|
SUMMARY OF
PRODUCT CHARACTERISTICS
|
|
1.
|
NAME OF THE VETERINARY MEDICINAL
PRODUCT
HydroDoxx 500 mg/g Powder for use
in drinking water
for chickens and pigs (All MS
except ES)
DiluDox 500 mg/g Powder for use
in drinking water for chickens and pigs (ES)
|
|
|
|
2.
|
QUALITATIVE AND QUANTITATIVE
COMPOSITION
One gram contains:
Active
substance:
Doxycycline (as doxycycline
hyclate) 500 mg
For the full list of
excipients, see section 6.1.
|
|
|
|
3.
|
PHARMACEUTICAL FORM
Powder for use in drinking
water.
Yellow powder.
|
|
|
|
4.
|
CLINICAL PARTICULARS
|
|
|
|
4.1
|
Target species
Chickens (broilers)
Pigs (Fattening pigs)
|
|
|
|
4.2
|
Indications for use (specifying
the target species)
Chickens
(broilers) : Prevention and treatment of Chronic Respiratory
Disease (CRD) caused
by Mycoplasma
gallisepticum susceptible to
doxycyclin.
Fattening
pigs: prevention and treatment of clinical respiratory infection
caused by strains of Pasteurella
multocida susceptible to doxycyclin
.
|
|
Use of the
product should be based on susceptibility testing of the bacteria
isolated from the animal. If this is not possible, therapy should
be based on local (regional, farm level)
epidemiological information about susceptibility of the target
bacteria.
The presence of the
clinical disease in the herd should be established before
preventive treatment is started
|
|
4.3
|
Contraindications
Do not use in
cases of hypersensitivity to the active substance, to other
tetracyclines or to any excipient.Do not
use in animals with hepatic disorders.
Do not use in animals with
renal disorders
See section 4.7.
|
|
|
|
4.4
|
Special warnings (for each
target species)
The uptake of medication by
animals can be altered as a consequence of illness. In case of
insufficient uptake of drinking water, animals should be treated
parenterally
|
|
|
|
4.5
|
Special precautions for use
|
|
|
|
Special precautions for use in
animals
Due to variability
(time, geographical) in susceptibility of bacteria for doxycycline,
bacteriological sampling and susceptibility testing of
micro-organisms from diseased animals on farm are highly
recommended.If this is not possible,
therapy should be based on local (regional and farm level)
epidemiological information about susceptibility of the target
bacteria as well as by taking into account official national
antimicrobial policies.
As eradication of the target
pathogens may not be achieved, medication should therefore be
combined with good management practices, e.g. good hygiene, proper
ventilation, no overstocking.
Avoid administration in
oxidised drinking equipment
Inappropriate use of the
product may increase the prevalence of bacteria resistant to
doxycyclin and may decrease the effectiveness of treatment with
other tetracyclines due to the potential for cross-resistance.
Do not use at concentrations
lower than 0.23 g of powder /l in drinking water with pH higher or
equal to 7.5 to avoid precipitation.
Do not add acid to the
medicated drinking water.
|
|
|
|
Special precautions for the
person administering the veterinary medicinal product to
animals
People with known
hypersensitivity to tetracyclines should avoid contact with the
veterinary medicinal product During preparation and administration
of the medicated drinking water, skin contact with the product and
inhalation of dust particles should be avoided. Wear impermeable
gloves (e.g. rubber or latex) and an appropriate dust mask (e.g.
disposable half-mask respirator conforming to European Standard
EN149) when applying the product.
In the event of eye or skin
contact, rinse the affected area with large amounts of clean water
and if irritation occurs, seek medical attention. Wash hands and
contaminated skin immediately after handling the product.
If you develop symptoms
following exposure such as skin rash, you should seek medical
advice and show this warning to the physician. Swelling of the
face, lips or eyes, or difficulty with breathing are more serious
symptoms and require urgent medical attention.
Do not smoke, eat or drink
while handling the product.
Take measures to avoid
producing dust when incorporating the product into water. Avoid
direct contact with skin and eyes when handling the product to
prevent sensitisation and contact dermatitis.
|
|
4.6
|
Adverse reactions (frequency and
seriousness)
Allergic reactions.
