PHARMACOLOGICAL ACTION
Procaine benzylpenicillin: Penicillins impair the development of bacterial cell walls by interfering with transpeptidase enzymes responsible for the formation of the cross-links between peptidoglycan strands. During bacterial cell growth, while the peptidoglycan structure is being formed, autolysins continuously cleave the lattice to provide acceptor sites for new strands. Normal bacterial growth depends on a balance between cell wall deposition and autolysis. When penicillin interacts with penicillin-binding proteins (PBP) and inhibits the synthetic enzymes, defective cell walls are formed which lead to abnormal elongation of cells, formation of spheroplasts or osmolysis. The effect of the penicillins is generally bactericidal, although bacteriolysis may also occur.
It has been shown to be effective in vitro against Gram-positive bacteria such as Staphylococcus aureus, Streptococci, most Trueperella pyogenes and Erysipelothrix spp. Sensitive anaerobic bacteria include most Clostridia. It is also effective in vitro against certain Gram-negative bacteria such as Pasteurella multocida, Leptospira and Actinobacillus (Haemophilus) pleuropneumoniae.
Dihydrostreptomycin: The aminoglycosides (e.g. dihydrostreptomycin) are most effective against rapidly multiplying organisms and possess several mechanisms by which it affects and ultimately destroy bacteria. The main site of action is the membrane-associated bacterial ribosome through which it interferes with protein synthesis.
To reach the ribosome, it must first cross the bacterial cell wall and then the cell membrane. Transport of aminoglycosides across bactericidal cell membranes is facilitated by an alkaline pH. Dihydrostreptomycin has been shown to be effective in vitro against Gram-negative bacteria such as E. coli, Pasteurella spp., Salmonella spp. and Klebsiella spp. as well as some Gram-positive bacteria and Leptospira.
Combination of penicillins with aminoglycosides
The combination of benzylpenicillin and dihydrostreptomycin has been demonstrated to have a synergistic action both in vivo and in vitro. The benzylpenicillin disrupts the integrity of the cell membrane and thereby facilitating easier access and increased uptake of dihydrostreptomycin, i.e. the synergistic action enhances the permeability of the bacterial cell to streptomycin caused by penicillin. The dosage of the respective components is lowered without loss of activity while improving the tolerance of the product. The duration of action of the individual components does not differ significantly. The combination broadens the spectrum of activity while the risk of development of resistance by bacteria against either active component is reduced.
INDICATIONS
Depomycin® injection is for the treatment of respiratory tract, gastrointestinal tract, genital tract infections, meningitis, arthritis and dermal infections in cattle, pigs, sheep, horses, dogs and cats caused by or associated with bacteria sensitive to penicillin and/or dihydrostreptomycin.
CONTRAINDICATIONS
Not to be administered to animals known to be allergic to penicillins and dihydrostreptomycin.
Psittacine birds are sensitive to procaine.
Aminoglycosides may impair neuromuscular transmission and should not be given to animals with myasthenia gravis, or animals suffering from myasthenia gravis-like symptoms.
Do not use if β-lactamase producing organisms are known to be present.
WARNINGS
Withdrawal periods for food-producing animals
Meat : 14 days
Liver and kidneys of cattle and pigs : 21 days
Liver and kidneys of sheep : 35 days
Milk : 4 milkings
Do not use in small herbivores (rabbits, guinea pigs, hamsters, chinchillas).
Procaine benzylpenicillin may occasionally cause transient pyrexia, vomiting, shivering, listlessness and incoordination in pigs. Additionally, in pregnant sows and gilts, abortion has been reported in a few cases.
With animals known to be sensitive to penicillin, anaphylactic shock may occur. Adrenaline, corticosteroids and antihistamines should be used to treat anaphylaxis.
Do not use concurrently with other aminoglycosides as this may increase the risk of toxicity.
Do not administer simultaneously with furosemide.
Do not administer concurrently with non-steroidal anti-inflammatory drugs as this may increase the animal’s susceptibility to aminoglycoside-induced nephrotoxicity.
Aminoglycosides enhance the neuromuscular blocking activity of skeletal muscle relaxants and general anesthetics resulting in prolonged skeletal muscle weakness and respiratory depression or paralysis.
Cardiovascular depressant effects of aminoglycosides have been noted in animals anaesthetised with pentobarbitone.
Concurrent and/or sequential use of parenteral polymyxins with aminoglycosides should be avoided since the potential for nephrotoxicity and/or neuromuscular blockade may be increased. Co-administration with amphotericin B enhances the potential for nephrotoxicity.
Antagonism between Depomycin® and bacteriostatic preparations may occur. Resistant bacteria might emerge that show a cross resistance to other ß-lactam antibiotics or aminoglycosides.
Do not administer intravenously.
KEEP OUT OF REACH AND SIGHT OF CHILDREN, UNINFORMED PERSONS AND ANIMALS.
DOSAGE AND DIRECTIONS FOR USE – USE ONLY AS DIRECTED
SHAKE WELL BEFORE USE
Given by intramuscular injection to large animals.
Dogs and cats may be injected by either the subcutaneous or intramuscular route.
Horses and cattle : 20 mℓ/500 kg body weight (1 mℓ/25 kg)
Sheep and pigs : 4 mℓ/80 kg body weight (1 mℓ/20 kg)
Small animals (cats, dogs) : 1 mℓ/10 kg body weight
Injections may be repeated at 24-hour intervals depending on clinical judgment.
Repeat injection should be given at a different injection site.
The usual aseptic precautions should be taken when administering the injections. Use sterile equipment when administering Depomycin®.
SIDE EFFECTS AND SPECIAL PRECAUTIONS
Penicillins
Hypersensitivity reactions to penicillins range from mild and transitory skin reactions to fatal anaphylactoid shock.
Pharyngitis or sore throat has been reported in dogs following 4 days of penicillin therapy.
Aminoglycosides
Nephrotoxicity, ototoxicity, neuromuscular blockade.
Total volume of distribution may decrease with dehydration or hypovolemia leading to an increase in serum drug concentrations that may result in toxicity.
Ascites, oedema or congestive heart failure may result in an increased volume of distribution resulting in subtherapeutic serum drug concentrations.
Neonates have a large extracellular fluid compartment relative to body weight. The large volume of distribution may also necessitate longer dosage intervals.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See SIDE EFFECTS
Signs of acute poisoning following injection include restlessness, nausea, laboured respiration, loss of consciousness and coma. Death appears to be from respiratory failure and vasomotor depression.
Treatment is symptomatic and supportive.
IDENTIFICATION
White to off-white, ready-to-use sterile aqueous suspension.
On standing the colour of the sediment and upper layer is as follows:
Sediment: white to off-white suspension.
Upper layer: light greenish-yellow opaque solution.
PRESENTATION
Clear 100 mℓ and 250 mℓ polyethylene terephthalate, (PET) vials. The 100 mℓ vial is closed with a grey halogenated butyl rubber stopper and sealed with an orange aluminium cap. The 250 mℓ vial is closed with a red halogenated butyl rubber stopper and sealed with an orange aluminium cap. Placed in outer carton.
Not all pack sizes may necessarily be marketed.
STORAGE
Store between 2 °C – 8 °C in a refrigerator.
Do not freeze.
Store in the original package in order to protect from light.
Do not use Depomycin® after the expiry date which is stated on the container label.
Shelf life after first opening the container: use within 8 weeks.
REGISTRATION NUMBER
83/660 (Act 101/1965)
Namibia Reg. No. V22/17.1.10/1504 NS2
