Monograph: |
Phenazone
Colourless, odourless crystals or white or almost white crys-
talline powder. Very soluble in water and in dichloromethane;
freely soluble to very soluble in alcohol: freely soluble in
chloroform: sparingly soluble in ether. Solutions in water are
neutral to litmus. Store in airtight containers and protect
from
light.
Adverse Effects and Precautions
Phenazone is liable to give rise to skin eruptions and in sus-
ceptible individuals even small doses may have this effect.
Hypersensitivity reactions and nephrotoxicity have been re-
ported. Large doses by mouth may cause nausea, drowsiness.
coma. and convulsions.
Effects on the blood. Phenazone had been shown to cause
haemolytic anaemia in certain individuals with a deficiency
of glucose-6-phosphate dehydrogenase. Episodes of agranu-
locytosis were reported in 6 women using a cream containing
phenazone; all recovered on withdrawal.
Effects on the kidneys. Phenazone is considered nephro-
toxic but only limited clinical information on phenazone is
available because it has been mainly used in association with
phenacetin.
Effects on the skin. In a summary of 77 cases of fixed drug
eruption phenazone derivatives were considered to be the
causative agent in 9 of the 14 cases that were severe general-
ised reactions.
Hypersensitivity. Immediate allergic reactions to phena-
zone have been reported. In one patient leucopenia was de-
tected 8 weeks later.
Porphyria: Phenazone was considered to be unsafe in pa-
tients with acute porphyria because it has been shown to be
porphyrinogenic in animals or in vitro systems.
Interactions
Phenazone affects the metabolism of some other drugs and its
metabolism is affected by other drugs that increase or reduce
the activity of liver enzymes.
Pharmacokinetics
Phenazone is absorbed from the gastro-intestinal tract and
peak plasma concentrations are obtained within I to 2 hours
of ingestion. It is distributed throughout the body fluids with
concentrations in the saliva and breast milk reaching about
the same levels as those in plasma. Less than 10% is bound to
plasma proteins and it has an elimination half-life of about 12
hours. Phenazone is metabolised in the liver to 3 major me-
tabolites 3-hydroxymethylphenazone, 4-hydroxyphenazone,
and norphenazone. Phenazone, 3-hydroxymethylphenazone.
and plucuronidated metabolites are all excreted in the urine
Uses and Administration
Phenazone is an NSAID and has been given by mouth;
phenazone and caffeine citrate and phenazone salicylate have
similarly been given by mouth as analgesics.
Solutions containing about 5% of phenazone have been used
topically as ear drops in disorders such as acute otitis
media(but see below),
Phenazone is used as a test for the effect of other drugs or
the effect of a disease state on the activity of drug-
metabolizing enzymes in the liver.
Diagnosis and testing. A review' of normal plasma-phen-
azone pharmacokinetics. urinary metabolite disposition, and
total body clearances of phenazone in the presence of cirrho
sis, fatty liver, hepatitis, and cholestasis.
Otitis media. There seems to be no justification for the in-
clusion of phenazone in local preparations used in treating
acute otitis media . It is presumably included in such
preparations because it is believed to have a local anti-
inflammatory, and therefore, analgesic action. It would,
however,seem unlikely that phenazone would have any action on
the skin of the intact tympanic membrane and. therefore, on the
pain which is due primarily to the stretching and distention
of the membrane.
In general, no topical treatment is considered effective in
acute otitis media.
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