Panacef

PACKAGE LEAFLET

PANACEF 375 mg modified-release tablets, 500 mg modified-release tablets, 750 mg modified-release tablets

Cefaclor
PHARMACOTHERAPEUTIC CATEGORY
Antibiotic belonging to the cephalosporin class.
THERAPEUTIC INDICATIONS
Treatment of the following infections caused by susceptible microorganisms:
Acute bronchitis and acute exacerbation of chronic bronchitis
Pharyngitis and tonsillitis
Uncomplicated lower urinary tract infections
Skin and soft tissue infections
CONTRAINDICATIONS
Panacef modified-release tablets are contraindicated in patients with hypersensitivity to the
active substance, to other cephalosporin antibiotics, or to any of the excipients.
PRECAUTIONS FOR USE
Before initiating therapy with Panacef modified-release tablets, careful investigation should be conducted to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.
Severe reactions (including anaphylaxis) have occurred in patients following administration of penicillins or cephalosporins, including cefaclor. These are IgE-mediated reactions that usually manifest at the cutaneous, gastrointestinal, respiratory, and cardiovascular levels.
Symptoms may include: severe and sudden hypotension, tachycardia or bradycardia, unusual fatigue or weakness, anxiety, restlessness, dizziness, loss of consciousness, difficulty breathing or swallowing, 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 localized on extremities, external genitalia, and face, particularly around the eyes and lips), skin redness especially around the ears, cyanosis, profuse sweating, nausea, vomiting, cramp-like abdominal pain, and diarrhea.
If an allergic reaction to Panacef modified-release tablets occurs, discontinue administration of the drug.
Treatment with broad-spectrum antibiotics, including Panacef modified-release tablets, alters the normal colonic flora and leads to an overgrowth of clostridia. Various studies have demonstrated that a toxin produced by Clostridium difficile is the primary cause of severe diarrhea associated with antibiotic therapy, including pseudomembranous colitis. Pseudomembranous colitis has been reported with the use of broad-spectrum antibiotics (including macrolides, semisynthetic penicillins, and cephalosporins); therefore, this diagnosis should be considered in patients who develop diarrhea during antibiotic therapy.
Mild cases of colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, appropriate therapeutic measures should be taken, 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, during treatment with Panacef modified-release tablets, the possible emergence of resistant microorganisms should be considered, which may lead to superinfection requiring appropriate management.
Panacef modified-release tablets should be administered with caution in patients with severely impaired renal function. In such conditions, the dosage should be lower than that generally recommended.
INTERACTIONS
The extent of absorption of Panacef modified-release tablets decreases if antacids containing magnesium or aluminium hydroxide are administered within one hour of taking the antibiotic. H2-receptor antagonists do not alter the rate or extent of absorption of Panacef modified-release tablets.
Similarly to other beta-lactam antibiotics, renal excretion of cefaclor (and presumably of Panacef modified-release tablets) is inhibited by the administration of probenecid (an antigout drug that promotes uric acid elimination). No other clinically significant drug interactions have been observed in clinical studies.
After administration of cefaclor, false positive reactions for urinary glucose may occur with Benedict's and Fehling's solutions and with copper sulfate tests.
SPECIAL WARNINGS
Pregnancy and breastfeeding
Consult your doctor or pharmacist before taking any medicine.
The safety of cefaclor during pregnancy has not been sufficiently established.
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 and under medical supervision.
The use of Panacef modified-release tablets during labour and delivery has not been studied; therefore, the drug should be administered only if clearly necessary.
Small amounts of cefaclor have been found in breast milk after administration of single 500 mg doses. The effects of Panacef on the nursing infant are unknown. Caution is recommended when using this drug during breastfeeding.
Use in children
The efficacy and tolerability of Panacef modified-release tablets in children have not been adequately established.
Effects on ability to drive and use machines
Panacef modified-release tablets have no effect on the ability to drive or operate machinery.
DOSAGE, ADMINISTRATION AND DURATION
Panacef modified-release tablets are administered orally and may be taken independently of meals. However, concomitant intake of food increases the absorption of Panacef modified-release tablets. The tablets must be swallowed whole and should 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. For infections caused by S. pyogenes (group A streptococci), treatment with Panacef modified-release tablets should be continued for up to 10 days.

