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Facts on
Novalgin
Baralgan
Aclivc ingredient
J Analgin
Fenpivennium Brom do
P.lolononc H,droch;orido
Hoechst
CONTENTS
Novalgin
Page 3
Baralgan
Page 23
Wovalgiri*
FOR THE RESPONSIBLE
MANAGEMENT OF
PAIN & FEVER
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ch3
NaSO3-CH2 —Nx
CH3
Analgin
Norammopyrme methane sulphonate
Metamizol sodium
Novalgm (analgin) is a non-narcotic analgesic, which
was first introduced to medicine in 1922 It was
developed as an improved derivative of pyramidon
(aminopynne, aminophenazone) and differs from the
parent substance both in terms of toxicity and in terms
of its medicinal potential.
Novalgm has several distinguishing characteristics
• It has strong analgesic and antipyretic effects as well
as anti-inflammatory and antispasmodic properties
This latter effect distinguishes Novalgm from all
other non-narcotic analgesics.
4
Novalgin is an outstanding analgesic and antipyretic. In
addition to its anti-inflammatocy effects Novalgin is
the only substance with antispasmodic effects (30).
5
• Novalgin's high water solubility has led to a wide
variety of administration 'forms, including the rapidly
acting injectable formulations. The injection has
rapid and potent analgesic and antipyretic effects. In
indications such as post-operative pain or carcinoma
pain, Novalgm is a suitable alternative to
administration of opiates
• Novalgin has the lowest toxic potential of all nonnarcotic analgesics. It is also less likely to adversely
affect the liver, kidneys or gastro-intestinal mucosa
Possibly owing to its general lack of toxic effects,
Novalgin has been closely scrutinized with regdrd to
hypersensitivity reactions. Its structural relationship to
aminopyrine, which was considered to give rise to a
high incidence of agranulocytosis, has led to the
assumption that analgin shared this characteristic
Newer, more reliable data shows that whereas analgin
is one of the over 100 drugs which can give rise to
agranulocytosis, the likelihood is considerably lower
than formerly postulated, and is no greater than
equivalent risks associated with the use of other nonnarcotic analgesics
Each of the currently available non-narcotic analgesics
has specific properties which render it hazardous in
some patients while at the same time being
irreplaceable in others.
6
Historical note
The currently available non-narcotic analgesics were all
developed as synthetic alternatives to quinine, which
was the natural antipyretic most commonly used in the
nineteenth century
The first non-narcotic analgesic to find widespread
acceptance was Antipyrine (phenazone), a pyrazolone
derivative, which was developed by Hoechst in 1884.
Further work on this class of compounds led to
Pyramidon (aminopyrine, aminophenazone) in 1897
More than three decades of research were required at
Hoechst for the subsequent development of Novalgin
(analgin), which was introduced in Germany in 1922’
Despite its close chemical relationship to its precursor
Pyramidon. Novalgin differs in terms of its physical
properties, pharmacological effects and toxicology .
Novalgin is, for example, considerably less toxic and
cannot give rise to dimethyl nitrosamine (the reason
for Pyramidon's disappearance from modern medicine).
(1) Novalgin is also characterized by greater
therapeutic versatility than its precursor, and all other
non-narcotic analgesics
Novalgin is highly water-soluble It also has the widest
safety margin of all non narcotic analgesics These
qualities permit use-of a 50% solution of analgin for ■
intramuscular or intravenous injection. In this form'
Novalgin transcends the ceiling effects of non-narcotic
analgesics and, for many indications, becomes ah
alternative to opiates
7
Pharmacological properties
Novalgin has analgesic, antipyretic and anti
inflammatory effects Unlike other non-narcotic
analgesics, it also has antispasmodic properties.
Like other non-narcotic analgesics. Novalgin's
analgesic, antipyretic and anti-inflammatory effects
result from inhibition of prostaglandin biosynthesis.
Novalgin's antispasmodic property derives from a
direct relaxant effect on visceral smooth muscle.
