Vancomycin "Lederle" 500 mg; powder for oral solution/for solution for infusion

Transcription

1 Package leaflet: Information for the user Vancomycin "Lederle" 500 mg; powder for oral solution/for solution for infusion Active substance: vancomycin hydrochloride Read all of this leaflet carefully before you start taking/using this medicine because it contains important information for you. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or pharmacist. This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What Vancomycin "Lederle" 500 mg is and what it is used for 2. What you need to know before you take/use Vancomycin "Lederle" 500 mg 3. How to take/use Vancomycin "Lederle" 500 mg 4. Possible side effects 5. How to store Vancomycin "Lederle" 500 mg 6. Contents of the pack and other information 1. What Vancomycin "Lederle" 500 mg is and what it is used for Vancomycin "Lederle" 500 mg is a glycopeptide antibiotic. Vancomycin "Lederle" 500 mg is used In oral use Once dissolved, Vancomycin "Lederle" 500 mg powder can be taken for the treatment of certain types of bowel inflammation: - antibiotic-associated pseudomembranous enterocolitis (a severe inflammatory bowel disease caused by toxin-producing strains of Clostridium difficile) - staphylococcal enterocolitis (an inflammatory bowel disease caused by staphylococci) When parenterally administered, vancomycin is not effective in these diseases. For intravenous infusion Parenteral administration is to be restricted to severe infections caused by other antibioticresistant pathogens, or in patients with an allergy to beta-lactam antibiotics. - endocarditis (inflammation of the inner lining of the heart) - infections of the bone (osteitis, osteomyelitis) and joints - pneumonia - blood poisoning (septicaemia, sepsis) - soft tissue infections. For perioperative prophylaxis when the patient is at increased risk of infections with Grampositive pathogens in cardiovascular surgery, as well as in bone and joint surgery. Antibacterial spectrum Vancomycin is generally effective against the following pathogens: Aerobic and anaerobic Gram-positive germs, such as Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative staphylococci, Streptococcus pneumoniae, group A, B, C, D, E, F, G streptococci including Streptococcus pyogenes, Enterococcus faecalis and Enterococcus faecium, Corynebacterium spp., Listeria monocytogenes, Clostridium spp., especially C. difficile, as well as Bacillus species. Nearly all Gram-negative bacteria (e.g. Enterobacteriaceae), mycobacteria, Bacteroides and fungi are always or mostly resistant. pal-al-vancomycin-lederle-500mg en-clean Page 1 of 9

2 Increasing cases of resistance can be observed in some countries, particularly to Enterococcus faecium. Multi-resistant strains of Enterococcus faecium are of particular concern. Partial cross-resistance may exist with teicoplanin. 2. What you need to know before you take/use Vancomycin "Lederle" 500 mg Do not take/use Vancomycin "Lederle" 500 mg - if you are allergic to vancomycin or any of the other ingredients of this medicine (listed in section 6). Warnings and precautions Talk to your doctor or pharmacist before taking/using Vancomycin Lederle 500 mg. Take special care with Vancomycin "Lederle" 500 mg if you have acute kidney failure or preexisting hearing loss. For the elderly, there are no special precautions, provided that they do not have severe kidney dysfunction or severe hearing impairment. For patients with poor liver function, there are no special precautions. As too-rapid infusion may give rise to anaphylactoid reactions with blood pressure drop and shortness of breath, vancomycin should only be infused slowly (not more than 10 mg/min; single doses of less than 600 mg should also be infused over at least 60 min) and in sufficient dilution (at least 100 ml per 500 mg). Vancomycin is ototoxic. For this reason, its use should be avoided in patients with hearing damage. A lower dose should be considered if vancomycin is needed for such patients. Blood levels should be regularly determined and the dose fixed accordingly. The start of deafness may be preceded by tinnitus. The risk of hearing damage is greater in elderly patients. In patients taking vancomycin for prolonged periods of time or receiving other co-medications that can cause neutropenia or agranulocytosis, the leukocyte count should be regularly monitored. Paediatric use: Vancomycin should be used with particular caution in premature babies and children, as their kidney function has not yet fully developed and there may be a rise in serum levels of the substance. For this reason, blood concentrations of vancomycin should be carefully monitored. Anaesthesia: Use of anaesthetics during the vancomycin infusion can cause anaphylactoid reactions such as hypotension, erythema or urticaria. These symptoms can be avoided by administering the vancomycin infusion at least 60 minutes before induction of anaesthesia. In patients with impaired kidney function or if aminoglycosides are given at the same time, kidney function should be regularly monitored and the dosage adjusted to the degree of impairment of kidney function. Monitoring of vancomycin serum concentrations during therapy is indicated in these cases. Pseudomembranous colitis, which can be life-threatening, should be considered in cases of severe and persistent diarrhoea during or after administration of vancomycin. In such cases, termination of therapy with Vancomycin "Lederle" 500 mg must therefore be considered depending on the indication and, if necessary, appropriate treatment must be initiated immediately (e.g. intake of specific antibiotics/chemotherapeutic agents with proven clinical efficacy). Medications that inhibit peristalsis must not be taken. pal-al-vancomycin-lederle-500mg en-clean Page 2 of 9

