BNF for Children 2011-2012

280 5.1.5 Macrolides BNFC 2011–20125 InfectionsChild 12–18 years 1 mg/kg every 8 hours; insevere infections up to 5 mg/kg daily in divideddoses every 6–8 hours (reduced to 3 mg/kg dailyas soon as clinically indicated). Once daily dose regimen by intravenous infusionChild 1 month–18 years initially 7 mg/kg, thenadjusted according to serum-tobramycin concentrationPseudomonal lung infection in cystic fibrosis. Multiple daily dose regimen by slow intravenousinjection over 3–5 minutesChild 1 month–18 years 8–10 mg/kg/daily in 3divided doses. Once daily dose regimen by intravenous infusionover 30 minutesChild 1 month–18 years initially 10 mg/kg (max.660 mg), then adjusted according to serum-tobramycinconcentrationChronic pulmonary Pseudomonas aeruginosainfection in patients with cystic fibrosis. By inhalation of nebulised solutionChild 6–18 years 300 mg every 12 hours for 28days, subsequent courses repeated after 28-dayinterval without tobramycin nebuliser solutionNote Local dosage guidelines may varyAdministration for intravenous infusion, dilute withGlucose 5% or Sodium Chloride 0.9%; give over 20–60 minutesParenteralTobramycin (Non-proprietary) AInjection, tobramycin (as sulphate) 40 mg/mL, netprice 1-mL (40-mg) vial = £4.00, 2-mL (80-mg) vial =£4.16, 6-mL (240-mg) vial = £19.20InhalationBramitob c (Chiesi) ANebuliser solution, tobramycin 75 mg/mL, net price56 x 4-mL (300-mg) unit = £1187.00Tobi c (Novartis) ANebuliser solution, tobramycin 60 mg/mL, net price56 5-mL (300-mg) unit = £1187.205.1.5 MacrolidesErythromycin has an antibacterial spectrum that issimilar but not identical to that of penicillin; it is thusan alternative in penicillin-allergic patients.Indications for erythromycin include respiratory infections,whooping cough, legionnaires’ disease, andcampylobacter enteritis. It is active against many penicillin-resistantstaphylococci but some are now alsoresistant to erythromycin; it has poor activity againstHaemophilus influenzae. Erythromycin is also activeagainst chlamydia and mycoplasmas.Erythromycin causes nausea, vomiting, and diarrhoea insome children; in mild to moderate infections this canbe avoided by giving a lower dose or the total dose in 4divided doses but if a more serious infection, such asLegionella pneumonia, is suspected higher doses areneeded.Clarithromycin is an erythromycin derivative withslightly greater activity than the parent compound.Tissue concentrations are higher than with erythromycin.It is given twice daily.Azithromycin is a macrolide with slightly less activitythan erythromycin against Gram-positive bacteria butenhanced activity against some Gram-negative organismsincluding H. influenzae. Plasma concentrations arevery low but tissue concentrations are much higher. Ithas a long tissue half-life and once daily dosage isrecommended. Azithromycin is also used in the treatmentof trachoma [unlicensed indication] (section11.3.1).For the role of erythromycin, azithromycin, andclarithromycin in the treatment of Lyme disease, seesection 5.1.1.3.Spiramycin is also a macrolide (section 5.4.7).Oral infections Clarithromycin or erythromycin is analternative for oral infections in penicillin-allergicpatients or where a beta-lactamase producing organismis involved. However, many organisms are now resistantto macrolides or rapidly develop resistance; their useshould therefore be limited to short courses. Metronidazole(section 5.1.11) may be preferred as an alternativeto a penicillin.Cautions Macrolides should be used with caution inchildren with a predisposition to QT interval prolongation(including electrolyte disturbances and concomitantuse of drugs that prolong the QT interval).Side-effects Nausea, vomiting, abdominal discomfort,and diarrhoea are the most common side-effects of themacrolides, but they are mild and less frequent withazithromycin and clarithromycin than with erythromycin.Hepatotoxicity (including cholestatic jaundice)and rash occur less frequently. Other side-effectsreported rarely or very rarely include pancreatitis, antibiotic-associatedcolitis, QT interval prolongation,arrhythmias, generally reversible hearing loss (sometimeswith tinnitus) after large doses, Stevens-Johnsonsyndrome, and toxic epidermal necrolysis. Intravenousinfusion may cause local tenderness and phlebitis.AZITHROMYCINCautions see notes above; interactions: Appendix 1(macrolides)Hepatic impairment manufacturers advise avoid insevere liver disease—no information availableRenal impairment use with caution if estimatedglomerular filtration rate less than 10 mL/minute/1.73 m 2Pregnancy manufacturers advise use only if adequatealternatives not availableBreast-feeding present in milk; use only if no suitablealternativeSide-effects see notes above; also anorexia, dyspepsia,flatulence, syncope, dizziness, headache,drowsiness, convulsions, arthralgia, and disturbancesin taste and smell; rarely constipation, hypotension,insomnia, agitation, anxiety, asthenia, paraesthesia,hyperactivity, thrombocytopenia, haemolytic anae-