OVERDOSE
Signs and symptoms: may include nausea, vomiting, epigastric disturbances, and diarrhea; the severity of gastrointestinal disturbances and diarrhea is dose-related. If other symptoms are present, they are likely secondary to an underlying pre-existing condition, an allergic reaction, or another toxic state.
Treatment: in managing overdose, consider the possibility of multiple drug overdose, drug interactions, or unusual pharmacokinetics in the patient. Ensure adequate airway ventilation and perfusion.
Carefully monitor and maintain within acceptable limits the patient's 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.
Airway protection is necessary 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 treating Panacef overdose.
UNDESIRABLE EFFECTS
After oral administration of Panacef modified-release tablets in clinical studies, a low number of adverse effects (with incidence generally less than 1%) have been observed, most of which were mild and transient.
Gastrointestinal manifestations: diarrhea, nausea, vomiting, and dyspepsia (digestive discomfort).
Allergic manifestations: skin rash, urticaria, and pruritus have been reported. In controlled clinical trials involving 3,272 patients treated with Panacef modified-release tablets, a serum-sickness-like reaction (0.03%) was observed, characterized by the appearance of erythema multiforme, skin rash, and other cutaneous manifestations accompanied by arthritis/ararthralgia (inflammatory or painful joint disorders), with or without fever. These manifestations typically occur during or after a course of cefaclor therapy and have been observed more frequently in children than in adults. Signs and symptoms generally appear a few days after the start of therapy and resolve a few days after treatment ends. Antihistamines and corticosteroids promote recovery. No severe 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 uncertain, have been observed in patients treated with Panacef modified-release tablets: headache, dizziness, somnolence, transient increases in transaminases and alkaline phosphatase, transient increases in blood urea nitrogen and creatinine, transient thrombocytopenia, leukopenia, lymphocytosis, neutropenia, and urinary abnormalities.
In patients treated with cefaclor, the following have occasionally been observed: erythema multiforme, fever, anaphylaxis (more frequent in patients with a history of penicillin allergy), Stevens-Johnson syndrome, positive direct Coombs test, genital pruritus, toxic epidermal necrolysis, reversible interstitial nephritis, impaired liver function including cholestasis, prolonged prothrombin time in patients receiving cefaclor concomitantly with warfarin (an anticoagulant), reversible hyperactivity, nervousness, insomnia, confusion, hypertonia (increased muscle tone), aplastic anemia, agranulocytosis, and hemolytic anemia.
Treatment with broad-spectrum antibiotics may alter intestinal bacterial flora, occasionally leading to pseudomembranous colitis.
Anaphylactoid reactions may present as isolated manifestations, including angioedema (abnormal fluid retention in tissues of allergic origin), asthenia (lack of strength), facial or limb edema, dyspnea (difficulty breathing), paresthesias (tingling sensations), syncope (sudden loss of strength), and vasodilation.
Following the instructions in this leaflet reduces the risk of adverse effects.
It is important to inform your doctor or pharmacist of any adverse effect, even if not described in this leaflet.
Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa
By reporting adverse effects, you can help provide more information on the safety of this medicine.
EXPIRY DATE AND STORAGE
Expiry date: see the date printed on the packaging.
DO NOT USE THIS MEDICINE AFTER THE EXPIRY DATE STATED ON THE PACKAGING
The expiry date refers to the product stored in its original intact packaging under recommended storage conditions.
Store below 30°C.
KEEP THIS MEDICINE OUT OF THE SIGHT AND REACH OF CHILDREN
COMPOSITION
Panacef 375 mg modified-release tablets
Each modified-release tablet contains:
Active substance: Cefaclor monohydrate equivalent to cefaclor 375 mg
Excipients: Mannitol, hypromellose, hydroxypropylcellulose, methacrylic acid copolymer, stearic acid, magnesium stearate.
Coating: Blue dye mixture, propylene glycol.
Panacef 500 mg modified-release tablets
Each modified-release tablet contains:
Active substance: Cefaclor monohydrate equivalent to cefaclor 500 mg
Excipients: Mannitol, hypromellose, hydroxypropylcellulose, methacrylic acid copolymer, stearic acid, magnesium stearate.
Coating: Blue dye mixture, propylene glycol.
Panacef 750 mg modified-release tablets
Each modified-release tablet contains:
Active substance: Cefaclor monohydrate equivalent to cefaclor 750 mg
Excipients: Mannitol, hypromellose, hydroxypropylcellulose, methacrylic acid copolymer, stearic acid, magnesium stearate.
Coating: Blue dye mixture, propylene glycol.
PHARMACEUTICAL FORM AND CONTENT
Panacef 375 mg modified-release tablets in packs of 12
Panacef 500 mg modified-release tablets in packs of 8
Panacef 750 mg modified-release tablets in packs of 6
Panacef 750 mg modified-release tablets in packs of 12
For oral use.
MARKETING AUTHORISATION HOLDER
NEOPHARMED GENTILI S.p.A – Via San Giuseppe Cottolengo 15 – 20143 Milan
MANUFACTURER
ACS Dobfar Spa – Via Laurentina Km 24.730 – Pomezia (Rome)
REVISION OF THE PACKAGE LEAFLET BY THE ITALIAN MEDICINES AGENCY (AIFA):

