Phenoxymethylpenicillin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Prophylaxis of recurrence of rheumatic fever
• Mild to moderate infections caused by penicillin-sensitive organisms such as
  - Pneumococcal infections of the middle ear
  - Streptococcal otitis media and sinusitis
  - Streptococcal pharyngitis caused by Streptococcus pyogenes
  - Mild to moderate pulmonary and periodontal anaerobic infections
  - Gingivostomatitis
  - Early Lyme disease

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• History of sensitivity to penicillins or other beta-lactam antibiotics, such as cephalosporins
• Severe acute infections

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment (eGFR ≤29ml/min/1.73m²)
• History of allergy, especially to other medicines
• Allergic diathesis
• Bronchial asthma
• Severe illness
• Gastrointestinal disease
• Prolonged use
• History of antibiotic-associated colitis
• High doses in patients receiving potassium-containing agents or potassium-sparing diuretics
• Fructose intolerance (sus)
• Sucrase-isomaltase insufficiency (sus)
• Galactose intolerance (tab)
• Lapp lactase deficiency (tab)
• Glucose-galactose malabsorption (sus)
• Patients on low potassium diets

Forms avail. in SA and covered in this monograph: sus, tab

Dosages below include:

• General dosing range
• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Some gram-positive aerobes and anaerobes such as Bacillus anthracis, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheria, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Peptostreptococcus spp., Streptococcus agalactiae (Group B), Streptococcus pneumoniae, Streptococcus pyogenes (Group A); Some gram-negative bacteria such as Neisseria meningitidis, Neisseria gonorrhoeae; Actinomyces sp., P. multocida, Strep. anginosus gp, Strep. gp C,F,G

General dosing range

• Oral (tab, sus): 250-500mg, 6-8hrly, before meals and at bedtime

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Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Acute rheumatic fever
- Eradication of streptococci in throat
Tonsillitis
Pharyngitis

• Oral (sus, tab): 500mg, 12hrly; Treatment duration: 10 days
  (STG, Adult 2019; PHC 2020) 

Prophylaxis of rheumatic fever

• Oral (sus, tab): 250mg, 12hrly; Treatment duration: 10 years or until the age of 21 years for all patients with confirmed rheumatic fever and no persistent rheumatic valvular disease OR lifelong for all patients with confirmed rheumatic fever and persistent rheumatic valvular disease 
  (STG, Adult 2019; PHC 2020) 

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South African registered indications and dosages

Infections caused by penicillin-sensitive organisms - mild to moderate
- Pneumococcal infections of the middle ear
- Streptococcal otitis media and sinusitis
- Mild to moderate pulmonary and periodontal anaerobic infections
- Gingivostomatitis
- Early Lyme disease

• Oral (tab, sus): 250-500mg, 6hrly, depending on the severity of the infection

- Streptococcal pharyngitis caused by Streptococcus pyogenes 

• Oral (tab): 250-500mg, 6hrly, depending on the severity of the infection; Treatment duration: ≥10days

Prophylaxis for the recurrence of rheumatic fever

• Oral (tab, sus): 125-250mg, 12hrly; Treatment duration: Continuous basis

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See additional prescribing points for administration directions

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Doses should be administered 1hr before meals or at least 2hrs after a meal

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Indications and dosages registered in other jurisdictions

Infections caused by penicillin-sensitive organisms - mild to moderately severe

Streptococcal infections
- Pharyngitis
- Scarlet fever
- Skin and soft tissue infections (e.g. erysipelas)

Pneumococcal infections
- Pneumonia
- Vincent's gingivitis and pharyngitis

• Oral (tab,sus): 250-500mg, 6hrly

- Acute otitis media

• Oral (tab,sus): 250-500mg, 6hrly; Treatment duration: 5 days; In patients with potential complications: Treatment duration 5-10 days

Prophylaxis of rheumatic fever/ chorea

• Oral (tab,sus): 250mg, 12hrly; Treatment duration: Continuous basis

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To avoid late complications (rheumatic fever), infections with β-haemolytic streptococci should be treated for 10 days

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Prophylaxis of pneumococcal infection
- Asplenia
- Sickle cell disease

• Oral (tab,sus): 500mg, 12hrly

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All indications: Each tablet should be swallowed whole with water, at least 30min before food. The suspension should be taken at least 30min before or 2hrs after food. Ingestion with meals slightly reduces the absorption of phenoxymethylpenicillin 

Forms avail. in SA and covered in this monograph: sus, tab

Dosages below include:

• General dosing range
• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Some gram-positive aerobes and anaerobes such as Bacillus anthracis, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheria, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Peptostreptococcus spp., Streptococcus agalactiae (Group B), Streptococcus pneumoniae, Streptococcus pyogenes (Group A); Some gram-negative bacteria such as Neisseria meningitidis, Neisseria gonorrhoeae; Actinomyces sp., P. multocida, Strep. anginosus gp, Strep. gp C,F,G

General dosing range

28 days and younger

• No information available

Older than 28 days

• Oral (tab, sus): 25-75mg/kg/day, in 3-4 divided doses, 6-8hrly

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Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Post splenectomy

