Issued: September 2016
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
Doxatib 500 mg/g powder for use in drinking water for pigs and chickens (BE, BG,
CZ, DE, EE, ES, HR, HU, IE, LT, LV, NL, PL, PT, RO, SI, SK, UK)
Doxatib 433 mg/g powder for use in drinking water for pigs and chickens (FR)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 g of powder contains:
Doxycycline hyclate 500 mg
(corresponding to 433 mg of doxycycline)
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Powder for use in drinking water.
Pale yellow to yellow powder.
4. CLINICAL PARTICULARS
4.1 Target species
Pigs and chickens (broilers, pullets, broiler breeders).
4.2 Indications for use, specifying the target species
Pigs: For the treatment of the clinical signs associated with porcine respiratory
disease caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, and
Mycoplasma hyopneumoniae susceptible to doxycycline.
Chickens: Where clinical disease is present in the flock, to reduce mortality, morbidity,
and clinical signs and to reduce lesions due to Pasteurellosis caused by Pasteurella
multocida or to reduce morbidity and lesions in respiratory infections caused by
Ornithobacterium rhinotracheale (ORT).
Do not use in known cases of hypersensitivity to tetracyclines or to any of the
Do not use in animals with an impaired liver function.
Do not use in animals with renal disorders.
4.4 Special warnings for each target species
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Issued: September 2016
4.5 Special precautions for use
Special precautions for use in animals
Official, national and regional antimicrobial policies should be taken into account
when the product is used.
Use of the product deviating from the instructions given in the SPC may increase the
prevalence of bacteria resistant to doxycycline and may decrease the effectiveness
of treatment with other tetracyclines due to the potential for cross-resistance.
Due to likely variability (time, geographical) in susceptibility of bacteria for
doxycycline bacteriological sampling and susceptibility testing are recommended. In
particular susceptibility of A. pleuropneumoniae and O. rhinotracheale may differ
from country to country and even farm to farm. Use of the product should be based
on culture and sensitivity of micro-organisms from diseased cases on farm. If this is
not possible, therapy should be based on local (regional, farm level) epidemiological
information about susceptibility of the target bacteria.
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.
Special precautions to be taken by the person administering the veterinary medicinal
product to animals
People with known hypersensitivity to tetracyclines such as doxycycline should avoid
contact with the veterinary medicinal 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.
During preparation and administration of the medicated drinking water, skin and eye
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 or a non-
disposable respirator to European Standard EN140 with a filter to EN143) when
reconstituting or administering 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.
Do not smoke, eat or drink while 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
4.6 Adverse reactions (frequency and seriousness)
Tetracyclines may - in very rare cases - induce photosensitivity and allergic reactions.
If suspected adverse reactions occur, treatment should be discontinued.
4.7 Use during pregnancy, lactation or lay
Doxycycline has a low affinity for forming complexes with calcium and studies have
demonstrated that doxycycline scarcely affects skeleton formation.
In the absence of specific studies the use of the product is not recommended during
pregnancy or lactation.
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4.8 Interaction with other medicinal products and other forms of interaction
Do not combine with antibiotics that are bactericidal e.g. penicillins or cephalosporins.
Absorption of doxycycline can be decreased in the presence of high quantities of
calcium, iron, magnesium or aluminium in the diet. Do not administer concurrently
with antacids, kaolin and iron preparations.
It is advised that the interval between the administration of the product and
administration of other products containing polyvalent cations should be 1-2 hours
because the latter 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
Do not store the drinking water in metallic containers.
4.9 Amounts to be administered and administration route
To be administered orally via drinking water.
Pigs: the recommended dose is:
12.5 mg doxycycline hyclate (25 mg product) per kg body weight per day for 4
If no improvement in clinical signs is seen within this time, the diagnosis should be
reviewed and treatment changed. In case of severe infections the medication period
may be prolonged for a maximum of 8 consecutive days as determined by the
attending veterinary surgeon.
Chickens: the recommended dose is:
10 mg doxycycline hyclate (20 mg product) per kg body weight per day for 3-4
consecutive days in case of infections caused by P. multocida and
20 mg doxycycline hyclate (40 mg product) per kg body weight per day for 3-4
consecutive days in case of infections caused by O. rhinotracheale.
Based on the dose to be used, and the number and weight of the animals to be
treated, the exact daily amount of product can be calculated. The following formula
can be used to calculate the concentration of the product in drinking water:
mg product / kg body
weight / day x Mean body weight of
animals to be treated
water Mean daily water consumption per animal (Litres)
To ensure a correct dosage body weight should be determined as accurately as
The uptake of medicated drinking water depends on the clinical condition of the
pigs/chickens. In order to obtain the correct dosage the concentration of doxycycline
has to be adjusted accordingly.
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 replaced every 24
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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.
Solubility of the product is pH dependent and it may precipitate if it is mixed in hard
alkaline drinking water. Use at minimum concentrations of 200 mg powder per litre
drinking water in areas with hard alkaline drinking water (hardness above 10.2 °d and
pH more than 8.1).
