Unasyn - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Sulbactam, Ampicillin

UNASYN 250 mg + 500 mg / 1.6 ml powder and solvent for solution for injection
UNASYN 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intramuscular use
UNASYN 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intravenous use
UNASYN 1 g + 2 g powder for solution for injection for intravenous use

Indications Why is Unasyn used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Antibacterials for systemic use

THERAPEUTIC INDICATIONS

The use of the product will be limited to:

  • infections with germs that have become ampicillin-resistant through the production of beta-lactamase;
  • severe infections in which it is suspected that the responsible germ may have become ampicillin-resistant through the production of beta-lactamase.

Contraindications When Unasyn should not be used

Hypersensitivity to the active substance, to penicillins or to any of the excipients (as well as to lidocaine, for preparations containing it).

Precautions for use What you need to know before taking Unasyn

As with other antibiotics, during treatment with UNASYN (sulbactamampicillin) it is important to carefully monitor the patient, in order to detect the onset of any superinfections from resistant organisms, or from fungi.

In the event of superinfection, the drug should be discontinued and appropriate therapy instituted.

As with any other potent drug for systemic use, it is advisable, during prolonged therapies with UNASYN (sulbactam / ampicillin), to periodically monitor the functionality of the main systems and apparatuses, including the renal, hepatic and haematopoietic systems. This monitoring is particularly important in newborns, especially if they are premature, and in other pediatric ages.

Pregnancy and breastfeeding

Talk to your doctor or pharmacist before taking any medicine. Although no teratogenic effects have been observed in laboratory animal experiments, it has not been demonstrated that UNASYN (sulbactam / ampicillin) can be used safely during pregnancy and during lactation. Therefore, in pregnant and lactating women. lactation, the product should be administered in cases of real need, under the direct supervision of the doctor.

Sulbactam and ampicillin are found in low concentrations in breast milk.

Sulbactam crosses the placental barrier.

Interactions Which drugs or foods can change the effect of Unasyn

Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.

Sulbactam sodium is compatible with most intravenous solutions, but ampicillin sodium and therefore also UNASYN (sulbactam sodium / ampicillin sodium) is less stable in solutions containing glucose and other carbohydrates and should not be mixed with blood products or hydrolysates proteins (see "Dose, method and time of administration", section Stability and compatibility).

Allopurinol: Compared to the administration of ampicillin alone, the concomitant administration of allopurinol and ampicillin substantially increases the incidence of exanthematous skin reactions.

Aminoglycosides: The mixing of ampicillin with aminoglycosides in vitro resulted in the mutual inactivation of the two drugs. In the event that the two medicines must be administered simultaneously, it is necessary that the administration takes place in two different injection sites and after a time interval of at least one hour.

Anticoagulants: Penicillins administered parenterally can produce alterations in platelet aggregation and coagulation tests. These effects can be added to the action of anticoagulants.

Bacteriostatic medicines (chloramphenicol, erythromycin, sulfonamides and tetracyclines): bacteriostatic medicines can interfere with the bactericidal activity of penicillins; it is therefore advisable to avoid their concomitant administration.

Oral contraceptives containing estrogen: In women receiving ampicillin, there have been cases of reduced contraceptive efficacy leading to unscheduled pregnancies. Although the association is not entirely clear, alternative or additional contraceptive measures may be used during ampicillin therapy.

Methotrexate: The concomitant use of penicillins and methotrexate has resulted in a reduction in the clearance of methotrexate and its toxicity. Patients should be carefully monitored. Doses of folinic acid may need to be increased and the administration time extended.

Probenecid: co-administration of probenecid decreases the secretion of ampicillin and sulbactam by the renal tubules; this effect leads to an increase and prolongation of serum concentrations, a prolongation of the half-life and an increase in the risk of toxicity.

Interactions in laboratory tests: In urinalysis, a false positive result for glycosuria can be obtained using Benedict's reagent, Fehling's reagent and Clinitest®. Following administration of ampicillin to pregnant women it is A transient decrease in plasma concentrations of estriol conjugate, estriol-glucuronide, estrone conjugate and estradiol has been observed. This effect may also occur with the combination of sulbactam sodium / ampicillin sodium.

Warnings It is important to know that:

In the event of an allergic reaction, therapy must be interrupted and appropriate treatment instituted (antihistamines, corticosteroids, vasopressor amines) or, in the presence of anaphylaxis, immediate treatment with adrenaline or other appropriate emergency measures (oxygen, assisted breathing, including l "intubation, etc.).