Unlike acetylsalicylic acid. Novalgm does not bind
cyclo-oxygenase (prostaglandin synthetase) irreversibly.
Pharmacological studies have shown that Novalgin
inhibits prostaglandin synthesis most markedly in brain
tissues. This may explain its potent analgesic and
antipyretic effects (2)
The effects of the non-narcotic analgesics differ from
substance to substance. This may be partly explained
by their differing concentrations in various tissues (2).
As opposed to acidic analgesics, non-acidic analgesics,
such as analgin metabolites, do not accumulate in the
gastric mucosa or in the renal cortex (2)
In addition, unlike acetylsalicylic acid, Novalgin does
not depress prostacyclin synthesis in the gastric
mucosa. Novalgin has only a weak inhibitory effect on
renal cyclo-oxygenase (3)
The above findings explain how Novalgin is so well
tolerated by the gastro-intestinal mucosa and the
kidneys. Toxicological testing has also confirmed that
Novalgin is extremely well tolerated by the liver (4).
Neither analgin nor its metabolites affect the
lipoxygenase pathway. Thus there is no production of
leukotrienes (5).
8
Degree o/pM’rrtel
In a placebo-controlled double-blind study on 299
patients with initial severe pain after episiotomy,
analgin provided stronger analgesia than the same
dosage of paracetamol (1 x 500 mg p.o.) Analgin
achieved statistically significant superiority over
placebo within half an hour (6)
9
Degree of pain relief (0 — severe pain, 3 — no pain)
Clinical results
Novalgm is effective in a wide range of pain conditions,
e g , from headache to post-operative pain, as
confirmed repeatedly during the six decades since its
introduction to medicine (6. 7, 8, 9, 10, 1 1).
When injected, its potency is comparable to pethidine
(11, 12) or dextropropoxyphene (13)
In a double-blind comparative study, 51 patients
received 2 5g analgin i.m (corresponding to 1
ampoule Novalgm 5 ml) and 49 patients received
100 mg pethidine i.m They were suffering from pain of
moderate to severe intensity after exploratory
laparotomy. Both groups were comparable in terms of
the onset, intensity and duration of pain relief (11)
In pain due to»malignant diseases, Novalgm may be
used to delay the administration of opiates or to
reduce the dosage of opiate required (14)
Analgin has undisputed advantages in the treatment of
smooth muscle spasm (7) and potentiates the
therapeutic effects of pure antispasmodic substances
Alone or in combination it is more suited to the
treatment of renal or biliary colic than opiates, which
have spasmogenic effects Analgin also lacks the
tendency of opiates to induce respiratory depression
or constipation Analgin has no euphoric potential and
does not lead to habituation
Novalgm s antipyretic effects are potent, and Novalgm
is effective even in cases where other measures have
failed (14) Novalgm has been shown to be a more
effective antipyretic than other non-narcotic
analgesics (15, 31)
Novalgm's low toxic potential and high efficacy
recommend it to paediatric use Clinical trials in
children (32) have shown that there is no effect on
normal body temperature.
Novalgm also has a long duration of action (up to 6-8
hours). This avoids fever spikes during the night and
therefore, allows sick children to enjoy a full night's rest
COMMUNITY HEALTH CEU
10
326. V Main, 1 Block
mean reduction in temperature
HOURS AFTER ADMINISTRATION
Safety data
REDUCTION IN TEMPERATURE (oC)
Analgin has been in use since 1922 and is currently
being used in over 100 countries Based on the WHO
Daily defined dose (1 5 g per patient per day) almost
20 milliqn patients are treated with analgin every day
A vast amount of experience has. therefore, been
accumulated.
Analgin's wide safety margin is undisputed and is un
equalled by other non-narcotic analgesics. Few cases
of toxicity due to accidental or deliberate overdosage
have ever been seen A published case report describesan
18-yea'r old girl who took 98 tablets of Novalgin
(equivalent to 49 g or more than 10 times the
recommended daily dose). Apart from transient nausea
and vomiting there were no toxic symptoms
whatsoever Nor were there any after effects on
circulation, central nervous system, liver, kidneys or
any other organs (18).
