Durobac DS Tablets

DUROBAC and DUROBAC D/S is effective against a wide range of Gram-positive and Gram-negative organisms. It is indicated for:

• Upper and lower respiratory tract infections e.g. acute and chronic bronchitis, bronchiectasis, tonsillitis, sinusitis and pharyngitis, otitis media, pneumonia and pneumocystis carinii pneumonitis (see also section 4.8 Pneumocystis jirovecii Pneumonitis (PJP)).
• Renal and urinary tract infections e.g. pyelitis, pyelonephritis, urethritis, acute and chronic cystitis and cystopyelitis, including prostatitis.
• Gastrointestinal tract infections e.g. enteritis, typhoid and paratyphoid fever, typhoid carriage, bacillary dysentery and cholera. (as an adjunct to fluid and electrolyte replacement).
• Genital tract infections: both male and female including gonococcal infections.
• Skin infections e.g. pyoderma, boils, furuncles, abscesses.
• Other bacterial infections: acute brucellosis, mycetoma except those caused by true fungi, nocardiosis, acute and chronic osteomyelitis.

Posology

Adults and children over 12 years: Two DUROBAC tablets or one DUROBAC DOUBLE STRENGTH tablet twice daily, morning and evening after meals. Minimum dosage and dosage for long-term treatment (more than 14 days): one DUROBAC tablet twice daily or half a DUROBAC DOUBLE STRENGTH twice daily. Maximum dosage (for particularly severe cases): Three DUROBAC tablets or one and a half DUROBAC DOUBLE STRENGTH tablets twice daily.

In acute infections, DUROBAC should be given for at least 5 days or until the patient has been symptom free for 2 days.

Special populations

Renal Impairment

If DUROBAC is indicated for patients with renal impairment, the following dosage scheme, based on creatinine clearance is suggested: Above 25 mL/min: Standard dosage 15 u2013 25 mL/min: Standard dosage for a maximum of 3 days followed by half the standard daily dosage. Below 15 mL/min: Not to be administered unless haemodialysis facilities are available when half the standard daily dosage may be given. Measurements of plasma concentrations of sulfamethoxazole at intervals of 2 days are recommended in samples obtained 12 hours after administration of DUROBAC. If the concentration of total sulfamethoxazole exceeds 150 ug/mL then treatment should be interrupted until the value falls below 120 ug/mL. No Information is available for children with renal failure.

Method of administration

The tablets must be taken by mouth, after food. The tablets must be swallowed with a drink of water.

• Hypersensitivity to sulfamethoxazole, trimethoprim, sulfonamides or to any of the excipients listed in section 6.1.
• Patients suffering from porphyria
• Liver parenchymal damage
• Megaloblastic anaemia due to folic acid deficiency
• Severe renal insufficiency
• Pregnancy, in women prior to delivery or by nursing mothers
• Infants during the first 6 weeks of life

Immunocompromised patients

A high incident of side-effects occurs in immunocompromised patients such as those suffering from AIDS or patients receiving immunosuppressive therapy. The adverse effects include skin rash, recurrent fever, neutropenia, thrombocytopenia and raised liver enzyme values.

Life threatening skin adverse reactions

DUROBAC may cause the occurrence of erythema multiforme, toxic dermal necrolysis and allergic vasculitis. Treatment should be discontinued immediately when a rash appears because the danger of severe allergic reactions.

Folate

DUROBAC should be given with caution to patients with actual or possible folate deficiency because of possible interference with human folate metabolism by trimethoprim as in DUROBAC. Administration of folinic acid could be considered.

Cross-sensitivity

Cross-sensitivity has been observed between sulfamethoxazole as in DUROBAC and chemically related compounds such as some diuretics, particularly acetazolamide and thiazides, and the sulfonylurea hypoglycaemic medicines.

Prolonged treatment

All patients receiving prolonged treatment with DUROBAC should be given regular blood examinations.

Special Populations

Elderly patients

Adverse effects on the blood may be more severe in malnourished or elderly patients: there also appears to be an increased risk of thrombocytopenia in elderly patients concurrently receiving diuretics, mainly thiazides.

Renal impairment

DUROBAC should be used cautiously and in reduced dosage in patients with impaired renal function (see section 4.2). Because of the risk of crystalluria, an adequate fluid intake should be maintained and the administration of alkalis may be necessary if very large doses are used.

Oral anticoagulants, methotrexate and phenytoin

Sulfamethoxazole as in DUROBAC may potentiate the effects of some medicines such as oral anticoagulants, methotrexate, phenytoin; this may be due to displacement of the compound from plasma protein binding sites or to inhibition of metabolism. Trimethoprim as in DUROBAC may potentiate the anticoagulant effect of warfarin. It also prolongs the half-life of phenytoin.

