Active ingredients: Ceftibuten
Isocef 200 mg hard capsules
Isocef 400 mg hard capsules
Isocef package inserts are available for pack sizes: - Isocef 200 mg hard capsules, Isocef 400 mg hard capsules
- Isocef 36 mg / ml granules for oral suspension
- Isocef 400 mg granules for oral suspension, Isocef 200 mg granules for oral suspension
Indications Why is Isocef used? What is it for?
Isocef contains the active substance ceftibuten.
Ceftibuten is an antibiotic that belongs to the beta-lactam class and to a family of medicines called cephalosporins.
Isocef is used against bacteria that are sensitive to the medicine.
Isocef is indicated in the treatment of:
- infections of the upper respiratory tract: of the throat (pharyngitis, tonsillitis), of the cavities near the nose (sinusitis) and of the ears (otitis media)
- infections of the lower respiratory tract: of the bronchi (bronchitis), of the lungs (primary community-acquired pneumonia) and of the bronchi and lungs simultaneously (bronchopneumonia)
- infections of the urinary tract: of the kidneys, bladder and the duct that carries urine from the bladder to the outside (acute and chronic pyelitis, cystopyelitis, cystitis, urethritis) and as a second choice drug in acute uncomplicated gonococcal urethritis.
Contraindications When Isocef should not be used
Do not use Isocef
- if you are allergic to the active substance, any other cephalosporin or any of the other ingredients of this medicine (listed in section 6)
- if you have experienced severe and sudden allergic reactions (anaphylaxis) to other antibiotics called penicillins or other antibiotics of the beta-lactam family
- if you are pregnant or suspect you are pregnant (see Pregnancy and breastfeeding)
- if it is for a baby under six months of age (see "Warnings and precautions").
Precautions for use What you need to know before taking Isocef
Talk to your doctor or pharmacist before using Isocef if:
- have severe kidney damage (kidney failure) or are on dialysis, in which case your doctor will decide which dose of Isocef to use. If you are on dialysis, your doctor will closely monitor your health and schedule Isocef to be administered immediately after dialysis.
- you have stomach and bowel problems, particularly if you have chronic inflammation of the colon (chronic colitis) your doctor will use caution when prescribing this medicine
- During therapy with Isocef, an "alteration of the intestinal flora (bacteria present in the" intestine) may occur with the onset of moderate to severe diarrhea (including pseudomembranous colitis due to Clostridium difficile toxins)
- have a history of allergy or suspect an allergy to a class of antibiotics called penicillins. If you are allergic to penicillins you may also be allergic to cephalosposrins (cross reactivity) and can undergo severe and sudden allergic reactions (anaphylaxis). In these cases, your doctor will stop Isocef therapy and give you appropriate therapy. convulsions or allergic shock occur during the use of Isocef, your doctor will immediately stop administering the medicine and promptly initiate appropriate medical treatment you are taking medicines that delay blood clotting as Isocef may reduce the ability to stop bleeding. your doctor will prescribe specific blood tests (thromboplastin time or the International Normalized Ratio - INR).
Children
Isocef is not indicated in children under six months of age.
Interactions Which drugs or foods can modify the effect of Isocef
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.
Isocef does not interact with medicines that reduce stomach acidity based on aluminum-magnesium and ranitidine and medicines for asthma based on theophylline (single dose administered intravenously).
Cephalosporins, including Isocef, can in rare cases interact with medicines that delay blood clotting and may reduce the ability to stop bleeding. In these cases, your doctor will prescribe specific blood tests (prothrombin time).
Isocef with foods
Concomitant food intake does not interfere with the efficacy of Isocef capsules.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
The administration of Isocef during pregnancy and lactation must be evaluated in terms of the potential risk and benefit for both the mother and the fetus.
Feeding time
Ceftibuten passes into breast milk, therefore infants may experience diarrhea such as to require a possible suspension of breastfeeding.
Due to the development of a possible allergy, Isocef should only be administered during breastfeeding when the benefits outweigh the risks.
Driving and using machines
Isocef has no effect on the ability to drive and use machines.