INSTRUCTIONS FOR USE

PANACEF 500 mg, hard capsules, 250 mg/5 ml, oral suspension granules

Cefaclor
THERAPEUTIC PHARMACOLOGICAL CATEGORY
Oral antibiotic (cephalosporins).
THERAPEUTIC INDICATIONS
Treatment of the following infections caused by susceptible microorganisms:

• Respiratory tract infections, such as pneumonia, bronchitis, acute exacerbations of chronic bronchitis, pharyngitis and tonsillitis.
• Otitis media (bacterial inflammatory processes affecting the middle ear).
• Skin and soft tissue infections.
• Urinary tract infections, including pyelonephritis and cystitis.
• Sinusitis.
• Gonococcal urethritis.

CONTRAINDICATIONS
Panacef is contraindicated in patients with hypersensitivity to the active substance, to other cephalosporins, or to any of the excipients.
PRECAUTIONS FOR USE
Before initiating therapy with Panacef, it is recommended to investigate any history of hypersensitivity reactions to cephalosporins and penicillins.
Severe reactions (including anaphylaxis) have occurred in patients following administration of penicillins or cephalosporins, including Cefaclor. These are IgE-mediated reactions, which typically manifest on the skin, gastrointestinal tract, respiratory system, and cardiovascular system.
Symptoms may include: severe and sudden hypotension, accelerated or slowed heart rate, unusual fatigue or weakness, anxiety, restlessness, dizziness, loss of consciousness, difficulty breathing or swallowing, 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 localized on extremities, external genitalia, and face, particularly around the eyes and lips), skin redness especially around the ears, cyanosis, profuse sweating, nausea, vomiting, cramp-like abdominal pain, diarrhea.
If allergic reactions occur, administration of the drug must be discontinued and the patient appropriately treated.
Since pseudomembranous colitis may occur during treatment with broad-spectrum antibiotics (including macrolides, semisynthetic penicillins, and cephalosporins), this possibility should be considered during therapy with these drugs.
Panacef should be administered with caution in patients with severely impaired renal function. In these cases, the dosage should be lower than that generally recommended.
Broad-spectrum antibiotics should be used cautiously in patients who have previously experienced intestinal disorders, due to the risk of developing antibiotic-associated colitis.
Prolonged use of Panacef may lead to overgrowth of non-susceptible microorganisms; if bacterial superinfection occurs during treatment with Panacef, it should be appropriately managed.
Use in newborns
The efficacy and tolerability of Panacef in neonates under one month of age have not been established.
INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicinal products, including those without a prescription.
There is evidence of partial cross-allergenicity between penicillins and cephalosporins.
