Generality
Co-trimoxazole is nothing but the association of sulfamethoxazole (a sulfonamide) and trimethoprim (another antibacterial) in a fixed ratio of 5: 1.
Most likely, this association of active ingredients is best known under the trade name of Bactrim®.
Sulfamethoxazole - Chemical Structure
Trimethoprim - Chemical Structure
Unlike the single active ingredients that possess bacteriostatic activity (ie they are able to inhibit bacterial growth), their association allows to obtain a bactericidal action (ie, when used together, they are able to kill bacterial cells) .
Co-trimoxazole is available in pharmaceutical formulations suitable for administration both orally and parenterally.
Indications
For what it uses
The use of co-trimoxazole is indicated for the treatment of:
- Respiratory tract infections (oral administration);
- Infections of the digestive system (oral administration);
- Infections of the kidneys and urinary tract (oral administration);
- Infections of the genital apparatus (oral administration);
- Pneumonia caused by Pneumocystis carinii or other opportunistic infections in immunocompromised patients (parenteral administration).
Warnings
If - during treatment with co-trimoxazole - any type of allergic reaction occurs, therapy with the drug should be stopped and a doctor should be contacted immediately.
A lot of caution should be used in the use of co-trimoxazole in patients suffering from liver and / or kidney diseases, in patients suffering from folate deficiency and in patients suffering from severe allergies.
During the period of treatment with co-trimoxazole - especially if continued for a long time - it is good to carry out regular checks of liver and kidney function and of blood crasis.
A lot of caution should be used when administering co-trimoxazole in patients already on anticoagulant therapy.
Co-trimoxazole should not be used for the treatment of infections due to β-haemolytic streptococcus of group A.
Interactions
Concomitant administration of co-trimoxazole and amantadine (a drug used in the treatment of Parkinson's disease) can cause the onset of toxic delirium.
Concomitant administration of co-trimoxazole and dofetilide (a potent antiarrhythmic agent) is contraindicated. This is because co-trimoxazole can increase the activity of dofetilide thus causing severe changes in heart rhythm.
Co-administration of co-trimoxazole and indomethacin may cause an increase in sulfamethoxazole plasma concentration.
In any case, it is always a good idea to inform your doctor if you are taking - or have recently been taken - drugs of any kind, including non-prescription medicines and herbal and / or homeopathic products.
Side effects
Co-trimoxazole can induce various types of adverse effects, although not all patients manifest them. The type of side effects and the intensity with which they occur depend on the different sensitivity that each individual has towards the drug.
The main side effects that may occur during the co-trimoxazole therapy are listed below.
Blood and lymphatic system disorders
Treatment with co-trimoxazole may cause:
- Leukopenia, ie the decrease in the number of white blood cells in the bloodstream, with consequent increased susceptibility to the contraction of infections;
- Plateletopenia, or the decrease in the number of platelets in the bloodstream, with consequent increased risk of the onset of abnormal bleeding and / or bleeding;
- Agranulocytosis, ie the decrease in the number of granulocytes in the blood;
- Aplastic anemia;
- Hemolytic anemia;
- Megaloblastic anemia;
- Hypoprothrombinemia, a blood disorder characterized by a prothrombin deficiency with consequent bleeding defects;
- Methaemoglobinaemia.
Allergic reactions
Co-trimoxazole can trigger allergic reactions in sensitive individuals. These reactions can occur with:
- Temperature;
- Angioedema;
- Urticaria;
- Exfoliative dermatitis;
- DRESS syndrome (drug rash with eosinophilia and systemic symptoms);
- Interstitial pneumonia;
- Serum disease;
- Anaphylactic reactions.
Gastrointestinal disorders
Therapy with co-trimoxazole can cause nausea, vomiting, diarrhea, abdominal pain, glossitis, stomatitis, pseudomembranous colitis and acute pancreatitis.
Nervous system disorders
Treatment with co-trimoxazole may cause:
- Neuropathy;
- Uveitis;
- Ataxia;
- Dizziness;
- Headache;
- Asthenia;
- Convulsions.
Psychiatric disorders
Co-trimoxazole therapy can cause hallucinations and insomnia.
Hepatobiliary disorders
During treatment with co-trimoxazole, an increase in blood levels of transaminases and bilirubin may occur. Furthermore, the drug can promote the onset of hepatitis, hepatic necrosis, cholestasis and jaundice.
Skin and subcutaneous tissue disorders
Co-trimoxazole therapy may cause:
- Photosensitization reactions;
- Erythema multiforme;
- Purple and purple of Henoch-Schönlein;
- Stevens-Johnson syndrome;
- Toxic epidermal necrolysis.
Kidney and urinary tract disorders
Treatment with co-trimoxazole may cause:
- Decreased renal function;
- Interstitial nephritis;
- Increased azotemia, albuminuria and creatinine levels;
- hematuria;
- Crystalluria.
Other side effects
Other side effects that may occur during co-trimoxazole therapy are:
- Hyperkalemia which can be very dangerous;
- Superinfections with resistant bacteria or fungi;
- Tinnitus;
- arthralgia;
- Myalgia;
- Rhabdomyolysis;
- Phlebitis or venous pain (when co-trimoxazole is administered parenterally).
Overdose
In case of overdose of co-trimoxazole, they can occur:
- crystalluria;
- Oliguria or anuria;
- Nausea or vomiting;
- Diarrhea;
- Dizziness;
- Headache.
In the event of overdosage, gastric lavage, hemodialysis and adequate fluid intake may be useful in order to accelerate the renal elimination of excess medication.
If an overdose of co-trimoxazole is suspected, however, it is necessary to notify the doctor immediately or contact the nearest hospital.
Action mechanism
As mentioned above, cotrimoxazole consists of the combination of sulfamethoxazole and trimethoprim.
Both of these antibacterials interfere with the synthesis of tetrahydrofolic acid, an essential intermediate for the synthesis of purine and pyrimidine bases that will then constitute the bacterial DNA.
More in detail, sulfamethoxazole competitively inhibits one of the enzymes involved in the first steps of the synthesis of tetrahydrofolic acid: dihydropteroate synthetase.
Trimethoprim, on the other hand, is able to inhibit the enzyme involved in the last stage of the aforementioned synthesis, the dihydrofolate reductase.
With the association of these two antibacterials, therefore, we are witnessing a sequential block of two fundamental passages of the same metabolic pathway, in this way, it is very difficult for bacteria to survive.
Mode of Use - Posology
Co-trimoxazole is available for oral administration (in the form of tablets, soluble tablets and oral suspension) and for intravenous administration (in the form of a concentrate for solution for infusion).
The cotrimoxazole dosage and the route of administration with which to take the drug must be established by the doctor, depending on the type and severity of the infection to be treated.
Pregnancy and breastfeeding
The use of co-trimoxazole by pregnant women and by mothers who are breast-feeding is contraindicated.
Contraindications
The use of co-trimoxazole is contraindicated in the following cases:
- In patients with known hypersensitivity to sulfamethoxazole and / or trimethoprim;
- In patients with known hypersensitivity to other sulfonamides;
- In children less than two months old;
- In patients with glucose-6-phosphate dehydrogenase deficiency;
- In patients already on dofetilide therapy;
- Pregnant;
- During breastfeeding.