Dosage and method of use How to use Isocef: Dosage
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose for adults is:
- lower respiratory tract infections
- pneumonia: 200 mg 2 times / day
- bronchitis: 400 mg 1 time / day
- upper respiratory tract infections
- 400 mg once / per day
- urinary tract infections
- 400 mg once / per day
Isocef capsules can be taken regardless of meal times. The capsules should be swallowed with some water.
If you forget to use Isocef
Do not use a double dose to make up for a forgotten dose.
If you stop taking Isocef
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Isocef
No toxic manifestations were found following an accidental overdose of Isocef.
In case of accidental ingestion / intake of an excessive dose of Isocef, notify your doctor immediately or go to the nearest hospital.
Side Effects What are the side effects of Isocef
Like all medicines, this medicine can cause side effects, although not everybody gets them.
In clinical studies, which were conducted in approximately 3000 patients, the most frequently reported side effects were:
- nausea (3%)
- diarrhea (3%)
- headache (headache) (2%).
The following undesirable effects have been observed in clinical trials and post-marketing surveillance:
Common (may affect up to 1 in 10 people)
- headache (headache)
- nausea
- diarrhea
Uncommon (may affect up to 1 in 100 people)
- fungal infection (oral candidiasis)
- vaginal infection - increased eosinophils (a type of blood cell) (eosinophilia)
- positive direct Coombs test * (a laboratory test)
- decrease in hemoglobin (a protein that carries oxygen in the blood
- prolonged prothrombin time (which indicates how long the blood clots)
- increase in INR (a value that indicates the blood clotting time)
- loss of appetite (anorexia)
- decreased sense of taste (dysgeusia)
- stuffy nose (nasal congestion)
- difficulty in breathing (dyspnoea)
- stomach inflammation (gastritis)
- He retched
- abdominal pain
- constipation
- dry mouth difficulty digesting (dyspepsia)
- emission of air from the anus (flatulence)
- fecal incontinence
- increase in some parameters of liver function: bilirubin and transaminases (hyperbilirubinemia *, increase in AST and ALT)
- difficulty urinating (dysuria)
- renal impairment *
- kidney damage (toxic nephropathy *)
- presence of sugars and other substances called ketone bodies in the urine (renal glycosuria * and ketonuria *)
* observed with other cephalosporins and which can occur with the use of Isocef.
Rare (may affect up to 1 in 1000 people)
- inflammation of a part of the intestine called the colon caused by a bacterial infection (Clostridium difficile colitis)
- reduction in the number of a type of blood cell called white blood cells (leukopenia)
- reduction in the number of platelets (thrombocythemia)
- reduction in the number of red blood cells (aplastic anemia, haemolytic anemia)
- bleeding disorders
- reduction in the number of all types of blood cells (pancytopenia)
- reduction in the number of a type of white blood cell called neutrophils (neutropenia)
- severe reduction in the number of white blood cells (agranulocytosis)
- convulsions
- increase in blood values of some parameters of liver function (lactate dehydrogenase - LDH)
Very rare (may affect up to 1 in 10,000 people)
- impaired sensation (paraesthesia)
- drowsiness
- vertigo
- fatigue
Not known (frequency cannot be estimated from the available data)
- infections that overlap (superinfection)
- serum sickness (characterized by skin rash, joint pain, fever, swollen lymph nodes, decreased blood pressure and enlarged spleen)
- hypersensitivity reactions including severe and sudden reactions (anaphylactic reaction)
- contraction of the bronchial muscles (bronchospasm)
- rash
- urticaria
- sensitivity to light (photosensitivity)
- itch
- severe skin reactions (angioedema, Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis)
- mental (psychotic) disorders
- impaired speech (aphasia)
- dark stools (melena)
- liver (hepatobiliary) disorders and yellowing of the skin and eyes (jaundice).
Additional side effects in children
Uncommon (may affect up to 1 in 100 children)
- inflammation of the skin (diaper rash)
- blood in the urine (haematuria)
Very rare (may affect up to 1 in 10,000 children)
- agitation
- insomnia
- excess movement (hyperkinesis)
- irritability
- cooling down
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at "www.agenziafarmaco.it/it/responsabili". By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Do not store above 25 ° C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "Expires".
