BERLOCID 960

They derive from the antibacterial and antiparasitic activity of the product, the pharmacokinetic characteristics of sulfamethoxazole and trimethoprim, the risk of adverse effects (particularly haematological and cutaneous) and must take into account, in a given country, the evolution of germ sensitivity to the product and other available antibiotics. Depending on the indications and the germs involved, the antibiotic presenting the best benefit/risk ratio should be used as first-line treatment.

They are limited to adult infections due to sensitive germs (see sections 4.2, 4.3, 4.4, 4.8 and 5.1).

Particularly:

· Curative treatment:

o of Pneumocystis jirovecii infections;

o of male urogenital infections, notably prostatitis;

· Prevention of Pneumocystis jirovecii infections, in the immunocompromised, and notably:

o in patients infected with HIV and at risk of pneumocystosis. In these cases, the incidence of cerebral toxoplasmosis also appears to be decreased during studies conducted in patients receiving the trimethoprim-sulfamethoxazole combination and tolerating it for long periods;

o in case of bone marrow graft or organ transplantation.

On the other hand:

Taking into account the benefit/risk ratio compared to other products, the epidemiology and the bacterial resistances observed in these pathologies.

Treatment:

· of upper and lower urinary tract infections in women; notably single-dose treatment of uncomplicated acute cystitis in women under 65 years of age (see section 4.4);

· of otitis and sinusitis, but only after bacteriological documentation (see section 4.4);

· of certain broncho-pulmonary infections;

· of digestive infections, and typhoid fever.

Official recommendations concerning the appropriate use of antibacterials should be taken into account.

Not applicable.

The following adverse effects have been reported in the general population treated with COTRIMOXAZOLE TEVA.

The frequency categories used are the following:

Very frequent ≥ 1/10 ; frequent ≥ 1/100 and < 1/10 ; uncommon ≥ 1/1000 and < 1/100 ; rare ≥ 1/10 000 and < 1/1000 ; very rare < 1/10 000 ; undetermined (cannot be estimated on the basis of available data).

Cases of death related to certain serious adverse effects have been reported with COTRIMOXAZOLE TEVA, in particular hematological involvement (bone marrow aplasia, agranulocytosis, thrombocytopenia), toxidermia (Stevens-Johnson syndrome, Lyell syndrome), drug hypersensitivity syndrome (DRESS syndrome) and potentially fatal hepatic involvement.

Description of certain adverse effects:

The reported adverse effects, in descending order of frequency, are the following:

General disorders

Hypersensitivity reactions have been reported:

Hyperthermia, angioedema, anaphylactic shock and anaphylactoid reactions.

Exceptional cases of interstitial pneumopathy have been reported.

Respiratory disorders

The presence of pulmonary infiltrates reported in the context of eosinophilic or allergic alveolitis may manifest through symptoms such as cough or shortness of breath. (See section 4.4)

Skin manifestations

As with any other medication, allergic reactions such as pruritic rash and urticaria may occur in patients with hypersensitivity to the components of the drug. Very rare cases of acute generalized exanthematous pustulosis (see section 4.4). Like other drugs containing sulphonamides, the sulfamethoxazole-trimethoprim combination has been associated with skin manifestations of the type erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome), fixed pigment erythema, drug hypersensitivity syndrome (DRESS syndrome) (see section 4.4) and vascular purpura.

Photosensitivity reactions may be observed with COTRIMOXAZOLE TEVA (see section 4.4).

Digestive disorders

Epigastralgia.

Among patients with acute pancreatitis, several presented with serious illnesses, notably AIDS.

Hepatic disorders

Acute cytolytic hepatic impairments (hepatic necrosis), cholestatic and/or mixed, sometimes serious and rarely with a fatal evolution.

Haematological manifestations

Cases of thrombocytopenia with or without purpura, leuco-neutropenia, agranulocytosis, bone marrow aplasia, haemolytic anaemia seem to preferentially relate to an immuno-allergic mechanism.

In subjects aged over 65 years and/or folate deficient, these haematological accidents, in particular cases of megaloblastic anaemia and cytopenias, seem rather to relate to a dose and duration dependent toxic mechanism. Indeed, the product may interfere with folate metabolism (see section 4.4).

Neurological manifestations

Rare cases of tremors have been reported.

Metabolic disorders

The administration of high doses of COTRIMOXAZOLE TEVA, as in pneumocystoses due to Pneumocystis jirovecii, leads to a progressive but reversible increase in serum potassium in a substantial number of patients.

The administration of COTRIMOXAZOLE TEVA even at recommended doses may lead to hyperkalaemia in patients presenting with underlying disorders of potassium metabolism, suffering from renal insufficiency, or taking hyperkalaemic drugs.

In these cases, the increase in kaliemia was progressive and reversible upon discontinuation of treatment (see section 4.4).

Cases of hyponatraemia and metabolic acidosis have been reported.

In non-diabetic patients, rare cases of hypoglycaemia occurring usually after a few days of treatment have been observed (see section 4.5). Patients with impaired renal function, liver disease, suffering from malnutrition or receiving high doses of COTRIMOXAZOLE TEVA are particularly at risk.

Urinary disorders

Cases of urinary lithiasis formed by the aggregation of sulfamethoxazole metabolites (100 % or partial) have been described. Data suggest an interaction with the drug itself and other risk factors for urinary lithiasis.

Manifestations in patients with HIV/AIDS infection

In the population of patients with HIV / AIDS infection, the adverse effects observed are the same as those observed in the general population. However, some adverse effects may occur with a higher frequency and a different clinical picture.

Differences in frequency concern the following organ system classes:

Cases of pancreatitis and rhabdomyolysis have been reported in patients receiving other treatments likely to cause such effects.

Circulatory shock

Cases of circulatory shock, often accompanied by fever and not responding to standard hypersensitivity treatment, have been reported with sulfamethoxazole + trimethoprime, mainly in immunocompromised patients.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorization of the medicinal product is important. It allows continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/