The data available also demonstrates that no relevant
renal (19) or hepatic adverse effects have been seen.
This evidence is also supported by toxicological data
In a double-blind study comparing 500 mg of analgin
with 500 mg of paracetamol in 53 patients suffering
from typhoid fever, it was seen that
1 Analgin causes significantly higher reduction in
temperature
2. The onset of action is significantly faster with analgin
3. The total antipyretic effect is significantly higher
compared to paracetamol (16)
12
13
Hypersensitivity reactions
In spite of the vast amount of evidence demonstrating
Novalgin’s excellent tolerability it has been subject to
(often very vague) discussion concerning two groups
of hypersensitivity reactions
One of these reaction types are the anaphylactoid
reactions (analgesic asthma/analgesic intolerance) As
with other prostaglandin synthetase inhibitors, analgin
can give rise to anaphylactoid reactions characterzied
by rhinitis, conjunctivitis, urticaria, angio-oedema,
bronchial asthma and possibly shock
As would be expected, shock is the most alarming of
the anaphylactoid reactions. It is very rare and is
generally associated with too rapid injection, though
some cases probably represent genuine anaphylaxis
As Novalgm injection contains a 50% solution of
analgm, it is necessary that the injection be given-very
slowly (1 ml per minute) The advantages which the
injection formulation offers (rapid action and high
potency) are in no way dissipated by the need for
slow mjectiQn
The other hypersensitivity reaction discussed with
regard to Novalgm is agranulocytosis (20) Here it
must be remembered that Novalgm is chemically
related to ammopyrine, which was one of the first
drugs to be associated with agranulocytosis (21).
However, even for ammopyrine, the postulated
incidence of this reaction was always subject to
speculation, and was not based on acceptable scientific
data (by modern standards). Patients who developed
agranulocytosis had invariably taken several drugs
(this also holds true today) and attribution of blame
was usually an act of faith For analgm itself there was
an almost complete lack of relevant data
14
It was for clarification of this issue that Hoechst agreed
to co-fmance an international study on the incidence of
blood dyscrasias called the International
Agranulocytosis and Aplastic Anaemia Study.
The International Agranulocytosis and Aplastic
Anaemia Study (22)
This study was carried out in 7 countries and
monitored some 22 million people fora 5-year period
The design of the study (case-control method)
provided for a control group and allowed for
mathematical calculation of the likelihood of causality.
As such, this study (which was run by the Drug
Epidemiology Unit of Boston Medical School) broke
new ground m the study of blood dyscrasias.
Among the findings are the fact that (23)
Agranulocytosis is a rare event On average only six
cases occur per million persons per year.
Agranulocytosis has a survival rate of over 90%.
The primary risk group are persons over 60 years of
age with multiple drug use, particularly if they are
female (twice as frequently as males). The risk
decreases exponentially towards younger age groups,
so that children are hardly at risk.
Of the more than 100 drugs potentially associated
with agranulocytosis treatment with analgin was
found to involve an excess risk, if any, of at most 1 in a
million (24) users/week/year, which gives an
incidence rate as low as 0.0001 %1
15
Other recent safety data
PRESCRIBING INFORMATION
Novaigin is very unlikely to give rise to interactions due
to its low plasma protein binding (60%) (25). There is
no interaction with anticoagulants (26), with alcohol
(27) or with antidiabetic drugs (28)
It has also been estalished that Novalgm s metabolites
only pass m very small quantities into human breast
milk (29) and are no longer detectable 48 hours after
drug administration.
Novaigin0
COMPOSITION
Tablets
Each tablet contains
Analgin IP
Injection
Each ml contains.
Analgin I P
0 5 g.
0 5g
PROPERTIES
Novaigin is a non-narcotic analgesic, antipyretic, anti
inflammatory and antispasmodic agent.
