Trends in the consumption of analgesic drugs in Lithuania in 2005 - 2007.

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KAUNAS UNIVERSITY OF MEDICINE FACULTY OF PHARMACY

DEPARTMENT OF BASIC AND CLINICAL PHARMACOLOGY

Trends in the consumption of analgesic drugs in Lithuania

in 2005 - 2007.

MASTER WORK (Pharmacoepidemiology)

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ABBREVIATIONS

AGs Analgesics

ATC Anatomical Therapeutic Chemical classification COX-2 Cyclooxygenase-2

DDD Defined daily dose

ENSS Spanish National Health Survey

FDA Food and drug administration GA Gastric bleeding

GI Gastrointestinal system

HF Heart failure

LTY Liver toxicity

NSAIDs Non-steroidal antiinflamatory drugs

OA Osteoarthritis

OTC Over-the-counter

EU European Union

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1. INTRODUCTION

In the current public health framework, the importance of medication as a determinant of citizens’ health emerges as a factor warranting special attention. [1, 2] Within the overall context of medicine, medication is regarded as an element having differential features for two specific reasons, these being its role in medical practice and, secondly, the value of knowing how it is used in such practice. [3]

At the present time, consumption of drugs without medical prescription has risen to a significant level, and development that may, in turn, have serious consequences on the individual and collective health of the population. [4–6] This circumstance has been accentuated by the growing replacement of prescribed medicines by over-the-counter (OTC) remedies, which are not always correctly used. [7–11] However, one cannot ignore the fact that, while the term ‘self-medication’ has negative connotations, it now constitutes the most significant form of self-care in the population.

Almost half of all medicines globally are used irrationally. This, say medicines experts at the World Health Organization (WHO), can have severe consequences: adverse drug reactions, drug resistance, protracted illness and even death. [12]

Rational drug therapy means the use of right medicine in the right manner (dose, route and frequency of administration, duration of therapy etc.) in right patient at a right cost. Rational drug therapy also means using the drug when necessary. Hence, the drug chosen for a patient should be effective, safe and acceptable quality and cost. [13]

The use of analgesics (pain relievers) and other medications is the most common method of chronic pain treatment.Pain medications can be helpful for some patients in chronic pain, but they are not universally effective.

Short-term use of medications for pain is rarely worrisome, but prolonged use increases the possibility of adverse reactions including gastrointestinal distress, internal organ problems, balance troubles, and memory and concentration problems. It is important to remember, everyone responds in a different manner to the same dose of medication. Therefore, each person with chronic pain should be medically managed individually, and medication use should be determined by benefit, cost, potential side effects, and the person’s other medical problems. [14]

Relevance and novelty of this work

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In the mentioned analysis the drug consumption data was taken from the year 2005 – 2007, so the results are topical, confident and upto-date.

The performed estimations are topical because:

□ Every day millions of people use analgesics to relieve pain in the whole world. □ Consumption of OTC drugs has risen to a high level.

□ Most, pain experienced by the general public is treated without consulting a health professional. [15]

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2. REVIEW

2.1. Pain types and chronic pain classification

Acute pain is distinguished as being of recent onset, transient, and usually from an identifiable cause.

Chronic pain can be described as persistent or recurrent pain, lasting beyond the usual course of acute illness or injury or more than 3 to 6 months, and which adversely affects the individual’s well-being. A simpler definition for chronic pain is pain that continues when it should not. It is usually treated with medicine that you take at specific times every day (rather than as needed) so that you get pain relief throughout the day.

Breakthrough or Flare-up pain can be described as transient pain beyond the normal pain baseline which is severe or excruciating. Breakthrough or flare-up pain consists of unpredictable pain flares that "break through" the medicine taken around-the-clock to treat persistent pain. Breakthrough or flare-up pain may be caused by changes in an underlying disease, including treatment, or involuntary or voluntary physical actions - such as coughing or getting up from a chair. Breakthrough or flare-up pain may also occur at the end of the scheduled pain medicine dose. Treatment for moderate-to-severe breakthrough pain is a strong, short-acting pain medicine, such as an opioid, that works quickly and lasts about as long as a breakthrough or flare-up pain episode. Some pain physicians feel that if you are taking pain medication for breakthrough or flare-up pain regularly, your regular long-acting pain medicine may not be effective. Alternative pain management strategies may be needed.

