Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Adult Patients: ampicillin and sulbactam is generally well tolerated. The following adverse reactions have been reported in clinical trials.

Local Adverse Reactions
Pain at IM injection site – 16%
Pain at IV injection site – 3%
Thrombophlebitis – 3%
Phlebitis – 1.2%

Systemic Adverse Reactions
The most frequently reported adverse reactions were diarrhea in 3% of the patients and rash in less than 2% of the patients

Additional systemic reactions reported in less than 1% of the patients were: itching, nausea, vomiting, candidiasis, fatigue, malaise, headache, chest pain, flatulence, abdominal distension, glossitis, urine retention, dysuria, edema, facial swelling, erythema, chills, tightness in throat, substernal pain, epistaxis and mucosal bleeding.

Pediatric Patients: Available safety data for pediatric patients treated with ampicillin and sulbactam demonstrate a similar adverse events profile to those observed in adult patients.
Additionally, atypical lymphocytosis has been observed in one pediatric patient receiving ampicillin and sulbactam.

Adverse Laboratory Changes
Adverse laboratory changes without regard to drug relationship that were reported during clinical trials were: Hepatic: Increased AST (SGOT), ALT (SGPT), alkaline phosphatase, and LDH.
Hematologic: Decreased hemoglobin, hematocrit, RBC, WBC, neutrophils, lymphocytes, platelets and increased lymphocytes, monocytes, basophils, eosinophils, and platelets.
Blood Chemistry: Decreased serum albumin and total proteins.
Renal: Increased BUN and creatinine.
Urinalysis: Presence of RBC’s and hyaline casts in urine.

Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following have been identified during post-marketing use of ampicillin sodium/sulbactam sodium or other products containing ampicillin. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency, or potential causal connection to ampicillin sodium/sulbactam sodium.

Blood and Lymphatic System Disorders: Hemolytic anemia, thrombocytopenic purpura and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Some individuals have developed positive direct Coombs Tests during treatment with ampicillin and sulbactam , as with other beta-lactam antibacterials.
Very rare (< 1/10,000) :
Changes of the blood count such as reversible anaemia, leucopoenia, eosinophilia, Impairment of blood coagulation.

Gastrointestinal Disorders: Abdominal pain, cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, melena, gastritis, stomatitis, dyspepsia, black "hairy" tongue and Clostridium difficile associated diarrhea (see CONTRAINDICATIONS and WARNINGS sections).
meteorism can occur. If severe and persistent diarrhoea occurs, the possibility of antibiotic-related pseudomembranous colitis should be considered, which can be life-treating. Therefore in these cases Ampicillin/Sulbactam should be discontinued immediately and a suitable therapy (e.g. oral vancomycin 250 mg four times daily) instituted. Peristaltic-inhibiting drugs are contraindicated.

General Disorders and Administration Site Conditions: injection site reaction Common (> 1/100, <1/10)
In some patients phlebitis or reactions in the area of the injection site may occur.
Rare (> 1/10,000 <1/1000):
Asthenia, sleepiness.

Immune System Disorders: Serious and fatal hypersensitivity (anaphylactic) reactions (see WARNINGS section), Acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction.

Hypersensitivity reactions
Hypersensitivity reactions like urticaria, fever, maculopapular eruptions are possible.
If such symptoms occur, the drug should be discontinued and the doctor consulted.
An immediate reaction in the form of urticaria generally indicates a true penicillin allergy and requires discontinuation of the treatment.
Severe acute hypersensitivity reactions can appear such as: facial oedema, swelling of the tongue, swelling of the larynx narrowing of the airways, severe skin reactions such as erythema exudativum multiforme, tachycardia, dyspnoea, drug fever, eosinophilia, serum sickness, haemolytic anaemia, allergic vasculitis and nephritis, hypotension, anaphylactoid reaction, anaphylactic shock.
On occurrence of these signs, immediate medical assistance may be necessary.
Skin fungi and penicillin can share antigenic properties, so that hypersensitivity reactions as seen after a second contact may occur even on the first administration of a penicillin in a person currently or previously suffering from a fungal skin infection.

Nervous System Disorders: Convulsion and dizziness
Uncommon (> 1/1,000 <1/100) : Vertigo
Neurotoxic reactions (cramps) in events of meningitis or epilepsy, particularly after administration of high doses and impaired renal function respectively.

Renal and Urinary Disorders: Tubulointerstitial nephritis
Rare(> 1/10,000 <1/1000): interstitial nephritis; crystalluria by high intravenous dosage.

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea
Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, Acute generalized exanthematous pustulosis (AGEP), erythema multiforme, exfoliative dermatitis and urticaria (see CONTRAINDICATIONS and WARNINGS sections).
Uncommon (> 1/1,000 <1/100) : pruritus, and other skin reactions.
The typical, meales-like ampicillin rash (ampicillin-associated exanthema) that occurs 5 to 11 days after the start of the treatment, does not necessarily preclude subsequent treatment with penicillin derivates.

Hepato-biliary disorders
Very rare (< 1/10,000): bilirubinaemia, abnormal liver function tests, jaundice.

Musculoskeletal, connective tissue and bone disorders
Very rare (< 1/10,000): Transient and minor increases of the creatinphosphokinase (CPK).
Adverse reactions usually associated with ampicillin alone may also occasionally occur with ampicillin/sulbactam. Further side effects which were described in rare cases for ampicillin such as arthralgia, stomatitis, black tongue discoloration, hereditary angioneurotic edema, exfoliative dermatitis and erythema multiform as well as the occurrence of an anaphylactic shock with a penicillin-hypersensitivity, can not be totally excluded with the use of ampicillin/sulbactam.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/