Dermatologic

Very common (10% or more): Rash, pruritus, exanthema, itching

Common (1% to 10%): Morbilliform rash

Uncommon (0.1% to 1%): Angioneurotic edema, allergic vasculitis, exfoliative dermatitis,

exudative erythema multiforme, urticaria, Stevens-Johnson syndrome, toxic epidermal
necrolysis

Frequency not reported: Erythematous maculopapular rash (including mildly pruritic), macular
rash, purpura, maculopapular rash, skin reactions (e.g., erythema multiforme, Stevens-Johnson
syndrome, toxic epidermal necrolysis), other skin rashes, erythematous eruptions, acute
generalized exanthematous pustulosis[Ref]

Gastrointestinal
Very common (10% or more): Diarrhea, nausea, vomiting, flatulence/meteorism, soft
stools, abdominal pain

Uncommon (0.1% to 1%): Glossitis, stomatitis, enterocolitis, pseudomembranous colitis

Frequency not reported: Oral candidiasis/moniliasis, black hairy tongue, Clostridium difficile-

associated diarrhea, hemorrhagic colitis, sore mouth/tongue, pancreatitis, gastritis,
generalized abdominal cramps[Ref]

Glossitis, stomatitis, black hairy tongue, nausea, vomiting, enterocolitis, pseudomembranous

colitis, and diarrhea were typically associated with oral formulations.

Acute pancreatitis has been reported and confirmed by rechallenge with this drug in a patient in
whom there was no other obvious cause of pancreatitis.[Ref]

Local
Common (1% to 10%): Localized phlebitis

Frequency not reported: Phlebitis at IV administration site, pain at IM administration site[Ref]

Other
Common (1% to 10%): Swelling and pain, exanthema and enanthem in the oral region

Uncommon (0.1% to 1%): Infection with fungi/resistant bacteria (especially during prolonged

and/or repeated use), drug fever

Frequency not reported: Fever (including high fever)[Ref]

Hypersensitivity
Uncommon (0.1% to 1%): Serious allergic reactions (e.g., serum sickness, allergic nephritis)

Rare (0.01% to 0.1%): Life-threatening anaphylactic shock

Frequency not reported: Anaphylaxis, serum sickness-like reactions, hypersensitivity reactions

(including urticarial rash, erythema multiforme, exfoliative dermatitis, edema, hypotension,
fever, eosinophilia, dyspnea, interstitial nephritis, Henoch-Schonlein purpura, focal
glomerulonephritis, Stevens-Johnson syndrome, bullous pemphigoid, hypersensitivity
myocarditis, toxic epidermal necrolysis, fixed drug eruptions)[Ref]
Hematologic
Uncommon (0.1% to 1%): Thrombocytopenia, thrombocytopenic purpura, leukopenia, anemia,
eosinophilia, agranulocytosis, hemolytic anemia

Very rare (less than 0.01%): Granulocytopenia, pancytopenia, prolonged bleeding time,

prolonged prothrombin time

Frequency not reported: Prolonged activated partial thromboplastin time, platelet aggregation
abnormalities, neutropenia, Henoch Schonlein purpura, red cell aplasia[Ref]

Anemia, thrombocytopenia, hemolytic anemia, thrombocytopenic purpura, eosinophilia,

leukopenia, and agranulocytosis have been reported during treatment with penicillins. In general,
these reactions were reversible after stopping therapy and were believed to be sensitivity
reactions.

Neutropenia was described in a case report of 3 pediatric patients who received high doses (150
to 400 mg/kg) of this drug IV. In all 3 cases, white blood cell and neutrophil counts returned to
normal after discontinuation of therapy.[Ref]

Nervous system
Rare (0.01% to 0.1%): Headache, dizziness, myoclonus, seizures

Frequency not reported: Encephalopathy, drowsiness, hyperreflexia, myoclonic twitches,

convulsions, coma[Ref]

Seizures have been reported with renal dysfunction or at very high IV doses.

Seizures have been reported in patients with high serum drug levels, although these patients were
otherwise very ill. High cerebral spinal fluid (CSF) levels of some penicillins were known to be
potentially neurotoxic, and the CSF level of this drug increased significantly in meningitis.

Generalized seizures have been described in 2 patients during use of this drug, although in both
cases, there were underlying disease factors that may have predisposed the patients to seizure
activity.

Encephalopathy has occurred when blood drug level reached 800 mg/L.

Toxic symptoms (e.g., drowsiness, hyperreflexia, myoclonic twitches, convulsions, coma) have
occurred at lower drug levels in patients with meningitis; the blood-brain barrier became more
permeable in meningitis.[Ref]

Renal
Uncommon (0.1% to 1%): Acute interstitial nephritis

Very rare (less than 0.01%): Acute renal failure with excretion of urine crystals

Frequency not reported: Interstitial nephritis, nephropathy, glomerulonephritis[Ref]

Hepatic
Mild, temporary elevation in AST reported in patients who received larger (2 to 4 times) and more
frequent IM injections than usual. Evidence indicated AST was released at IM injection sites for
this drug and increased AST did not necessarily indicate liver involvement.[Ref]

Uncommon (0.1% to 1%): Transaminase elevation

Frequency not reported: Hepatitis, cholestatic jaundice, elevated AST, moderately increased
transaminases (transient), elevated ALT, cholestasis[Ref]

Genitourinary
Crystalluria has been reported with high-dose IV administration.[Ref]

Uncommon (0.1% to 1%): Crystalluria

Frequency not reported: Vaginal candidiasis/moniliasis[Ref]

Respiratory
Uncommon (0.1% to 1%): Laryngeal edema

Frequency not reported: Laryngeal stridor[Ref]

Musculoskeletal
Frequency not reported: Arthralgia

Metabolic
Frequency not reported: Anorexia