DBL Sulfamethoxazole & Trimethoprim Adverse Reactions

The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria).
Clinical signs such as rash, sore throat, fever, arthralgia, cough, shortness of breath, pallor, purpura or jaundice may be early indications of serious reactions.
Adverse reactions have been reported in approximately 5 to 7% of patients treated in the published literature. In general, the adverse reactions correspond to those of a sulfonamide of moderately low toxicity.
Gastrointestinal disorders: Nausea and vomiting are the most frequent gastrointestinal reactions to sulfamethoxazole/trimethoprim, but glossitis, stomatitis, abdominal pain, pancreatitis, pseudomembranous colitis and diarrhoea have also been reported.
Blood and lymphatic system disorders: Haematological changes have been observed in some patients, particularly the elderly. The majority of these changes were mild, asymptomatic and proved reversible on withdrawal of the drug. The reported changes consist primarily of neutropenia and thrombocytopenia. Leucopenia, eosinophilia, megaloblastic anaemia, methaemoglobinaemia, hypothrombinaemia, aplastic and haemolytic anaemia, purpura, agranulocytosis and bone marrow depression have been observed less frequently. Haematological toxicity may occur with increased frequency in folate depleted patients including geriatric, malnourished, alcoholic, pregnant or debilitated patients; in patients receiving anti-folates (e.g. phenytoin or methotrexate) or diuretics; in patients with haemolysis or impaired renal function; and in patients receiving sulfamethoxazole/trimethoprim in high dosages and/or for prolonged periods (e.g. longer than 6 months). In geriatric patients receiving some diuretics (principally thiazides) and sulfamethoxazole/trimethoprim concomitantly, an increased incidence of thrombocytopenia with purpura has been reported. The risk of leucopenia, neutropenia and thrombocytopenia also appear to be increased in patients with AIDS.
Immune system disorders: Several cases of Stevens-Johnson syndrome (erythema multiforme bullosa) and Lyell's syndrome (toxic epidermal necrolysis) have been reported. Together with exfoliative dermatitis, serum sickness and allergic myocarditis, these are the most severe allergic reactions reported with sulfonamides alone, or in combination with trimethoprim. Other reported allergic and anaphylactoid reactions include angioedema, serum sickness-like syndrome, generalised allergic reactions, generalised skin eruptions, anaphylaxis, erythema multiforme, drug fever, chills, Schönlein-Henoch purpura, pruritus, urticaria, periorbital oedema, corneal ring infiltrates, conjunctival and scleral redness and oedema, and photosensitivity. In addition, periarteritis nodosa and a positive lupus erythematous phenomenon, and systemic lupus erythematosus have been reported. Mild to moderate rashes, when they occur, usually appear within 7 to 14 days after initiation of sulfamethoxazole/trimethoprim. Rashes are generally erythematous, maculopapular, morbilliform, and/or pruritic. Generalised pustular dermatosis and fixed drug eruption have also been reported. Patients with AIDS appear to be at particular risk of developing rash (usually diffuse, erythematous and maculopapular) during sulfamethoxazole/trimethoprim therapy.
Hepatobiliary disorders: Hepatitis, hepatic changes (as indicated by abnormal elevations in alkaline phosphatase and serum transaminase levels) including cholestatic jaundice and hepatic necrosis have been reported rarely and may be fatal. Jaundice rarely occurs and has usually been mild and transient, frequently occurring in patients with a past history of infectious hepatitis. Elevation of bilirubin levels has also been reported.
Renal and urinary disorders: Dysuria, oliguria, anuria, haematuria, urgency and functional kidney changes (as indicated by abnormal elevations in serum urea, serum creatinine and urine protein concentrations) have been reported occasionally. Renal failure, interstitial nephritis and nephrotoxicity in association with ciclosporin have been reported. Crystalluria and stone formation have occurred in patients receiving sulfamethoxazole/trimethoprim.
Metabolism and nutrition disorders: Anorexia.
High doses of trimethoprim as used in patients with Pneumocystis jirovecii pneumonia induces progressive but reversible increase of serum potassium concentration in a substantial number of patients. Even treatment with recommended doses may cause hyperkalaemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalaemia are given concomitantly. Cases of hyponatraemia have also been reported (see Precautions).
Nervous system disorders: Aseptic meningitis, seizures, peripheral neuritis, ataxia, vertigo, tinnitus, headache. Tremor and other neurologic manifestations (e.g. ataxia, ankle clonus, apathy) developed during sulfamethoxazole/trimethoprim therapy in several patients with AIDS; although such manifestations have also been associated with the underlying disease process, they resolved in these patients within 2 to 3 days after discontinuing the drug.
Psychiatric disorders: Adverse nervous system effects of sulfamethoxazole/trimethoprim include insomnia, apathy, nervousness, mental depression, and hallucinations.
Endocrine disorders: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycaemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycaemia has occurred rarely in patients receiving sulfonamides.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, muscle weakness. Cases of rhabdomyolysis have been reported with sulfamethoxazole/trimethoprim, mainly in AIDS patients.
Respiratory, thoracic and mediastinal disorders: Cough, shortness of breath, pulmonary infiltrates, acute eosinophilic pneumonia, and acute respiratory failure. Epistaxis has been reported rarely.
General disorders and administration site conditions: Weakness, fatigue, pain, local irritation, inflammation, and thrombophlebitis may occasionally occur with intravenous sulfamethoxazole/trimethoprim, especially if extravasation of the drug occurs.
Skin and subcutaneous tissue disorders: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), acute febrile neutrophilic dermatosis have been reported with certain antibiotics. Alopecia has been reported rarely.
Vascular disorders: Hypotension.
Eye disorders: Vision problems have been reported rarely.
Post-marketing experience: The following adverse reactions have been identified during post-approval use of sulfamethoxazole/trimethoprim. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Thrombotic thrombocytopenia purpura; Idiopathic thrombocytopenic purpura; QT prolongation resulting in ventricular tachycardia and torsade de pointes.