Ampicillin 250mg & 500mg Fresenius Injection

AMPICILLIN FRESENIUS is effective in conditions caused by the Gram-positive non-penicillinase producing Staphylococci, haemolytic and non-haemolytic streptococci, Diplococcus pneumoniae, Clostridia sp. and Streptococcus faecalis. Also the Gram-negative cocci Neisseria sp., H. influenzae, E. coli, Proteus mirabilis and many strains of Brucellae, Salmonellae and Shigellae. Parenteral usage is indicated where oral dosage is inappropriate.

Posology
The usual dose for adults is 500 mg six-hourly. In severe infections this dose may be given up to 6 times in one day. In the treatment of beta-haemolytic streptococcal infections, a therapeutic dose must be administered for at least 10 days. Meningitis: 2 g six-hourly intravenously. (Childrenu2019s dosage: 150 mg/kg daily intravenously in 4 divided doses). The above dosages may be increased in particularly severe infections.
Paediatric population
The recommended intravenous and intramuscular dosages for children are u00bc to u00be of the adult dose and are increased in relation to the age from infants to 15 years. Children < 20 kg: 10 - 25 mg/kg six-hourly. Children u2265 20 kg: Adult dose. Meningitis or severe infections: 50 mg/kg six-hourly. Neonates: 5 mg/kg/dose (meningitis: 100 mg/kg/day 12 hourly in the first week of life, and then eight-hourly. Then 1 - 3 g/kg/day six-hourly.
Method of administration
Intramuscular Use: 250 mg, 500 mg - add 1,5 to 2,0 mL water for injection. Direct Intravenous Use: Dissolve the contents of a vial in the specified volume of water for injection. 250 mg - 5,0 mL; 500 mg - 10,0 mL. If AMPICILLIN 250 mg FRESENIUS or AMPICILLIN 500 mg FRESENIUS is administered, administration should be by slow injection over a period of 3-4 minutes. CAUTION: More rapid administration may result in convulsive seizures. Intravenous Drip: Reconstitute as directed above (Direct Intravenous Use) prior to diluting with Intravenous solution. Stability studies on ampicillin sodium at several concentrations in various intravenous solutions indicate the drug will lose less than 10 % activity at the temperatures noted for the time periods stated (see Table 1). Intrathecal: Intrathecal administration is not recommended, because it is a potent convulsant when given by this route. Infants 0 to 2 years, 5 to 10 mg daily - dissolve in 0,5 mL. *Single injection daily. Children 2 to 12 years, 10 to 20 mg daily - dissolve in 0,5 to 1 mL. *Single injection daily. Adults up to 40 mg daily - dissolve in up to 2 mL. *Single injection daily. *(Only sterile solutions should be used i.e. water for injection, sterile normal saline or cerebrospinal fluid [CSF]). Intraperitoneal: Dialysis: 50 mg per litre of dialysate. Therapeutic: Dissolve 500 mg in 5 to 10 mL water for injection. Intrapleural: Dissolve 500 mg in 5 to 10 mL water for injection. Intra-articular: 50 - 100 mg/mL of water for injection or 0,5 lignocaine (lidocaine) hydrochloride to make up to volume of 2,5 mL. Topical: Sprinkle 500 mg to 1 g dry powder extraperitoneally before closure and suturing. Stability and compatibility: Injectable solution: Only freshly prepared solution should be used. Intravenous infusion: AMPICILLIN FRESENIUS is compatible with the following intravenous fluids, but solutions must be used within the periods shown below: Table 1: Period of stability of AMPICILLIN FRESENIUS intravenous infusion solutions at room temperature Normal saline 6 - 8 hours 5 % Dextrose 1 hour Dextrose saline 1 hour M/6 Sodium lactate 4 hours Ringeru2019s solution 6 - 8 hours 1,4 % Sodium bicarbonate 4 hours AMPICILLIN FRESENIUS should not be added to infusion bottles containing Dextran 40 injection but may be injected into the drip tubing of such an infusion. Blood and plasma: A dilute solution (i.e. 500 mg dissolved in 20 mL water for injection) should be injected slowly into the drip tubing rather than added to the infusion bottle.

