Product Name: DOXYZONE C

Type: Oral Water-Soluble Powder - Antibiotic Combination

COMPOSITION

Each gram contains:

• Doxycycline (as Doxycycline Hyclate) ...... 100 mg
• Colistin Sulfate ...... 1 MIU (Million International Units)

DESCRIPTION

DOXYZONE C is a broad-spectrum antibiotic combination powder containing doxycycline hyclate and colistin sulfate. This synergistic formulation provides enhanced antibacterial activity against both gram-positive and gram-negative pathogens, making it an effective treatment for respiratory and gastrointestinal infections in poultry

Doxycycline is a semi-synthetic tetracycline with broad-spectrum bacteriostatic activity against a wide range of gram-positive and gram-negative bacteria, as well as Mycoplasma species. It is highly lipophilic, allowing it to penetrate tissues effectively and achieve high concentrations in the respiratory tract

Colistin sulfate (polymyxin E) is a polypeptide antibiotic with potent bactericidal activity specifically against gram-negative bacteria. It acts by disrupting the bacterial cell membrane, leading to cell death

MECHANISM OF ACTION

Doxycycline:

• Inhibits bacterial protein synthesis by binding reversibly to the 30S ribosomal subunit
• Prevents the attachment of aminoacyl-tRNA to the mRNA-ribosome complex, blocking the addition of new amino acids to the growing peptide chain
• Exhibits bacteriostatic activity with broad-spectrum coverage
• Well absorbed after oral administration; widely distributed throughout body tissues

Colistin Sulfate:

• Acts as a cationic surface-active agent, binding to lipopolysaccharides in the outer membrane of gram-negative bacteria
• Displaces divalent cations (Ca²⁺, Mg²⁺), destabilizing the cell membrane
• Increases membrane permeability, leading to leakage of cellular contents and cell death
• Poorly absorbed from the gastrointestinal tract, exerting its primary effect in the gut lumen

Synergistic Combination:

• Research has demonstrated that the concurrent use of doxycycline and colistin is more effective against E. coli than either drug alone
• The combination provides enhanced efficacy in controlling colibacillosis, reducing mortality rates, and improving body weight gain in infected chicks
• This combination is particularly effective against mixed infections involving both Mycoplasma and enteric bacteria

ANTIMICROBIAL SPECTRUM

DOXYZONE C is effective against a broad range of microorganisms:

Mycoplasma:

• Mycoplasma gallisepticum - chronic respiratory disease (CRD)
• Mycoplasma synoviae - infectious synovitis, respiratory disease

Gram-Positive Bacteria:

• Staphylococcus spp.
• Streptococcus spp.
• Clostridium spp.

Gram-Negative Bacteria (Doxycycline):

• Escherichia coli - colibacillosis
• Salmonella spp. - salmonellosis, fowl typhoid, pullorum disease
• Pasteurella multocida - fowl cholera
• Haemophilus paragallinarum - infectious coryza
• Klebsiella spp., Bordetella spp., Campylobacter spp.

Gram-Negative Bacteria (Colistin):

• Escherichia coli - highly susceptible
• Salmonella spp. - highly susceptible
• Klebsiella spp., Proteus spp., Enterobacter spp.
• Pseudomonas aeruginosa - moderately susceptible

INDICATIONS

DOXYZONE C is indicated for the treatment and control of respiratory and gastrointestinal infections in poultry caused by doxycycline and colistin-sensitive bacteria

Disease Conditions:

• Chronic Respiratory Disease (CRD) - mycoplasmosis caused by Mycoplasma gallisepticum
• Complex Chronic Respiratory Disease (CCRD) - mixed infections involving Mycoplasma and E. coli
• Colibacillosis - E. coli infections causing airsacculitis, pericarditis, perihepatitis, and enteritis
• Salmonellosis - fowl typhoid, pullorum disease, paratyphoid infections
• Fowl Cholera - Pasteurella multocida infection
• Infectious Coryza - Haemophilus paragallinarum infection
• Necrotic Enteritis - Clostridium perfringens infection
• Ornithobacterium rhinotracheale (ORT) infection
• Secondary bacterial infections associated with viral diseases

DOSAGE & ADMINISTRATION

DOXYZONE C is administered via drinking water. For optimal results, fresh medicated water should be prepared daily.