Younger than 5 years 

• Oral (sus): 125mg, 12hrly; Treatment duration: Indefinitely, until at least 18 years 
  (STG, Paed. 2017)

Older than 5 years

• Oral (sus, tab): 250mg, 12hrly; Treatment duration: Indefinitely, until at least 18 years 
  (STG, Paed. 2017)

Sickle cell anaemia
- Prophylaxis against infection

Younger than 5 years 

• Oral (sus): 125mg, 12hrly; Treatment duration: Indefinitely 
  (STG, Paed. 2017)

Older than 5 years

• Oral (sus, tab): 250mg, 12hrly; Treatment duration: Indefinitely 
  (STG, Paed. 2017)

Post-streptococcal glomerulonephritis
- Eradication of streptococci

• Oral (sus, tab): 50mg/kg/24hrs, 6hrly; Treatment duration: 10 days
  (STG, Paed. 2023) 

Diphtheria

• Oral (sus, tab): 15mg/kg, 6hrly; Treatment duration: 14 days; Max: 500mg/dose
  (STG, Paed. 2017)

Sydenham chorea
- Streptococcal infection

• Oral (sus, tab): 500mg, 12hrly; Treatment duration: 10 days; Then: 250mg, 12hrly; Treatment duration: Until 21 years old
  (STG, Paed. 2023) 

Acute rheumatic fever
- Eradication of streptococci in throat
Tonsillitis
Pharyngitis

Between 18 months–11 years 

• Oral (sus): 250mg, 12hrly; Treatment duration: 10 days
  (STG, PHC 2020)

Older than 11 years

• Oral (sus, tab): 500mg, 12hrly; Treatment duration: 10 days
  (STG, PHC 2020) 

Prophylaxis for rheumatic fever

• Oral (sus): 125mg, 12hrly; Treatment duration: 10 years or until the age of 21 years for all patients with confirmed rheumatic fever and no persistent rheumatic valvular disease OR lifelong for all patients with confirmed rheumatic fever and persistent rheumatic valvular disease  
  (STG, PHC 2020) 

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South African registered indications and dosages

Infections caused by penicillin-sensitive organisms - mild to moderate
- Pneumococcal infections of the middle ear
- Streptococcal otitis media and sinusitis
- Mild to moderate pulmonary and periodontal anaerobic infections
- Gingivostomatitis
- Early Lyme disease

Younger than 1 year

• Oral (sus): 60mg, 6hrly

Between 1-5 years

• Oral (sus): 125mg, 6hrly

Between 6-12 years

• Oral (sus): 250mg, 6hrly

Older than 12 years

• See adult dosage

- Beta-haemolytic streptococcus infections without associated bacteraemia

• Oral (sus): 125-250mg, 6-8hrly; Treatment duration: ≥10days

Routine streptococcus prophylaxis in patients with a history of rheumatic fever or congenital heart disease 

• Oral (sus): 125-250mg, 12hrly; Treatment duration: Continuous basis

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South African manufacturer recommendations for the tablet formulation do not mention specific dosage recommendations for children

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Doses should be administered 1hr before meals or at least 2hrs after a meal

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See additional prescribing points for administration directions

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Indications and dosages registered in other jurisdictions

Infections caused by penicillin-sensitive organisms - mild to moderately severe

Streptococcal infections
- Pharyngitis
- Scarlet fever
- Skin and soft tissue infections (e.g. erysipelas)

Pneumococcal infections
- Pneumonia
- Vincent's gingivitis and pharyngitis

Younger than 1 year

• Oral (sus): 62.5mg, 6hrly

Between 1-5 years

• Oral (tab,sus): 125mg, 6hrly

Between 6-12 years

• Oral (tab, sus): 250mg, 6hrly

- Acute otitis media

Younger than 1 year

• Oral (sus): 62.5mg, 6hrly

Between 1-5 years

• Oral (tab, sus): 125mg, 6hrly; Treatment duration: 5 days; In patients with potential complications: Treatment duration 5-10 days

Between 6-12 years

• Oral (tab, sus): 250mg, 6hrly; Treatment duration: 5 days; In patients with potential complications: Treatment duration 5-10 days

Prophylaxis of pneumococcal infection
- Asplenia
- Sickle cell disease

Younger than 5 years

• Oral (tab, sus): 125mg, 12hrly

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In children <5 years of age, tablets are not usually administered. The more appropriate formulation for this age group should be used. Sometimes older children may have difficulties swallowing tablets

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Between 6-12 years

• Oral (tab, sus): 250mg, 12hrly

Older than 12 years 

• See adult dosage

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All indications: Each tablet should be swallowed whole with water, at least 30min before food. The suspension should be taken at least 30min before or 2hrs after food. Ingestion with meals slightly reduces the absorption of phenoxymethylpenicillin 

Pregnancy

• Caution
• Animal studies with phenoxymethylpenicillin have shown no teratogenic effects. Phenoxymethylpenicillin has been in extensive clinical use and its suitability in human pregnancy has been well documented in clinical trials. However, as with other drugs, caution should be exercised when prescribing to pregnant patients

