Oritavancin

Oritavancin is a long-acting lipoglycopeptide given as a single infusion for skin and skin structure infection. It also has activity against vancomycin-resistant enterococci in vitro and is used off-label for deep infection.

Classification. Lipoglycopeptide.

Mechanism. Binds the D-alanyl-D-alanine and D-alanyl-D-lactate terminus of cell wall precursors, dimerises and anchors to the membrane, and disrupts membrane integrity.

Spectrum. MRSA, MSSA, streptococci, vancomycin-resistant enterococci (vanA and vanB) in vitro. Not active against Gram-negative bacilli.

Pharmacokinetics. IV only. Terminal half-life about 245 hours. Protein binding about 85%. Slow elimination in urine and faeces.

Availability in East Africa is very limited.

Adults, acute bacterial skin and skin structure infection. 1200 mg IV as a single infusion over 3 hours (older formulation) or 1 hour (newer formulation), as the product label states.

Off-label (specialist). Osteomyelitis, bacteraemia and endocarditis: 1200 mg on days 1 and 8, with repeat doses by specialist direction.

Children. Not established.

Alternatives. Dalbavancin, vancomycin, teicoplanin, linezolid.

Contraindications. Hypersensitivity to oritavancin; use of IV unfractionated heparin within 120 hours of the dose.

Adverse effects. Headache, nausea, vomiting, diarrhoea, infusion-site reactions, rash, raised liver enzymes, osteomyelitis or abscess reported in studies. Serious: hypersensitivity, infusion reaction, Clostridioides difficile infection.

Coagulation tests. Oritavancin falsely prolongs PT, INR, aPTT and ACT, for up to 120 hours for aPTT-based assays and 12 hours for PT and INR. Avoid IV unfractionated heparin for 120 hours or use anti-Xa or chromogenic assays.

Interactions. Warfarin: oritavancin is a weak inhibitor of CYP2C9 and CYP2C19 and an inducer of CYP3A4 and CYP2D6, so INR may rise (monitor for bleeding). Substrates with narrow windows need monitoring.

Common prescribing errors. Diluting in saline (use 5% glucose only), ignoring coagulation interference, and repeating doses without specialist direction.

Special groups. - Pregnancy and breastfeeding: limited data; use only if needed. - Older adults: no adjustment. - Kidney impairment: no adjustment in mild or moderate impairment; data are limited in severe impairment and haemodialysis. - Liver impairment: no adjustment in mild and moderate disease.

Preparation. Reconstitute only with sterile water for injection, then dilute in 5% glucose to a total of 1000 mL (older formulation) or the volume the label states; infuse as stated. Do not use saline.

Baseline and monitoring. - Baseline: allergy history, creatinine, liver tests, INR if on warfarin, cultures. - During treatment: clinical review at 1 to 2 weeks; INR and bleeding signs in warfarin users; use anti-Xa assays for heparin monitoring.

Stop rules. Stop for anaphylaxis or severe infusion reaction.

Referral and escalation. Infectious diseases consultation is needed for every off-label use.