The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What Isocef contains
- The active ingredient is ceftibuten. Each capsule contains 200 mg or 400 mg of ceftibuten
- The other ingredients are: microcrystalline cellulose, sodium amidoglycolate, magnesium stearate. Capsule components: gelatin, titanium dioxide, sodium lauryl sulfate. Sealing band components: gelatin, polysorbate 80
What Isocef looks like and contents of the pack
Isocef comes in the form of hard capsules for oral use.
It is available in the following packs:
- 200 mg: 6 and 12 hard capsules in blisters.
- 400 mg: 4 and 6 hard capsules in blisters.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ISOCEF
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
ISOCEF 200 mg hard capsules
Active principle:
Each hard capsule contains 200 mg of ceftibuten.
ISOCEF 200 mg granules for oral suspension
Active principle:
Each sachet contains 200 mg of ceftibuten.
Excipients with known effects
Each sachet contains 1.11 g of sucrose and 5.56 mg of sodium benzoate.
ISOCEF 400 mg hard capsules
Active principle:
Each hard capsule contains 400 mg of ceftibuten.
ISOCEF 400 mg granules for oral suspension
Active principle:
Each sachet contains 400 mg of ceftibuten.
Excipients with known effects
Each sachet contains 2.23 g of sucrose and 11.12 mg of sodium benzoate.
ISOCEF 36 mg / ml granules for oral suspension
Active principle:
100 g of granules contain 14.40 g of ceftibuten.
Excipients with known effects
Each bottle contains 80.31 g of sucrose and 0.40 g of sodium benzoate.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsules.
Granules for oral suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Isocef is indicated in the treatment of infections due to sensitive pathogens, in particular:
• Upper respiratory tract infections: pharyngitis, tonsillitis, sinusitis, otitis media.
• Lower respiratory tract infections: bronchitis, primary community-acquired pneumonia, bronchopneumonia.
• Urinary tract infections: acute and chronic pyelitis, cystopyelitis, cystitis, urethritis. As a second-line drug in uncomplicated acute gonococcal urethritis.
04.2 Posology and method of administration
Dosage
Adults
Lower respiratory tract infections
Pneumonia: 200 mg twice / day;
bronchitis: 400 mg once / day.
Upper respiratory tract infections: 400 mg once / day.
Urinary tract infections: 400 mg once / day.
Pediatric population
Children over 6 months of age
Uncomplicated lower respiratory tract infections: 9.0 mg / kg once / day.
Upper respiratory tract infections (e.g. otitis media): 9.0 mg / kg once / day.
Urinary tract infections: 9.0 mg / kg once / day.
The maximum daily dose in children should not exceed 400 mg / day.
The safety and efficacy in children under 6 months of age have not yet been established.
Method of administration
Isocef granules for oral suspension can be taken one to two hours before or after a meal.
Isocef capsules can be taken regardless of meal times.
04.3 Contraindications
Hypersensitivity to the active substance, to any other cephalosporin, or to any of the excipients listed in section 6.1.
Isocef must not be used in patients who have experienced known serious or acute hypersensitivity reactions (anaphylaxis) to penicillins or other beta-lactam antibiotics.
Experience in children under six months of age is insufficient to establish the safety of ceftibuten in this patient population.
Pregnancy (see section 4.6)
04.4 Special warnings and appropriate precautions for use
Renal impairment
In patients with marked renal insufficiency or in patients undergoing dialysis the dosage of Isocef may require adjustment. Isocef is readily dialysable. Patients on dialysis should be closely monitored, with Isocef being administered immediately after dialysis.
The pharmacokinetics and posology of ceftibuten are not affected by a modest impairment of renal function (creatinine clearance between 50-79 ml / min). In patients with creatinine clearance between 30-49 ml / min the daily dose should be halved. At lower creatinine clearance values, further dose adjustment is required. Dose adjustment may be necessary in patients with renal insufficiency undergoing dialysis treatment. In patients on dialysis treatment 2/3 times per week, it is recommended to administer a single 400 mg dose of Isocef at the end of each dialysis treatment.