Before initiating therapy with a penicillin, a thorough medical history should be taken in order to highlight any previous hypersensitivity reactions to penicillins, cephalosporins or other drugs. In fact, severe and sometimes fatal hypersensitivity (anaphylactic) reactions have been reported in patients undergoing penicillin therapy, including the combination sulbactam sodium / ampicillin sodium. These reactions arise more easily in subjects with a history of hypersensitivity to penicillins and / or to various allergens. There have been reports of patients with a history of hypersensitivity to penicillins who have experienced severe reactions when treated with cephalosporins. The onset of any allergic-type reaction requires discontinuation of treatment and the institution of appropriate therapy.

Cases of Clostridium difficile associated diarrhea (CDAD) have been reported with the use of nearly all antibiotics, including sulbactam / ampicillin, and can range in severity from mild diarrhea to fatal colitis. Treatment with antibiotics alters normal colon flora and leads to an overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of diarrhea. Strains of C. difficile that produce excess toxins cause increased morbidity and mortality rates, as these infections are typically refractory to antibacterial therapy and often require colectomy. The possibility of C. difficile-associated diarrhea should be considered in all patients who present with diarrhea following antibiotic treatment. A careful medical history is also required as cases of C. difficile associated diarrhea have been reported even more than two months after antibiotic administration.

Patients with renal insufficiency

In patients with severe renal insufficiency (creatinine clearance less than 30 ml / min.), The elimination kinetics of sulbactam and ampicillin appear to be similarly affected, so that the plasma concentration ratio of the two antibiotics remains constant. The dosage of UNASYN (sulbactam / ampicillin) in these patients should be done with less frequent dosing, in accordance with what is usually done with ampicillin (see "Dose, method and time of administration").

The drug should be administered after the dialysis session. When treating patients who need to take restricted amounts of sodium, it should be borne in mind that:

  • 0.750 g of UNASYN (sulbactam / ampicillin) contains about 55 mg (2.5 millimoles) of sodium.
  • 1.5 g of UNASYN (sulbactam / ampicillin) contains about 115 mg (5 millimoles) of sodium.
  • 3 g of UNASYN (sulbactam / ampicillin) contains about 230 mg (10 millimoles) of sodium.

Since infectious mononucleosis is a viral disease, UNASYN (sulbactam sodium / ampicillin sodium) should not be the treatment. In a high percentage of patients with infectious mononucleosis treated with ampicillin, skin rash occurs.

Dosage and method of use How to use Unasyn: Dosage

Children

150 mg / kg / day (corresponding to 50 mg / kg / day of sulbactam and 100 mg / kg / day of ampicillin), administered every 6-8 hours. In neonates during the first week of life (especially if premature), the recommended dose is 75 mg / kg / day (corresponding to 25 mg / kg / day of sulbactam and 50 mg / kg / day of ampicillin) refracted in two doses. the same every 12 hours.

UNASYN (sulbactam / ampicillin) has been successfully administered to pediatric patients. While in children aged 1 year or more it has been shown to possess pharmacokinetic characteristics similar to those of adults, in newborns and premature babies (probably due to the immaturity of renal function in the first days of life), the half-life of both active ingredients is prolonged with an average of 7.9 hours for sulbactam and 9.4 hours for ampicillin. In such subjects, the drug must be administered in two equal doses daily, one every 12 hours, in accordance with the usual practice for ampicillin.

Adults

The total daily dose of UNASYN (sulbactam / ampicillin) recommended for adults varies within a normal range of 3 to 12 grams and can be refracted into equal doses every 12, 8 or 6 hours. The maximum daily dose that can be taken. be achieved for sulbactam is 4 g. The choice of dosage and administration schedule will depend on the severity of the infection:


Severity of the infection Sulbactam-Ampicillin IM / IV daily dosage (g) Mild 3 (IM) Moderate up to 6 (IM / EV) Serious up to 12 (IM / EV)

The recommended dosage of UNASYN (sulbactam / ampicillin) for outpatient treatment is 1.5 g intramuscularly every 12 hours.

Use in case of renal insufficiency

In patients with severe renal insufficiency (creatinine clearance <30 ml / min.), The dosage of UNASYN (sulbactam / ampicillin) should be done with less frequent dosing, in accordance with what is usually done for "ampicillin (see" Special warnings").

In both adults and children, treatment is usually continued for 48 hours after the fever subsides and after the other signs of infection have resolved. The duration of therapy is usually between 5 and 14 days, but the The treatment period may be prolonged or an additional dose of ampicillin may be added, in case of very severe infection.