Photosensitivity reactions.
|
|
If suspected adverse reactions
occur, treatment should be discontinued. Inform your veterinary
surgeon if adverse reactions occur that are not indicated.
|
|
4.7
|
Use during pregnancy, lactation
or lay
The product should not be used during pregnancy
or lactation.
Do not use within 4 weeks of
onset of the laying period.
|
|
4.8
|
Interaction with other medicinal
products and other forms of interaction
Do not administer together with
bactericidal antibiotics (penicillins, aminoglycosides, etc.).
Absorption of doxycycline can be decreased in the presence of high
quantities of calcium, iron, magnesium or aluminium in the diet. Do
not administered together with antacids, kaolin and iron
preparations.
It is advised that the interval
between the administration of other products containing polyvalent
cations should be 1-2 hours because they limit the absorption of
tetracyclines.
Doxycycline increases the
action of anticoagulants.
The solubility of the product
is pH dependent and will precipitate if mixed in alkaline
solution.
Do not store the drinking water
in metallic containers.
|
|
4.9
|
Amount(s) to be administered and
administration route
To be administered in drinking
water.
Chickens (broilers):
20 mg of doxycycline (equivalent to 40 mg of the veterinary
medicinal product) / kg BW / day for 3 - 5 days
Fattening pigs: 10 mg of
doxycycline (equivalent to 20 mg of the veterinary medicinal
product) / kg b.w / day for 5 days.
For the
preparation of the medicated water the body weight of the animals
to be treated and their actual daily water intake should be taken
into due account. Consumption may vary depending on factors like
age, state of health, breed, husbandry system. Based on the recommended dose, and the number
and weight of the animals to be treated, the exact daily amount of
hydroDoxx should be calculated according to the following
formula:
|
…… mg HydroDoxx/
|
|
Mean body weight (kg)
|
|
|
|
kg bodyweight / day
|
x
|
of the animals to be treated
|
=
|
…..mg HydroDoxx/
|
|
Mean daily water consumption (l)
per animal
|
|
l of drinking water
|
To ensure a correct dosage body
weight should be determined as accurately as possible to avoid
underdosing.
The uptake of
medicated water is dependent on the clinical conditions of the
animals. In order to obtain the correct dosage the concentration in
drinking water may have to be adjusted. Do
not use at concentrations lower than 0.23 g of powder /l in
drinking water with pH higher or equal to 7.5 to avoid
precipitation.
Sufficient access to the system
of water supply should be available for the animals to be treated
to ensure adequate water consumption. No other source of drinking
water should be available during the medication period.
The use of
suitably calibrated weighing equipment is recommended if part packs
are used. The daily amount is to be added to the drinking water
such that all medication will be consumed in 24 hours. Medicated
drinking water should be freshly prepared every 24 hours. It is
recommended to prepare a concentrated pre-solution - approximately
100 grams product per litre drinking water - and to dilute this
further to therapeutic concentrations if required. Alternatively,
the concentrated solution can be used in a proportional water
medicator.
|
|
|
|
4.10
|
Overdose (symptoms, emergency
procedures, antidotes), if necessary
The administration of
40 mg/kg BW in pigs and 80 mg/kg in chickens (in both species
corresponding to 4 times the recommended dose), for 5 days did not
cause any adverse reaction.
In case of overdose the
treatment should be suspended and symptomatic treatment
established.
|
|
4.11
|
Withdrawal period(s)
Meat and offal
Pigs: 6 days
Chickens 6 days
Not authorised for use in
laying birds producing eggs for human consumption.
Do not use within 4 weeks of
onset of the laying period.
|
|
|
|
5.
|
PHARMACOLOGICAL OR
IMMUNOLOGICAL PROPERTIES
|
|
|
|
ATC Vet Code:
QJ01AA02. Doxycycline
hyclate.
Therapeutic
group: Antibacterial for systemic use;
tetracyclines
|
|
|
|
5.1
|
Pharmacodynamic properties
|
|
Doxycycline is a bacteriostatic
antibiotic that acts by interfering with the bacterial protein
synthesis of sensitive species.