Chronic pain is classified by pathophysiology (the functional changes associated with or resulting from disease or injury) as nociceptive (due to ongoing tissue injury) or neuropathic (resulting from damage to the brain, spinal cord, or peripheral nerves), with mixed or undetermined causes as well. Pain relievers or analgesics are generally effective for nociceptive pain but less effective for neuropathic pain.

The American Academy of Pain Medicine has characterized pain by a new terminology, namely, eudynia for nociceptive pain, and maldynia for neuropathic pain. Eudynia (nociceptive pain) is a normal physiologic response to noxious events and injury to somatic (muscle or soft tissue) or visceral (internal organ) tissue. It can be beneficial and serves as an early warning mechanism. Eudynia often is acute, but can also be persistent (e.g., cancer pain).

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2.2. Over-the-counter (OTC) pain relievers

OTC drugs are those drugs that are available to consumers without a prescription. A trip to the local drug store reveals numerous tablets, suppositories, patches, sprays, creams and ointments, all with claims of providing pain relief.

The traditional OTC pain group currently includes aspirin, acetaminophen, naproxen sodium, ketoprofen, ibuprofen and various combinations.

Most OTC drugs are based on one of these ingredients. Many manufacturers add other ingredients in an effort to tailor the medication to particular symptoms. For example, a pain reliever and an antihistamine may be combined and sold as a nighttime pain and cold medication since the antihistamine induces drowsiness. Adding a decongestant makes a medication marketable for sinus problems.

When using OTC drugs, be aware that the brand name is often specific to the manufacturer and may not indicate the product’s active ingredients. Look for active ingredients, usually listed by generic name, on the label.

Some OTC medications are labeled extra strength. This usually indicates that it contains more amounts (e.g., milligrams) of drug per dosage unit than the standard product by the same manufacturer. The key to the effective use of OTC medications is understanding, what you are taking and how much of it. You need to read the medication’s ingredients to know what you are taking. Be sure the medication you select contains an appropriate amount of the drug you need for your symptoms and does not include medications or ingredients you do not need.

To do this, you must read the label. You also should discuss with your doctor any OTC medications you use or are considering using, especially if you also take a prescription medication. The pharmacist can be very helpful as well.

2.3. The safety of OTC medications

Used occasionally, OTC medications rarely cause significant health problems. In certain situations, however, they can be dangerous.

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The nonsteroidal anti-inflammatory drugs or NSAIDs (aspirin, ibuprofen, and others) cause an increase in stomach acid, but at the same time they reduce the stomach’s protective mucous layer. Thus, they are associated with gastric bleeding, and such risk increases with dose and duration of use. They also may cause kidney failure in people with damaged kidneys, liver disease, and certain other conditions. Use with diuretics can increase this danger.

Over-the-counter pain medications can be useful and effective. Even though they are considered safe enough to be dispensed without a prescription, remember they are real medicines. It is important to discuss their use with a physician, especially if they are being combined with prescription medications.

Individuals taking medications for any of these conditions should check with their doctor before taking any NSAID medication.

2.4. Non-opioid analgesic pain relievers

Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are the most widely used medications for most pain conditions. But these drugs are not without risk. NSAIDs can cause gastric distress with ulceration and bleeding while acetaminophen can cause liver toxicity.

Fortunately, they do not produce physical or psychological dependence.

Aspirin and acetaminophen are available over-the-counter while most NSAIDs are available both by prescription and by non-prescription over-the-counter purchase.

The NSAIDs are indicated for pain that involves inflammation; acetaminophen does not have anti-inflammatory activity.

Some of these medications are more effective than others in some individuals, which indicate that it makes sense to try several different ones to determine which medication works best for you.