3 Vancomycin should only be administered with caution to patients who show an allergic response to teicoplanin, as allergic cross-reactions between vancomycin and teicoplanin have been reported. Regular blood level and auditory function monitoring is indicated in cases where duration of use is prolonged, particularly in patients with impaired kidney function or impaired hearing, or with co-administration of ototoxic/nephrotoxic substances. Careful monitoring is required particularly if aminoglycosides are co-administered. Other medicines and Vancomycin Lederle 500 mg Tell your doctor or pharmacist if you are taking/using, or have recently taken/used or might take/use any other medicines. Warning: In patients with an inflammatory bowel infection, clinically significant serum concentrations may also occur after oral use of vancomycin, particularly if their kidney function is poor. In such cases, interactions such as those occurring after intravenous infusion are possible. Vancomycin / other medicines that can potentially damage the kidneys or hearing: If vancomycin is given at the same time as - or just after - other potentially ototoxic or nephrotoxic medications, ototoxicity and/or nephrotoxicity may be increased. Careful monitoring is required particularly if aminoglycosides are given at the same time. In such cases, the maximum dose of vancomycin must be restricted to 500 mg every 8 hours. Vancomycin / anaesthetics: There have been reports of an increase in frequency of possible side effects occurring in temporal association with intravenous vancomycin infusions (e.g. hypotension, skin redness, erythema, nettle rash and itching) (see also section Side effects ), when vancomycin and anaesthetics are given at the same time. Vancomycin / muscle relaxants: If vancomycin is given during or immediately after surgery, the effect (neuromuscular blockade) of co-administered muscle relaxants (e.g. succinylcholine) may be enhanced and prolonged. Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Pregnancy There is inadequate experience regarding the safety of vancomycin during pregnancy. Animal studies do not suggest any adverse effects on embryo-foetal development or the gestational period. However, vancomycin passes the placenta, and a potential risk of embryonic and neonatal ototoxicity and nephrotoxicity cannot be ruled out. Therefore, vancomycin should be used during pregnancy only if absolutely necessary and after careful risk-benefit assessment. Breast-feeding Vancomycin passes into breast milk and should therefore only be used during breast-feeding when other antibiotics have failed. Disturbances of the gastrointestinal flora, with diarrhoea and colonisation with yeast-like fungi, may occur in the infant, as well as possible sensitisation. Discontinuation of breast-feeding should be considered, taking the importance of this drug for the nursing mother into account. Driving and using machines Vancomycin Lederle 500 mg has no or negligible influence on the ability to drive and use machines. pal-al-vancomycin-lederle-500mg en-clean Page 3 of 9