As Novalgm can be injected intravenously, it is possible
to obtain extremely potent analgesia in a variety of
conditions and thus to control pain which would
otherwise respond only to opiates
Even in high doses, Novaigin, unlike opiates, does not
cause either addiction or respiratory depression. It
does not impair peristalsis of the intestine, labour
contractions or renal and biliary stone elimination.
INDICATIONS
For the Relief of Pain
Novlgin is indicated for all types of pain like headaches,
neuralgia, muscle pain, arthralgia, post-operative pain,
traumatic pain associated with burns, injuries,
fractures, dental procedures, etc.
For the Relief of Fever
For lowering raised temperature in febrile diseases as
well as in cases of high fever which do not respond to
other measures
16
17
ADMINISTRATION AND DOSAGE
In mild and moderate pain, the oral route is generally
adequate In acute painful conditions requiring rapid
relief, the parenteral (i m or i.v.) route should be
preferred.
Generally, the following dosage is recommended
Tablets
Adults and adolescents over 15 years
An initial dose of 1-2 tablets followed by 1 tablet 3-4
times daily is recommended
Children
In the age group between 5-14 years the dose is
calculated on the basis of approximately 30-60 mg/kg
body weight per day in divided doses
5 — 7 years
8 — 11 years
12—14 years
’/z — 1 tablet
’/? — 1 tablet
1 to 1% tablet
up to a total of 2 tablets/day
up to a total of 3 tablets/day
up to a total of 4 tablets/day
Injections:
Intravenous injections must be administered slowly
(not more than 1 ml per minute) with the patient lying
down attention must be given to cardiovascular
functions. In patients with hypersensitivity reactions of
any type, also to substances other than drugs, it is
recommended to stop the injection after 0 1 -0 2 ml
and to observe the reaction of the patient for 1 to 2
minutes.
The injection should be administered with the solution
warmed to body temperature
18
In adults, an initial intravenous dose of 1-2 ml. is
recommended The daily dose may, if necessary, be
increased to 5 ml in divided doses.
The average adult intramuscular daily dose is 2 ml
2-3 times daily The solution should be brought to
body temperature and should be slowly injected into
the gluteal muscle
Smallest
single dose
i.m./i.v.
Maximum
daily dose
i.m./i.v.
Adults and adolescents
aged 15 years or over
2 ml.
5 ml.
Children (1-14 years)
1-2 years
3-4 years
5-7 years
8-11 years
12-14 years
0 2 ml.
0.2 ml
0 4 ml.
0.5 ml
0 8 ml
4 x 0.4 ml
4 x 0.6 ml.
4 x 0.8 ml.
4 x 1.0 ml.
4 x 1.2 ml
Age of patient
Intramuscular injection only
Infants
Smallest
Single dose
Maximum
daily dose
3-5 months
6-11 months
0.1 ml.
0 1 ml.
4 x 0.2 ml.
4 x 0.3 ml
19
CONTRAINDICATIONS
Novalgin must not be used in patients with pyrazolone
allergy, collapse states, hepatic porphyria or congenital
glucose-6 phosphate dehydrogenase deficiency ‘
PRECAUTIONS
During pregnancy, particularly the first three months
and the last six weeks, m infants less than three
months old or weighing less than 5 kg. and in patients
with disorders of haematopoiesis Novalgm should only
be employed, if strictly indicated or prescribed by a
doctor.