The cyclooxygenase (COX)-2 inhibitors are NSAIDs that have less gastrointestinal side effects with short term use. Currently available is celecoxib however, serious stomach ulceration can still occur without warning with this drug. As with other NSAIDs, patients should be monitored during long-term use. There is no evidence that meloxicam or other somewhat COX-2 selective NSAIDs are gastroprotective. These medications additionally have potential kidney effects and heart (cardiovascular) complications, especially when taken for prolonged periods.

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While the increased risk of vascular events associated with cyclooxygenase-2 (COX-2) inhibitors has been well established, data are emerging that demonstrate similar risk increases associated with non-steroidal anti-inflammatory drugs (NSAIDs) that are not selective for COX-2. You are advised to discuss the risk-benefit ratio of NSAIDs with your physician.

Flavocoxid is a new prescription-only medical food/nutraceutical product, indicated for the clinical dietary management of osteoarthritis, including associated inflammation. It may also possess general analgesic and antioxidant properties, however currently no studies have shown whether flavocoxid is as effective as NSAIDs. Concomitant use with NSAIDs may increase the risk of stomach irritation.

2.5. Long-term pain management

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Chronic pain often arises from multiple types of pain, which involve different pathways and chemical mediators. This means that no single drug is likely to be completely effective in managing persistent pain for many patients; there are simply too many different pain mechanisms involved for a single agent to target them all. Another issue that can complicate prescribing analgesia for these patients is that persistent pain demands chronic treatment. Hence, any analgesic agent prescribed should combine efficacy with minimal long-term safety risks, including end-organ effects on the heart, liver, kidneys and gastrointestinal (GI) system. Good tolerability is also important to optimise the patient’s quality of life, as well as encouraging adherence to therapy. The extent of the complexity of chronic pain – and hence its management – becomes clear if a common example such as low back pain is considered. A patient with this type of pain experiences painful signals from several types of tissue, such as nerve, muscle, ligament and bone. The same pattern occurs in other types of musculoskeletal pain, including neck pain and osteoarthritis (OA). The complexnature of pain is reflected further by the range of terms that are used to describe different pains according to their cause,such as ‘sprain’, ‘strain’ or ‘spasm’. [17]

The main analgesic options that are currently available include non-steroidal anti-inflammatory drugs (NSAIDs; both traditional non-selective and cyclo-oxygenase (COX) - 2 selective agents), paracetamol and opioids. The atypical weak opioid tramadol may be considered separately because it has major pharmacological and clinical differences from pure opioid agents.

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2.6. Performed studies

Most pain experienced by the general public is treated without consulting a health professional. [19] In line with this, mild analgesics such as paracetamol and ibuprofen are amongst the most commonly used over-the-counter (OTC) drugs in the Western world. It has been estimated that they constituted approximately 23% of OTC sales in the United Kingdom in 2004. [20] Although these drugs are readily available, there are a number of risks associated with their use. Paracetamol is one of the leading causes of drug-related poisoning [21-23], high doses being particularly harmful to the liver. In addition, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen or aspirin can lead to potentially serious side effects, particularly gastrointestinal inflammation and ulceration. [24] Moreover, the prolonged use of mild analgesics to treat daily headaches can lead to dependence and consequent rebound headaches on withdrawal. [25] Given the prevalence of pain and mild analgesic use, and the associated risks even when used appropriately, it is important to understand how people view their risks and benefits. There is good information on the demographic correlates of mild analgesic use. [26] However, little is known about what beliefs people possess regarding mild analgesics, and whether these beliefs are associated with the use of mild analgesics. What little data is available suggests that people view OTC medication as ‘‘weak’’ and hence less risky than other forms of medication. [27, 28]

A convenience sample of 333 students studying at a large English University, were approached on the University campus. Of these, 291 agreed to participate, yielding an 87% response rate. This study employed a cross-sectional design, with all participants completing the same questionnaire concerning their use of mild painkillers, such as paracetamol and ibuprofen, and beliefs about their use. The aim of this study is to fill the current gap in knowledge by examining which beliefs are associated with the use and over-use of mild analgesics. Perceptions of risks have been found to predict a number of health-related behaviours in a variety of contexts. [29, 30] In the context of beliefs about medicines for chronic medical conditions, there is increasing evidence that not only is patients’ concerns about the risks of taking medicines important in determining their use, but also beliefs about their necessity. [31] The study therefore examines whether concerns about the risks of mild analgesics, as well as beliefs about the extent to which mild analgesics are necessary, predict mild analgesic use.

