Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Hypersensitivity
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients treated with penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or hypersensitivity reactions to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity that have experienced severe reactions when treated with cephalosporins. Before starting a treatment with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins and other drugs/ allergens.
If an allergic reaction occurs, the treatment should be discontinued and the appropriate therapy instituted.
Serious anaphylactic reactions require an emergency treatment with adrenalin. Oxygen, intravenous steroids and airway management, including intubation, should also be administered when required.

Hepatotoxicity
Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of AmpiSulVenir. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
Severe Cutaneous Adverse Reactions
AmpiSulVenir may cause severe skin reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), dermatitis exfoliative, erythema multiforme, and Acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash they should be monitored closely and AmpiSulVenir discontinued if lesions progress (see CONTRAINDICATIONS and ADVERSE REACTIONS sections).

As for other systemic drugs, in case of prolonged therapy (more then one to two weeks) the monitoring of the function of the principal systems and apparatuses is recommended, including renal and hepatic systems and the haematopoietic system. The monitoring is very important in neonates, particularly in premature, and in the other paediatric patients.
In patients with impaired renal function the elimination kinetics of ampicillin and of sulbactam are similarly affected, hence the ratio of their plasmatic levels will remain constant.
The dose of ampicillin and sulbactam in such patients should be monitored, and less frequently administered, according to the usual practice for ampicillin.

In the treatment of patients who may assume a limited quantity of sodium it should be considered that the package of ampicillin 1 g and sulbactam 500 mg contains approximately 115 mg (5 mmol) of sodium.
In the treatment of patients who may assume a limited quantity of sodium it should be considered that the package of ampicillin 2 g and sulbactam 1 g contains approximately 230 mg (10 mmol) of sodium.

In case of severe and persistent diarrhoea, the possibility of pseudomembraneous colitis must be considered and if not refuted, therapy should be discontinued and appropriate measures should be taken. The use of antiperistaltics is contraindicated in such cases.
In neonates, the half-life of the two drugs substances is prolonged; it is approximately 7,9 hours for sulbactam and 9,4 hours for ampicillin. In these subjects the therapeutic dosage should be administered in two divided doses, according to the usual practice for ampicillin.
Ampicillin impairs colonic fermentation of carbohydrates and a diet high in unabsorbable carbohydrate increases the risk of antibiotic-associated diarrhoea. Consult a health practitioner to learn about sources of indigestible carbohydrates.

Clostridium difficile-Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AmpiSulVenir, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents 
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS
General:
A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash.
Thus, ampicillin class antibacterial should not be administered to patients with mononucleosis. In patients treated with AmpiSulVenir the possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.
Prescribing AmpiSulVenir in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for Patients:
Patients should be counseled that antibacterial drugs including AmpiSulVenir should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When AmpiSulVenir is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by AmpiSulVenir or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibacterial which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible.

Effects on Driving

4.7 Effects on ability to drive and use machines
Ampicillin and sulbactam may not have an influence on the ability to drive and use machines, but there are reports of undesirable effects (see section 4.8) and patients should know how they react to ampicillin/sulbactam before they drive or operate machinery. These effects may be enhanced by alcohol.