Septopal Minichains
Package leaflet: information for the user xxxxxxxxxx/xx
Septopal® Minichains (Chains of 10 or 20 beads) _
Each bead contains 2.8 mg gentamicin sulphate, equivalent to 1.7 mg gentamicin base
Read all of this leaflet, before you start having
this medicine.
• Please keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or nurse.
• If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.
In this leaflet:
1 WHAT SEPTOPAL MINICHAINS ARE AND WHAT THEY ARE USED FOR
2 READ THIS, BEFORE YOU HAVE SEPTOPAL MINICHAINS
3 HOW SEPTOPAL MINICHAINS WILL BE GIVEN TO YOU
4 POSSIBLE SIDE EFFECTS
5 HOW SEPTOPAL MINICHAINS ARE STORED
6 FURTHER INFORMATION
1 WHAT SEPTOPAL MINICHAINS ARE AND WHAT THEY ARE USED FOR
What Septopal Minichains are
Septopal Minichains are an antibiotic implant. It is made up of tiny beads strung together on stainless steel wire.
Each minichain consists of 10 or 20 beads. Each bead contains the active ingredient gentamicin sulphate. This is the antibiotic. The gentamicin is slowly released from the beads at the place of a possible or existing infection, so that it can provide protection against future infection or treat an existing one.
What Septopal Minichains are used for
They are used for:
• the short and longer term treatment of bone infections, such as:
- infection of the bone marrow and the surrounding bone (osteomyelitis);
- infection of a break in a bone that has not knitted together properly (infected pseudoarthroses);
- infection where a broken bone has been fixed together by something like a metal plate (infected osteosynthesis);
• the short term prevention of infection in bone injuries.
Types of surgery for which Septopal Minichains have been specifically developed are hand and foot surgery, face and jaw surgery and surgery on children.
2 READ THIS, BEFORE YOU HAVE SEPTOPAL MINICHAINS
You will not have Septopal Minichains if:
• you are known to have a bad reaction to any of the ingredients in Septopal Minichains
(see Section 6 for a list of these).
Special care will be taken in giving you Sep-topal Minichains
If tests have identified bacteria which may not respond when Septopal Minichains are used on their own, you will have treatment with another antibiotic, as well as with these minichains.
In the young (under 18) and elderly (65+), there is no evidence that Septopal Minichains can cause damage to the kidneys or to the hearing. But, if you receive these minichains and you have moderate or severe kidney disease, then the state of your kidneys and the level of gentamicin in your blood will be checked during your treatment.
Septopal Minichains and medical devices
• Tell your doctor, if you already have any implants containing metal. This is because of the possibility that the stainless steel wire and the implant might become corroded.
• If you already have any implants which contain metal, Septopal Minichains will not be placed next to them.
• If, during your treatment, it is decided that you will need a metallic implant, the minichains will be removed beforehand.
Taking other medicines
Please tell your doctor or nurse if you are taking, or have recently taken any other medicines, including medicines obtained without a prescription.
Pregnancy and breast-feeding
Septopal Minichains are not recommended for use if you are pregnant because there is a faint possibility that gentamicin might damage the hearing of an unborn child.
If you are breast-feeding, talk to your doctor before receiving Septopal Minichains.
3 HOW SEPTOPAL MINICHAINS WILL BE GIVEN TO YOU
Where the minichains will be placed
The minichains are placed, during your operation, in the space left after the surgeon has thoroughly removed damaged or infected bone.
How many minichains you will have
• The number of minichains you receive will depend on the size of the space left after the damaged or infected bone has been removed.
• The surgeon usually places from one to three minichains in the cavity, but may use up to four.
How the minichains will be inserted
This will depend on whether you are going to have the minichains for a short or longer period of time. Your doctor will let you know.
Short term
If you will be having the minichains for a short time, they will be inserted as follows:
• The surgeon will leave the last bead in each minichain sticking out above skin level, and held in position by a loose stitch, so that, later on, a few beads at a time can be withdrawn, each day, from the wound.
Longer term
If you will be having the minichains for a longer time, they will be implanted:
• either with the last bead sticking out,
(as described in ‘Short term’ above),
• or they will be completely enclosed in the wound, perhaps with a drain in place to let fluid out.
When and how the minichains will be removed
Short term
If you received the minichains for a short time, then:
• All the minichains should normally be completely removed 10 - 14 days after the surgeon inserted them.
• The number of beads removed each day will be counted carefully.
• When a minichain is being removed, there is a small chance that either some of the beads are left behind or, very unusually, the wire may break.
If this happens, then your doctor will try to remove the remaining beads and/or wire. If an operation is required to do this, the doctor may decide that it is safer to leave them where they are.
• If your doctor finds that an infection continues for more than four days after the operation, the mini-chains may be removed, and the cause of the infection identified before treatment with further antibiotics.
Longer term
If you received the minichains for a longer time, then:
• If the minichains were completely enclosed in the wound, they will be removed through another operation, up to 3 months later, depending on the original operation.