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Rather, respondents who thought analgesics were more necessary were more likely to report taking analgesics, report taking more analgesics, and report exceeding the maximum dose. These results indicate the need for caution in current moves to encourage self-medication. If people are unaware of the risks of drugs such as paracetamol or ibuprofen, then they may only contact health professionals after they experience adverse effects

In Spain, demand for and sale of prescribed drugs without medical prescription is a relatively frequent practice. [32, 33] Indeed, in recent years the Spanish Health Authorities have launched specific campaigns targeted at raising public awareness about the need for rational use of medicines and informing people of the dangers posed to health by self-medication. [34]

For this reason, was made descriptive, cross-sectional study covering the Spanish adult population, using data drawn from the 2003 Spanish National Health Survey (ENSS). A total of 19 514 subjects were analysed. The independent variables were socio-demographic and health-related, and the dependent variable was self-medicated drug use. Using logistic multivariate regression models they have estimated the independent effect of each of these variables on the self-medicated consumption. The study aimed at describing the prevalence of self-medicated drug use among the Spanish adult population and to identify the predictive factors of such self-medication in Spain.

The 18.1% of all Spaniards indulge in self-medication. The study shows that 45% of all cold and influenza medication and 39.4% of analgesics consumed by the population involve self-medication. The variables that were independently and significantly associated with a greater probability of self-medicated consumption were: sex; lower age; higher educational level; consumption of alcohol; smoking habit; use of alternative medical products; absence of chronic disease and a positive perception of health. In Spain, the prevalence of self-medicated drug use is higher in women than men. In their population, the influence of unhealthy lifestyles, such as alcohol and tobacco consumption, is related to a higher likelihood of selfmedication.

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two different products containing the same ingredient. Analysis of non-prescription analgesic data from the third National Health and Nutritional Examination Survey (NHANES III, 1988 – 1994) showed that 10% of U.S. adults reported frequent monthly use (>14 days/month) of aspirin, 3% used ibuprofen frequently and 5%used acetaminophen frequently. [41] Based on the Nurses Health Study, Curhan et al. also reported high frequent (6 days/week) analgesic use among women ages 33 – 77 years. [42] Given the potentially large numbers of chronic analgesic users, well-documented risks of chronic and long-term use, and the public availability of numerous non-prescription analgesics, more precise estimates of current chronic analgesic use are needed for public health planning.

The objective of the study was to estimate frequent monthly non-narcotic analgesic use among U.S. adults, identifying socio-demographic trends and potentially at-risk groups.

Analysis of adult medication use data from the 1999 – 2000 National Health and Nutrition Examination Survey household interview (n¼4880). Some 20% of U.S. adults used non-prescription or non-prescription non-narcotic analgesics on a frequent basis that is nearly every day for a month, at some point during their lifetime. Also, 14% of U.S. adults were currently using analgesics frequently. Aspirin was most commonly used (8%), followed by non-aspirin non-steroidal anti-inflammatory drugs (NANSAID, 3%) and acetaminophen (3%). Three-quarters of aspirin, 46% of NANSAID and 63% of acetaminophen users were long-term frequent monthly users. Seven percent of frequent monthly analgesic users reported using two or more analgesics nearly every day during the month. Frequent analgesic use was most common among older adults and non-Hispanic whites with no differences by gender or education. Use patterns, however, varied by analgesic subgroups. Conclusions: Frequent monthly non-narcotic analgesic use, especially of over-the-counter analgesics, is widely prevalent among U.S. adults. Health-care providers should heighten their awareness of this trend, and routinely monitor both non-prescription and prescription analgesic use in their patients to prevent adverse drug effects and inappropriate use.

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The NSAID prescribing pattern was found to be in discrepancy with their relative gastrointestinal toxicity.

With this objective in mind, we embarked upon this study in the City of Zagreb, the capital of Croatia, with some 25% of the population of Croatia living in and around Zagreb, and 43% of the national health resources being located in the area. Study results were evaluated in comparison with those reported from other capitals in Europe.

