Trycosil 250 mg/ 500 mg/ 1 g POWDER FOR INJECTION

TRYCOSIL INJECTION is indicated for the treatment of bacterial infections caused by non-penicillinase-producing ampicillin-sensitive organisms. Parenteral usage is indicated where oral dosage is inappropriate.

Recommended Adult Dosage: Adults (including elderly patients): 500 u2013 1000 mg 4 - 6 times a day intravenously for as long as IV therapy is required.

Meningitis: 2 g six-hourly intravenously. (Childrenu2019s dosage: 150 mg/kg daily intravenously in 4 divided doses). In the treatment of beta-haemolytic streptococcal infections, a therapeutic dose must be administered for at least 10 days. The above dosages may be increased in particularly severe infections.

Children < 20 kg: 10 - 25 mg/kg 6 hourly. Children u2265 20 kg: Adult dose. Meningitis or severe infections: 50 mg/kg 6 hourly. Neonates: 5 mg/kg/dose (meningitis: 100 mg/kg/dose) 12 hourly in the first week of life, and then 8 hourly in the second week. Then after the second week 1 - 3 mg/kg/dose 6 hourly.

Administration: When prepared for intramuscular or direct intravenous injection, TRYCOSIL INJECTION should be administered immediately after reconstitution (see u201cRECONSTITUTION AND STORAGE INSTRUCTIONSu201d). Intramuscular: 250 mg, 500 mg, 1 g u2013 add 1,0 to 3,5 ml Water for Injections. Intravenous: Dissolve the contents of a vial in the specified volume of Water for Injections. 250 mg u2013 5,0 ml; 500 mg u2013 5,0 ml; 1 g u2013 7,4 ml. The intravenous dose is given by slow injection (3-4 minutes). Alternatively it may also be added to infusion fluids or be injected, suitably diluted, into the drip tube over 3-4 minutes (refer to table under u201cSTABILITYu201d). Intraperitoneal: Dialysis: 50 mg per litre of dialysate. Therapeutic: Dissolve 500 mg in 5 to 10 ml Water for Injections. Intrapleural: Dissolve 500 mg in 5 to 10 ml Water for Injections. Intra-Articular: 50 - 100 mg/ml of Water for Injections or 0,5 % lignocaine hydrochloride to make up to volume of 2,5 ml.

TRYCOSIL should not be given to:

• Patients known to be hypersensitive or allergic to penicillins such as ampicillin or cephalosporins (see u201cWARNINGS AND SPECIAL PRECAUTIONSu201d).
• Babies in the neonatal period, born to mothers hypersensitive to ampicillin.

Serious and occasionally fatal hypersensitivity (severe anaphylactic) reactions have been reported in patients on ampicillin/penicillin therapy. Before initiating therapy with TRYCOSIL INJECTION, careful enquiry should be made concerning previous hypersensitivity or allergic reactions to penicillins, cephalosporins or other allergies. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity that have experienced severe reactions when treated with cephalosporins. Resuscitative equipment should be available when TRYCOSIL INJECTION is to be administered, and patients should be observed for at least one hour after administration of TRYCOSIL INJECTION. If an allergic reaction occurs, TRYCOSIL INJECTION should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with epinephrine (adrenaline), oxygen, intravenous steroids, anti-histamines and airway management, including intubation.

TRYCOSIL INJECTION should be used with caution in patients with known history of allergy. Caution is needed when administering TRYCOSIL INJECTION to patients with syphilis as the Jarisch-Herxheimer reaction may occur shortly after commencing treatment in these patients. This reaction, which manifests in fever, chills, headache and reactions at the site of the lesion, may be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as with optic atrophy.

TRYCOSIL INJECTION should be discontinued if a skin rash occurs. It should preferably be avoided if infectious mononucleosis, lymphatic leukemia or possibly HIV infection is suspected and also in patients receiving allopurinol treatment, because of an increased risk of rashes associated with these conditions, following the administration of TRYCOSIL INJECTION. When high doses are administered, adequate fluid intake and urinary output must be maintained.