Sulfonylurea compounds

High doses of sulfamethoxazole as in DUROBAC may have a hypoglycaemic effect. The antidiabetic effect of the sulfonylurea compounds may be enhanced by the concomitant administration of sulfamethoxazole.

Para-aminobenzoic acid and compounds

The action of sulfamethoxazole as in DUROBAC may be antagonised by para-aminobenzoic acid and compounds derived from it, particularly the procaine group of local anaesthetics. Paraldehyde has been reported to increase the acetylation of sulfamethoxazole with subsequent increased risk of crystalluria.

Digoxin, procainamide, and tolbutamide

Trimethoprim as in DUROBAC has been reported to interact with a number of other medicines by interfering with their clearance; such medicines include digoxin, procainamide, and tolbutamide.

Cyclosporine

Reversible deterioration in renal function has been reported in patients given trimethoprim as in DUROBAC and cyclosporine following renal transplantation.

Pyrimethamine

Patients receiving pyrimethamine may develop megaloblastic anaemia due to the trimethoprim component as in DUROBAC.

Zidovudine

Concomitant treatment with zidovudine may increase the risk of haematological adverse reactions to DUROBAC. If concomitant treatment is necessary, consideration should be given to monitoring of haematological parameters.

Lamivudine

Administration of trimethoprim/sulfamethoxazole 160 mg/800 mg as in DUROBAC causes a 40 % increase in lamivudine exposure because of the trimethoprim component. Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulfamethoxazole.

Repaglinide

Trimethoprim as in DUROBAC may increase the exposure of repaglinide which may result in hypoglycaemia.

Folinic acid

Folinic acid supplementation has been shown to interfere with the antimicrobial efficacy of trimethoprim sulfamethoxazole as in DUROBAC. This has been observed in Pneumocystis jirovecii pneumonia prophylaxis and treatment.

Contraceptives

Oral contraceptive failures have been reported with antibiotics such as, DUROBAC. The mechanism of this effect has not been elucidated. Women on DUROBAC treatment should temporarily use a barrier method in addition to the oral contraceptive or choose another method of contraception.

Azathioprine

There are conflicting clinical reports of interactions between azathioprine and trimethoprim sulfamethoxazole as in DUROBAC, resulting in serious haematological abnormalities.

Hyperkalaemia

Caution should be exercised in patients taking any other medicines that can cause hyperkalaemia, for example ACE inhibitors, angiotensin receptor blockers and potassium-sparing diuretics such as spironolactone. Concomitant use of trimethoprim-sulfamethoxazole (co-trimoxazole) may result in clinically relevant hyperkalaemia.

Diagnostic tests

Sulfamethoxazole may interfere with some diagnostic tests including those for urea, creatinine, and urinary glucose and urobilinogen. Trimethoprim may interfere with some diagnostic tests including serum methotrexate assay where dihydrofolate reductase is used, and the Jaffe reaction for creatinine.

Pregnancy

Trimethoprim and sulfamethoxazole as in DUROBAC cross the placenta and their safety in pregnant women has not been established. DUROBAC should not be used during pregnancy (see section 4.3).

Breastfeeding

The components of DUROBAC (trimethoprim and sulfamethoxazole) are excreted in breast milk. Administration of DUROBAC should be avoided in late pregnancy and in lactating mothers where the mother or infant has, or is at particular risk of developing, hyperbilirubinemia. DUROBAC should not be given to the new-born infant during the first weeks of life (see section 4.3).

It is not always possible to predict to what extent DUROBAC may interfere with the daily activities of a patient. DUROBAC can cause hallucinations, headache, dizziness and vertigo (see section 4.8). Patients should ensure that they do not engage in the above activities until they are aware of the measure to which DUROBAC affects them.

Summary of the safety profile

Hypersensitivity reactions particularly involving the skin are among the most common adverse effects of DUROBAC and are usually due to the sulfamethoxazole component. The Stevens-Johnson and Lyell's syndromes have been reported.

Adverse effects on the gastro-intestinal tract may also occur fairly frequently.

Tabulated summary of adverse reactions

Sulfamethoxazole

System Organ Class Frequency Adverse reactions

Infections and infestations Frequent Overgrowth fungal. Less frequent Pseudomembranous colitis

Blood and lymphatic system disorders Less frequent Agranulocytosis, aplastic anaemia, thrombocytopenia, leukopenia, hypoprothrombinaemia, eosinophilia, methaemoglobinaemia, acute haemolytic anaemia often associated with glucose-6-phosphate dehydrogenase deficiency, neutropenia

Nausea, vomiting, dizziness and confusion are likely signs/symptoms of overdosage (see also section 4.8). Bone marrow depression has been reported in acute trimethoprim overdosage. If vomiting has not occurred, induction of vomiting may be desirable. Dependent on the status of renal function, administration of fluids is recommended if urine output is low. Both trimethoprim and active sulfamethoxazole are moderately dialysable by haemodialysis. Peritoneal dialysis is not effective.