Gastrointestinal
Isocef should be prescribed with caution in individuals with a history of complicated gastrointestinal conditions, particularly chronic colitis.
Clostridium difficile
During therapy with Isocef and other broad-spectrum antibiotics, an "alteration of the intestinal flora with the onset of antibiotic-associated diarrhea" including pseudomembranous colitis due to toxins may occur. Clostridium difficile. Patients may present with moderate to severe or fatal diarrhea, with or without dehydration, both during and after treatment with the associated antibiotic. It is important to keep this diagnosis in mind for any patient who presents with persistent diarrhea during or until two months after the administration of Isocef or another broad spectrum antibiotic.
Mild forms of pseudomembranous colitis usually respond favorably to simply stopping the drug. In moderate or severe forms, treatment should include sigmoidoscopy, appropriate bacteriological research, and the administration of fluids, electrolytes and proteins. In cases where colitis does not improve after stopping the drug and in severe cases, oral vancomycin is the treatment of choice for pseudomembranous colitis. Clostridium difficile induced by antibiotics. Other causes of colitis must be excluded.
Hypersensitivity
Cephalosporin antibiotics should be administered with extreme caution to patients with known or suspected allergy to penicillins. Approximately 5% of patients with documented penicillin allergy cross-react to cephalosporin antibiotics. Severe acute hypersensitivity reactions (anaphylaxis) have also been observed in individuals receiving penicillins or cephalosporins, and cross-reactivity with anaphylaxis may be observed. If an allergic reaction is observed with Isocef it is recommended that its use be discontinued and administered appropriate therapy. Severe anaphylaxis requires appropriate emergency treatment as clinically indicated (adrenaline, intravenous fluid infusion, administration of oxygen, antihistamines, corticosteroids, other pressor amines).
Extreme caution should also be exercised when administering Isocef to patients with allergic reactions of any kind (eg hay fever or bronchial asthma), as these patients are at an increased risk of severe hypersensitivity reactions.
If convulsions or allergic shock occur during Isocef use, Isocef administration should be discontinued immediately and appropriate medical treatment initiated promptly.
Hematology
Cephalosporins, including ceftibuten, may in rare cases decrease prothrombin activity leading to prolongation of thromboplastin time, especially in patients previously stabilized on oral anticoagulant therapy. Thromboplastin time or the International Normalized Ratio (INR) should be monitored. If indicated, vitamin K should be administered to these patients.
Important information about some of the excipients
Isocef granules contains sucrose Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine
Isocef granules for oral suspension contains sodium benzoate. In newborns, it may increase the risk of jaundice.
Upon opening the bottle or sachets, a sulphurous odor may be detected which does not alter the quality of the product. After reconstitution, the sulphurous odor disappears.
04.5 Interactions with other medicinal products and other forms of interaction
Interaction studies have been conducted between Isocef and each of the following substances: antacids with a high content of aluminum-magnesium hydroxide, ranitidine and theophylline in a single dose administered intravenously. No significant interactions occurred. The effects of Isocef on plasma levels and pharmacokinetics of orally administered theophylline are not known.
Cephalosporins, including ceftibuten, may in rare cases decrease prothrombin activity leading to a prolonged prothrombin time, especially in patients previously stabilized on oral anticoagulant therapy. Prothrombin time should be monitored in patients at risk, administering Vitamin if necessary. K.
No significant interactions with other drugs have been reported to date. They have not been observed with chemical isocephalic interactions or with laboratory tests. A false positive in direct Coombs test has been reported with the use of other cephalosporins. Direct Coombs, did not show positive reactions even up to concentrations of 40 mcg / ml.
Concomitant food intake does not interfere with the efficacy of Isocef capsules, while it may delay and decrease the absorption of Isocef suspension.
04.6 Pregnancy and breastfeeding
Pregnancy
There are no adequate and controlled studies on the use of the medicinal product in pregnant women or during labor or delivery. As there is currently no clinical experience in the use of ceftibuten during pregnancy, the product should only be administered when really needed, under direct medical supervision. Since reproduction studies in animals are not always predictive for humans, administration of Isocef during pregnancy and lactation should be evaluated in terms of potential risk and benefit for both mother and the fetus.
