallucinations, feeling of instability and dizziness.

Digestive system: slight increases in the values of transaminases (SGOT and SGPT) or alkaline phosphatase.

Hematopoietic system: transient lymphocytosis, leukopenia and, rarely, hemolytic anemia, aplastic anemia, agranulocytosis and reversible neutropenia. Rare reports of prothrombin time prolongation with or without clinical consequences (e.g. bleeding) have been reported in patients receiving
warfarin sodium (antithrombotic drug) concurrently with Cefaclor.

Genitourinary system: mild increases in azotemia or creatinineemia and alterations in urine analysis have been reported.
If any undesirable effects occur, even if different from those described, the patient is advised to
report them to their doctor or pharmacist.

EXPIRY DATE AND STORAGE
Warning: do not use the medicine after the expiry date indicated on the packaging

SPECIAL PRECAUTIONS FOR STORAGE
Once prepared, the suspension should be stored in a refrigerator (between +2°C and +8°C) and used within 14
days.

DRUG:21 April 2007