Data on the number and size of packages of each individual NSAID dispensed at 32 and 31 pharmacies evenly distributed all over the City of Zagreb were obtained from the Zagreb Municipal Pharmacy owned by the state. These pharmacies represented a sample (16% in 2001 and 15% in 2002, respectively) of the total number of pharmacies registered in the City of Zagreb. The data were exclusively collected for prescription drugs in oral dosage form and referred to the years 2001 and 2002. The number of defined daily doses (DDDs) for each NSAID was calculated from the collected data classified according to the Anatomical Therapeutic Chemical System (ATC) of the World Health Organization (WHO) and DDDs for NSAIDs listed in the ATC Index with DDDs 2002. Then, each NSAID (ATC: M01A) was ranked according to DDD number to restrict our studies to those NSAIDs which accounted for 95% of total NSAID utilization, i.e. to the drug utilization 95% segment. This method is identical to that of Bergman, which has recently been introduced for assessing the quality of drug prescribing and usage. Within the drug utilization (DU95%) segment, we determined the proportion of high risk (piroxicam), medium risk (diclofenac, naproxen, indometacin and ketoprofen) and low risk (ibuprofen) NSAIDs with respect to the risk of upper GI bleeding/perforation (UGIB). The remaining drugs were categorized as unclassified due to the lack of epidemiologic GI safety data (meloxicam, nabumetone, tenoxicam) and ambiguities about the safety profile (rofecoxib).

DU95% segment was determined for the years 2001 and 2002 according to DDD number for each NSAID and overall DDD number for all NSAIDs in DU95%. Costs for each individual NSAID in DU95% were calculated. In addition, the cost per DDD for each NSAID in DU95% segment, mean total cost per DDD for all NSAIDs within and beyond DU95% segment, and mean cost per DDD for all NSAIDs dispensed at Zagreb Municipal Pharmacy units during 2001 and 2002 were also calculated. The price of NSAIDs was uniform in all pharmacies.

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segment in 2001 and 2002, respectively. Costs for each individual NSAID in DU95% segment, overall costs for NSAIDs within and beyond DU95% segment, and total costs for all NSAIDs. In addition to absolute amounts, the proportion for each drug within DU95% and cost per DDD for each drug in DU95% segment, mean cost per DDD for drugs within and beyond DU95% segment, and mean cost per DDD for all NSAIDs on the market are presented for 2001 and 2002. The respective costs for NSAIDs in DU95% segment accounted for 88.3% and 90.0% of total cost for all NSAIDs on the market. The medium risk drugs in DU95% segment accounted for 57.4% and 60.4%, the low risk ibuprofen for 17.0% and 16.3%, and the high risk piroxicam for 25.6% and 23.3% of the cost in DU95% segment in 2001 and 2002, respectively.

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3. OBJECTIVE

1. To evaluate the consumption of analgesics in Lithuania in the year 2005 - 2007.

4. AIMS

1. To evaluate the utilization of analgesics in Lithuania by the means of the DDD methodology.

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5. METHODOLOGY

5.1. The purpose of the ATC/DDD system

The purpose of the ATC/DDD system is to serve as a tool for drug utilization research in order to improve quality of drug use. One component of this is the presentation and comparison of drug consumption statistics at international and other levels. A major aim of the Centre and Working Group is to maintain stable ATC codes and DDDs over time to allow trends in drug consumption to be studied without the complication of frequent changes to the system. There is a strong reluctance to make changes to classifications or DDDs where such changes are requested for reasons not directly related to drug consumption studies. For this reason the ATC/DDD system by itself is not suitable for guiding decisions about reimbursement, pricing and therapeutic substitution. []

5.2. The ATC classification – structure and principles

Structure

In the Anatomical Therapeutic Chemical (ATC) classification system, the drugs are divided into different groups according to the organ or system on which they act and their chemical, pharmacological and therapeutic properties. Drugs are classified in groups at five different levels. The drugs are divided into fourteen main groups (1st level), with one pharmacological/therapeutic subgroup (2nd level). The 3rd and 4th levels are chemical/pharmacological/therapeutic subgroups and the 5th level is the chemical substance. The 2nd, 3rd and 4th levels are often used to identify pharmacological subgroups when that is considered more appropriate than therapeutic or chemical subgroups.