In the treatment of uncomplicated gonorrhea, UNASYN (sulbactam / ampicillin) can be used as a single administration of 1.5 g in combination with 1 g of Probenecid orally (which increases the half-life of sulbactam and ampicillin).

Method of intramuscular administration

The powder contained in the bottle of UNASYN (sulbactam / ampicillin) for intramuscular use must be dissolved with the solvent ampoule (attached to the package) containing sterile water for injections or 0.5% lidocaine hydrochloride. Administration should be carried out by deep intramuscular injection at the level of bulky muscle masses, such as the buttocks or the anterior aspect of the thighs.

The concentrated solution for intramuscular administration should be used within one hour of reconstitution (see also below: stability and compatibility).

Method of intravenous administration

For intravenous administration, UNASYN (sulbactam / ampicillin) must be reconstituted with a vial of sterile water for injections (enclosed with the package) or any other compatible solution and allowed to stand until completely dissolved. Intravenous administration can be done by direct injection (bolus) in about 3 minutes, or by infusion, using higher dilutions, in 15-30 minutes.

The combination sulbactam sodium-ampicillin sodium in dosages of 0.750 g and 1.5 g can be administered both intramuscularly and intravenously.

The following dilutions should be used:


TOTAL DOSAGE (grams) DOSAGE OF SULBACTAM AND AMPICILLIN RESPECTIVELY (grams) DILUENT E VOLUME (ml) MAXIMUM FINAL CONCENTRATION (mg / ml) 0,750 1,5 0,250 - 0,500 0,5 - 1,0 1,6 3,2 125 - 250 125 - 250

The combination sulbactam sodium-ampicillin sodium in the 3 g strength should be administered intravenously at a maximum final concentration of 125-250 mg / ml.

Stability and compatibility

Sulbactam sodium is stable with most intravenous solutions, but ampicillin sodium (and therefore also sulbactam sodium / ampicillin sodium) is less stable in solutions containing glucose or other carbohydrates and should not be added to blood products or protein hydrolysates. a physical incompatibility between aminoglycosides and ampicillin (and therefore between aminoglycosides and sulbactam-ampicillin). These two antibiotics should therefore not be administered in the same syringe.

The concentrated solution for intramuscular administration should be used within 1 hour of reconstitution.

The period of time within which to use the drug, after reconstitution with the various diluents for the infusion, is shown below:


Diluent Concentration of sulbactam / ampicillin Stability (in hours) Sterile water for injections up to 45 mg / ml 8 hours at 25 ° C 45 mg / ml 48 h at 4 ° C up to 30 mg / ml 72 h at 4 ° C Physiological solution up to 45 mg / ml 8 hours at 25 ° C 45 mg / ml 48 h at 4 ° C up to 30 mg / ml 72 h at 4 ° C Sodium lactate up to 45 mg / ml 8 hours at 25 ° C up to 45 mg / ml 8 hours at 4 ° C 5% glucose in water 15 to 30 mg / ml 2 hours at 25 ° C up to 3 mg / ml 4 hours at 25 ° C up to 30 mg / ml 4 hours at 4 ° C 5% glucose in 0.45% NaCl up to 3 mg / ml 4 hours at 25 ° C up to 15 mg / ml 4 hours at 4 ° C Sucrose 10% in water up to 3 mg / ml up to 30 mg / ml 4 h at 25 ° C 3 h at 4 ° C Lactated Ringer's Solution up to 45 mg / ml up to 45 mg / ml 8 h at 25 ° C 24 h at 4 ° C

Overdose What to do if you have taken too much Unasyn

There is limited information available on the acute toxicity of ampicillin sodium and sulbactam sodium in humans. Overdose of the medicinal product may cause manifestations that are generally more intense, or concomitant, than the adverse reactions reported for the medicinal product. It should be borne in mind that high concentrations of antibiotics. CSF beta-lactams can cause neurological effects, including seizures. Since both ampicillin and sulbactam are removed from the circulation by hemodialysis, this procedure can be used in the event of overdose in patients with impaired renal function.

If you accidentally take an overdose of the medicine, notify your doctor immediately or go to the nearest hospital.

If you have any questions about the use of UNASYN, ask your doctor or pharmacist.

Side Effects What are the side effects of Unasyn

Secondary reactions associated with the use of ampicillin alone can be observed with the combination sulbactam sodium / ampicillin sodium (IM / IV).