4 3. How to take/use Vancomycin "Lederle" 500 mg Always take/use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The recommended dose is For oral administration Adults with enterocolitis usually take 500 mg to 2 g vancomycin daily in 3 or 4 divided doses. Children are given 40 mg/kg bodyweight daily in 3 or 4 divided doses. A daily dose of 2 g vancomycin should not be exceeded. For intravenous infusion Patients with normal kidney function - Adults and children aged 12 years and older - The usual intravenous dose is 500 mg (or 7.5 mg/kg) every 6 hours or 1000 mg (or 15 mg/kg) every 12 hours. - Elderly patients - The natural decline in the glomerular filtration rate with increasing age can lead to increased vancomycin serum concentrations if the dose is not adjusted (see dosage table for patients with poor kidney function) - Children under 12 years - The usual intravenous daily dose is 40 mg/kg bodyweight, in most cases divided into 4 separate doses, i.e. 10 mg/kg bodyweight every 6 hours. - Infants and newborn babies - The dose may be lower for young infants and newborn babies. A starting dose of 15 mg/kg and maintenance doses of 10 mg/kg every 12 hours are recommended in the first week of life and every 8 hours up to the age of one month. Serum concentrations should be monitored (see Warnings and precautions section). Perioperative prophylaxis Proposed dosage: Adults are given 1 g vancomycin IV before surgery (whilst being put under anaesthesia) and one or several 1 g doses of vancomycin IV after surgery, depending on their height and type of surgery involved. Children are given 20 mg vancomycin/kg bodyweight IV at these same times. Patients with poor kidney function In patients with poor kidney function, the dose must be adjusted to excretion capacity..this is helpful, particulary in critically ill patients with fluctuation renal performance. Serum levels must be determined regularly. For many patients with poor kidney function, the following table can be used. Creatinine clearance can be determined or approximately calculated. The overall daily dose of vancomycin (in mg) is approximately 15 times the glomerular filtration rate (in ml/min). The initial dose should always be at least 15 mg/kg. Dosage table for adults with poor kidney function (according to Moellering et al., Ann.Intern.Med. (1981); 94:343) Creatinine clearance [ml/min] Subsequent vancomycin doses [% of the initial dose] above pal-al-vancomycin-lederle-500mg en-clean Page 4 of 9

5 The table cannot be applied to patients with anuria (virtually no kidney function). These patients should be given a dose of 15 mg/kg, in order to reach therapeutic serum concentrations. The maintenance doses are 1.9 mg/kg/24 hours. Dosage in patients on haemodialysis In patients with no kidney function, receiving regular haemodialysis, the following dosage is also possible: Loading dose 1000 mg, maintenance dose 1000 mg every 7-10 days. The half-life of vancomycin is shortened if polysulphone membranes are used in haemodialysis ( high-flux dialysis ). In patients receiving regular haemodialysis, an additional maintenance dose may be required. If only the serum creatinine level is known, creatinine clearance levels can be roughly calculated using the following formulae (according to Cockroft and Gault): Cl Cr (ml/min) = body weight (in kg) x (140 minus age in years) A x serum creatinine (mg/100 ml) A for men = 72 or A for women = 85 The serum creatinine level must correlate to a stable renal function status. In the following patient groups, the approximated level is above actual creatinine clearance in most cases: in patients with decreasing kidney function (e.g. in cases of shock, severe heart failure or oliguria), obese patients or patients with liver disease, oedema or ascites; debilitated, malnourished or immobilised patients. Whenever possible, creatinine clearance should be directly determined. Patients with impaired liver function No specific precautions apply for patients with impaired liver function. Patients co-administered aminoglycosides In these cases the maximum dose of vancomycin should be limited to 500 mg every 8 hours. Method of administration For oral administration The contents of one 500 mg vancomycin vial can be dissolved in 30 ml water and given to the patient to drink in divided amounts or administered via a gastric tube. A taste enhancer can be added to this preparation. For intravenous infusion Parenterally, vancomycin may only be given as a slow IV infusion (no more than 10 mg/min; also, single doses of less than 600 mg given over at least 60 min.) after adequate dilution (at least 100 ml per 500 mg) to reduce the risk of anaphylactoid reactions (see also sections 4.4 and 4.8). Patients requiring fluid restriction can also be given a solution of 500 mg/50 ml. At this higher concentration, the risk of infusion-related symptoms may be increased. Preparing the solution Prior to use, dissolve the contents of one vial in 10 ml water for injections and further dilute to ml with other compatible solutions for infusion. The vancomycin concentration must not exceed mg/ml solution for infusion. pal-al-vancomycin-lederle-500mg en-clean Page 5 of 9