Principles for classification

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The ATC system is not strictly a therapeutic classification system. At all ATC levels, ATC codes can be assigned according to the pharmacology of the product. Subdivision on the mechanism of action will, however, often be rather broad, since a too detailed classification according to mode of action often will result in having one substance per subgroup which as far as possible is avoided.

Some ATC groups are subdivided in both chemical and pharmacological groups. If a new substance fits in both a chemical and pharmacological 4th level, the pharmacological group should normally be chosen. Substances classified in the same ATC 4th level cannot be considered pharmacotherapeutically equivalent since their mode of action, therapeutic effect, drug interactions and adverse drug reaction profile may differ.

5.3. The DDD – definition and principles

The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. A DDD will only be assigned for drugs that already have an ATC code. It should be emphasized that the defined daily dose is a unit of measurement and does not necessarily reflect the recommended or prescribed daily dose. Doses for individual patients and patient groups will often differ from the DDD and will necessarily have to be based on individual characteristics (e.g. age and weight) and pharmacokinetic considerations. Drug consumption data presented in DDDs only give a rough estimate of consumption and not an exact picture of actual use. DDDs provide a fixed unit of measurement independent of price and formulation enabling the researcher to assess trends in drug consumption and to perform comparisons between population groups. DDDs are not established for topical preparations, sera, vaccines, antineoplastic agents, allergen extracts, general and local anesthetics and contrast media. [44]

5.4. Drug utilization

The ATC/DDD system can be used for collection of drug utilization statistics in a variety of settings and from a variety of sources.

Examples are:

• Sales data such as wholesale data at a national, regional or local level.

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generally called "claims" data. Similar data are often available through health insurance or health maintenance organizations. These databases can sometimes allow collection of demographic information on the patients, and information on dose, duration of treatment and co-prescribing. Less commonly, linkage to hospital and medical databases can provide information on indications, and outcomes such as hospitalization, use of specific medical services and adverse drug reactions.

• Patient encounter based data. This is usually collected by specially designed sampling studies such as those carried out by market research organizations. However, increasing use of information technology at the medical practice level will make such data available more widely in the near future. These methods have the advantage of potentially providing accurate information on Prescribed Daily Doses, patient demographics, duration of therapy, co-prescribing, indications, morbidity and co-morbidity, and sometimes outcomes.

• Patient survey data. Collection of data at the patient level can provide information about actual drug consumption and takes into account compliance in filling prescriptions and taking medications as prescribed. It can also provide qualitative information about perceptions, beliefs and attitudes to the use of medicines.

• Health Facility data. Data on medication use at all the above levels is often available in health care settings such as hospitals and health centers at regional, district or village level. [45]

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6. RESULTS

6.1. Analysis of plain drugs consumption in DDD

The calculated data of analgesics (ATC NO2B and M01A) consumption over a 3-year period (2005–2007) are shown in Tables 1–3. The analgesics usage was analyzed using the value of the defined daily dosage (DDD) per 1000 inhabitants (DDD/1000 inhabitants/day).

Table 1. The calculated data of plain analgesic drugs (solid oral form) consumption in 2005*