All adverse drug reactions are presented according to MedDRA system organ class. Within each frequency category, adverse drug reactions are listed in order of severity. The severity of adverse drug reactions was determined by clinical significance


System and organ classification Common ≥ 1/100 e Uncommon ≥1 / 1,000 and Rare ≥1 / 10,000 e Not known (frequency cannot be estimated from the available data) Disorders of the blood and lymphatic system Anemia Thrombocytopenia Eosinophilia Leukopenia Neutropenia Haemolytic anemia Agranulocytosis Thrombocytopenia purpura Disorders of the immune system Anaphylactoid shock Anaphylactoid reaction Nervous system disorders Convulsions Drowsiness Headache Vascular pathologies Phlebitis Gastrointestinal disorders Diarrhea He retched Nausea Glossitis Pseudomembranous colitis Enterocolitis Stomatitis Discoloration of the tongue Hepatobiliary disorders Hyperbilirubinemia Cholestatic hepatitis Cholestasis Abnormal liver function Jaundice Skin and subcutaneous tissue disorders Skin rash Itching Stevens-Johnson syndrome Toxic epidermal necrolysis Erythema multiforme Maculopapular eruptions Urticaria Acute generalized exanthematous pustulosis Exfoliative dermatitis Renal and urinary disorders Tubulointerstitial nephritis Elevated azotemia Elevated creatinine General disorders and administration site conditions Pain at the injection site Injection site reaction Fever Asthenia Diagnostic tests Increased alanine aminotransferase Increased aspartate aminotransferase

MedDRA frequency convention: common: ≥1 / 100 e

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects

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. Undesirable effects can also be reported directly through the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

Expiry: see the expiry date indicated on the package.

Warning: do not use the medicine after the expiry date indicated on the package. The expiry date refers to the last day of the month. The expiry date indicated refers to the product in intact packaging, correctly stored.

There are no special precautions for storage

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

KEEP OUT OF THE SIGHT AND REACH OF CHILDREN.

COMPOSITION

UNASYN 250 mg + 500 mg / 1.6 ml powder and solvent for solution for injectionab

active principles:

sulbactam sodium 273.5 mg equal to 250 mg of sulbactam

ampicillin sodium 531.5 mg equal to 500 mg of ampicillin

with attached 1.6 ml solvent vial containing water for injections

UNASYN 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intramuscular use

active principles:

sulbactam sodium 547 mg equal to 500 mg of sulbactam

ampicillin sodium 1,063 mg equal to 1000 mg of ampicillin

with attached 3.2 ml solvent vial containing 0.5% lidocaine HCl for injections

UNASYN 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intravenous use

active principles:

sulbactam sodium 547 mg equal to 500 mg of sulbactam 99

ampicillin sodium 1,063 mg equal to 1000 mg of ampicillin

with attached 3.2 ml solvent vial containing water for injections

UNASYN 1 g + 2 g powder for solution for injection for intravenous use

active principles:

sulbactam sodium 1,099 mg equal to 1,000 mg of sulbactam

ampicillin sodium 2,132 mg equal to 2,000 mg of ampicillin

PHARMACEUTICAL FORM AND CONTENT

  • 250 mg + 500 mg / 1.6 ml powder and solvent for solution for injection for intramuscular and intravenous use: 1 vial of powder + 1 vial of solvent 1.6 ml.
  • 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intramuscular use: 1 vial powder + 1 solvent vial 3.2 ml
  • 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intravenous use: 1 vial powder + 1 solvent vial 3.2 ml
  • 1 g + 2 g powder for solution for injection for intravenous use: 1 bottle of 3 g.

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.

More information about Unasyn can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

UNASYN

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

UNASYN 250 mg + 500 mg / 1.6 ml powder and solvent for solution for injection:

active principles:

sulbactam sodium 273.5 mg equal to 250 mg of sulbactam

ampicillin sodium 531.5 mg equal to 500 mg of ampicillin

UNASYN 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intramuscular use:

active principles:

sulbactam sodium 547 mg equal to 500 mg of sulbactam

ampicillin sodium 1,063 mg equal to 1000 mg of ampicillin

UNASYN 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intravenous use:

active principles:

sulbactam sodium 547 mg equal to 500 mg of sulbactam

ampicillin sodium 1,063 mg equal to 1000 mg of ampicillin

UNASYN 1 g + 2 g powder for solution for injection for intravenous use:

active principles:

sulbactam sodium: 1,099 mg equal to 1,000 mg of sulbactam

ampicillin sodium: 2,132 mg equal to 2,000 mg of ampicillin

For the full list of excipients, see section 6.1

03.0 PHARMACEUTICAL FORM

- 250 mg + 500 mg / 1.6 ml powder and solvent for solution for injection for intramuscular and intravenous use: 1 vial of powder + 1 vial of solvent 1.6 ml.