Feeding time
Ceftibuten is excreted in breast milk, therefore infants may experience changes in the intestinal flora with diarrhea and colonization of yeasts, such as to require the eventual suspension of breastfeeding.
Due to the development of possible sensitization, Isocef should only be administered during lactation when the benefits clearly outweigh the risks.
04.7 Effects on ability to drive and use machines
Isocef does not affect the ability to drive or use machines.
04.8 Undesirable effects
Summary of the safety profile
In clinical studies, which were conducted in approximately 3000 patients, the most frequently reported adverse effects were nausea (3%), diarrhea (3%) (see section 4.4) and headache (2%).
Within the system organ classification, adverse events are listed using the following frequency categories: common (≥1 / 100,
Table of adverse reactions
Within each frequency group, undesirable effects are presented in order of decreasing severity.
* observed with other cephalosporins and which can occur with the use of Isocef.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
No toxic manifestations were found following an accidental overdose of Isocef.
Gastric lavage may be indicated, there is no specific antidote. Large amounts of Isocef can be removed from the bloodstream by hemodialysis. The actual removal by peritoneal dialysis has not been determined.
In adult healthy volunteers who received single doses of up to two grams of Isocef, no serious adverse reactions were observed and all laboratory and clinical tests showed normal values.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Beta-lactam antibacterials. Cephalosporins. ATC code: J01DD14
ISOCEF is a semi-synthetic cephalosporin antibiotic.
Ceftibuten has a broad spectrum of bactericidal activity against Gram-negative and Gram-positive bacteria.
Ceftibuten has been shown to have high activity (low MIC) against E. Coli, Klebsiella sp., Proteus, Salmonella spp., Haemophilus influenzae and Streptococcus pyogenes.
It is also active against Citrobacter sp., Moraxella (Branhamella) catarrhalis, Morganella morganii, Enterobacter spp., Serratia spp. and Streptococcus pneumoniae.
Susceptible microorganisms include species frequently involved in upper and lower respiratory tract infections and acute and complicated urinary tract infections.
It is not active against Staphylococci, Enterococci or Pseudomonas spp.
However, these organisms are not commonly implicated in the proposed indications for ceftibuten.
Antibacterial activity and mechanism of action
As with most beta-lactam antibiotics, the bactericidal activity of ceftibuten results from the inhibition of cell wall synthesis.
Thanks to its chemical structure, ceftibuten is highly stable towards beta-lactamases.
Many beta-lactamase-producing microorganisms resistant to penicillins or other cephalosporins can be inhibited by ceftibuten.
Ceftibuten is highly stable against chromosomal cephalosporinases and plasmid-mediated penicillinases, except for the beta-lactamases produced by B. fragilis.
Ceftibuten essentially binds to the PBP-3 of E. Coli, giving rise to doses equal to ¼-½ of the minimum inhibitory concentration (MIC), to the formation of filamentous forms, while lysis is observed at doses equal to 2 times the MIC.
The minimum bactericidal concentration (CMB) for E. Coli sensitive and resistant to ampicillin is almost equal to the MIC.
A high bioavailability in extracellular fluids allows ceftibuten to act on only moderately sensitive pathogens "in vitro" (see pharmacokinetics).
Sensitivity test
Diffusion technique: the laboratory results obtained using single discs containing 30 mcg of ceftibuten, must be interpreted according to the following criteria: diameter of the zone ≥21 mm indicates sensitivity; 18-20 mm moderate sensitivity; ≤17 mm resistance. For the "Haemophilus a zone> 28 mm indicates sensitivity. Pneumococcus isolates with an oxacillin zone greater than 20 mm are sensitive to ceftibuten.
Standard procedures require the use of laboratory control organisms. The 30 mcg disc should give a zone with a diameter of 29-35 mm for E.Coli ATCC 25922 and of 29-35 mm for the "H.influenzae ATCC 9247.
