Sensiblex® - Veyx-Pharma GmbH

� Eased parturition
� Improved dilation
� Fewer injuries during
parturition
� Minimised neonatal
mortality
Sensiblex®
Tocospasmolytic

In parturient cattle and dogs Sensiblex® promotes the elasticity of the soft birth canal
and regulates labour contractions. The birth is eased via the rapid effect and if necessary,
aids to birth that are benefi cial to the patient can be applied.
General
Sensiblex® is a drug with a specifi cally tone reducing effect on the smooth musculature.
Denaverine hydrochloride contained in Sensiblex® has a regulating and relaxing
effect on the uterus prepared for parturition and provides an increased fl exibility of
the soft birth canal. Through an optimal intensifi cation of the labour contractions
and a simultaneous support of the fl exibility of the cervix, the hymenal area and the
vulva, the parturition is facilitated and thus the risk for the dams and the fetuses is
decreased. In cases of pathological births, the application of Sensiblex® is primarily
advised, if complications occur during the course of the opening and dilation phase
and the labour contractions, provided no mechanical obstacles exist (e. g., too large
fetus, abnormal position, torsio uteri). Sensiblex® opens up new opportunities in medicinal
obstetrics in comparison to the administration of tone increasing medicines
(Oxytocin preparations) only.
Sensiblex® opens up new opportunities in medicinal obstetrics in comparison to the
administration of tone increasing medicines (Oxytocin preparations) only. The preparation
has the property to provide effi cient support and more effectiveness in obstetrics
in case of complications regarding the soft birth canal and/or the expulsion
forces. Denaverine hydrochloride has also proven to be effective in human medicine
through easing and speeding up the parturition.

Chemistry
Denaverine hydrochloride is a derivative of benzilic acid from which a number of
medications have gained signifi cance as relaxing agents and thus belong to the most
useful spasmolytics. Its chemical designation is 2-dimethylamino-ethyl-0-(2-ethylbutyl)benzilate-hydrochloride.
The molecular weight of the substance is 420 and it
has the following molecular and structural formulae:
(C 24 H 33 NO 3 ) HCl
Denaverine hydrochloride
The active substance has the form of a white or yellowish powder with a weak odour
at most and a bitter taste. It is soluble in water, organic solvents (e.g. chloroform,
acetone, methanol and ethanol) and sparingly soluble in diethyl ether. The base corresponding
to the hydrochloride is released with alkali.
The Sensiblex® preparation is a clear, colourless to yellowish, sterile liquid with a pH
of 2.5 - 3.5.
Pharmacology
Denaverine hydrochloride has a pronounced spasmolytic effect with good tolerance
and low toxicity. The spasmolytic effect is mainly musculotropic and is stronger than
that of papaverine. The level of analgesic effi cacy is between 40 and 90 % of morphine
strength, depending on the trial design.
Application of denaverine is followed by a pronounced tone reduction and labour
contraction regulating effect in rat uteri in situ spastically contracted with Oxytocin.
The infl uence on the cardiovascular system is minimal. The effect on blood pressure in
anaesthetized cats and rats was hardly noticeable. Relatively high doses were required
before a drop in blood pressure was recorded. Respiration frequency and volume are
increased in anaesthetized rabbits. The antihistamine effect of denaverine hydrochloride
was minimal, the antipyretic effect good. About one-third of the dose administered
was recovered unchanged in urine. Maximum elimination was reached between
the 4 th and 8 th hour after administration. No more unaltered substance was recovered
in the urine on the 2 nd day following application.

Local tolerance is very good. Acute LD 50 is as follows: in mice 137.5 mg/kg body
weight, in rats 112 mg/kg body weight, following intravenous application. Following
long-term treatment of mice, rats and dogs with denaverine hydrochloride in tests
of chronic toxicity, no signifi cant differences in the test parameters (behaviour, feed
intake, growth, blood picture, organ histology) were determined between the control
and denaverine groups.
Sensiblex® meets the basic requirements for good effi cacy combined with no accumulation
of residues and no environmental contamination. Therefore, denaverine
hydrochloride is approved under Appendix II of Regulation (EEC) 2377/90. Thus there
is no withdrawal period required for Sensiblex®.
Pharmacotherapy
Tolerance and effi cacy of Sensiblex® in parturition were tested in numerous cows and
dogs. Both primiparous and pluriparous dams with normal births and pathological
births from various genesis were treated with the product.
A pronounced effect on the course of parturition was recorded following intramuscular
administration of doses of denaverine hydrochloride as listed below:
Cattle: 200 – 400 mg
Dogs: 20 – 60 mg
Onset of effect is 5 -10 minutes after intramuscular injection; the full effect is seen
after further 10 - 15 minutes. No local or generalized undesirable effects were observed
at the dosage levels indicated except for occasional short-term swellings at the
injection site. No negative infl uences on the fetuses, the postnatal or postparturient
period, or milk yield occurred.
Cattle
Sensiblex® reduces tension in the soft birth canal in cattle when administered towards
the end of the opening stage or in the dilation stage. The tone reducing effect
is in some cases outwardly recognizable as a relaxation of the hard and tense vulva
tissue. The enhancement of elasticity in the soft birth canal is also achieved in dams
with delivery complications. Improved cervical expansion and less distinctive on the
nymenal area and the vulva is not only detectable in spontaneous births, but also in
cases of protracted labour. In cases of insuffi cient opening or width, where the cervical
ring frequently does not completely disappear, the tissue does lose its rigidity,
softens and expands and widens relatively well once the calf has entered the cervical
canal. In dystocia with a live calf, Sensiblex® has a regulatory infl uence on the labour