If you receive more Septopal Minichains than you should
These minichains are given to you by healthcare professionals. It is extremely unlikely that you will receive more minichains than you should.
If you have any further questions about taking Septopal Minichains, please ask your doctor or nurse.
4 POSSIBLE SIDE EFFECTS
Like all medicines, Septopal Minichains can cause side effects, although not everybody gets them. If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse as soon as possible.
The beads in the minichains are strung on stainless steel wire. If you find you experience an allergic reaction, please tell your doctor or nurse as soon as possible.
Because new tissue grows in the spaces between the beads during the healing of the wound, this may cause some difficulty when the doctors are removing the beads.
Please remember: the benefits you get from having these Septopal Minichains will usually be greater than the risk of suffering any harmful side effects.
5 HOW SEPTOPAL MINICHAINS ARESTORED
The hospital staff will ensure that the following
instructions for the storage of Septopal Minichains
are observed:
• Store at room temperature.
• Do not freeze.
• Keep out of the reach and sight of children.
• Once the inner pouch is opened, any unused minichains will be discarded.
• These minichains will not be used after the expiry date stated on the carton and the aluminium pouch. The expiry date refers to the last day of that month.
These minichains are supplied in packs of 1 or 5 sachets. Each sachet contains one chain of 10 or 20 impregnated methylmethacrylate-methylacrylate copolymer (PMMA) beads threaded on a stainless steel wire.
Not all pack sizes and minichain lengths are marketed.
Marketing Authorisation Holder
Biomet UK Ltd.
Waterton Industrial Estate Bridgend South Wales CF31 3XA
Manufacturer
European Medical Contract Manufacturing bv
Middenkamp 17
NL - 6545 CH Nijmegen
Netherlands.
This leaflet was last approved in [10/2008]
6 FURTHER INFORMATION
What Septopal Minichains contain
Each bead contains the active ingredient gentamicin sulphate 2.8 mg (equivalent to
1.7 mg gentamicin base).
Other, non-active, ingredients in Septopal Minichains are: glycine, methylmethacrylate-methylacrylate copolymer, zirconium dioxide, stainless steel.
What Septopal Minichains look like and contents of the pack
Each minichain is contained in an inner sachet, which is then contained in a transparent peel-pouch, which is then contained in a protective aluminium pouch, which is then packaged in an outer carton.
TECHNICAL INFORMATION FOR THE MEDICAL PROFESSIONAL
1 NAME OF THE MEDICINAL PRODUCT
Septopal Minichains
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Chain of 10 or 20 beads.
Each contains 2.8 mg Gentamicin Sulphate BP (equivalent to 1.7 mg gentamicin base).
3 PHARMACEUTICAL FORM
Impregnated methylmethacrylate-methacrylate copolymer (PMMA) beads for surgical use. Each minichain consists of 10 or 20 beads threaded on multiple surgical wire.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Short term and longer term administration in bone infection, e.g. osteomyelitis, infected pseudoarthroses, infected osteosynthesis.
Short term preventative treatment of potentially infected bone injuries.
Surgical fields for which Septopal Minichains have been expressly developed are: hand and foot surgery, face and jaw surgery and paediatrics.
4.2 Posology and method of administration
For implanting in the cavity resulting from thorough surgical removal of sequestrated bone or infected tissue.
The number of chains used will depend upon the size of the cavity which results after thorough surgical removal of infected tissue and/or sequestrated bone. Usually 1-3 chains are inserted but up to 4 chains have been used. The chains are laid in the cavity in such a way as to facilitate easy removal.
Short term application
When implanting the chains, it is recommended to take into account the direction in which the chain will later be pulled out and to let the last bead project above the skin level, through a separate stab incision anchored by a loose suture, in order that the chain may be removed by careful steady traction, a few beads at a time daily. The chains should normally be completely removed by 10-14 days following insertion and preferably no more than 10 days after the operation. Where there is evidence of persisting local infection beyond 4 days post-operatively, it is recommended that the chain is removed and the cause of infection determined prior to recommending further antibacterial therapy.
The less the chains are fixed to connective tissue, the easier it is to remove them, thus making the procedure more comfortable for the patient.
If the beads become fixed to connective tissue to a great extent, or if the traction of the beads is not adapted to the tissue conditions then there is a small possibility that one or several may become detached from the wire or, in exceptional circumstances the wire may break on removal of the chain. In such an event, attempt should be made to remove the individual beads and the remaining wire. Should, however, extensive surgery be necessary then the risk of reoperation should be considered carefully. In high-risk patients, it may be preferable to leave the beads in situ permanently. For the above reasons the beads should always be counted on their removal.
Longer term application
This may be as above or if circumstances require it, the chains may be implanted completely, and removed by reoperation up to 3 months later. The length of time the chains are left in situ prior to secondary intervention will depend on the orthopaedic procedure. Inserted chains will be completely enclosed by primary wound closure. Control of local infection allows subsequent surgical procedures e.g. cancellous bone grafting.