The use of lidocaine together with TRYCOSIL INJECTION should be considered only when administering an intramuscular injection, and must not be given intravenously. Prolonged use may result in overgrowth of non-susceptible organisms. Antibiotic-associated pseudomembranous enterocolitis has been reported, with ampicillin contained in TRYCOSIL INJECTION. It may range in severity from mild to life threatening. Therefore it is important to consider this side-effect in patients who present with diarrhoea during or subsequent to administration of TRYCOSIL INJECTION. Increases in the INR have been reported in patients receiving TRYCOSIL INJECTION. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Periodic assessment of organ function, including renal, hepatic and haematopoietic functions, is advisable during prolonged therapy.

TRYCOSIL INJECTION should not be mixed in the same syringe or administration set with aminoglycosides such as gentamycin, or with other beta-lactam antibacterials such as cephalosporins (see u201cINTERACTIONSu201d). Do not add to containers of infusions containing dextrose. It may be piggybacked via the same administration set. High doses of sodium penicillins such as TRYCOSIL INJECTION may cause hypokalaemia and sometimes hypernatraemia. Use of a potassium sparing diuretic may be helpful. Care should be taken when high doses of TRYCOSIL INJECTION are given to patients with renal impairment (due to the risk of neurotoxicity) or congestive heart failure. In the presence of impaired renal function large doses of TRYCOSIL INJECTION (e.g. more than 8 g per day in an adult) may cause cerebral irritation, convulsions and coma. Renal systems should be monitored during prolonged and high dose therapy. When high doses are administered, adequate fluid intake and urinary output must be maintained. Contact with TRYCOSIL INJECTION should be avoided since skin sensitisation may occur. The sodium content must be taken into account in patients on a sodium-restricted diet if the administration of high doses is necessary as each gram of ampicillin sodium contains 2, 7mmol of sodium. If symptoms due to overgrowth of non-susceptible organisms such as Aerobacter, Pseudomonas, or Candida species appear, TRYCOSIL INJECTION should be discontinued and supportive therapy instituted. There have been reports of paraesthesia following long-term administration.

TRYCOSIL INJECTION should not be mixed in the same syringe or administration set with aminoglycosides such as gentamycin, as substantial inactivation of the aminoglycosides may result, or with other beta-lactam antibacterials such as cephalosporins, as substantial mutual inactivation may result. If these groups of antibacterials are to be administered concurrently, they should be administered at separate sites, at least 1 hour apart (see u201cWARNINGS AND SPECIAL PRECAUTIONSu201d).

TRYCOSIL INJECTION markedly decreases the clearance of methotrexate given intravenously for the treatment of neoplasms, which may result in toxicity. The combination should be avoided or patients should be closely monitored; and leucovorin doses may need to be increased and administered for longer periods of time. Concurrent use of TRYCOSIL INJECTION with ACE inhibitors, potassium-sparing diuretics, potassium-containing medications or potassium supplements may promote serum potassium accumulation with possible resultant hyperkalaemia, especially in patients with renal insufficiency; concurrent administration with ACE inhibitors may result in hyperkalaemia since reduction of aldosterone production induced by ACE inhibitors may lead to elevation of serum potassium.

Concurrent use of medication with an antiplatelet function with TRYCOSIL INJECTION may increase the risk of haemorrhage due to additive inhibition of platelet aggregation. In addition, hypoprothrombinaemia induced by large doses of salicylates, and the gastrointestinal ulcerative or haemorrhagic potential of NSAIDs or salicylates may also increase the risk of haemorrhage when these medications are used concurrently with TRYCOSIL INJECTION. Patients receiving anticoagulants, heparin or thrombolytic agents may experience a prolonged INR and bleeding following treatment with TRYCOSIL INJECTION.

