Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
VI.2 Elements for a Public summary VI.2.1 Overview of disease epidemiology Infections like endocarditis, infections of the bones (osteomyelitis), pneumonia, soft tissue infections are often difficult to treat. The epidemiology of infectious disease varies according to the organism but in general occur in vulnerable groups, particularly the elderly and those with impaired resistance to infection. All age groups may be affected. Vancomycin is used RMP vancomycin Version 01, DLP 26-Aug-2014 50 | P a g e particularly in infections which are resistant to the use of other antibiotics and these are commonly found in hospital patients. VI.2.2 Summary of treatment benefits Vancomycin effectively treats a variety of bacterial infections which cannot be treated effectively by more commonly used drugs. It is especially useful for very ill and vulnerable patients who need intensive treatment and so is most frequently used in intensive care units. This includes patients with severe infections of the blood stream and patients with severe infections following operation. The effectiveness varies from patient to patient and the treatment dose has to be carefully adjusted with the help of experts in the treatment of the disease. VI.2.3 Unknowns relating to treatment benefits There are no significant unknowns as vancomycin is a drug which has been used for many years so that its role in treatment is well-defined. VI.2.4 Summary of safety concerns The safety concerns of vancomycin have been well documented based on many years clinical use. There are no outstanding concerns or new signals that relate to this generic product. Known serious possible hazards (identified risks) according to the SmPC of the Brand Leader are detailed in the table below along with the appropriate risk-minimisation measures in the Section “Summary of risk minimisation measures by safety concern”. RMP vancomycin Version 01, DLP 26-Aug-2014 51 | P a g e Important identified risks RISKS WHAT IS KNOWN PREVENTABILITY Hypersensitivity to vancomycin. This is a very infrequent problem. Patients with frequent allergies are more at risk and should mention this to the healthcare professional. Concomitant administration of vancomycin and anaesthetic agents has been associated with marked red flushing of the skin in children. Reports have shown that this occurs more frequently when the young patient is given an anaesthetic agent. Toxicity at injection sites. Vancomycin when not being administered correctly can cause pain at the injection site and sometimes the surrounding tissues may die. Avoiding the product when allergies to vancomycin or other substances in the tablet are known will avoid the problem in most cases. Concomitant administration of vancomycin and an anaesthetic agent should be avoided whenever possible. Infusion-related reactions may be minimised by giving vancomycin slowly (over 60 minutes) before the anaesthetic is given. The problem may be avoided by infusing slowly (for more than 60 minutes). Your doctor should consult the information leaflet to ensure its correct administration. Difficulty in controlling the dose as small changes may lead to toxic effects or to a lack of effectiveness (this is called “a narrow therapeutic index”). Small increases of vancomycin dose may result in it a toxic effect, especially when your kidney is not functioning optimally. On the other hand modest dose reductions may lead to the blood levels being too low for the drug to be effective in fighting the infection. This is especially evident in very old or very young patients. The natural decrement of kidney function with increasing age may lead to elevated amount of vancomycin retained in the bloodstream. There are marked differences in dose requirements for This problem can be avoided by measuring the levels of vancomycin in the blood by experts as necessary. which should be closely monitored and the doses adjusted. Adjustment of the dosage and ensure blood concentrations are carefully monitored. Vancomycin should always be administered to neonates and infants by experts according to established dosing regimes. Monitoring blood levels of vancomycin allows your doctor to establish correct serum levels to effectively treat the infection while avoiding too high a dose. RISKS Development of red neck syndrome (Red Man Syndrome). Toxicity to the gastrointestinal tract, causing inflammation of the colon (colitis). WHAT IS KNOWN PREVENTABILITY vancomycin the first months and years of life. In premature neonates and young infants, it may be appropriate to confirm the desired amount of vancomycin remaining in the blood. The time taken for the amount of vancomycin to be halved (known as the half-life) ranges from approximately 2 to 10 hours depending on age. There is an approximately two fold difference in their half-lives, between patients aged 3 months to 4 years old compared to those older than 4 years which can lead to a huge difference in the dosing strategies of vancomycin. This is a combination of flushing and/or a red rash that affects the face, neck, and upper torso. Less frequently, low blood pressure and swelling of the tissues especially around the mouth and throat may also occur. It usually appears within 4–10 minutes after the commencement or soon after the completion of an injection directly into your bloodstream (an infusion). In very rare cases, you may suffer from a serious bowel condition. This may occur when vancomycin kills the usual bacteria in your bowel leading to an overgrowth of harmful bacteria. These bacteria are toxic to the bowel wall and may lead to abdominal pain and bloody diarrhoea. This condition ( which is called antibioticassociated colitis or pseudomembranous colitis) may vary from mild effects with minimal diarrhoea to dramatic diarrhoea with bleeding which can be lifethreatening. Less than 1 out of 10,000 patients treated RMP vancomycin, Version 01, DLP 26-Aug-2014 53 | P a g e Your doctor will administer vancomycin in a dilute solution slowly, over at least 60 minutes (maximum rate of 10 mg/minute for doses >500 mg). This is due to the high incidence of pain and thrombophlebitis and to avoid an infusion reaction known as the red man syndrome or red neck syndrome. Symptoms may be treated or prevented with antihistamines, including diphenhydramine, and are less likely to occur with slow infusion. It is important that your doctor considers the diagnosis of antibiotic-associated colitis or pseudomembranous colitis in patients who suffer from diarrhoea during or subsequent to the administration of vancomycin. Discontinuation