Phenoxymethylpenicillin

Phenoxymethylpenicillin (penicillin V) is the acid-stable oral form of natural penicillin, used for mild to moderate infections with susceptible streptococci and for long-term prophylaxis against rheumatic fever and pneumococcal sepsis.

Classification. Beta-lactam, natural penicillin, oral.

Mechanism. Blocks penicillin-binding proteins and cell wall cross-linking. Destroyed by staphylococcal penicillinase.

Spectrum. Streptococcus pyogenes, other beta-haemolytic streptococci, penicillin-susceptible pneumococci, oral anaerobes and Treponema pallidum in vitro. Not active against staphylococci that produce penicillinase, Haemophilus or enteric bacilli.

Pharmacokinetics. Oral bioavailability is 60 to 73%, reduced by food; peak levels occur in 30 to 60 minutes. Half-life is 30 to 60 minutes. Renal elimination by tubular secretion. Serum levels are lower than with intravenous benzylpenicillin, so it is not used for serious infection.

No loading dose is needed. Take on an empty stomach, 30 to 60 minutes before food. Usual adult maximum is 4 g daily orally.

Streptococcal pharyngitis and tonsillitis. - Adults and children 12 years and over: 500 mg every 6 hours or 1 g every 12 hours. - Children under 27 kg: 250 mg every 12 hours; 27 kg and over: 500 mg every 12 hours. - Duration: 10 days (5 to 7 days in some regions for non-severe disease; 10 days remains safest if rheumatic fever risk is high).

Mild skin and soft tissue infection (erysipelas, streptococcal cellulitis). Adults 500 mg to 1 g every 6 hours for 5 to 7 days. Children 12.5 to 25 mg/kg every 6 hours.

Dental and oral infections. Adults 500 mg to 1 g every 6 hours for 5 days.

Secondary prevention of rheumatic fever (alternative to benzathine penicillin). 250 mg every 12 hours for all ages. Duration is 5 years or until age 21 (whichever is longer) without carditis, 10 years or until age 21 after carditis without residual valve disease, and until age 40 or lifelong after significant valve disease or surgery.

Pneumococcal prophylaxis in sickle cell disease and after splenectomy. - Under 3 years: 125 mg every 12 hours. 3 to 5 years: 250 mg every 12 hours. Over 5 years and adults: 250 to 500 mg every 12 hours. - Duration: to at least age 5 in sickle cell disease; adults after splenectomy for at least 2 years and often lifelong in high-risk patients.

Alternatives. Amoxicillin if adherence to a twice-daily pharyngitis course is needed; macrolides or clindamycin in penicillin allergy.

Contraindications. Immediate hypersensitivity to penicillin.

Adverse effects. Nausea, diarrhoea, rash. Serious: anaphylaxis, interstitial nephritis, cytopenias with prolonged use, Clostridioides difficile infection, seizures at very high exposure in renal failure.

Interactions. Methotrexate (reduced clearance), warfarin (INR changes), oral typhoid vaccine, probenecid raises levels. Penicillin V does not reduce the effect of combined oral contraceptives in current evidence, though vomiting or severe diarrhoea can.

Common prescribing errors. Using it for deep or severe infection; giving with food; stopping prophylaxis early; under-dosing in children by age instead of weight band.

Special groups. - Pregnancy and breastfeeding: acceptable. - Children: use the weight bands given here; give the dispersible or syrup form accurately. - Older adults: usual doses. - Kidney impairment: reduction is rarely needed at usual doses; in creatinine clearance under 10 mL/min use 250 to 500 mg every 8 to 12 hours. - Liver impairment: no adjustment. - Region: in East Africa rheumatic heart disease is common, and continuous prophylaxis adherence is a major determinant of outcome.

Formulations. 250 mg and 500 mg tablets; oral solution 125 mg and 250 mg in 5 mL. Check local formulations before calculating volumes.

Baseline and monitoring. - Baseline: allergy history; creatinine if there is kidney disease. - Courses over 2 weeks: full blood count. - Prophylaxis: yearly review of adherence, cardiac status and echocardiography where available; review the end date.

Stop rules. Stop for hypersensitivity. Never stop rheumatic prophylaxis early without cardiology review.

Referral and escalation. Refer for failure to improve at 48 to 72 hours of a pharyngitis course, suspected quinsy or retropharyngeal abscess, new murmur or heart failure, and formal allergy testing when allergy status limits prophylaxis.