No Analgesics Drug quantity, mg DDD U DDD/1000 inhabitants/ day Price, Lt Price/DDD, Lt 1. Diclofenac 1814513323 100 mg 19.260 5159854.26 0.28 2. Glucosamine 9007093100 1500 mg 6.375 8553189.44 1.42 3. Ibuprofen 4997504000 1200 mg 4.421 3756266.55 0.90 4. Nimesulide 627669180 200 mg 3.332 5776159.21 1.84 5. Ketorolac 85413000 30 mg 3.023 2513441.42 0.88 6. Paracetamol 8338118080 3000 mg 2.951 1681240.69 0,60 7. Meloxicam 25977906,75 15 mg 1.839 2757883.84 1.59 8. Indometacin 170120475 100 mg 1.806 357612.55 0.21 9. Acetylsalicylic acid 4943304960 3000 mg 1.749 775371.18 0.47 10. Metamizole sodium 3664565000 3000 mg 1.297 332200.06 0.27 11. Lornoxicam 6704440 12 mg 0.593 898860.96 1.61 12. Dexketoprofen 19758250 75 mg 0.280 738837.30 2.80 13. Ketoprofen 37883500 150 mg 0.268 174749.25 0.69 14. Celecoxib 49566000 200 mg 0.263 468816.91 1.89 15. Piroxicam 2306200 20 mg 0.122 39464.82 0.34 16. Nabumetone 94540000 1000 mg 0.100 224771.24 2.38 17. Oxaprozin 82374000 900 mg 0.097 221697.92 2.42 18. Dexibuprofen 13086000 800 mg 0.017 36782.58 2.25 19. Etoricoxib 890040 60 mg 0.016 11983.60 0.81 Total: 47.812 34479183.77

DDD – defined daily dose. * 275 days (2005 04 - 12). 3425.3 thousand inhabitants.

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second popular medicine is glucosamine (ATC M01A), which showed 29.80% increase: from 6.38 DDDs/1000 inhabitants/day in 2005, to 8.28 DDDs/1000 inhabitants/day in 2007. It managed to keep the value below the value of 10.00 DDDs/1000 inhabitants/day from 2005 to 2007, the peak was in 2007 with the meaning of 8.28 DDDs/1000 inhabitants/day.

The following example is ibuprofen, which showed great increase from 4.42 to 7.26 DDDs/1000 inhabitants/day, thus its consumption increased 64.25% during three-year period (2005 - 2007).

Paracetamol and nimesulide managed to keep the trend between the values of 3.00 to 5.00 DDDs per 1000 inhabitants per day. During analyzed period nimesulide and paracetamol showed 47.15% and 33.56% increase respectively.

No Analgesics Drug quantity, mg DDD U DDD/1000 inhabitants/ day Price, Lt Price/DDD, Lt 1. Diclofenac 2372393625 100 mg 19.098 6453990.90 0.27 2. Glucosamine 14115408300 1500 mg 7.575 13448239.27 1.43 3. Ibuprofen 8670592800 1200 mg 5.817 6993330.39 0.97 4. Nimesulide 1024550000 200 mg 4.124 9493942.27 1.85 5. Paracetamol 13276916600 3000 mg 3.563 2839473.86 0.64 6. Ketorolac 98102600 30 mg 2.632 3005659.98 0.92 7. Meloxicam 48248925 15 mg 2.589 4004586.39 1.24 8. Acetylsalicylic acid 7034515220 3000 mg 1.888 1300776.85 0.55 9. Indometacin 229794375 100 mg 1.850 465133.35 0.20 10. Metamizole sodium 3477555000 3000 mg 0.933 464045.10 0.40 11. Lornoxicam 9348480 12 mg 0.627 1357523.71 1.74 12. Piroxicam 10702400 20 mg 0.431 532732.20 1.00 13. Dexketoprofen 31873750 75 mg 0.342 1184005.76 2.79 14. Ketoprofen 49679250 150 mg 0.267 220093.02 0.66 15. Celecoxib 60102000 200 mg 0.242 771157.53 2.57 16. Nabumetone 174110000 1000 mg 0.140 364445.61 2.09 17. Etoricoxib 4613460 60 mg 0.062 167720.74 2.18 18. Oxaprozin 68208000 900 mg 0.061 250927.70 3.31 19. Dexibuprofen 13650000 800 mg 0.014 38690.37 2.27 Total: 52.255 53356475.01

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In mentioned period meloxicam (M01A) showed the biggest increase of all TOP 10 (Fig.1.) pain relievers: from 1.84 to 3.35 DDDs/1000 inhabitants/day, its consumption increase dramatically - 82.07 %.

In addition, Ketorolac showed the opposite tendency, from 2005 to 2007 the mentioned value decreased from 3.02 to 2.50 DDDs/1000 inhabitants/day.