of therapy with vancomycin and early start of a specific treatment should be considered. Medicinal products that inhibit gut motility (peristalsis) should not be given. RISKS WHAT IS KNOWN PREVENTABILITY with vancomycin may develop this more serious form. Use in pregnancy and lactation. There is not sufficient safety experience available regarding the use of vancomycin during human pregnancy to ensure its safety during pregnancy. Studies in animals do not suggest any ill effects on the development of the embryo, foetus or gestation period. However Vancomycin penetrates the placenta and a potential risk of embryonal and neonatal toxicity cannot be excluded. Vancoymcin is excreted in human milk Toxicity to the kidney especially The body excretes vancomycin through the kidneys and in patients with reduced kidney if these are not working properly vancomycin levels in function (renal insufficiency) or the body increase. In the first 24 hours, about 75% of those receiving other drugs an administered dose of vancomycin is excreted in urine which may be toxic to the by the kidney. Thus if the kidneys are not working kidneys. adequately the vancomycin may accumulate in the blood. This accumulation of vancomycin in the blood stream leads to an increased risk of toxicity to the kidney. If you receive medicines that can cause damage to your kidneys, vancomycin can make these problems worse Toxicity to the ears (ototoxicity) especially in patients who already have some hearing loss, or those receiving other drugs which may be toxic to the ears. Vancomycin is known to be a drug that can affect hearing. It is not clear what the exact risk of this is but reports of cases in which patient’s hearing is affected are rare. In patients whose kidneys are not functioning normally and in patients taking other drugs known to affect hearing (especially antibiotic drugs known as aminoglycosides) the risk of hearing damage is higher. If you receive medicines that can cause damage to your RMP vancomycin, Version 01, DLP 26-Aug-2014 54 | P a g e The problems associated with the use of vancomycin in pregnancy or breastfeeding can be avoided only by ensuring that the drug is not given during pregnancy. It should be only given if absolutely necessary, and only after careful discussion with between the patient and the expert prescriber, with consideration of all the potential risks. Vancomycin should only be considered only if other antibiotics have failed. If you have kidney disease it is important to inform your doctor before being treated with vancomycin. This will allow the dose you take to be carefully adjusted or complete avoidance. Careful monitoring can prevent the occurrence of serious problems. Your doctor will know which medicines may cause kidney problems and should avoid prescribing these with vancomycin. If the combination is unavoidable careful monitoring of vancomycin levels is recommended, along with kidney function tests to detect any potential issues. Vancomycin is best avoided in individuals at increased risk of hearing damage such as those with existing hearing loss, those with poorly functioning kidneys and those taking other drugs (such as aminoglycoside antibiotics) which may damage hearing. When it is essential to give the drug it should be given cautiously and blood levels should be monitored carefully. These precautions RISKS WHAT IS KNOWN PREVENTABILITY hearing, vancomycin can make these problems worse. Severe skin reactions Very rarely (1<10,000) vancomycin can cause fluidfilled blisters. Blistering may be localised and mild, or widespread and severe, even life-threatening. When vancomycin is uses in patients receiving drugs given to relax the muscles (called neuromuscular blocking agents and often given during surgical operations) , there may be an increase in the relaxation of the muscles and paralysis may occur Giving vancomycin and a neuromuscular blocking agent at the same time has been shown to increase the effects on muscles leading to too much muscle relaxation. This can cause breathing to be affected for a longer period than required for the operation so making recovery after the operation difficult. RMP vancomycin, Version 01, DLP 26-Aug-2014 55 | P a g e will minimise the occurrence and limit the extent of any hearing loss. Your doctor will know which medicines may cause hearing problems and avoid prescribing these with vancomycin. If the combination is unavoidable, careful monitoring of vancomycin levels is recommended, along with hearing tests to detect any potential issues. IF you experience any skin problems whilst on vancomycin, inform your doctor at once. Your doctor may decide to discontinue vancomycin or offer treatment to help improving the skin problems. Neuromuscular blocking agents are often only used in surgical procedures or in a hospital. Patients receiving vancomycin are also treated in hospital . It can be necessary to administer these drugs at the same time. This situation can be managed by your doctors who need to use considerable caution requiring dosage and need to monitor the response of the muscles carefully. Important potential risks None Missing information None VI.2.5 Summary of risk minimisation measures by safety concern Safety concern Proposed pharmacovigilance activities (routine and additional) Proposed risk minimisation activities (routine and additional) Routine pharmacovigilance activities are considered sufficient and no further actions are required. Important identified risks are adequately described in the product information. No further risk management activities are necessary. Important identified risks Hypersensitivity reactions. Toxicity at injection sites. Narrow therapeutic index (resulting in possible underdosing or overdosing) Developing Red Man syndrome. Toxicity to the gastrointestinal tract, causing colitis. Use in pregnancy and lactation. Nephrotoxicity especially in patients with renal insufficiency. Ototoxicity especially in patients with previous hearing loss. Severe bullous skin reactions Increase in neuromuscular blockage when used concomitantly with neuromuscular blocking agents. These additional risk minimisation measures are for the following risks: VI.2.6 Planned post authorisation development plan At present, there is no plan to clinical develop vancomycin further than up to the status within the current marketing authorisation procedure. VI.2.7 Summary of changes to the Risk Management Plan over time This is the first risk management plan for vancomycin therefore no changes to the previous version can be addressed. RMP vancomycin Version 01, DLP 26-Aug-2014 57 | P a g e