Doripenem

Doripenem is a carbapenem with a spectrum similar to meropenem. It has been withdrawn from many markets and is rarely stocked, so meropenem is used instead.

Classification. Beta-lactam, carbapenem.

Mechanism. Blocks penicillin-binding proteins; resists hydrolysis by most beta-lactamases including ESBL and AmpC, but not carbapenemases.

Spectrum. Streptococci, MSSA, Enterococcus faecalis, Enterobacterales including ESBL and AmpC producers, Pseudomonas aeruginosa, Bacteroides and other anaerobes. Not active against MRSA, Enterococcus faecium, Stenotrophomonas or carbapenemase producers.

Pharmacokinetics. IV only. Half-life about 1 hour. Protein binding about 8%. About 70% excreted unchanged in urine.

Confirm availability and local licence before prescribing. No loading dose. Maximum 1.5 g daily in adults.

Adults. - Complicated intra-abdominal infection: 500 mg IV over 1 hour every 8 hours for 5 to 14 days. - Complicated urinary tract infection including pyelonephritis: 500 mg over 1 hour every 8 hours for 10 days (14 days if bacteraemic). - Use for ventilator-associated pneumonia with a short high-dose course is not supported because mortality was higher; the indication was withdrawn.

Children. Not established.

Alternatives. Meropenem, imipenem cilastatin, ertapenem.

Contraindications. Hypersensitivity to carbapenems; severe hypersensitivity to other beta-lactams.

Adverse effects. Headache, nausea, diarrhoea, rash, phlebitis, anaemia, raised liver enzymes. Serious: seizures, anaphylaxis, Clostridioides difficile infection, severe skin reactions, interstitial pneumonitis with prolonged use.

Interactions. Valproate: carbapenems lower valproate levels by 60 to 100% within 24 hours; avoid the combination. Probenecid raises doripenem levels.

Common prescribing errors. Using the short high-dose course for pneumonia, giving full doses in renal impairment and giving with valproate.

Special groups. - Pregnancy and breastfeeding: limited data. - Older adults: adjust by kidney function. - Kidney impairment: creatinine clearance over 50 mL/min no change; 30 to 50 mL/min 250 mg every 8 hours; over 10 and under 30 mL/min 250 mg every 12 hours. - Liver impairment: no adjustment. - Region: availability in East Africa is poor.

Preparation. Reconstitute each 500 mg vial with 10 mL water for injection or 0.9% sodium chloride, then dilute in 100 mL of 0.9% sodium chloride or 5% glucose and infuse over 1 hour.

Baseline and monitoring. - Baseline: allergy history, medication review (valproate), creatinine, cultures. - During treatment: creatinine and full blood count twice weekly; liver tests weekly. - No therapeutic drug monitoring.

Stop rules. Stop for seizures, anaphylaxis, severe skin reaction or respiratory symptoms suggesting pneumonitis.

Referral and escalation. Infectious diseases involvement for resistant Gram-negative infection; switch to meropenem when doripenem is not obtainable.