SIDE EFFECTS
The more important but rare side effects of pyrazolone
preparations, such as Novalgm, arise from
hypersensitivity reactions The most serious reaction is
a reduction in the number of white blood cells
(granulocytopenia) or their complete disappearance
(agranulocytosis). Therefore, if there is an unexpected
deterioration m the patient s general condition, if the
fever fails to subside or recurs, if painful mucous
membrane changes occur, especially in the mouth and •
throat, it is essential to discontinue Novalgin
immediately and consult a doctor Symptoms are
febrile infections with predominant localisation in the
skin-muco.us membrane boderlme regions If
agranulocytosis is suspected, blood counts must be
performed After immediate discontinuation of
Novalgin and Under protective treatment (mainly with
antibiotics) regeneration of the leucocytes is to be
expected
20
Occasionally, hypersensitivity reactions manifesting in
the skin and the mucous membranes of the eyes and
the nose throat region may occur
Shock is the other serious but rare hypersensitivity
reaction mainly after parenteral administration Its
first signs are pruritus, cold sweat, dizziness, stupor,
nausea, flushing or pallor of the skin, dyspnoea. If they
occur, medical help must be called in without delay
Until the doctor arrives, ensure that the patient is kept
flat with legs raised and airways patent
The signs of imminent shock may appear already
during the injection In this case, interrupt the injection
immediately, leave the venous cannula in place or
perform venous cannulation, ensure that the patient is
kept flat with the legs raised and airways patent and
immediately adopt standard emergency procedures for
shock treatment
SPECIAL NOTES
Patients who suffer from bronchial asthma or chronic
respiratory infections and patients with
hypersensitivity reactions also to substances other
than drugs belong to a risk group which, on using
analgesic or antirheumatic agents of all kinds, may
develope shock (analgesic intolerance) They should
consult the doctor before taking such drugs
A red coloration of the urine may be seen. It is due to
excretion of a harmless metabolite of Novalgin and
disappears after the end of the treatment.
?
pJ'K ^(l 0
COMMUNITY HEALTH CELL,
32b- V Main- I Block
Analgesics must not be used in high doses or over
prolonged periods of time without the doctor's advice
Novalgm must not be mixed with other drugs in the
syringe
Baralgari*
Active ingredients
Analgin
Fenpivermum Bromide
Pitofenone Hydrochloride
Your sure answer
to spasmodic pain
22
23
Modo of action
Medulla
Cortex
Thalamus
At the level of the pyramidal decussation (cholinergic
fibres) by the constituent fenpivermium bromide
At the level of pain integration by the constituent
analgin
C6 h5
ch3
ch2ch2 c conh2
c6 h5
24
25
CLINICAL RESULTS
Viscera
Baralgan provides rapid relief in colicky pain
In a trial of patients with intestinal or renal colic, 40
patients were given Baralgan 5 ml. (corresponding to
analgin 2 5g, fenpiverimum bromide 0 1 mg.
pitofenone hydrochloride 10 mg j
At the level of the end plate of cholinergic nerve fibres
by the constituent pitofenone hydrochloride
26
While 28 patients were given Drug 'B' 3 ml
(corresponding to 72 mg. of avapyrazone and 720 mg
of analgin), within 30 minutes, 85% of patients with
intestinal colic were relieved after Baralgan, as against
none with Drug‘B (33).
27
Baraigan provides long-lasting relief, cycle after cycle.
m spasmodic dysmenorrhoea
In primary dysmenorrhoea Baraigan (1 tablet =
analgin 0.5 gm , fenpiverimum bromide 0 1 mg ,
pitofenone hydrochloride 5 mg ) was found to be
significantly superior to Drug 'X' {1 cap = dicyclomine
hydrochloride 10 mg dextropropoxyphene
hydrochloride 65 mg . acetaminophen 400 mg .
chlordiazepoxide 5 mg ) In the cross over phase of
the study, 84% of patients on Drug X’ were further
relieved by Baraigan However, when patients were
switched from Baraigan to Drug X', no significant
improvement occurred (34)
28
Baraigan provides rapid action in renal colic
comparabale with that of opiates
In a comparative trial of Baraigan (3 ml i.v. along with
2 ml. i.m ) and pethidine (50-100 mg ) in renal colic,
95% of patients were relieved within 30 minutes after
Baraigan, as compared to 87% patients who were
relieved with pethidine.
29
Baralgan does not only combat pain effectively at the
site of pain perception; but also acts on the cholinergic
nerve fibres which are responsible for painful spasm.