Ceftibuten 30 mcg discs should be used for all tests in vitro of the blocks. The class of discs (cephalothin) used to test for sensitivity to cephalosporin is not appropriate due to differences in the spectrum with ceftibuten.
Dilution technique: Microorganisms can be considered sensitive to ceftibuten if the MIC is ≤ 18 mcg / ml and resistant if the MIC is ≥ 32 mcg / ml. Organisms with an MIC of 16 mcg / ml are moderately sensitive.
Like standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard ceftibuten powder gives MIC values between 0.125 and 0.5 mcg / mL per liter.E.Coli ATCC 25922, ≥ 32 mcg / mL for the S. Aureus ATCC 29213, and 0.25-1.0 mcg / ml per l "H.influenzae ATCC 49247.
"In vitro" antibacterial activity
Ceftibuten shows a marked bactericidal activity; the number of live bacterial cells declines sharply at concentrations equal to 50% or more of the MIC; at concentrations equal to 2 times the MIC mortality is 99.9% with no regrowth observed in 24 hours.
In healthy volunteers treated with doses up to 2 g of ISOCEF, no serious side effects were observed and all laboratory parameters remained within normal limits.
05.2 Pharmacokinetic properties
Doses administered orally are well absorbed, reaching maximum plasma concentration in 2-3 hours.
The mean plasma peak after oral administration of a single 200 mg dose is 9.9 mcg / ml (range: 7.7-11.9 mcg / ml); while after administration of a single oral dose of 400 mg the mean plasma peak is about 17.0 mcg / ml (range: 9.5-29.9).
When administered in the absence of food, absorption is around 90% of the dose, assessed on the basis of urinary recovery.
The concomitant administration of 400 mg of ISOCEF capsules with a high calorie (800 calorie) and lipid-rich meal slows down but does not decrease the absorption of ceftibuten, while, as shown by some studies, it slows and decreases the absorption of ISOCEF. Suspension.
Ceftibuten easily penetrates interstitial fluids, reaching concentrations similar to those in serum, which are maintained longer.
The main metabolite, trans-ceftibuten, which has an antibiotic activity 8 times lower than ceftibuten, represents 7.2-9.2% of the total amount of drug excreted.
Ceftibuten is excreted via the kidney and 62-68% of the administered dose is excreted unchanged in the urine.
Renal clearance is nearly identical to total clearance, indicating that ceftibuten is eliminated primarily via the kidney.
The half-life of ceftibuten in healthy subjects is approximately 2-2.3 hours. In subjects with modest renal impairment (creatinine clearance 30 to 49 ml / min) the mean plasma half-life is prolonged to 7.1 hours.
The drug can be dialyzed with both hemodialysis and peritoneal dialysis in an amount equal to 65% of the dose.
05.3 Preclinical safety data
Ceftibuten exhibits very low toxicity when administered to laboratory animals at doses 250 to 1000 times higher than the dose used in humans.
Unlike other cephalosporins, ceftibuten does not show nephrotoxicity when administered i.v. at doses of 1000 mg / kg to rabbits. Ceftibuten has a protein binding of about 80% in monkeys, about 30% in rats, about 17% in mice and about 65% in humans.
Ceftibuten does not show a relevant antigenic potential.
Ceftibuten does not show any "disulfiram-like" effect in rats, while it shows very low acute and chronic toxicity in rats and dogs at the doses studied (acute toxicity: rat 5000-10000 mg / kg; dog 2500-5000 mg / kg ; chronic toxicity: rat 100-1000 mg / kg; dog 150-600 mg / kg).
Ceftibuten does not alter the sexual cycle and reproductive capacity of both rats and their offspring.
Ceftibuten does not show any teratogenic effect in rats up to 4000 mg / kg / day and in rabbits up to 40 mg / kg / day, as well as does not induce mutagenic effects in all the tests examined.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
ISOCEF 200 mg hard capsules
Microcrystalline cellulose, Sodium amidoglycolate, magnesium stearate. Capsule components: Gelatin, Titanium dioxide, Sodium lauryl sulfate. Sealing band components: Gelatin, Polysorbate 80.