contractions, normalizing both excessively strong and excessively weak contractions.
The contraction-activating effect is less pronounced in protracted labour with a dead
calf.
Cases of fi rst and in most cases second degree inadequate opening or width can usually
be infl uenced so that the calf can be extracted without signifi cant injuries - assuming
a presentation position adequate for birth and a fetus that is not oversized.
The dilating effect of Sensiblex® is good in cases of a narrowed cervix following uterine
torsion of up to 270° with a live or recently dead calf. The effect is unreliable in
cases of more severe or longer lasting uterine torsion.
Sensiblex® is also a useful agent in fetotomy due to the increased elasticity of the
soft birth canal. Obstetric aid measures (fetal extraction, correction of an anomalous
presentation position, fetotomy, etc.) can begin 10 - 20 minutes after the Sensiblex®
injection.
The risk of injuries to the soft birth canal tissue is reduced through the administration
with Sensiblex® in medium to severe problem cases requiring assistance. Thus the
incidence of post parturient disorders is also minimised. A prophylactic or therapeutic
treatment with this product produces a positive effect in respect of calf vitality. The
level of perinatal calf mortality can be considerably reduced.
Dogs
In these species, tone reduction and expansion-enhancing effects on the soft birth canal
are also observed following the administration of the preparation. The labour contraction-regulating
effect of denaverine hydrochloride is most apparent when treating
particularly strong or irregular contractions and in hypertonic myometric states.
This means the agent can be used to reactivate birth in dogs delayed or interrupted by
insuffi cient opening and dilation stages and/or spastic uterine contractions.
In dystocia due to contraction insuffi ciency, Sensiblex® alone is not always suffi cient
and the additional administration of oxytocin is recommended. The effect is uncertain
in cases with uniparous states, pathological multiple pregnancies and emphysematous
(putrefactive) fetuses.

Sensiblex®
40 mg/ml solution for injection for cattle and dogs
Denaverine hydrochloride
Statement of the active substance and other ingredients
1 ml contains:
Active substance:
40 mg Denaverine hydrochloride, equivalent to 36.5 mg Denaverine
Excipient:
20 mg Benzyl alcohol
Indications
Cattle:
Facilitation of parturition in heifers; activation of interrupted parturitions; insuffi cient
opening of the soft birth canal; narrowness of the cervix of fi rst and second degree
after the correction of uterine torsions; improvement of the conditions for foetotomy;
regulation of labour contractions in uterine inertia and hypertonic muscular contractions
of the uterus.
In order to facilitate parturition, Sensiblex® should be administered towards the end
of the opening or dilation phase. Cases of foetotomy require an additional epidural
anaesthesia.
Dogs:
Activation of interrupted parturition.
Dosage for each species, method and route(s) of administration
For subcutaneous and intramuscular injection.
Cattle:
Heifers 200 - 400 mg Denaverine hydrochloride/animal
corresponding to 5.0 - 10.0 ml Sensiblex®/animal
Cows 400 mg Denaverine hydrochloride/animal
corresponding to 10.0 ml Sensiblex®/animal
If necessary, the injection can be repeated once after 40 to 60 minutes.
Dogs: 20 - 60 mg Denaverine hydrochloride/animal
corresponding to 0.5 - 1.5 ml Sensiblex®/animal
Advice on correct administration
Not applicable.

Contraindications
An administration during the early dilation stage is without effect.
Dogs: uniparous state, pathological multiple pregnancy, oversized foetus.
Adverse reactions
Increased restlessness; swellings at the injection site; absent or insuffi cient effectivity
necessitating further obstetric measures.
If you notice any serious effects or other effects not mentioned in this leafl et, please
inform your veterinary surgeon.
Withdrawal period
Cattle:
Meat and offal: zero days
Milk: zero days
Special storage precautions
Keep out of the reach and sight of children.
Do not store above 25 °C.
Do not use after the expiry date which is stated on the label and box.
Once broached, use within 28 days.
Following the expiry of thus period the remainder of the drug in the container is to
be disposed of.
Special warnings
Interaction with other medicinal products and other forms of interaction:
Sensiblex® should not be mixed with other medicinal products. In case of an additional
administration of Oxytocin, its careful dosing is advised for reason of the possible
amplifi cation of its effect together with Denaverine.
Overdose (symptoms, emergency procedures, antidotes), if necessary:
In case of overdose or intravenous application anticholinergic effects, e.g. increased
heart and respiration rate, have to be reckoned with.
Incompatibilities:
Do not mix with other medicinal products.
Special precautions for the disposal of unused product or waste materials,
if any
Medicines should not be disposed of via wastewater or household waste.
Ask your veterinary surgeon how to dispose of medicines no longer required.
Package sizes
10 ml vial and 50 ml bottle

Author:
Priv. Doz. Dr. Dr. habil. Wolfgang Zaremba
Veyx-Pharma is GMP, DIN EN ISO 9001: 2000 and QS certifi ed.
Veyx-Pharma GmbH Soehreweg 6 34639 Schwarzenborn Germany
Phone 0049 5686 9986-0 Fax 0049 5686 1489 E-Mail zentrale@veyx.de
www.veyx.de 11/2009