- 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intramuscular use: 1 vial powder + 1 solvent vial 3.2 ml

- 500 mg + 1 g / 3.2 ml powder and solvent for solution for injection for intravenous use: 1 vial powder + 1 solvent vial 3.2 ml

- 1 g + 2 g powder for solution for injection for intravenous use: 1 bottle of 3 g.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

The use of the product will be limited to:

- infections with germs that have become ampicillin-resistant through the production of beta-lactamase;

- severe infections in which it is suspected that the responsible germ may have become ampicillin-resistant through the production of beta-lactamase.

04.2 Posology and method of administration

CHILDREN

150 mg / kg / day (corresponding to 50 mg / kg / day of sulbactam and 100 mg / kg / day of ampicillin), administered every 6-8 hours. In infants during the first week of life (especially if premature), the recommended dose is 75 mg / kg / day (corresponding to 25 mg / kg / day of sulbactam and 50 mg / kg / day of ampicillin) split in two equal doses. every 12 hours.

UNASYN (sulbactam / ampicillin) has been successfully administered to pediatric patients.

While in children aged 1 year or more it has been shown to possess pharmacokinetic characteristics similar to those of adults, in newborns and premature babies (probably due to the immaturity of renal function in the first days of life), the half-life of both active ingredients is prolonged with an average of 7.9 hours for sulbactam and 9.4 hours for ampicillin. In such subjects, the drug must be administered in two equal doses daily, one every 12 hours, in accordance with the usual practice for ampicillin.

ADULTS

The total daily dose of UNASYN (sulbactam / ampicillin) recommended for adults varies within a normal range of 3 to 12 grams and can be refracted into equal doses every 12, 8 or 6 hours. The maximum daily dose that can be taken. be achieved for sulbactam is 4 g. The choice of dosage and administration schedule will depend on the severity of the infection:


Severity of the infection Sulbactam-Ampicillin IM / IV daily dosage (g) Mild 3 (IM) Moderate up to 6 (IM / EV) Serious up to 12 (IM / EV)

The recommended dosage of UNASYN (sulbactam / ampicillin) for outpatient treatment is 1.5 g intramuscularly every 12 hours.

In patients with severe renal insufficiency (creatinine clearance

In both adults and children, treatment is usually continued for 48 hours after the fever subsides and after the other signs of infection have resolved. The duration of therapy is usually between 5 and 14 days, but the The treatment period may be prolonged or an additional dose of ampicillin may be added, in case of very severe infection.

In the treatment of uncomplicated gonorrhea, UNASYN (sulbactam / ampicillin) can be used as a single administration of 1.5 g in combination with 1 g of Probenecid orally (which increases the half-life of sulbactam and ampicillin).

Method of intramuscular administration

The powder contained in the bottle of UNASYN (sulbactam / ampicillin) for intramuscular use must be dissolved with the solvent ampoule (attached to the package) containing sterile water for injections or 0.5% lidocaine hydrochloride. Administration should be carried out by deep intramuscular injection at the level of bulky muscle masses, such as the buttocks or the anterior aspect of the thighs. The concentrated solution for intramuscular administration should be used within one hour of reconstitution.

Method of intravenous administration

For intravenous administration, UNASYN (sulbactam / ampicillin) must be reconstituted with a vial of sterile water for injections (enclosed with the package) or any other compatible solution and allowed to stand until completely dissolved. Intravenous administration can be given by direct injection (bolus) over approximately 3 minutes, or by infusion, using higher dilutions, over 15-30 minutes (see section 6.2 Incompatibilities and 6.6 Special precautions for disposal and handling).

04.3 Contraindications

Hypersensitivity to the active substance, to penicillins or to any of the excipients (as well as to lidocaine, for preparations containing it).

04.4 Special warnings and appropriate precautions for use

In the event of an allergic reaction, therapy must be interrupted and appropriate treatment instituted (antihistamines, corticosteroids, vasopressor amines) or, in the presence of anaphylaxis, immediate treatment with adrenaline or other appropriate emergency measures (oxygen, assisted breathing, including l "intubation, etc.).

As with other antibiotics, it is important to carefully monitor the patient treated with UNASYN (sulbactam / ampicillin) in order to detect the onset of any superinfection from resistant organisms or fungi. In case of superinfection, the drug should be discontinued and appropriate " therapy will be instituted.