TRYCOSIL INJECTION may reduce the efficacy of oral contraceptives and patients should be warned accordingly to use alternative or additional measures of contraception. The concomitant administration of allopurinol and TRYCOSIL INJECTION substantially increases the incidence of skin rashes in patients receiving both agents as compared to patients receiving ampicillin alone. This is especially so for hyperuricaemic patients. It is not known whether this potentiation of rashes is due to allopurinol or the hyperuricaemia present in these patients. No information is available about the concurrent use of TRYCOSIL INJECTION and alcohol. However, the ingestion of alcohol whilst being treated with some other beta-lactam antibiotics has precipitated a disulfiram-like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with TRYCOSIL INJECTION. It is recommended that when testing for the presence of glucose in urine during treatment with TRYCOSIL INJECTION, enzymatic glucose oxidase methods should be used. Due to the high urinary concentrations of penicillins such as TRYCOSIL INJECTION, false positive or falsely elevated readings are common with chemical methods such as copper sulphate.

Safety in pregnancy and lactation has not been established. Animal studies with TRYCOSIL INJECTION have shown no teratogenic effects.

Use in lactation: TRYCOSIL INJECTION are distributed into breast milk. The use of TRYCOSIL INJECTION by breast-feeding mothers may lead to sensitisation, diarrhoea, candidiasis and skin rash in the infant.

TRYCOSIL INJECTION may cause drowsiness. Caution must be exercised when driving or operating machinery.

Immune system disorders: If any hypersensitivity reaction occurs, treatment should be discontinued immediately. Less frequent: Severe allergic reactions including angioedema, anaphylaxis, serum sickness and vasculitis. Skin rashes such as erythema multiforme and Stevens-Johnson syndrome, toxic epidermal necrolysis and bullous and exfoliative dermatitis and other skin rashes. A generalised sensitivity reaction with urticaria, fever, joint pains and eosinophilia can develop within a few hours to several weeks after starting treatment.

Infections and infestations: The following side-effects have been reported and frequencies are unknown: Superinfection by resistant or non-susceptible species such as Pseudomonas or Candida or Aerobacter species.

Blood and the lymphatic system disorders: Less frequent: Leucopenia, thrombocytopenia, and coagulation disorders such as prolongation of bleeding time and defective platelet function. The following side-effects have been reported and frequencies are unknown: Haemolytic anaemia, granulocytopenia and agranulocytosis. Haematological parameters should be monitored during prolonged and high dose therapy.

Investigations: Increased sodium plasma concentrations with higher doses of TRYCOSIL INJECTION. The following side-effects have been reported and frequencies are unknown: Disturbances of blood electrolytes may follow administration of large doses of TRYCOSIL INJECTION and may interfere with some diagnostic tests, such as those for urinary glucose using copper sulphate, direct anti-globulin (Coombsu2019) tests, and some tests for urinary or serum proteins. TRYCOSIL INJECTION may interfere with tests that use bacteria, for example the Guthrie test for phenylketonuria using Bacillus subtilis organisms.

Nervous system disorders: Less frequent: Convulsions, paraesthesia. The following side-effects have been reported and frequencies are unknown: Hyperkinesia and dizziness.

Gastrointestinal disorders: Frequent: Nausea, vomiting and diarrhoea. Less frequent: Antibiotic-associated colitis (pseudomembranous colitis). The following side-effects have been reported and frequencies are unknown: Stomatitis, glossitis, black hairy tongue and heartburn. Mucocutaneous candidiasis and antibiotic-associated colitis (haemorrhagic colitis).

Hepato-biliary disorders: The following side-effects have been reported and frequencies are unknown: A moderate rise in liver enzyme (aspartate transaminase (AST) and/or alanine transaminase (ALT) values. Hepatitis and cholestatic jaundice.

Skin and subcutaneous tissue disorders: Frequent: Urticaria, skin rashes.

Renal and urinary disorders: The following side-effects have been reported and frequencies are unknown: Crystalluria, interstitial nephritis.

Overdosage with ampicillins such as TRYCOSIL INJECTION is usually asymptomatic. Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and symptoms of water and electrolyte imbalance should be treated symptomatically. Adequate fluid intake and urinary output must be maintained to minimise the crystalluria. TRYCOSIL INJECTION may be removed from the circulation by haemodialysis. Peritoneal dialysis is not effective in the removal thereof. Treatment is symptomatic and supportive (see u201cSIDE - EFFECTSu201d).