After administration of Panacef, false-positive urinary glucose tests may occur when using Benedict's or Fehling's solutions, or Clinitest, but not with Tes-Tape (urine glucose test strip, Lilly).
Positive Coombs test results (sometimes false positives) have been reported during treatment with cephalosporins.
Renal excretion of cefaclor is inhibited by probenecid (an antigout drug that promotes uric acid elimination).
SPECIAL WARNINGS
Patients allergic to starch (but not suffering from celiac disease) should not take this medicine.
The oral suspension granules and oral drops suspension contain sucrose. In case of diagnosed sugar intolerance, consult your physician before taking this medicine.
Panacef has no effect on the ability to drive vehicles or operate machinery.
Pregnancy and breastfeeding
Consult your doctor or pharmacist before taking any medicine.
The tolerability of cefaclor during pregnancy has not been sufficiently proven.
In pregnant women, the drug should be used only when clearly needed and under direct medical supervision.
Small amounts of cefaclor have been detected in breast milk after single 500 mg doses. Caution is advised when using the drug during breastfeeding.
DOSAGE, ROUTE AND DURATION OF ADMINISTRATION
Panacef is administered orally and may be taken independently of meals.
Adults: 250 mg every 8 hours; higher doses may be required 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 dose of 3 g of cefaclor is recommended, possibly in combination with 1 g of probenecid.
Children: 20 mg/kg/day divided into doses every 8 hours; in more severe infections (such as otitis media), a dosage of 40 mg/kg/day is recommended, up to a maximum daily dose of 1 g.
In the treatment of infections caused by beta-hemolytic streptococcus, cefaclor therapy should be maintained for at least 10 days.
MEASURING CUP AND SYRINGE FOR PANACEF 250 mg/5 ml GRANULES FOR ORAL SUSPENSION

oral
For example, for a daily dose of 40 mg/kg
(Panacef 250 mg/5 ml granules for oral suspension)
Up to 8 kg From 8 to 16 kg From 16 to 21 kg Over 21 kg
syringe syringe or syringe or measuring cup
measuring cup measuring cup

Alternative dosing schedule: in otitis media and pharyngitis, the total daily dose
may be administered in divided doses every 12 hours; the amount of reconstituted product to be taken
should follow the scheme below:
For example, for a daily dose of 40 mg/kg
(Panacef 250 mg/5 ml oral suspension granules)
Up to 8 kg From 8 to 16 kg From 16 to 21 kg Over 21 kg
syringe measuring spoon measuring spoon measuring spoon

Note: The tables refer to the maximum daily dosage of 40 mg/kg; the doses of 20 mg/kg
correspond to half the values reported above.
Instructions for preparing the suspension
Shake the bottle well before preparation; then add water up to the level indicated by the
arrow on the label, close the bottle 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.

