Ampicillin 250 & 500 Injection Unimed

AMPICILLIN INJECTION UNIMED (ampicillin) is indicated in the treatment of infections caused by susceptible strains of the following microorganisms:

• Infections of the genitourinary tract caused by E coli, P. mirabilis and enterococci.
• Respiratory tract and ENT infections e.g. pharyngitis, tonsillitis, sinusitis, laryngitis, otitis media, bronchitis, pneumonia caused by various bacteria including non-penicillinase-producing H. influenzae, staphylococci, and streptococci including Streptococcus pneumoniae.
• Infections of the gastro-intestinal tract caused by Shigella, S. typhosa and other Salmonella, E. coli, P. mirabilis, and enterococci.
• Meningitis - N. meningitidis (after confirmation by sensitivity testing).
• Miscellaneous infections e.g. Septicaemia, endocarditis and biliary tract infections.
• Skin and soft tissue infections, bacteremia and as an adjunct in the treatment of sepsis caused by Gram-negative bacteria.

Dosage varies with the type and the severity of the infection, renal function, and age. Doses for children should not exceed doses recommended for adults.

Parenteral administration is reserved for severe infections that cannot be treated by oral ampicillin.

Recommended Adult Dosage:

• Adults (including elderly patients): 500 - 1000 mg 4 - 6 times a day intravenously for as long as IV therapy is required.
• Meningitis: 2 g six-hourly intravenously. (Children 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. Then 1 - 3 mg/kg/dose 6 hourly.

Renal impairment: Dosage should be adjusted in patients with renal impairment.

Method of administration:

DIRECTIONS FOR USE OF PARENTERAL AMPICILLIN INJECTION UNIMED: Use only freshly-prepared solutions.

• Intramuscular use: Dissolve 250 mg or 500 mg in 1 to 2 ml of sterile water for injection and withdraw the entire contents.
• Direct intravenous injection: Dissolve 250 mg or 500 mg in 5 to 10 ml of sterile water for injection. Administer the dose by slow injection over a period of 3 to 5 minutes.
• Intravenous drip: Stability studies on ampicillin sodium at concentration of 2 mg/ml and 30 mg/ml in various intravenous solutions indicate that the medicine will lose less than 10 % activity at room temperature (25 u00b0C) for the time periods stated below:
• Isotonic sodium chloride: 8 hours
• 5 % Dextrose in water: 4 hours
• 10 % Invert sugar in water: 4 hours
• M/6 Sodium lactate solution (in concentration of 30 mg/ml): 8 hours

u2014 AMPICILLIN INJECTION UNIMED is contraindicated in individuals with a history of a previous hypersensitivity reaction to any of the pencillins, such as ampicillin in AMPICILLIN INJECTION UNIMED.

u2014 Patients allergic to cephalosporins or cephamycins may be allergic to penicillins, such as ampicillin in AMPICILLIN INJECTION UNIMED also.

u2014 It is contraindicated in babies born of hypersensitive mothers in the neonatal period.

Serious and occasionally fatal hypersensitivity (severe anaphylactic) reactions have been reported in patients on ampicillin/penicillin therapy. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction (see section 4.8). Careful history of sensitivity to allergens, including previous hypersensitivity reactions to penicillins and cephalosporins should be taken before instituting therapy with AMPICILLIN INJECTION UNIMED.

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 INJECTION UNIMED is to be administered, and patients should be observed for at least one hour after administration of AMPICILLIN INJECTION UNIMED. If an allergic reaction occurs, AMPICILLIN INJECTION UNIMED should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline (epinephrine), oxygen, intravenous steroids, anti-histamines and airway management, including intubation.

Use with caution in patients with known history of allergy.

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 with optic atrophy.

AMPICILLIN INJECTION UNIMED should be discontinued if any 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 AMPICILLIN INJECTION UNIMED.

When high doses are administered, adequate fluid intake and urinary output must be maintained. In prolonged therapy, and particularly with high dosage regimens, periodic evaluation of the renal, hepatic and hematopoietic systems is recommended. Care should be taken when high doses are given to patients with renal impairment (because of the risk of neurotoxicity) or congestive heart failure. Dosage should be adjusted in patients with renal impairment (see section 4.2).