PRESCRIBING INFORMATION
Baralgan
COMPOSITION
Range of indications
Gastric colic
Intestinal colic
Biliary colic
Renal colic
Ureteric colic
Dysmenorrhoea
Pain associted with pancreatitis
Pain associated with neoplasms
Vasomotor headache
Post operative pain & spasm
Preparation for surgery
TABLETS DROPS
INJECTIONS
Each Tab Each ml.
Each ml
( = 30 drops)
Analgin 1 P.
Pitofenone Hydrochloride
Fenpiverinium Bromide
0.5 g
5.0 mg
0.1 mg.
0.5 g.
5-0 mg
0.1 mg.
0.5 g.
2.0 mg.
0 02 mg.
PROPERTIES
Baralgan is ideally suited for the treatment of
spasmodic pain because of its rapid and sustained
antispasmodic effect on the smooth muscles Even in
very severe forms of spasmodic pain, Baralgan almost
invariably renders the administration of opium
alkaloids unnecessary.
Together with the analgesic and antispasmodic
properties of analgin, Baralgan contains Pitofenone
Hydrochloride, a papaverine-like compound as well as
Fenpiverimum Bromide, a substance with
parasympatholytic action which reinforces the
spasmolytic effect
30
INDICATIONS
Renal colic
Biliary colic
Painful spasmodic conditions of the gastrointestinal
tract
Spasmodic dysmenorrhoea. and
Other painful conditions due,to spasm of smooth
musculature
A/
0 iq 'LZ-'
COMMUNITY HEALTH CELL
ADMINISTRATION AND DOSAGE
Unless otherwise prescribed, the following doses are
recommended
Adults
In case of spasmodic pain, slow intravenous injection of
2 ml may suffice.
Tablets and drops
In acute severe colic, 5 ml Baralgan should be
administered by slow intravenous injection. This may be
repeated twice daily if required.
Smallest single dose Maximum daily dose
Drops
Tablets
Drops
Tablets
Adults and adolescents
of 15 years or over
Infants and children
3-5 months
6-11 months
1 year
2 years
3-4 years
5-7 years
8-11 years
12-14 years
1
—
4x2
—
—
—
—
—
—
3-6
4-9
5-11
6-12
8-18
—
—
—
—
—
—
—
—
4x
4x 1
4x 1)4
4x6
4x9
4x11
4x 12
4x 18
—
—
—
'h
tablet
1 tablet
Injections
Baralgan injection must not be mixed with other drugs
in the same syringe.
During intravenous injection which should be
administered slowly (at a rate not exceeding 1 ml. per
minute), with the patient lying down, attention must be
given to cardiovascular functions In patients with
hypersensitivity reactions of any type, also to
substances other than drugs, it is recommended to stop
the injection-after 0.1 -0.2 ml. and to observe the
reaction of the patient for 1 to 2 minutes.
The solution should be warmed to body temperature
prior to injection
Generally, the following dosage is recommended.
32
In less severe cases Baralgan injection may be given
intramusculary (2-5 ml , 2-3timesa day) However,
the total daily dose should not exceed 10 ml.
Children aged 1-14 years
Smallest single dose
i.m. or i.v.
Maximum daily dose
i.m. or i.v
1 -2 years
3-4 years
5-7 years
8-11 years
12-14 years
0.2 ml.
0.2 ml.
0.4 ml.
0.5 ml.
0.8 ml.
4 x 0.4 ml
4 x 0.6 ml.
4 x 0.8 ml.
4 x 1.0 ml.
4 x 1 2 ml.
Infants
Intramuscular injection only
3-5 months
6-11 months
Smallest single dose
Maximum daily dose
0.1 ml
0.1 ml.
4x0.2 ml
4 x 0.3 ml.