ISOCEF 200 mg granules for oral suspension
Polysorbate 80, Simethicone, Xanthan gum, Anhydrous colloidal silica, Cherry flavor, Titanium dioxide, Sodium benzoate (E211), Sucrose.
ISOCEF 400 mg hard capsules
Microcrystalline cellulose, Sodium amidoglycolate, magnesium stearate. Capsule components: Gelatin, Titanium dioxide, Sodium lauryl sulfate. Sealing band components: Gelatin, Polysorbate 80.
ISOCEF 400 mg granules for oral suspension
Polysorbate 80, Simethicone, Xanthan gum, Anhydrous colloidal silica, Cherry flavor, Titanium dioxide, Sodium benzoate (E211), Sucrose.
ISOCEF 36 mg / ml granules for oral suspension
Polysorbate 80, Simethicone, Xanthan gum, Silicon dioxide, Cherry flavor, Titanium dioxide, Sodium benzoate (E211), Sucrose.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
With intact packaging
Isocef 200 mg hard capsules 2 years
Isocef200 mg granules for oral suspension 18 months
Isocef 400 mg hard capsules 2 years
Isocef400 mg granules for oral suspension 18 months
Isocef36 mg / ml granules for oral suspension - bottle 18 months
After reconstitution
Reconstituted suspension: 14 days.
06.4 Special precautions for storage
Do not store above 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Isocef200 mg hard capsules - 6 hard capsules in blister
Isocef200 mg hard capsules - 12 hard capsules in blister packs
Isocef200 mg granules for oral suspension - 6 sachets
Isocef200 mg granules for oral suspension - 12 sachets
Isocef400 mg hard capsules - 4 hard capsules in blister
Isocef 400 mg hard capsules - 6 hard capsules in blister packs
Isocef400 mg granules for oral suspension - 4 sachets
Isocef400 mg granules for oral suspension - 6 sachets
Isocef36 mg / ml granules for oral suspension - 1 bottle
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Capsules: the capsules should be swallowed with a little water.
Sachets: the contents of the sachets should be dispersed in a small amount of water and drunk immediately.
Preparation of the oral suspension: Shake the bottle before adding the water to facilitate the dispersion of the granulate. Fill the attached meter with water up to the "water level" mark engraved on it. Add half of this water to the bottle, close it, turn it upside down and shake it vigorously. the water left in the meter in the bottle, close and shake vigorously until a complete dispersion of the granulate is obtained. After reconstitution, the suspension is stable for 14 days. Shake the suspension before each administration.
15 g of granules, dispersed in the expected quantity of water, provide 60 ml of suspension containing 36 mg / ml of ceftibuten.
INSTRUCTIONS FOR USING THE DOSER
After reconstitution of the suspension proceed as follows:
1) Remove the colored protective cap of the dispenser
2) Insert the dispenser all the way into the bottle
3) Aspirate the suspension by pulling only the graduated piston until reaching the notch corresponding to the weight of the child.
ADMINISTER 1 TIME A DAY
07.0 MARKETING AUTHORIZATION HOLDER
RECORDATI Chemical and Pharmaceutical Industries S.p.A. - via Civitali, 1- 20148 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Isocef200 mg hard capsules - 6 hard capsules A.I.C. n. 027850066
Isocef200 mg hard capsules - 12 hard capsules A.I.C. n. 027850167
Isocef200 mg granules for oral suspension - 6 sachets A.I.C. n. 027850080
Isocef 200 mg granules for oral suspension-12 sachets A.I.C. n. 027850179
Isocef 400 mg hard capsules - 4 hard capsules A.I.C. n. 027850078
Isocef 400 mg hard capsules - 6 hard capsules A.I.C. n. 027850142
Isocef 400 mg granules for oral suspension - 4 sachets A.I.C. n. 027850092
Isocef 400 mg granules for oral suspension - 6 sachets A.I.C. n. 027850155
Isocef36 mg / ml granules for oral suspension-1 bottle A.I.C. n. 027850104
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 03 March 1992
Date of most recent renewal: 03 March 2007
10.0 DATE OF REVISION OF THE TEXT
01/12/2015