Prolonged use may result in overgrowth of non-susceptible organisms. Pseudomembranous enterocolitis has been reported. It may range in severity from mild to life threatening.

Increases in the INR have been reported in patients receiving AMPICILLIN INJECTION UNIMED. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.

There have been rare reports of paraesthesia following long-term administration.

The use of lignocaine or benzyl alcohol together with AMPICILLIN INJECTION UNIMED should be considered only when administering an intramuscular injection, and must not be given intravenously.

Paediatric use: Pencillins are excreted primarily unchanged by the kidney; therefore, the incompletely developed renal function in neonates and young infants will delay the excretion of ampicillin in AMPICILLIN INJECTION UNIMED. Administration to neonates and young infants should be limited to the lowest dosage compatible with an effective therapeutic regimen.

AMPICILLIN INJECTION UNIMED contains sodium: Sodium content must be taken into account in patients on a sodium-restricted diet if the administration of high doses is necessary.

AMPICILLIN 250 INJECTION UNIMED: This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially u2018sodium-freeu2019.

AMPICILLIN 500 INJECTION UNIMED: This medicinal product contains 30,96 mg sodium per 500 mg vial, equivalent to 1.55 % of WHO recommended maximum daily intake of 2 g sodium for an adult.

AMPICILLIN INJECTION UNIMED 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.

AMPICILLIN INJECTION UNIMED 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.

Probenecid may decrease renal tubular secretion of ampicillin resulting in increased blood levels and/or ampicillin toxicity.

AMPICILLIN INJECTION UNIMED may decrease the efficacy of oral contraceptives and increased breakthrough bleeding may occur.

Allopurinol increases possibility of skin rash, particularly in hyperuricemic patients, when AMPICILLIN INJECTION UNIMED is given concurrently. 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 AMPICILLIN INJECTION UNIMED 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 INJECTION UNIMED.

Chloramphenicol, erythromycin, sulfonamides, or tetracycline may interfere with the bactericidal effect of AMPICILLIN INJECTION UNIMED.

After treatment with AMPICILLIN INJECTION UNIMED, a false-positive reaction for glucose in the urine may occur with copper sulfate tests but not with enzyme based tests. Due to the high urinary concentrations of penicillins such as AMPICILLIN INJECTION UNIMED, false positive or falsely elevated readings are common with chemical methods such as copper sulphate.

Concurrent use of AMPICILLIN INJECTION UNIMED 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 AMPICILLIN INJECTION UNIMED 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 AMPICILLIN INJECTION UNIMED.

Patients receiving anticoagulants, heparin or thrombolytic agents may experience a prolonged INR and bleeding following treatment with AMPICILLIN INJECTION UNIMED.

Pregnancy: Safety in pregnancy and lactation has not been established. Animal reproduction studies with ampicillin as in AMPICILLIN INJECTION UNIMED have failed to demonstrate a risk to the foetus. There are no adequate and well controlled studies in pregnant women.

Lactation: Ampicillin-class antibiotics are excreted in milk. AMPICILLIN INJECTION UNIMED use by nursing mothers may lead to sensitisation, diarrhoea, candidiasis and skin rash of infants. Use with caution when administered to lactating women.

Fertility: No fertility data is available.

Adverse effects on the ability to drive or operate machinery have not been observed. Caution is advised for patients not to drive or use machines, until their individual susceptibility to the effects of AMPICILLIN INJECTION UNIMED is known.

Table 1: Tabulated list of adverse reactions

* A generalised sensitivity reaction with urticaria, fever, joint pains and eosinophilia can develop within a few hours to several weeks after starting treatment. If hypersensitivity reaction occurs, treatment should be discontinued immediately.

** Haematological parameters should be monitored during prolonged and high dose therapy.

*** Contact with AMPICILLIN INJECTION UNIMED should be avoided since skin sensitisation may occur.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

In the event of overdosage, medicine should be discontinued and symptomatic and supportive measures should be instituted as required. Overdosage with ampicillins such as AMPICILLIN INJECTION UNIMED 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. In patients with renal function impairment, ampicillin-class antibiotics can be removed by haemodialysis but not by peritoneal dialysis. Treatment is symptomatic and supportive).