33
CONTRAINDICATIONS
Pyrazolone allergy, collapse states, hepatic porphyria
congenital glucose 6-phosphate dehydrogenase
deficiency, tachyarrhythmia, narrow-angle glaucoma
prostatic hypertrophy with a tendency to urinary
retention, gastrointestinal obstruction megacolon
PRECAUTIONS
Patients who suffer from bronchial asthma or chronic
respiratory infections and patients with
hypersensitivity reactions also to substances other
than drugs belong to a risk group which, on using
analgesics or antirheumatic agents of all kinds, may
develop shock (analgesic intolerance) They should
consult the doctor before taking such drugs. The same
applies to patients who react to alcohol, even to small
amounts with sneezing, running eyes and severe facial
reddening
During pregnancy, particularly the first three months
and the last six weeks, as well as in infants less than
three months old or weighing less than 5 kg and in
patients with disorders of haematopoiesis, Baralgan
should only be administered if strictly indicated
SIDE EFFECTS
On rare occasions hypersensitivity reactions may
occur as for any pyrazolone derivative. Isolated
instances of granulocytopenia or agranulocytosis have
been reported Hence, if there is an unexpected
deterioration in the patient's general condition, if there
is fever or if painful mucous membrane changes occur
especially in the mouth and throat, it is essential to
discontinue Baralgan immediately and consult the
doctor Symptoms are febrile infections with
predominant localization in the skin-mucous
membrane borderline regions. If agranulocytosis is
suspected, blood counts must be performed After
immediate discontinuation of Baralgan and under
protective treatment (mainly with antibiotics)
regeneration of the leucocytes is to be expected.
Clinical features of shock may on rare occasions be
observed following parenteral administration. The
signs of imminent shock may appear already during
the injection In this case, interrupt the injection
immediately, leave the venous cannula in place or
perform venous cannulation, ensure that the patient is
kept flat, the legs raised and airways patent and
immediately adopt standard emergency procedures for
shock treatment
Occasionally, cutaneous or mucocutaneous
hypersensitivity reactions of the eyes, nose and throat
may occur
34
35
Anticholinergic side effects such as dryness of the
mouth, a decrease in perspiration, disorders of
accommodation, accelerated heart rate and micturition
difficulties are practically never seen, provided
Baralgan is administered in recommended doses
SPECIAL NOTES
Analgesics must not be used in high doses over
prolonged periods of time without the doctor's advice
Patients in whom Baralgan has caused a
HYPERSENSITIVITY reaction of any type should avoid
future use of all pyrazolone-containing preparations.
Red coloration of the urine may occasionally be seen.
This is due to the excretion of rubazonic acid, a
harmless metabolite of Baralgan
The contents of the R.C. Vial are not recommended
for intravenous administration.
INTERACTIONS
If quinidine is administered at the same time as
Baralgan, a potentiation of the anticholinergic effect is
possible The patient must be warned that, tne effect is
possible.
The patient must be warned that the effect of alcoholic
beverages may be enhanced by Baralgan medication
36
References
1. KRAMER, M . Chronic toxicity of pyrazolones the
problems of nitrosation
Br. J elm Pharmac 10,313 S (1980)
2. BRUNE. K et al Biodistribution of mild analgesics.
Br. J clin. Pharmac 10, 279 S (1980)
3. DEMBINSKA-KIEC, A et. al Inhibition of prosta
glandin synthetase by Aspirin-like drugs in different
microsomal preparations.
Advances in Prostaglandin and Thromboxane
Research 1, 99 (1976)
4 Data on file (Hoechst AG).
5.
WEITHMANN. K. U. and H G Alpermann Bio
chemical and pharmacological effects of dipyrone
and its metabolites in model systems related to the
arachidonic acid cascade. Arzneim -Forsch/Drug
Res 35, 947 (1985)
6. DAFTARY, S N et al A controlled comparison of
dipyrone and paracetamol in post-episiotomy pain
Current Medical Research and Opinion 6, 614
(1980)
7. GERBERSHAGEN. H U Non narcotic analgesics
Advances in Pain Research and Therapy 2, 255
(1979)
8. GOMEZ-JIMENEZ. J. et at Clinical efficacy of
mild analgesics in pain following gynaecological or
dental surgery Report on multicentre studies
Br, J elm Pharmac 10, 355 S (1980)
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37
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