Cases of diarrhea associated with Clostridium difficile (CDAD), the severity of which can range from mild diarrhea to fatal colitis. Treatment with antibiotics alters the normal flora of the colon and leads to an overgrowth of C. hard.

The C. difficult produces toxins A and B which contribute to the development of diarrhea. The strains of C. hard that produce excess toxins cause increased morbidity and mortality rates, as these infections are typically refractory to antibacterial therapy and often require a colectomy.

The possibility of associated diarrhea should be considered C. difficult in all patients who present with diarrhea following antibiotic treatment. A careful medical history is also required since cases of diarrhea associated with C. difficult they have also been reported over two months after antibiotic administration.

As with any other potent drug for systemic use, it is advisable, during prolonged therapies with UNASYN (sulbactam / ampicillin), to periodically monitor the functionality of the main systems and apparatuses, including the renal, hepatic and haematopoietic systems. This monitoring is particularly important in newborns, especially if they are premature, and in other pediatric ages.

Before initiating antibiotic therapy with a penicillin, a thorough medical history must be taken to highlight any previous hypersensitivity reactions to penicillins, cephalosporins or other drugs. In fact, serious and sometimes fatal hypersensitivity reactions have been reported in patients undergoing therapy. with penicillins, including the combination sulbactam sodium / ampicillin sodium. These reactions arise more easily in individuals with a history of hypersensitivity to penicillins and / or other allergens. There have been reports of patients with a "history of hypersensitivity to penicillins, who have experienced severe reactions when treated with cephalosporins. The onset of any allergic-type reaction requires discontinuation of treatment and the institution of" appropriate therapy.

In patients with severe renal insufficiency (creatinine clearance less than 30 ml / min.), The elimination kinetics of sulbactam and ampicillin appear to be similarly affected, so that the plasma concentration ratio of the two antibiotics remains constant. UNASYN (sulbactam / ampicillin) dosing in these patients should be done with less frequent dosing, in accordance with what is usually done with ampicillin (see section 4.2 Posology and method of administration).

The drug should be administered after the dialysis session.

When treating patients who need to take restricted amounts of sodium, it should be borne in mind that:

- 0.750 g of UNASYN (sulbactam / ampicillin) contains about 55 mg (2.5 millimoles) of sodium.

- 1.5 g of UNASYN (sulbactam / ampicillin) contains about 115 mg (5 millimoles) of sodium.

- 3 g of UNASYN (sulbactam / ampicillin) contains about 230 mg (10 millimoles) of sodium.

Since infectious mononucleosis is a viral disease, UNASYN (sulbactam sodium / ampicillin sodium) should not be the treatment. In a high percentage of patients with infectious mononucleosis treated with ampicillin, skin rash occurs.

04.5 Interactions with other medicinal products and other forms of interaction

Sulbactam sodium is compatible with most intravenous solutions, but ampicillin sodium (and therefore also sulbactam sodium / ampicillin sodium) is less stable in solutions containing glucose and other carbohydrates and should not be mixed with blood products or protein hydrolysates ( See sections 6.2 Incompatibilities and 6.6 Special precautions for disposal and handling).

Allopurinol: Compared to the administration of ampicillin alone, the concomitant administration of allopurinol and ampicillin substantially increases the incidence of exanthematous skin reactions.

Aminoglycosides: the mixing of ampicillin with aminoglycosides in vitro led to the mutual inactivation of the two drugs. In the event that the two drugs must be administered simultaneously, it is necessary that the administration takes place in two different injection sites and after a time interval of at least one "hour.

Anticoagulants: Penicillins administered parenterally can produce alterations in platelet aggregation and coagulation tests. These effects can be added to the action of anticoagulants.

Bacteriostatic medicines (chloramphenicol, erythromycin, sulfonamides and tetracyclines): Medicinal products with bacteriostatic action can interfere with the bactericidal activity of penicillins; it is therefore advisable to avoid their concomitant administration.

Oral contraceptives containing estrogen: in women receiving ampicillin, there have been cases of reduced contraceptive efficacy leading to unscheduled pregnancies. Although the association is not entirely clear, alternative or additional contraceptive measures may be used during ampicillin therapy.

Methotrexate: the concomitant use of penicillins and methotrexate resulted in a reduction of clearance methotrexate and its toxicity. Patients should be carefully monitored. The doses of folinic acid may need to be increased and the administration time extended.