6 Compatibility with intravenous fluids Based on trials with 0.4% vancomycin solutions, the following solutions are physically and chemically compatible: - 5% glucose solution - 5% glucose solution with 0.9% sodium chloride - Ringer s lactate solution - 5% glucose solution in Ringer s lactate solution - Physiological saline solution - Ringer s acetate solution If there is no proof of chemical/physical compatibility with other solutions for infusion, vancomycin solutions must generally always be administered separately from these. Major incompatibilities Vancomycin solutions have a low ph value. This can lead to chemical or physical instability when mixed with other substances. All parenteral solutions should therefore be visually inspected for precipitation and discolouration prior to use. The reconstituted solution may be colourless to pink. Cloudiness has occurred when vancomycin solutions were mixed with solutions containing the following substances: aminophylline; barbiturates; benzyl penicillins; chloramphenicol hydrogen succinate; chlorothiazide sodium; dexamethasone-21-dihydrogen phosphatedisodium; heparin sodium; hydrocortisone-21-hydrogen succinate; methicillin sodium; sodium hydrogen carbonate; nitrofurantoin sodium; novobiocin sodium; phenytoin sodium; sulphadiazine sodium; sulphafurazole diethanolamine. When mixed together, vancomycin solutions and beta-lactam antibiotic solutions have been shown to be physically incompatible. The likelihood of precipitation increases with the vancomycin concentration. It is recommended that the intravenous tubes be thoroughly rinsed when sequentially administering these antibiotics. It is also recommended that vancomycin solutions be diluted to a concentration of 5 mg/ml or less. Combination therapy In the event of combination therapy with vancomycin and other antibiotics / chemotherapy agents, the products must be given separately. The duration of treatment is guided by the severity of infection and its clinical and bacteriological progression. In enterocolitis, vancomycin should be taken orally for 7-10 days. If you take/use more Vancomycin "Lederle" 500 mg than you should There is no known specific antidote. High serum concentrations can be effectively reduced by haemodialysis using polysulphone membranes, as well as by haemofiltration or haemoperfusion procedures using polysulphone resins. For the rest, symptomatic treatment is required in the event of an overdose, with maintenance of kidney function. If you forget to take/use Vancomycin Lederle 500 mg You should make up for any forgotten dose before your next usual dose. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. The following frequency data are used for evaluating side effects: pal-al-vancomycin-lederle-500mg en-clean Page 6 of 9

7 Very common: Common: Uncommon: Rare: Very rare: Not known more than 1 in 10 patients treated 1 to 10 out of 100 patients treated 1 to 10 out of 1,000 patients treated 1 to 10 out of 10,000 patients treated less than 1 in 10,000 patients treated (frequency cannot be estimated from the available data) Warning: In patients with an inflammatory bowel infection, clinically significant serum concentrations may occur after oral use of vancomycin, particularly if their kidney function is also impaired. In such cases, interactions such as those occurring after intravenous infusion are possible. Possible side effects Hypersensitivity reactions Hypersensitivity reactions of all degrees of severity including shock are possible. During or shortly after rapid infusion of vancomycin, anaphylactoid reactions may occur, including a fall in blood pressure, shortness of breath, nettle rash or itching. Severe anaphylactoid reactions may in some cases require appropriate emergency measures. Skin redness of the upper body ( red neck or red man ) may also occur, as well as pain and spasms in the chest or back muscles. When the infusion is stopped, such reactions generally wear off within 20 minutes to a few hours. Rash can commonly occur, as can mucosal inflammation, with and without itching. More serious hypersensitivity reactions are uncommonly observed, with symptoms such as drug fever, eosinophilia (increase in the number of certain white blood cells), shivering and vasculitis (inflammation of the blood vessels). There have been rare reported cases of severe skin manifestations in temporal association with vancomycin therapy, with life-threatening general reactions (such as IgA-linear dermatosis, exfoliative dermatitis, Stevens-Johnson syndrome, Lyell s syndrome). The latter three types of skin reaction are accompanied by life-threatening general reactions. Very rarely, severe lachrymation (excessive secretion of tears) persisting for up to 10 hours has been reported in temporal association with a vancomycin infusion. Renal and urinary disorders Kidney damage, mainly recognisable by increased serum creatinine or serum urea concentrations, has been commonly observed, mostly in patients receiving high vancomycin doses or with pre-existing kidney dysfunction, or when aminoglycosides were given at the same time. Very rarely, kidney inflammation (interstitial nephritis) and/or acute kidney failure has been reported. In most cases, the findings returned to normal when vancomycin was stopped. Ear and labyrinth disorders Uncommon: there have been reports of a temporary or permanent deterioration in hearing function. Those patients affected had been given very high doses of vancomycin or other ototoxic medications as well, or they were suffering from kidney dysfunction or pre-existing hearing impairment. Uncommon: dizziness and tinnitus (ringing in the ears) have been observed. Blood and lymphatic system disorders Uncommon: there is a temporary decrease in the number of certain white blood cells (neutropenia). This usually occurs one week or later after the start of treatment, or after infusion of a total dose of more than 25 g. In most cases, the blood count rapidly returns to normal when vancomycin is stopped. Uncommon: thrombocytopenia (a decrease in the number of blood platelets) and eosinophilia (an increase in the number of eosinophilic blood cells) have also been reported. There have been very rare reports of reversible agranulocytosis (a severe decrease in certain white blood cells). However, no causal relationship with vancomycin treatment has been proven. pal-al-vancomycin-lederle-500mg en-clean Page 7 of 9