AMPICILLIN FRESENIUS should not be given to:
u2022 patients known to be hypersensitive to penicillin or cephalosporins (see section 4.4)
u2022 babies in the neonatal period, born to mothers hypersensitive to ampicillin
u2022 Ocular administration

Hypersensitivity reactions
Before initiating therapy with AMPICILLIN FRESENIUS, careful enquiries should be made concerning previous hypersensitivity or allergic reactions to penicillins, cephalosporins or other allergies. (see section 4.3). When administered to a patient with penicillin sensitivity, anaphylactic shock may occur. Cases of cross-sensitivity with cephalosporins and other penicillins have been reported. 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 AMPICILLIN FRESENIUS is to be administered, and patients should be observed for at least one hour after administration of AMPICILLIN FRESENIUS. If an allergic reaction occurs, AMPICILLIN FRESENIUS should be discontinued and the appropriate therapy instituted. SERIOUS ANAPHYLACTIC REACTIONS MAY REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH ADRENALINE (EPINEPHRINE), OXYGEN, INTRAVENOUS STEROIDS, ANTIHISTAMINES AND AIRWAY MANAGEMENT, INCLUDING INTUBATION SHOULD BE ADMINISTERED AS INDICATED.
Jarisch-Herxheimer reaction
Care should be taken when treating patients with syphilis, as the Jarisch-Herxheimer reaction may occur shortly after starting treatment. This reaction, manifesting as fever, chills, headache and reactions at the site of the lesion, can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage, such as optic atrophy.
Antibiotic associated diarrhoea and Clostridium difficile associated diarrhoea (CDAD)
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including AMPICILLIN FRESENIUS and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Allergic skin reactions
A high percentage (43 to 100 percent) of patients with infectious mononucleosis develop a skin rash when treated with ampicillin, such as AMPICILLIN FRESENIUS. Typically, the rash appears 7 to 10 days after the start of oral ampicillin therapy and remains for a few days to a week after the drug is discontinued. In most cases, the rash is maculopapular, pruritic and generalized. Skin testing for hypersensitivity may be advisable before AMPICILLIN FRESENIUS is used in patients who have had penicillin rashes. AMPICILLIN FRESENIUS should be discontinued if a skin rash occurs.
Ampicillin should preferably not be given to patients with infectious mononucleosis, lymphatic leukaemia, HIV infection and patients receiving allopurinol treatment because of an increased risk of developing skin rashes.
Neutropenia
Neutropenia has been widely reported in patients given high doses of beta lactam antibiotics, such as AMPICILLIN FRESENIUS, particularly in patients treated for 10 days or more. Monitoring of the leucocyte count is recommended during long-term treatment with high doses.
Renal impairment
Care should be taken when high doses are given to patients with renal impairment (because of the risk of neurotoxicity) or congestive heart failure. Renal and haematological systems should be monitored during prolonged and high dose therapy. When high doses are administered, adequate fluid intake and urinary output must be maintained. Dosage should be adjusted in patients with renal impairment. Electrolyte disturbance should be monitored when high doses are given due to the sodium content of AMPICILLIN FRESENIUS.
Hepatic impairment
Hepatitis and cholestatic jaundice have been reported less frequently with many penicillins. Hepatic status should be monitored during prolonged and high dose therapy. Sodium content must be taken into account in patients on a sodium-restricted diet if the administration of high doses is necessary. Do not add to containers of infusions containing dextrose. It may be piggybacked via the same administration set.
The use of lignocaine (lidocaine) or benzyl alcohol together with AMPICILLIN FRESENIUS 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. The medicine should be discontinued and specific or supportive therapy instituted. Pseudomembranous enterocolitis has been reported. Increases in the International Normalized Ratio (INR) have been reported in patients receiving AMPICILLIN FRESENIUS. 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. AMPICILLIN FRESENIUS 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. There have been reports of paraesthesia following long-term administration.
General
The possibility of superinfections with mycotic organisms or bacterial pathogens should be kept in mind during therapy. In such cases, discontinue the medication and substitute appropriate treatment. Prescribing ampicillin for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria. Intrathecal administration is not recommended, because it is a potent convulsant when given by this route.