Probenecid: coadministration of probenecid decreases the secretion of ampicillin and sulbactam by the renal tubules; this effect leads to an increase and prolongation of serum concentrations, a prolongation of the half-life and an increase in the risk of toxicity.

Interactions in laboratory tests: In urinalysis, a false positive result for glycosuria can be obtained using Benedict's reagent, Fehling's reagent and Clinitest. A transient decrease in concentrations has been observed following administration of ampicillin to pregnant women of conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol. This effect may also occur with the combination of sulbactam sodium / amicillin sodium.

04.6 Pregnancy and breastfeeding

Although no teratogenic effects have been observed in laboratory animal experiments, it has not been demonstrated that UNASYN (sulbactam / ampicillin) can be used safely during pregnancy and lactation. Therefore in pregnant and lactating women. , the product should be administered in cases of real need, under the direct supervision of the doctor.

Sulbactam and ampicillin are found in low concentrations in breast milk.

Sulbactam crosses the placental barrier.

04.7 Effects on ability to drive and use machines

No effect of UNASYN (sulbactam / ampicillin) on the ability to drive and use machines has been reported.

04.8 Undesirable effects

As with other parenteral antibiotics, the main side effect is pain at the injection site after intramuscular administration. In a limited number of patients, phlebitis or infusion site reactions have occurred following intravenous administration.

Gastrointestinal disorders: nausea, vomiting, diarrhea, enterocolitis and psudomembranous colitis.

Blood and lymphatic system disorders: Cases of anemia, haemolytic anemia, thrombocytopenia, leukopenia and eosinophilia have been reported during therapy with sulbactam sodium-ampicillin sodium. These reactions are reversible on discontinuation of therapy and should be considered as symptoms of sensitivity to the drug.

Hepatobiliary disorders: hyperbilirubinaemia, impaired liver function and jaundice.

Skin and subcutaneous tissue disorders: rash, pruritus and other skin reactions. Maculo-papular eruptions and urticaria. Rare cases of Stevens-Johnson syndrome, epidermal necrolysis and erythema multiforme.

Immune system disorders: anaphylactoid reaction and anaphylactic shock.

Nervous system disorders: rare cases of convulsions, numbness and headache.

Renal and urinary disorders: rare cases of interstitial nephritis.

Investigations: possible transient increase in AST (SGOT) and ALT (SGPT).

General disorders and administration site conditions: fever, rarely observed asthenia, increased blood urea and creatinine.

Secondary reactions associated with the use of ampicillin alone can be observed with the combination sulbactam sodium / ampicillin sodium.

04.9 Overdose

There is limited information available on the acute toxicity of ampicilin sodium and sulbactam sodium in humans. Overdose of the medicinal product may cause manifestations that are generally more intense, or concomitant, than the adverse rations reported for the medicinal product. It should be borne in mind that high concentrations of antibiotics. CSF beta-lactams can cause neurological effects, including seizures. Since both ampicillin and sulbactam are removed from the circulation by hemodialysis, this procedure can be used in the event of overdose in patients with impaired renal function.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: antibacterials for systemic use.

Combination of penicillins, including beta-lactamase inhibitors.

ATC code: J01CR01.

UNASYN (sulbactam / ampicillin) is an antibiotic combination between an irreversible inhibitor of beta-lactamase, sulbactam, and a beta-lactamase-sensitive antibiotic, ampicillin. This combination, for parenteral use only, appears to have broad antibacterial activity. spectrum against numerous Gram-positive and Gram-negative, aerobic and anaerobic germs including beta-lactamase-producing species. It should be borne in mind that germs known to be resistant to ampicillin such as Pseudomonas , Citrobacter and Enterobacter they are not equally sensitive to UNASYN (sulbactam / ampicillin).

05.2 Pharmacokinetic properties

Not absorbed from the gastrointestinal tract.Sulbactam and ampicillin demonstrate similar pharmacokinetic characteristics: high serum concentrations of the two antibiotics are achieved after intramuscular and intravenous administration of their combination. Both drugs have a "half-life of approximately one" hour. Most of a dose of UNASYN (sulbactam / ampicillin) (75%) is excreted unchanged in the urine. UNASYN (sulbactam / ampicillin) reaches therapeutic concentrations in all fluids and tissues examined. Penetration to the cerebrospinal fluid is poor, except in inflamed meninges.