Doxycycline is a semi-synthetic
tetracycline derived from oxytetracycline. It acts on the subunit
30 S of the bacterial ribosome, to which is bound reversibly,
blocking the union between aminoacyl-tRNA(transfer RNA) to the
mRNA-ribosome complex, preventing the addition of new aminoacids
into the growing peptide chain an thus interfering with protein
synthesis.
Doxycycline
is active against, Mycoplasma
spp. (chickens
and Pasteurella multocida
(fattening pigs).
Sensitivity
of Doxycycline against Pasteurella
multocida strains isolated from fattening
pigs in 2004 has been determined, by means of agar dilution method.
MIC90 values found are shown in next table (source of breakpoints:
NCCLS 2000).
Concentration
range used : 0.065 – 16 g/ml.
-
|
NCCLS 2000
|
|
Pasteurella multocida
|
|
MIC90
|
|
0.250
|
|
Breakpoints
|
Sensitive
4g/ml
|
MIC90 of
microorganisms involved in porcine respiratory complex
|
|
There are at least
two mechanism of resistance to tetracyclines:
One
mechanism is evidenced by decreased ribosome affinity for the
tetracycline-Mg2+
complex owing to chromosomal mutations. It is a
ribosomal protection mechanism, in which protein synthesis is
resistant to inhibition through a cytoplasmic protein (Prescott et
al., 2000).
The most
important mechanism of acquired resistance to tetracyclines is
plasmid mediated, and is evidenced by a decrease in the cellular
accumulation of the drug. The basis of this decrease is a reduction
of the active transport of tetracyclines into the cell due to
alterations of the external cellular membrane and increased efflux
(or active pump elimination) by acquisition of new transport
systems of cytoplasmic membrane. (Prescott et al., 2000). The
alteration in the transport system is produced by inducible
proteins codified in plasmids and transposones. Because the action
mechanism of all tetracyclines has the same base, when resistance
occurs, normally there is cross-resistance and complete within its
group.
Resistance to tetracyclines may
not only be the result of therapy with tetracyclines, but may also
be caused by therapy with other antibiotics leading to selection of
multi-resistant strains including tetracyclines. although minimal
inhibitory concentrations (MIC) tend to be lower for doxycycline
than for older generation tetracyclines, pathogens resistant to one
tetracycline are generally also resistant to doxycycline (cross
resistance). both long term treatment and treating for an
insufficient length of time and/or sub-therapeutic dosages can
select for antimicrobial resistance and should be avoided.
|
|
|
|
5.2
|
Pharmacokinetic particulars
Doxycycline is bio-available
after oral administration. When orally administered, it reaches
values greater than 70% in most species.
Feeding can modify the oral
bioavailability of Doxycycline. In fasting conditions
bioavailability is around 10 – 15% greater than when the animal is
fed. Doxycycline is well distributed through the body as it is
highly lipid soluble. It reaches well irrigated tissues as well as
peripheral ones. It accumulates in liver, kidney, bones and
intestine; enterohepatic recycling occurs. In lungs it always
reaches higher concentrations than in plasma. Therapeutic
concentrations have been detected in aqueous humour, myocardium,
reproductive tissues, brain and mammary gland. Plasma protein
binding is 90 – 92%.
40% of drug is metabolized and
largely excreted through faeces (biliary and intestinal route),
mainly as microbiologically inactive conjugates.
CHICKENS
After oral administration,
doxycycline is quickly absorbed, achieving maximum concentrations
(Cmax) around 1.5 h. Bioavailability is 75%. Absorption is
decreased in the presence of feed in the gastrointestinal tract,
bioavailability is then around 60% and the time to achieve the
maximum concentration peak is significantly prolonged, (Tmax) 3.3
h.
FATTENING PIGS
Treatment
with the recommended dosage, maximum blood concentration in steady
state (Cmax-ss) was 0.83
g/ml (SD = 0.29) ,
minimum blood concentration in steady state
(Cmin–ss) was 0.22 (SD = 0.07) and Cave-ss= 0.49 (SD=
0.14)
After oral
administration of 10 mg doxycycline /kg bw in pigs the
bioavailability was 24.8
4.6%. The elimination half-life
(t1/2)
was 4.6 h; plasmatic clearance was 0.15 l/h.kg and apparent
distribution volume was 0.89 l/kg.
|
17/11/14