Allopurinol
The concomitant administration of allopurinol and AMPICILLIN FRESENIUS substantially increases the incidence of skin rashes in patients receiving both agents as compared to patients receiving ampicillin alone. (see section 4.4) 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.
Antibiotics
AMPICILLIN FRESENIUS 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 in separate sites, at least 1 hour apart.
Anticoagulants
Concurrent use of medication with an antiplatelet function with AMPICILLIN FRESENIUS may increase the risk of haemorrhage due to additive inhibition of platelet aggregation. (see section 4.4) 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 AMPICILLIN FRESENIUS. Patients receiving anticoagulants, heparin or thrombolytic agents may experience a prolonged INR and bleeding following treatment with AMPICILLIN FRESENIUS.
Oral contraceptives
AMPICILLIN FRESENIUS may decrease the efficacy of oestrogen-containing oral contraceptives.
Cytotoxic medicines
AMPICILLIN FRESENIUS markedly decreases the clearance of methotrexate given intravenously for the treatment of neoplasms, which may result in toxicity. Patients should be closely monitored; and leucovorin doses may need to be increased and administered for longer periods of time.
Potassium levels
Concurrent use of AMPICILLIN FRESENIUS 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.
Interference with diagnostic tests
It is recommended that when testing for the presence of glucose in urine during treatment with AMPICILLIN FRESENIUS, enzymatic glucose oxidase methods should be used. Due to the high urinary concentrations of penicillins such as AMPICILLIN FRESENIUS, false positive or falsely elevated readings are common with chemical methods such as copper sulphate. An increase in INR has been associated with intravenous administration of some penicillins such as AMPICILLIN FRESENIUS.
Alcohol
No information is available about the concurrent use of AMPICILLIN FRESENIUS 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 AMPICILLIN FRESENIUS.

Pregnancy
Safety in pregnancy has not been established.
Breastfeeding
Safety in lactation has not been established. Small amounts of AMPICILLIN FRESENIUS are distributed into breast milk. The use of AMPICILLIN FRESENIUS by breast-feeding mothers may lead to sensitization, diarrhoea, candidiasis and skin rash in the infant.

No information available.

Summary of the safety profile (see also section 4.4). Side effects are usually mild, transitory and infrequent and are similar to those found with other penicillins, however the administration of high doses to children may cause cerebral irritation and convulsions.
Hypersensitivity reactions: If any hypersensitivity reaction occurs, treatment should be discontinued immediately.
Tabulated list of adverse reactions
System Organ Class Frequency Side effect
Blood and lymphatic system disorders Less frequent Eosinophilia, leucopenia, thrombocytopenia, coagulation disorders Unknown Haemolytic anaemia, granulocytopenia, agranulocytosis, disturbances of blood electrolytes
Hepatobiliary disorders Unknown Elevated Aspartate Transaminase (AST) levels, Elevated Alanine Transaminase (ALT) levels, hepatitis, cholestatic jaundice
Immune system disorders Less frequent Hypersensitivity, serum sickness
Infections and infestations Unknown Jarisch-Herxheimer resulting in fever, chills, headache and reactions at site of lesion Unknown Superinfection (by resistant species such as pseudomonas or candida)
Investigations Unknown Disturbances of blood electrolytes, disturbance of diagnostic tests (urinary glucose using copper sulphate tests, direct anti-globulin-Coombs tests, urinary/serum protein tests, Guthrie tests for phenylketonuria)
Gastrointestinal disorders Frequent Nausea, vomiting, diarrhoea Less frequent Antibiotic-associated colitis (pseudomembranous colitis) Unknown Stomatitis, glossitis, black hairy tongue, sore mouth or tongue, pruritis ani, heartburn, mucocutaneous candidiasis, antibiotic-associated colitis (haemorrhagic colitis)
General disorders and administration site conditions Less frequent Fever, joint pains
Metabolism and nutrition disorders Unknown Electrolyte disturbances
Nervous system disorders Less frequent Convulsions, paraesthesia Unknown Hyperkinesia, dizziness
Renal and urinary disorders Less Frequent Interstitial nephritis Unknown Crystalluria, hypokalaemia, hypernatraemia, neurotoxicity, cerebral irritation, convulsions, coma
Skin and subcutaneous tissue disorders Less frequent Angioneurotic oedema, anaphylaxis Less frequent Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous, exfoliative dermatitis, skin rash, pruritus, urticaria, purpura, erythema multiforme
Vascular disorders Less frequent Vasculitis

See section 4.8 for possible symptoms of overdosage. In patients with renal impairment, because serum levels increase, dosage may be reduced if required. Should a serious allergic reaction occur, AMPICILLIN FRESENIUS should be discontinued and the patient treated specifically (antihistamines, pressor amines or corticosteroids). Treatment is symptomatic and supportive. Overdosage with ampicillins such as AMPICILLIN FRESENIUS 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. AMPICILLIN FRESENIUS may be removed from the circulation by haemodialysis. Peritoneal dialysis is not effective in the removal thereof.