During the treatment period animals should not have access to other water sources
than the medicated water.
Water uptake should be monitored at frequent intervals during medication.
After the end of the medication period, the water supply system should be cleaned
appropriately to avoid intake of sub-therapeutic amounts of the active substance.
4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
Overdoses up to 1.6 times the label recommended dose resulted in no clinical signs
that could be attributed to treatment. Poultry tolerate double overdoses of
doxycycline (40 mg/kg body weight) without any clinical effect.
4.11 Withdrawal period(s)
- Meat and offal: 4 days
- Meat and offal: 3 days (at a dose rate of 10 mg/kg b.w.).
- Meat and offal: 9 days (at a dose rate of 20 mg/kg b.w.).
- Eggs: 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 PROPERTIES
Pharmacotherapeutic group: Antibacterial for systemic use, Tetracyclines.
ATCvet code: QJ01AA02
5.1 Pharmacodynamic properties
Doxycycline belongs to the group of the tetracycline antibiotics. These antibiotics
have a broad spectrum of antimicrobial activity, sharing the same basic structure of
Doxycycline is primarily a bacteriostatic drug. It exerts its action by inhibiting the
protein synthesis of the bacterial cell. Inhibition of bacterial protein synthesis results
in disturbance of all functions necessary for the life of bacteria. In particular, cell-
division and the formation of the cell wall are impaired.
Doxycycline is a broad-spectrum antibiotic, active against a large number of Gram-
positive and Gram-negative, aerobic and anaerobic micro-organisms and
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For Ornithobacterium rhinotracheale results demonstrate a great variation from high
to low susceptibility, depending on the geographical region where isolates came from.
In pig pathogens resistance against doxycycline may also vary; in particular
susceptibility figures of A. pleuropneumoniae may differ from country to country and
even farm to farm.
Four resistance mechanisms acquired by microorganisms against tetracyclines in
general have been reported: Decreased accumulation of tetracyclines (decreased
permeability of the bacterial cell wall and active efflux), protein protection of the
bacterial ribosome, enzymatic inactivation of the antibiotic and rRNA mutations
(preventing the tetracycline binding to ribosome). Tetracycline resistance is usually
acquired by means of plasmids or other mobile elements (e.g. conjugative
transposons). Cross resistance between tetracyclines has also been described. Due
to the greater liposolubility and greater facility to pass through cell membranes (in
comparison to tetracycline), doxycycline retains a certain degree of efficacy against
microorganisms with acquired resistance to tetracyclines.
5.2 Pharmacokinetic particulars
Doxycycline is absorbed in the stomach and the first part of the duodenum.
Compared to the older tetracyclines the absorption of doxycycline is less affected by
the presence of bivalent cations in food. Bioavailability in non-fasted pigs is
Following oral administration at a dose of 12.8 mg/kg body weight, steady state
concentrations during medication range between a C
min of 0.40 μg/ml in the early
morning to a C
max of 0.87 μg/ml in the late afternoon in pigs.
Following administration of doxycycline hyclate at an actual dose of 21 mg/kg body
weight to chickens mean plasma concentrations above 1 μg/ml were reached within 6
hours and lasted for 6 hours after cessation of medication. From 24 h up to 96 h after
start of treatment the doxycycline plasma concentrations exceeded 2 μg/ml.
Following administration of doxycycline hyclate at an actual dose of 10 mg/kg body
weight steady state plasma concentrations ranged from 0.75 to 0.93 μg/g between
12 and 96 hours after start of medication.
Because doxycycline is highly lipid soluble, it has a good tissue penetration.
Respiratory tract tissue: plasma ratios of 1.3 (healthy lungs), 1.9 (pneumonic lungs)
and 2.3 (nasal mucosa) have been reported for doxycycline. Plasma protein binding
is high (over 90%).
Doxycycline is scarcely metabolised. Doxycycline is primarily excreted with the
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
In the absence of compatibility studies, this product must not be mixed with other
veterinary medicinal products.
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6.3 Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 2 years
Shelf life after first opening the immediate packaging: 1 year
Shelf life after dilution or reconstitution according to directions: 24 hours
6.4 Special precautions for storage
Store below 30 C.
Store in the original package.
Keep the bag tightly closed after first opening in order to protect from moisture.
Once opened, the medicinal product should be stored at temperatures below 25 °C.
6.5 Nature and composition of immediate packaging
Alu triplex (PET/Al/PE) bags.
Alu quadriplex (PET/Al/PET/PE) bags.
Pack sizes of 100 g, 1 kg and 5 kg.
Not all pack sizes may be marketed.
6.6 Special precautions for the disposal of unused veterinary medicinal
product or waste materials derived from the use of such products
Any unused veterinary medicinal product or waste materials derived from such
veterinary medicinal product should be disposed of in accordance with local
7. MARKETING AUTHORISATION HOLDER
Krka, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto
8. MARKETING AUTHORISATION NUMBER
9. DATE OF FIRST AUTHORISATION
08 September 2016
10. DATE OF REVISION OF THE TEXT
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