Sultamicillin

Alterations in platelet aggregation and coagulation tests have been reported with penicillin use. Increased anticoagulant activity may also be expected.

Bacteriostatic drugs (e.g., erythromycin, sulfonamides and tetracyclines) may interfere with the bactericidal effect of penicillins; therefore, concurrent therapy is not recommended.

Oral administration

In patients with severe renal impairment (creatinine clearance <30 mL/min), the elimination kinetics of ampicillin and sulbactam are similarly affected and hence the plasma ratio of one to the other will remain constant. The dose of sultamicillin in such patients should be administered less frequently in accordance with usual practice for ampicillin.

Intravenous administration

The dose of sultamicillin in patients with impairment of renal function should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

Possible decreased efficacy of estrogen-containing oral contraceptives and increased incidence of breakthrough bleeding have been reported with ampicillin.

Acetylsalicylic acid, indomethacin, and phenylbutazone may prolong the elimination of penicillins from the body, as demonstrated by an increase in the half-life of penicillins.

The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with sultamicillin and allopurinol administered concurrently.

The absorption of ampicillin has been reduced in patients taking chloroquine.

Concomitant use of penicillins may result in decreased renal clearance of methotrexate and subsequent increase in methotrexate toxicity.

Oral probenecid administered shortly before or concomitantly with ampicillin and sulbactam competitively inhibits renal tubular secretion of both ampicillin and sulbactam and produces higher and prolonged serum concentrations of the drugs.

Reproduction studies have been performed in mice, rats, and rabbits at doses up to ten (10) times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to sultamicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Use with caution in breastfeeding women. Low concentrations of ampicillin and sulbactam are excreted in human milk. This should be considered as the neonate may be exposed, particularly since renal function is not fully developed in neonates.

Oral administration

Sultamicillin is generally well-tolerated. Most adverse effects (AEs) are mild to moderate in severity and are normally tolerated with continued treatment.

Body as a Whole: Fatigue/malaise and headache have been rarely observed

Dermatologic/Hypersensitivity reactions: Rash, itching, pemphigus vulgaris, angioedema, dermatitis, urticaria; allergic reaction, anaphylaxis/anaphylactic shock, anaphylactoid reaction, superinfections, adult respiratory distress syndrome

Gastrointestinal (Gl): Vomiting, nausea, diarrhea, loose stools, epigastric distress, melena, abdominal pain/cramps

Nervous system: Taste disturbances, ototoxicity, dizziness, drowsiness/sedation

Renal: Kidney function disorder

Respiratory: Dyspnea

The following AEs have also been reported for aminopenicillin-class antibiotics including ampicillin and/or parenteral ampicillin/sulbactam:

Dermatologic/Hypersensitivity reactions: Pruritus, dry skin, erythema; rare reports of exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens- Johnson syndrome; serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever); systemic allergic reactions (characterized by neck tightness, difficulty and pain when breathing, generalized weakness, and hypertension); facial swelling; positive direct antiglobulin (Coombs' test)

Gl: Anorexia, gastritis, black hairy tongue, glossitis, stomatitis, CDAD and colitis; acute, transient enterocolitis with severe abdominal pain and bloody diarrhea, but without evidence of CDAD and colitis; acute pancreatitis; flatulence, abdominal discomfort or distension, rectal bleeding

Nervous system: Headache, confusion; rare reports of convulsions/myoclonic seizures; generalized seizures

Hematologic: Anemia, hemolytic anemia, hypothrombinemia, eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytopenic purpura, abnormal platelet aggregation, prolongation of bleeding time, and prolongation of activated partial thromboplastin time (APTT); decreased hemoglobin concentration, hematocrit, erythrocyte, lymphocyte, and platelet counts; increased lymphocyte, monocyte, basophil, eosinophil, and platelet counts

Hepatobiliary: Transient elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, lactate dehydrogenase (LDH), creatine kinase (CK), bilirubin, and y-glutamyltransferase (y-glutamyltranspeptidase, GT, GGTP); bilirubinemia, abnormal hepatic function, and jaundice

Renal: Rare reports of acute interstitial nephritis; glomerulonephritis; increased blood urea nitrogen (BUN) and serum creatinine concentrations; presence of red blood cells and hyaline casts in urine, urine retention, dysuria, hematuria, crystalluria

Other Adverse Effects

Decreased concentrations of serum albumin and total protein; chest pain or tightness, edema, chills, throat tightness, substernal pain, epistaxis, mucosal bleeding; changes in smell perception.

For suspected adverse drug reaction, seek medical attention immediately and report to the FDA at www.fda.aov.Dh AND Unilab at (+632) 858-1000 or Droductsafetv@unilab.com.Dh. By reporting undesirable effects, you can help provide more information on the safety of this medicine.

IV / IM administration

Adult Patients

Sultamicillin 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 sultamicillin demonstrate a similar adverse events profile to those observed in adult patients. Additionally, atypical lymphocytosis has been observed in one pediatric patient receiving sultamicillin.

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 sultamicillin, as with other beta-lactam antibacterials.

Gastrointestinal Disorders: Abdominal pain, cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, melena, gastritis, stomatitis, dyspepsia, black “hairy” tongue, and Clostridium difficile associated diarrhea.

General Disorders and Administration Site Conditions: Injection site reaction.

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

Nervous System Disorders: Convulsion and dizziness.

Renal and Urinary Disorders: Tubulointerstitial nephritis.

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.