05.3 Preclinical safety data

The LD50 in rats and mice (intravenously) is greater than 1,000 mg / kg in both males and females. In long-term studies in rats and guinea pigs UNASYN (sulbactam / ampicillin) did not cause significant histopathological lesions affecting the main organs and systems (kidney, liver, etc.). Likewise, the tests performed to evaluate the possible fetal toxicity, the teratogenic activity as well as fertility inhibitions of UNASYN (sulbactam / ampicillin) did not show any activity of this type on the drug. UNASYN (sulbactam / ampicillin) did not furthermore, it was shown to possess mutagenic activity and the general tolerability tested on the rabbit appeared to be excellent.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

For pediatric intramuscular and intravenous use: the solvent vial containing water for injections

For intramuscular use: the solvent vial contains 0.5% lidocaine HCl

For intravenous use: the solvent vial containing water for injections

06.2 Incompatibility

UNASYN (sulbactam / ampicillin) is physically compatible with the following solutions: physiological saline, sodium lactate, lactated Ringer's solution. UNASYN (sulbactam / ampicillin) is less stable in solutions containing dextrose or other carbohydrates (the reconstituted solution should be used within 2-4 hours of reconstitution) and should not be mixed with blood products or protein hydrolysates. For use with compatible diluents, see the relevant table in section 6.6. Special precautions for disposal and handling.

06.3 Period of validity

3 years.

06.4 Special precautions for storage

No particular precautions for storage.

06.5 Nature of the immediate packaging and contents of the package

Glass vial with solvent vial attached:

- 250 mg + 500 mg powder and solvent for solution for injection: 1 vial of powder + 1 vial of solvent 1.6 ml.

- 500 mg + 1 g powder and solvent for solution for injection for intramuscular use: 1 vial powder + 1 solvent vial 3.2 ml

- 500 mg + 1 g powder and solvent for solution for injection for intravenous use: 1 vial powder + 1 solvent vial 3.2 ml

- 1 g + 2 g powder for solution for injection for intravenous use: 1 bottle of 3 g powder

06.6 Instructions for use and handling

Diluent Concentration of sulbactam / ampicillin Stability (in hours) Sterile water for injections up to 45 mg / ml 8 hours at 25 ° C 45 mg / ml 48 h at 4 ° C up to 30 mg / ml 72 h at 4 ° C Physiological solution up to 45 mg / ml 8 hours at 25 ° C 45 mg / ml 48 h at 4 ° C up to 30 mg / ml 72 h at 4 ° C Sodium lactate up to 45 mg / ml 8 hours at 25 ° C up to 45 mg / ml 8 hours at 4 ° C 5% glucose in water 15 to 30 mg / ml 2 hours at 25 ° C up to 3 mg / ml 4 hours at 25 ° C up to 30 mg / ml 4 hours at 4 ° C 5% glucose in 0.45% NaCl up to 3 mg / ml 4 hours at 25 ° C up to 15 mg / ml 4 hours at 4 ° C Sucrose 10% in water up to 3 mg / ml up to 30 mg / ml 4 h at 25 ° C 3 h at 4 ° C Lactated Ringer's Solution up to 45 mg / ml up to 45 mg / ml 8 h at 25 ° C 24 h at 4 ° C

07.0 MARKETING AUTHORIZATION HOLDER

Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom

Representative for Italy

PFIZER ITALIA S.r.l.

Via Isonzo, 71 - 04100 Latina

08.0 MARKETING AUTHORIZATION NUMBER

- "UNASYN 250 mg + 500 mg powder and solvent for solution for injection" 1 vial powder + 1 solvent vial 1.6 ml - AIC n. 026360038

- "UNASYN 500 mg + 1 g powder and solvent for solution for injection for intramuscular use" 1 vial powder + 1 solvent vial 3.2 ml - AIC n. 026360014

- "UNASYN 500 mg + 1 g powder and solvent for solution for injection for intravenous use" 1 vial powder + 1 solvent vial 3.2 ml - AIC n. 026360026

- "UNASYN 1 g + 2 g powder for solution for injection for intravenous use" 1 bottle of 3 g powder - AIC n. 026360089

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

- "UNASYN 250 mg + 500 mg powder and solvent for solution for injection": 01 June 1990/31 May 2005

- "UNASYN 500 mg + 1 g powder and solvent for solution for injection for intramuscular use" e

- "UNASYN 500 mg + 1 g powder and solvent for solution for injection for intravenous use": 27 July 1987/31 May 2005

- "UNASYN 1 g + 2 g powder for solution for injection for intravenous use": 27 April 1993/31 May 2005

10.0 DATE OF REVISION OF THE TEXT

January 15, 2013

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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