Co-amoxiclav is generally well tolerated. The majority of adverse effects observed in clinical trials were of a mild and transient nature and <3% of patients discontinued therapy because of drug-related adverse effects. The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). The overall incidence of adverse effects, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported reactions include abdominal discomfort, flatulence and headache.
The following adverse reactions have been reported for ampicillin class antibiotics: Gastrointestinal: Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black "hairy" tongue, mucocutaneous candidiasis, enterocolitis and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see Warnings).
Hypersensitivity Reactions: Skin rashes, pruritus, urticaria, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia and frequently fever), erythema multiforme (rarely Stevens-Johnson syndrome), acute generalized exanthematous pustulosis and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. These reactions may be controlled with antihistamines and if necessary, systemic corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur with oral penicillin (See Warnings).
Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin class antibiotics but the significance of these findings is unknown. Hepatic dysfunction, including increases in serum transaminases (AST and/or ALT), serum bilirubin and/or alkaline phosphatase, has been infrequently reported with co-amoxiclav. It has been reported more commonly in the elderly, in males or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy have been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. On rare occasions, deaths have been reported (<1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications.
Renal: Interstitial nephritis and hematuria have been reported rarely. Crystalluria has also been reported (see Overdosage).
Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in <1% of the patients treated with co-amoxiclav. There have been reports of increased prothrombin time in patients receiving co-amoxiclav and anticoagulant therapy concomitantly.
Central Nervous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported rarely.
Miscellaneous: Tooth discoloration (brown, yellow or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.
The following convention has been utilized for the classification of frequency: Very common (>1/10), common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10,000). The majority of adverse effects listed as follows are not unique to co-amoxiclav and may occur when using other penicillins.
Infections and Infestations: Common: Mucocutaneous candidiasis.
Blood and Lymphatic System Disorders: Rare: Reversible leukopenia (including neutropenia) and thrombocytopenia. Very Rare: Reversible agranulocytosis and hemolytic anemia. Prolongation of bleeding time and prothrombin time (see Interactions).
Immune System Disorders: Very Rare: As with other antibiotics, severe allergic reactions, including angioneurotic edema, anaphylaxis, serum sickness-like syndrome and hypersensitivity vasculitis.
If hypersensitivity reaction is reported, the treatment must be discontinued.
Nervous System Disorders: Uncommon: Dizziness, headache. Very Rare: Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Vascular Disorders: Rare: Thrombophlebitis at the site of injection.
Gastrointestinal Disorders: Common: Diarrhea. Uncommon: Nausea, vomiting, indigestion. Very Rare: Antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis), less likely to occur after parenteral administration.
Hepatobiliary Disorders: Uncommon: Moderate rise in AST, the significance is unknown. Very Rare: Hepatitis and cholestatic jaundice.
Hepatic events have been reported predominately in males and elderly patients and may be associated with prolonged treatment.
Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances. Deaths have been reported.
Skin and Subcutaneous Tissue Disorders: Uncommon: Skin rash, pruritus, urticaria. Rare: Erythema multiforme. Very Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthemous pustulosis (AGEP).
If any hypersensitivity dermatitis reaction is reported, the treatment must be discontinued.
Renal and Urinary Disorders: Very Rare: Interstitial nephritis, crystalluria (see Overdosage).