When prepared according to these instructions, 5 ml of suspension contain cefaclor monohydrate equivalent to
250 mg of cefaclor.
Shake well before each administration.
OVERDOSE
Signs and symptoms: may include nausea, vomiting, epigastric disturbances and diarrhoea, the severity of which is related
to the dose ingested. If other symptoms are present, they are likely to be secondary to a pre-existing
disease, an allergic reaction or another toxic condition.
Treatment: always consider the possibility that overdose may be caused by multiple drugs, drug interactions or the patient's particular pharmacokinetics.
Gastric lavage is not necessary when the patient has not ingested a dose of Panacef 5 times
higher than the recommended dose.
The patient should be closely monitored, particularly ensuring airway patency, ventilation and perfusion, vital signs (heart rate and blood pressure), blood gas analysis, serum electrolytes, etc.
Intestinal absorption may be reduced by administering activated charcoal, which in many cases is more effective
than induced vomiting or gastric lavage; therefore, consider activated charcoal as an alternative or additional treatment to gastric emptying. Repeated administration of activated charcoal may enhance the elimination of other drugs that may have been ingested. Carefully monitor the patient's airway during gastric emptying and when using charcoal.
It is not known whether forced diuresis, peritoneal dialysis, haemodialysis or haemoperfusion with charcoal are beneficial to the patient.
UNDESIRABLE EFFECTS
Like all medicines, Panacef can cause undesirable effects, although not everyone experiences them.
Adverse reactions considered related to treatment with Panacef are 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" diseases, characterized by the presence of erythema multiforme, skin eruptions and other skin manifestations accompanied by arthritis and/or arthralgia (inflammatory or painful joint disorders), with or without fever, have also been reported.
"Serum-sickness-like" reactions occur more frequently during and after a course of treatment with cefaclor, and more commonly in children than in adults.
Signs and symptoms appear a few days after starting therapy and resolve a few days after its completion. Antihistamines and corticosteroids promote recovery. No serious complications have been observed.
More severe hypersensitivity reactions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis and anaphylaxis) have been observed rarely.
Gastrointestinal manifestations: may occur in approximately 2.5% of patients, sometimes accompanied by diarrhoea.
Pseudomembranous colitis may be observed during and after antibiotic treatment. Nausea and vomiting are rarely observed. With some penicillins and other cephalosporins, transient hepatitis and cholestatic jaundice have rarely been observed.
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 haemolytic anaemia have been reported following treatment with cephalosporins.
Effects for which a definite relationship with treatment is uncertain:
Central nervous system: rarely reversible hyperactivity, restlessness, insomnia, mental confusion, hypertonia (increased muscle tone), hallucinations, dizziness and ataxia, somnolence.
Digestive system: slight increases in transaminase values (SGOT and SGPT) or alkaline phosphatase.
Haematopoietic system: transient lymphocytosis, leucopenia and, rarely, haemolytic anaemia, aplastic anaemia, agranulocytosis and reversible neutropenia. There have been rare reports of increased prothrombin time, with or without clinical consequences (e.g. bleeding), in patients receiving cefaclor and sodium warfarin (antithrombotic drug) concurrently.
Genitourinary system: slight increases in blood urea nitrogen, serum creatinine and abnormalities in urine analysis.
Following the instructions contained in this leaflet reduces the risk of undesirable effects.
Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your
doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa
By reporting adverse reactions, you can help provide more information on the safety of this medicine.
EXPIRY DATE AND STORAGE
Expiry date: see the date printed on the packaging.
Warning: do not use the medicine after the expiry date stated on the packaging.
The expiry date refers to the product in its original, unopened packaging, stored correctly.
Store below 30°C.
Once the oral suspension has been prepared, store in the refrigerator (between +2°C and +8°C) and use within 14 days.
Keep the medicine out of the sight and reach of children.
COMPOSITION
PANACEF 500 mg hard capsules
Each capsule contains:
Active substance:
Cefaclor monohydrate equivalent to cefaclor 500 mg
Excipients:
Pregelatinized starch; magnesium stearate; dimethicone 350 cs
PANACEF 250 mg/5 ml granules for oral suspension
5 ml of suspension contain:
Active substance:
Cefaclor monohydrate equivalent to cefaclor 250 mg
Excipients:
Erythrosine E-127 aluminium lake; methylcellulose 15; sodium lauryl sulfate; dimethicone 350 cs; polysaccharide gum; pregelatinized starch; strawberry flavour; sucrose.
PHARMACEUTICAL FORM AND CONTENT
PANACEF 500 mg hard capsules – 8 capsules
PANACEF 250 mg/5 ml granules for oral suspension – 100 ml bottle
MARKETING AUTHORISATION HOLDER
NEOPHARMED GENTILI S.p.A. – Via San Giuseppe Cottolengo 15 – 20143 Milan
MANUFACTURER
ACS Dobfar S.p.A. – Pomezia (Rome)
REVISION OF THE PACKAGE LEAFLET BY THE ITALIAN MEDICINES AGENCY: