4.5 Interaction with other medicinal products and other forms of interaction
Other antibacterials: Since bacteriostatic drugs such as chloramphenicol and tetracycline may interfere with the bactericidal effect of penicillins in the treatment of meningitis or in other situations in which a rapid bactericidal effect is necessary, it is best to avoid concurrent therapy.
Immunosuppressants: There is reduced excretion of methotrexate (increased risk of toxicity).
Oral contraceptives: Flucloxacillin may decrease the efficacy of oestrogen-containing oral contraceptives.
Uricosuric agents: Plasma concentrations of flucloxacillin are enhanced if probenecid is given concurrently.
Interference with diagnostic tests: Penicillins may produce false-positive results with the direct antiglobulin (Coombs’) test, falsely high urinary glucose results with the copper sulphate test and falsely high urinary protein results, but glucose enzymatic tests (e.g. Clinistix) and bromophenol blue tests (e.g. Multistix or Albustix) are not affected.
4.6 Pregnancy and lactation
There has been no evidence of a teratogenic effect in animals or untoward effect in humans. However, use in pregnancy should be reserved for essential cases.
Trace quantities of penicillin can be detected in breast milk with the potential for hypersensitivity reactions (e.g. drug rashes) in the breast-fed neonate or acute alterations in the neonatal bowel flora with resultant diarrhoea.
4.8 Undesirable effects
The most common adverse effects are sensitivity reactions including urticaria, maculo-papular rashes, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), pruritus,
fever, joint pains and angioedema. Anaphylaxis occasionally occurs and has sometimes been fatal. Late sensitivity reactions may include serum sickness-like reactions, haemolytic anaemia, nephropathy and acute interstitial nephritis, which is reversible when treatment is discontinued.
Other adverse effects are generally associated with large intravenous doses of flucloxacillin or impaired renal function. These include transient leucopenia and thrombocytopenia, haemolytic anaemia, agranulocytosis and neutropenia (which might have some immunological basis); prolongation of bleeding time and defective platelet function; convulsions and other signs of central nervous system toxicity (encephalopathy has been reported following intrathecal administration and can be fatal); electrolyte disturbances due to administration of large amounts of sodium (see Section 4.4).
Hepatic effects: Changes in liver function test results may occur, but are reversible when treatment is discontinued. Hepatitis and cholestatic jaundice have been reported. These reactions are related neither to the dose nor to the route of administration; administration for more than two weeks and increasing age are risk factors. The onset of these effects may be delayed for up to two months post-treatment; in several cases the course of the reactions has been protracted and lasted for some months. In very rare cases, a fatal outcome has been reported, almost always in patients with serious underlying disease.
Some patients with syphilis may experience a Jarisch-Herxheimer reaction shortly after treatment is started. Symptoms include fever, chills, headache and reaction at the site of lesions. The reaction can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as with optic atrophy.
Gastrointestinal effects (diarrhoea, and nausea and vomiting) reported with flucloxacillin commonly occur after oral administration, not or parenteral administration. Pseudomembranous colitis has been reported with most antibiotics. Prolonged use of penicillins may lead to the development of oral candidiasis.
Phlebitis has followed intravenous infusion.
6.2 Incompatibilities
Flucloxacillin may be administered in combination with other antibiotics including ampicillin to produce a wider spectrum of antibacterial activity. If used concurrently with an aminoglycoside the two antibiotics should not be mixed in the syringe, container or giving set as precipitation may occur.
Flucloxacillin should not be mixed with blood products or other proteinaceous fluids (e.g. protein hydrolysates) or with intravenous lipid emulsions.
The following drugs are incompatible with flucloxacillin: amiodarone, atropine sulphate, buprenorphine, calcium gluconate, chlorpromazine hydrochloride, ciprofloxacin, diazepam, dobutamine, hydrochloride, erythromycin lactobionate, gentamicin sulphate, metoclopramide hydrochloride, morphine sulphate, netilmicin sulphate, ofloxacin, papaveretum, pethidine hydrochloride, prochlorperazine edisylate, promethazine hydrochloride, tobramycin and verapamil hydrochloride.
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