Monograph: |
Phenoxymethylpenicillin
Phenoxymethylpenicillin is an antimicrobial acid produced
by the growth of certain strains of Penicillium notatum or re-
lated organisms on a culture medium containing an appropri-
ate precursor, or obtained by any other means.
It is a white crystalline slightly hygroscopic powder. Very
slightly soluble in water: freely soluble in acetone; freely sol-
uble or soluble in alcohol: practically insoluble in fixed oils
and liquid paraffin. Suspensions in water have a pH of 2.4 to
4.0. Store in airtight containers.
Units
The first International Standard Preparation (1957)
of phenoxymethylpenicillin contained 1695 units
per mg but was discontinued in 1968. Despite this,
doses of phenoxymethylpenicillin are still expressed
in units in some countries.
Phenoxymethylpenicillin 250 mg is approximately
equivalent to 400 000 units.
Adverse Effects and Precautions
As for Benzylpenicillin.
Phenoxymethylpenicillin is usually well tolerated
but may occasionally cause transient nausea and di-
arrhoea.
Interactions
As for Benzylpenicillin.
Guar gum may reduce the absorption of phenoxymethylpen-
icillin. Reduced absorption was also reported when phe-
noxymethylpenicillin was given following a course of
neomycin by mouth. Beta blockers might have potentiated
anaphylactic reactions in 2 patients on nadolol and pro-
pranolol. respectively, who died following a dose of phe-
noxymethylpenicillin.
Antimicrobial Action
Phenoxymethylpenicillin has a range of antimicro-
bial activity similar to that of benzylpenicillin and a similar
mode of action. It may be less
active against some susceptible organisms particu-
larly Gram-negative bacteria.
The mechanisms and patterns of resistance to phe-
noxymethylpenicillin are similar to those of ben-
zylpenicillin.
Pharmacokinetics
Phenoxymethylpenicillin is more resistant to inacti-
vation by gastric acid and is more completely ab-
sorbed than benzylpenicillin from the gastro-
intestinal tract following administration by mouth.
Absorption is usually rapid, although variable, with
about 60% of an oral dose being absorbed. The cal-
cium and potassium salts are better absorbed than
the free acid. Peak plasma concentrations of 3 to
5 ng per mL have been observed 30 to 60 minutes
after a dose of 500 mg. The effect of food on absorp-
tion appears to be slight. The plasma half-life of
phenoxymethylpenicillin is about 30 to 60 minutes
and may be increased to about 4 hours in severe re-
nal impairment. About 80% is reported to be protein
bound. The distribution and elimination of phe-
noxymethylpenicillin is similar to that of ben-
zylpenicillin . It is metabolised in the liver to
a greater extent than benzylpenicillin; several me-
tabolites have been identified including penicilloic
acid. The unchanged drug and metabolites are ex-
creted rapidly in the urine. Only small amounts are
excreted in the bile.
Uses and Administration
Phenoxymethylpenicillin is used similarly to ben-
zylpenicillin in the treatment or prophylaxis
of infections caused by susceptible organisms, espe-
cially streptococci. It is used only for the treatment
of mild to moderate infections, and not for chronic.
severe, or deep-seated infections since absorption
can be unpredictable, Patients treated initially with
parenteral benzylpenicillin may continue treatment
with phenoxymethylpenicillin by mouth once a sat-
isfactory clinical response has been obtained. Spe-
cific indications for phenoxymethylpenicillin
include anthrax (mild uncomplicated infections),
Lyme disease (early stage in pregnant women or
young children), pharyngitis or tonsillitis, rheumatic
fever (primary and secondary prophylaxis), strepto-
coccal skin .infections, and spleen disorders (pneu-
mococcal infection prophylaxis). For details of
these infections and their treatment, see under
Choice of Antibacterial.
Administration and dosage. Phenoxymethylpenicil-
lin is administered by mouth, usually as the potassi-
um or calcium salt, preferably at least 30 minutes
before or 2 hours after food. Benzathine phe-
noxymethylpenicillin and hydrabamine phe-
noxymethylpenicillin have also been used.
Doses are expressed in terms of the equivalent
amount of phenoxymethylpenicillin.
Usual adult doses have been 250 to 500 mg every 6
hours, but authorities in the UK now recommend
500 to 750 mg every 6 hours. Children may be given
the following doses every 6 hours: up to I year.
62.5 mg; I to 5 years, 125 mg; and 6 to 12 years,
250 mg. Dosage may need to be modified in severe
renal impairment.
To prevent recurrences of rheumatic fever WHO and
other authorities recommend 250 mg twice daily.
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