8 In isolated cases, leukopenia has also been described. Gastrointestinal disorders Common: nausea may occur. There have been very rare reports of pseudomembranous enterocolitis (a severe inflammatory bowel disease caused by toxin-producing strains of Clostridium difficile) in patients given vancomycin via the intravenous route. Pseudomembranous enterocolitis must be considered if severe, persistent diarrhoea occurs during or after intravenous therapy, which must be treated immediately (see Warnings and precautions ). General disorders and administration site conditions Phlebitis (inflammation of a vein) may occur. This can be reduced by slow infusion of diluted solutions ( mg/100 ml) and by alternating the site of infusion. Inadvertent extravascular or intramuscular injections lead to pain, tissue irritation and necrosis. Infections and infestations Intake of vancomycin can lead to overgrowth with non-susceptible bacteria or fungi. Oral candidiasis has been commonly observed Hepatobiliary disorders (liver and gallbladder) Increased liver enzymes, hepatitis and jaundice have occurred in isolated cases Nervous system disorders Isolated cases of paraesthesia, somnolence, seizures, headache and tremor have been observed. In individual cases, confusion, hallucinations and anxiety have been described. Countermeasures if serious side effects occur The following side effects (see above for further details on these side effects) may be acutely life-threatening in some cases. For this reason, a doctor must be told immediately if such an event occurs or should take an unexpected turn for the worse. Severe acute hypersensitivity reactions (e.g. anaphylaxis): In such cases, treatment with Vancomycin "Lederle" 500 mg must be stopped immediately and the usual appropriate emergency measures instituted (e.g. antihistamines, corticosteroids, sympathomimetics and, if necessary, artificial respiration). Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Bundesinstitut für Arzneimittel und Medizinprodukte Abt. Pharmakovigilanz Kurt-Georg-Kiesinger Allee 3 D Bonn Website: By reporting side effects you can help provide more information on the safety of this medicine. 5. How to store Vancomycin "Lederle" 500 mg Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month. pal-al-vancomycin-lederle-500mg en-clean Page 8 of 9

9 Storage conditions This medicinal product does not require any special storage conditions. Notes on shelf life after opening or reconstitution For parenteral administration, the freshly prepared solution should be used as soon as possible, due to the risk of microbial contamination during reconstitution. In oral use, the prepared solution can be stored in a refrigerator for 96 hours. 6. Contents of the pack and other information What Vancomycin "Lederle" 500 mg contains The active substance is: vancomycin hydrochloride 1 vial contains vancomycin hydrochloride *, equivalent to 500 mg vancomycin. The other ingredient is: hydrochloric acid for ph adjustment. What Vancomycin "Lederle" 500 mg looks like and contents of the pack Vancomycin "Lederle" 500 mg is a fine, white to faintly pink or light brown powder and is available in packs of 1, 5, 10 or 10 (2x5) vials. Marketing Authorisation Holder and Manufacturer RIEMSER Pharma GmbH An der Wiek Greifswald Insel Riems Germany phone fax info@riemser.com This leaflet was last revised in November (* with an efficacy of at least 1,050 IU per milligram of substance, calculated with reference to the anhydrous substance) pal-al-vancomycin-lederle-500mg en-clean Page 9 of 9