TETRACYCLINE HYDROCHLORIDE 1% ophthalmic ointment

Please read leaflet carefully because it contains important information for you. If you have further question, please ask your doctor or pharmacist. 

PHARMACEUTICAL DOSAGE FORMS: COMPOSITION

X'trim Tablets: Each tablet contains Sulphamethoxazole BP 400mg and Trimethoprim BP 80mg.

X'trim Suspension: Each 5ml Suspension contains Sulphamethoxazole BP 200mg and Trimethoprim BP 40mg.

EXCIPIENTS

X'trim suspension: Propyl Paraben Sodium, Methyl Paraben Sodium, Carboxymethyl Cellulose, Sucrose, Glycerin, Banana Flavor.

X'trim tablet: Maize Starch, Povidone, Talc, Magnesium Stearate, Sodium Starch Glycolate, Microcrystalline Cellulose, Aerosol.

PHARMACODYNAMIC PROPERTIES

X'trim combines two active ingredients:

• Sulphamethoxazole, which belongs to the sulphonamide class. 
• Trimethoprim, which belongs to the diaminopyrimidine chemical class.

These two compounds exhibit a synergistic anti-infectious activity whose spectrum can be described as follows: Normally sensitive species: Escherichia coli, proteus, Citrobacter salmonella, shigella, haemophilus, Vibrio cholera, listeria, pneumococcus, Serratia, Klebsiella, Enterobacter, Providencia, staphylococcus, some species are naturally resistant to trimethoprim; however, when the strain is sensitive to sulphonamide, the combination is synergistic. The combination appears equally synergistic against the majority of sulphonamide-resistant and trimethoprim-sensitive strains: brucella, Acinetobacter, nocardia, actinomycetes; anaerobes, meningococcus, and gonococcus. The Sulphamethoxazole-trimethoprim combination is not active on: treponema, mycoplasma.

 PHARMACOKINETIC PROPERTIES

Up to 90% of the two active ingredients are absorbed. The Cmax is attained 2 to 4 hours following dosing. The Cmax is 40-60μg/ml for Sulphamethoxazole and 1 to 2μg/ml for trimethoprim following a dose of 960mg, the Sulphamethoxazole half-life is between 9 and 11 hours and the trimethoprim half-life is 10 to 12 hours. The respective half-lives are reduced in children. Distribution in the tissues and biological fluids is rapid. The active ingredients are found in cerebrospinal fluid, middle ear, amygdala, saliva, lungs, prostate, vaginal secretions, bones. Protein binding exceeds 66% for Sulphamethoxazole and 45% for trimethoprim. Elimination is mainly urinary (80% within 72 hours) and represents the unchanged ingredients up to 20% for Sulphamethoxazole is transformed into inactive glycoconjugated N-acetylated derivatives. Some trimethoprim metabolites are active.

INDICATIONS

X'trim is indicated in:

• Infections due to susceptible bacteria of the Genito-urinary (particularly prostatic), pulmonary and gastrointestinal systems (typhoid fever and sigmoiditis) and of middle ear.
• Infections caused by Pneumocystis carinii and Toxoplasma Gondi.

DOSAGE AND ADMINISTRATION

X'trim should be administered during meals.

Adults and children over 12 years:

• Usual dose: 2 tablets twice daily.
• Particularly severe cases: 3 tablets twice daily, morning and evening.

Infant and children (pediatric) suspension:

• From 6 weeks to 5 months: 2-5 ml twice daily.
• From 6 months to 5 years (body weight under 20kg): 5ml twice daily.

In severe infections, dosage can be increased by half.

Patients with renal failure: Creatinine clearance greater than 30ml/min: normal dosage; Creatinine clearance between 15 and 30ml/min: reduce dosage by half, i.e. single daily dose; Creatinine clearance lesser than 15ml/min: use should be avoided unless hemodialysis is available. If hemodialysis is possible, posology should be reduced by half and accompanied by the measurement of Sulphamethoxazole plasma concentration every 3 days.

SIDE EFFECTS

• Frequent: Nausea, vomiting, epigastralgia, pruriginous cutaneous eruption, urticarial. Rare: skin reactions: epidermal necrolysis: erythema multiforme, Lyell and Stevens-Johnson syndrome. Hematological reactions: Thrombocytopenia, leukoneutropenia, agranulocytosis, bone marrow aplasia, and hemolytic anemia. In patients over 65 years old and/or folate-deficient, hematological accidents and, particularly, cases of megaloblastic anemia and cytopenia.
• Others: Anaphylactic shock, Quincke'soedema, hyperthermia, Hepatitis, pseudomembranous colitis, renal function impairment, Neurological and sensory manifestations (aseptic meningitis) exceptionally reported. In HIV patients, on treatment against Pneumocystis carinii pneumopathy, the frequency of undesirable effects may be increased.

PRECAUTIONS AND WARNING

Warnings: In case of skin or hematological reactions, cease treatment immediately, Increased incidence of hematological accidents in patients over 65 years and/or with folate deficiency justify special care. Do not exceed 10 days of treatment and follow the recommended dosage. In case of severe renal failure (creatinine clearance lesser than 30ml/min), the dosage should be reduced.

Precaution for use: Periodic hematological monitoring in case of: Prolonged or repeated treatment, Patients over 65 years old, Patients with folate deficiency. Biological monitoring in case of hepatic failure, hematologic antecedents and renal failure.

CONTRA-INDICATIONS

History of intolerance to one of the components and/or to any sulphonamide, G6PD deficiency: risk of acute hemolysis, Pregnancy and lactation, New-born or premature infants,

PREGNANCY AND LACTATION

In animals, the sulphonamide-trimethoprim combination is teratogenic; its use is not recommended during pregnancy.

DRUG INTERACTIONS

Anticoagulants such as coumarin derivatives (augmentation of anticoagulant effect); Reversible renal function impairment with cyclosporine; X'trim (Co- trimoxazole) reduces the hepatic metabolism of phenytoin and may, thereby, potentiate its effect. Paraclinical examination: Trimethoprim can interfere with the measurement of plasma creatine concentration by the picric acid reaction. This may result in an under-examination of 10%.

OVERDOSE

No acute intoxication was observed following a massive administration of X'trim. If intoxication does occur, the following treatment should be implemented: Gastric lavage, Fluid administration in order to increase diuresis and drug elimination, Folinic acid IM injection.

STORAGE

• Do not store above 30°C.
• Keep out of the sight and reach of children.

FOR SUSPENSION

SHAKE WELL BEFORE EACH USE.

PRESENTATION

• SUSPENSION: 100ml Bottles
• TABLETS: 10x50 Blisters

DATE OF PUBLICATION 2015

DATE OF REVIEW 2018

Manufactured by: ENTRANCE TOBINCO Pharmaceuticals and Research Centre.

No.16 Okpoi Gonno, Spintex Road, Accra, Ghana.