Dalbavancin

The interaction potential of dalbavancin on medicinal products metabolised by CYP enzymes is expected to be low since it is neither an inhibitor nor an inducer of CYP enzymes in vitro. There are no data on dalbavancin as an inhibitor of CYP2C8.

In adult patients with chronic renal impairment whose creatinine clearance is <30 ml/min and who are not receiving regularly scheduled haemodialysis, the recommended dose is reduced to either 1,000 mg administered as a single infusion or 750 mg followed one week later by 375 mg.

There is insufficient information to recommend dosage adjustment for patients younger than 18 years with creatinine clearance less than 30 ml/min/1.73m².

Caution should be exercised when prescribing dalbavancin to patients with moderate or severe hepatic impairment (Child-Pugh B & C) as no data are available to determine appropriate dosing.

It is not known if dalbavancin is an inhibitor of transporters. Increased exposure to transporter substrates sensitive for inhibited transporter activity, such as statins and digoxin, cannot be excluded if combined with dalbavancin.

Studies in animals have shown reduced fertility. The potential risk for humans is unknown.

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin. Examples of such transporter inhibitors are boosted protease inhibitors, verapamil, quinidine, itraconazole, clarithromycin and cyclosporine.

Dalbavancin should be administered with caution in patients known to be hypersensitive to other glycopeptides since cross-hypersensitivity may occur. If an allergic reaction to dalbavancin occurs, administration should be discontinued and appropriate therapy for the allergic reaction should be instituted.

There are no data from the use of dalbavancin in pregnant women. Studies in animals have shown reproductive toxicity.

Dalbavancin is not recommended during pregnancy, unless the potential expected benefit clearly justifies the potential risk to the foetus.

It is unknown whether dalbavancin is excreted in human milk. However, dalbavancin is excreted in the milk of lactating rats and may be excreted in human breast milk. Dalbavancin is not well absorbed orally; however, an impact on the gastrointestinal flora or mouth flora of a breast-feeding infant cannot be excluded. A decision must be made whether to continue/discontinue breast-feeding or to continue/discontinue therapy with dalbavancin taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Studies in animals have shown reduced fertility. The potential risk for humans is unknown.

Dalbavancin may have a minor influence on the ability to drive and use machines, as dizziness has been reported in a small number of patients.

Summary of the safety profile

In Phase ⅔ clinical studies, 2,473 patients received dalbavancin administered as either a single infusion of 1,500 mg or as 1,000 mg followed one week later by 500 mg. The most common adverse reactions occurring in ≥1% of patients treated with dalbavancin were nausea (2.4%), diarrhoea (1.9%), and headache (1.3%) and were generally of mild or moderate severity.

Tabulated list of adverse reactions

The following adverse reactions have been identified in Phase ⅔ clinical trials with dalbavancin. Adverse reactions are classified according to System Organ Class and frequency. Frequency categories are derived according to the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000).

Description of selected adverse reactions

Class adverse reactions

Ototoxicity has been associated with glycopeptide use (vancomycin and teicoplanin); patients who are receiving concomitant therapy with an ototoxic medicinal product, such as an aminoglycoside, may be at increased risk.

Paediatric population

The safety of dalbavancin was evaluated in one Phase 3 clinical trial which included 168 paediatric patients from birth to less than 18 years of age with ABSSSI treated with dalbavancin (90 patients treated with a single dose of dalbavancin and 78 patients, all of them aged 3 months and older, treated with a two-dose regimen of dalbavancin). Overall, the safety findings of dalbavancin in these paediatric patients were similar to those observed in adults.