In considering wound closure/drainage, it should be remembered that excess drainage will dilute the gentamicin concentration at the site of infection so, if possible, primary wound closure should always be employed. Local circumstances and degree of inflammation should, however, be taken into consideration.
An overflow drain may be employed only when considered necessary. Suction drainage should not be employed but may be temporarily used in cases of obstructed wound secretion flow.
Toxic effects due to the antibiotic are not anticipated since, after use of Septopal Minichains, barely detectable gentamicin concentrations (no more than 0.42 micrograms/ml) are found in the systemic circulation for up to 4 days post-operatively.
There is no distinguishing factor between doses for the young, adults and elderly since the number of chains used depends on the size of the cavity in individual cases and the clinical conditions at the site of infection.
4.3 Contraindications
Established intolerance to Gentamicin.
4.4 Special warnings and precautions for use
Septopal Minichains should not be used alone in those situations where culture of wound secretion reveals the presence of anaerobic bacteria, or organisms which could be insensitive to gentamicin therapy. In these instances, additional systemic therapy with an appropriate antibiotic should be used.
Septopal may be used in all orthopaedic surgical procedures where gentamicin sensitive organisms are found to be present from routine bacteriological screening, where resistant organisms are encountered to the standard 10 microgram disc test, an MIC determination is recommended. In view of the high bactericidal gentamicin concentration at the infection site, organisms found resistant to the standard 10 microgram sensitivity disc screen may in fact be sensitive and therefore results of such screening may not give a true reflection of clinical efficacy.
In the young and elderly, there is no evidence to suggest that use of Septopal Minichains has caused either nephrotoxic or ototoxic effects. Nevertheless, if Septopal therapy is desirable in patients who have moderate to severe impairment or renal function, monitoring of renal state and plasma gentamicin levels is advised.
4.5 Interaction with other medicinal products and other forms of interaction
Septopal Minichains should not be used concurrently in apposition to metal-containing implants because of the theoretical possibility of surgical wire and implant corrosion. Septopal Minichains should be removed prior to implant of a metal prosthesis.
4.6 Pregnancy and lactation
Gentamicin crosses the placenta and may cause ototoxicity in the foetus although no problems in clinical use have positively been identified. Implantation of Septopal Minichains results in only a transient, barely detectable plasma concentration of Gentamicin (no more than 0.42 micrograms/ml). Therefore, no ototoxic effects on the foetus are to be expected. Nevertheless, it is recommended that the product should not be used in pregnancy.
4.7 Effects on ability to drive and use machines
No effect.
4.8 Undesirable effects
Because the beads are strung on surgical wire containing chrome and nickel, there is a potential for local sensitivity to these metals.
Granulation tissue grows into the hollow spaces between the beads during the healing process; this may cause difficulties at the time of removal.
4.9 Overdose
Not applicable.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Gentamicin, an aminoglycoside antibiotic, possesses an “in vivo” and “in vitro” broad antibacterial spectrum of action. Its activity covers grampositive bacteria and gram-negative micro-organisms such as E.Coli, Klebsiella, Enter-obacter, Pseudomonas and Proteus. It is effective against problem organisms which are resistant to other antibiotics. Gentamicin has a bactericidal effect on proliferating and latent organisms. Gentamicin is released gradually from the PMMA
beads over a prolonged period and the high bactericidal concentrations of the antibiotic reached at the site of the infection enable the infection to be controlled, or provide protection against infection.
5.2 Pharmacokinetic properties
Gentamicin is detectable in the serum for only a short time after implantation and only at low concentrations. Peak values occur 1-4 hours after chain implantation (maximum found is 0.42 |Jg/ml).
The concentration falls off very rapidly within 48 hours to below the lower limit of detection of 0.05 |jg/ml. Thus toxic side effects can be excluded
Gentamicin is detectable in the urine for several days after implantation (maximum found is
4.9 jg/ml) which is evidence of good release from implanted beads.
In wound secretions originating directly from the operation area, high gentamicin concentrations of between 1126 and 715 jg/ml are found. Therefore, at the site of implantation, levels of gentamicin are reached which far exceed those required for killing aetiologically imported pathogens.
5.3 Preclinical safety data
N/A.
Container: Inner sachet within a peel-off sachet placed in an aluminium sachet of drying agent. The aluminium sachet is packed in a cardboard box. Contents: Packs of 1 or 5 sachets each containing 1 minichain of 10 or 20 beads.
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Biomet UK Ltd.
Waterton Industrial Estate Bridgend South Wales CF31 3XA
8 MARKETING AUTHORISATION NUMBER(S)
PL 13442/0004
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
31 December 1998/ 23 October 2004.
10 DATE OF REVISION OF THE TEXT
November 2007
6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients
Glycine, methylmethacrylate-methytlacrylate copolymer, zirconium dioxide, polyfilic stainless steel.
11 DOSIMETRY (IF APPLICABLE)
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)
6.2 Incompatibilities
None.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store at room temperature. Do not freeze.
6.5 Nature and contents of container