Recommended Dosage:

• Poultry (Broilers, Layers, Breeders, Turkeys): 1 g per 2-4 liters of drinking water (equivalent to 0.25-0.5 g per liter) for 3-5 consecutive days
• Alternative Dosage (body weight): 10 mg doxycycline + 0.1 MIU colistin per kg body weight per day
• Treatment Duration: 3-5 consecutive days . For chronic or severe infections, up to 7 days may be required

Dosage Examples:

• 1 g per 2 liters of water: Provides 50 mg doxycycline + 0.5 MIU colistin per liter
• 1 g per 3 liters of water: Provides 33 mg doxycycline + 0.33 MIU colistin per liter
• 1 g per 4 liters of water: Provides 25 mg doxycycline + 0.25 MIU colistin per liter

Administration Guidelines:

• Calculate total daily water consumption based on flock size, age, and environmental temperature
• Dissolve the required amount of DOXYZONE C in a small volume of water, then add to the main drinking water tank
• For use in automatic water proportioners, prepare stock solution according to manufacturer specifications
• Prepare fresh medicated water daily; discard any unused solution after 24 hours
• Ensure medicated water is the sole source of drinking water during treatment
• For best results, administer over 4-8 hours; may withhold water for 1-2 hours before treatment to encourage rapid consumption

EFFICACY DATA

Synergistic Activity Against E. coli:

• A study on the concurrent use of doxycycline and colistin in chickens demonstrated that the combination was more effective against E. coli than either drug alone. Both the combination and doxycycline alone were highly effective in controlling experimental E. coli infection, reducing mortality rates and improving body weight gain, with the combination showing enhanced efficacy

Clinical Applications:

• The combination is widely used for treating colibacillosis and mixed respiratory infections in poultry, with documented efficacy against Mycoplasma gallisepticum and secondary E. coli infections
• The addition of colistin provides enhanced activity against gram-negative enteric pathogens, making this combination effective for both respiratory and gastrointestinal infections

DRUG INTERACTIONS

• Antagonistic: Do not use concurrently with bactericidal antibiotics such as penicillins, cephalosporins, quinolones, or cycloserine, as this may reduce efficacy
• Absorption interference: Tetracyclines chelate divalent or trivalent cations such as calcium, iron, magnesium, and aluminum. Concurrent administration of antacids, kaolin, pectin, or feed containing high levels of these minerals may decrease gastrointestinal absorption. Colistin efficacy may decrease in the presence of calcium ions
• Synergistic: The combination of doxycycline and colistin itself is synergistic, providing enhanced antibacterial activity

CONTRAINDICATIONS & PRECAUTIONS

• Egg production: Do not use in laying hens producing eggs for human consumption. Do not use within 2 weeks of the onset of the laying period
• Hypersensitivity: Do not use in animals with known hypersensitivity to tetracyclines or polymyxins
• Hepatic and renal impairment: Do not use in animals with severe liver or kidney dysfunction
• Young animals: Use with caution in very young animals; tetracyclines may cause discoloration of teeth
• Sensitive species: Do not allow horses, rabbits, hamsters, guinea pigs, or ruminants access to water containing this product
• Keep out of reach of children
• When handling the product, avoid inhalation, oral exposure, and direct contact with skin or eyes. People with known hypersensitivity to tetracyclines should avoid contact
• Store in a cool, dry place below 30°C, protected from direct sunlight and moisture
• Use within 28 days after first opening; medicated water should be used within 24 hours

ADVERSE REACTIONS

• At recommended doses, the combination is generally well tolerated in poultry
• Occasional mild diarrhea may occur due to intestinal flora changes
• Allergic reactions such as dermatitis, itching, or swelling may occur in rare cases
• Discoloration of teeth in young animals with prolonged use
• If adverse reactions occur, discontinue use and consult a veterinarian

WITHDRAWAL PERIOD

• Meat (Poultry): 7-8 days (consult local regulatory requirements)
• Eggs: Not for use in laying hens producing eggs for human consumption
• Note: Withdrawal periods may vary by country; always follow local regulatory requirements . Published data indicates a 7-day withdrawal period for doxycycline-colistin combinations in poultry

STORAGE

• Store in a cool, dry place below 30°C
• Protect from direct sunlight and moisture
• Keep container tightly closed when not in use
• Do not freeze

Target Species: Poultry (Broilers, Layers, Breeders, Turkeys, Ducks, Geese, Quail) - Not for use in laying hens producing eggs for human consumption

Pack Sizes: 1 Kg HDPE container

PRODUCT SUMMARY
DOXYZONE C Powder Antibiotic Doxycycline as Hyclate 100mg, Colistin Sulphate 1MIU per gram Poultry 1 Kg

FOR VETERINARY USE ONLY