Breastfeeding

• Caution
• Breastfeeding is not contraindicated with phenoxymethylpenicillin. Trace quantities of phenoxymethylpenicillin can be detected in breast milk. While adverse effects are apparently rare, two potential problems exist for the breastfeeding infant:
  - Modification of bowel flora
  - Direct effects on the infant such as allergy/ sensitisation
• Caution should therefore be exercised when prescribing for the breastfeeding mother

Renal Impairment

• eGFR ≥30-89ml/min/1.73m²: No dose adjustment recommended
• eGFR ≤29ml/min/1.73m²: Caution; dose adjustment recommended

eGFR (ml/min/1.73m2)	Dose
≥30-89	No dose adjustment recommended
≤29	Reduce daily dose by 50%

Hepatic Impairment

• No dose adjustment recommended
  Dosage adjustment may be necessary in patients with impaired hepatic function when they also have renal failure
  In this situation, the liver may be a major excretion route

Elderly

• No dose adjustment recommended
  The dosage should be reduced if renal function is markedly impaired

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Seizures
• Paraesthesia
• Neuropathy

Respiratory Disorders

• Laryngeal oedema

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Diarrhoea
• Stomatitis
• Glossitis
• Sore mouth
• Black hairy tongue (discolouration of tongue)
• Pseudomembranous colitis

Hepatobiliary Disorders

• Hepatitis
• Cholestatic jaundice

Genitourinary Disorders

• Interstitial nephritis
• Vulvovaginitis
• Nephropathy (usually associated with high doses of parenteral penicillin)

Musculoskeletal Disorders

• Joint pain

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Erythema multiforme
• Exfoliative dermatitis
• Pruritus
• Mobiliform rash

Immune, Blood and Lymphatic System Disorders

• Angioneurotic oedema
• Serum sickness-like reactions
  - Fever
  - Chills
  - Arthralgia
  - Oedema
• Haemolytic anaemia
• Anaphylactic shock (which could be fatal) with collapse
• Anaphylactoid reaction
  - Asthma
  - Purpura
  - Gastrointestinal symptoms
• Fatal anaphylaxis
• Eosinophilia
• Leukopenia
• Thrombocytopenia
• Agranulocytosis
• Neutropenia
• Coagulation disorders (including prolongation of bleeding time and defective platelet function)
• Candida overgrowth
• Allergic reactions
• Angioedema
• Fever

• Bacteriostatic antibiotics
• Chloramphenicol
• Erythromycin
• Tetracyclines
• Sulphonamides
• Uricosuric agents
• Probenecid
• Sulfinpyrazone
• Methotrexate
• Oral contraceptives
• Neomycin
• Oral anticoagulants
• Warfarin
• Coumarin
• Phenindione
• Typhoid vaccines
• Potassium-containing agents
• Potassium-sparing diuretics
• Amiloride
• Spironolactone

Other interactions

• Laboratory tests (See additional prescribing points)
• Guar gum

None routine. Specific cases may require 

• Renal function
• Hepatic function
• Full blood count

Additional observations

• Signs of anaphylaxis (during first dose)

Administration directions (sus)

• To reconstitute, loosen powder, add 60ml of water and shake until all powder is dispersed
• Store the reconstituted oral solution for 7 days in a refrigerator (2-8°C)
• For oral administration only

Interaction with laboratory tests

• Phenoxymethylpenicillin may interfere with some diagnostic tests, including non-enzymatic urinary glucose tests, direct antiglobulin (Coombs') tests, and certain urinary or serum protein tests. It can also interfere with tests which use bacteria, for example, the Guthrie test for phenylketonuria using Bacillus subtilis organisms

Phenoxymethylpenicillin exerts a bactericidal action against penicillin-susceptible bacteria by inhibition of biosynthesis of cell wall mucopeptides. Phenoxymethylpenicillin binds to penicillin-binding proteins located on the inner membrane of the bacterial cell wall and inactivates these proteins resulting in weakening of the bacterial cell wall and lysis.

Spectrum of activity: Some gram-positive aerobes and anaerobes, such as Bacillus anthracis, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheria, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Peptostreptococcus spp., Streptococcus agalactiae (Group B), Streptococcus pneumoniae, Streptococcus pyogenes (Group A); Some gram-negative bacteria, such as Neisseria meningitidis, Neisseria gonorrhoeae; Actinomyces sp., P. multocida, Strep. anginosus gp, Strep. gp C,F,G

Suspension (per 5ml) 125mg

• Athlone Phenoxymethylpenicillin (Medicine Developers International)
• Betapen (Be Tabs)
• Incil Vk (Alliance) 
• Len Vk (Pharmacare)

Suspension (per 5ml) 250mg

• Athlone Phenoxymethylpenicillin (Medicine Developers International) - only available in state

Tablet 250mg

• Betapen (Be tabs)
• Dezzpen (Dezzo trading) - only available in state
• Len Vk (Alliance)