No Analgesics Drug quantity, mg DDD U DDD/1000 inhabitants/ day Price, Lt Price/DDD, Lt 1. Diclofenac 2288990200 100 mg 18.577 6393138.99 0.28 2. Glucosamine 15294170447 1500 mg 8.275 14169858.42 1.39 3. Ibuprofen 10735173400 1200 mg 7.261 8758008.57 0.98 4. Nimesulide 1209175898 200 mg 4.907 10234160.97 1.69 5. Paracetamol 14572592600 3000 mg 3.942 2881181.82 0.59 6. Meloxicam 61854075 15 mg 3.347 4410605.49 1.07 7. Ketorolac 92219240 30 mg 2.495 2880652.83 0.94 8. Indometacin 225487500 100 mg 1.830 461351.49 0.20 9. Acetylsalicylic acid 5076949480 3000 mg 1.373 1138004.51 0.67 10. Metamizole sodium 4182030000 3000 mg 1.131 437426.72 0.31 11. Lornoxicam 11665680 12 mg 0.789 1716089.87 1.77 12. Celecoxib 141841998 200 mg 0.576 1803322.41 2.54 13. Piroxicam 13896600 20 mg 0.564 789132.83 1.14 14. Dexketoprofen 35863250 75 mg 0.388 1293789.35 2.71 15. Ketoprofen 48992000 150 mg 0.265 217580.77 0.67 16. Nabumetone 149728000 1000 mg 0.122 318326.01 2.13 17. Oxaprozin 60888000 900 mg 0.055 231874.56 3.43 18. Etoricoxib 3350550 60 mg 0.045 181504.13 3.25 19. Dexibuprofen 29214000 800 mg 0.030 82167.43 2.25 Total: 55.972 58398177.18

DDD – defined daily dose. * 365 days. 3375.7 thousand inhabitants.

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Fig.1. TOP 10 analgesic drugs in Lithuania, 2005–2007 DDD – defined daily dose.

Fig. 2 illustrates how the total consumption of analgesics in Lithuania increased by 16.55% in a 3-year period from 58.37 DDDs/1000 inhabitants/day in 2005 to 68.03 DDDs/1000 inhabitants/day in 2007.

Fig. 2. The total consumption of analgesic drugs (N02B and M01A) in Lithuania, 2005–2007 DDD – defined daily dose.

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The majority of drugs used for pain control belong to the ATC group titled “antiinflammatory and antirheumatic products, non-steroids” (M01A). Some are classified as “analgesics” (N02).

As we talk about pain relievers, two ATC groups N02B and M01A have to be mentioned. Fig. 3 shows how the total medicines consumption divided into two groups and how its consumption changed in a 3-year period (2005 - 2007).

ATC group NO2B (paracetamol, acetylsalicylic acid, metamizole sodium) showed 8.46% increase: from 12.77 in 2005 to 13.85 DDDs/1000 inhabitants/day in 2007, while ATC group M01A (diclofenac, glucosamine, ibuprofen, nimesulide, ketorolac, meloxicam, indometacin, lornoxicam, piroxicam, dexketoprofen, ketoprofen, celecoxib, nabumetone, etoricoxib, oxaprozin, dexibuprofen) showed two times bigger (18.82%) increase: from 45.60 DDDs/1000 inhabitants/day in 2005 to 54.18 DDDs/1000 inhabitants/day in 2007.

Fig. 3. The total consumption of analgesics in various ATC groups in different years DDD – defined daily dose.

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6.2. Analysis of combined analgesic drugs in DDD

Rational combinations of analgesic drugs offer a viable approach to managing acute pain that involves multiple sites or pathways. For example, the combination of paracetamol plus acetylsalicylic acid and caffeine brings together two well-known analgesics that have different but complementary mechanisms of analgesic action.

Acetylsalicylic acid in combinations was used more often than single. For example, acetylsalicylic acid in combinations in 2005 was 3.20 DDDs/1000 inhabitants/day, while pure acetylsalicylic acid consumption in 2005 was 1.75 DDDs/1000 inhabitants/day. The peak of combined acetylsalicylic acid consumption in a 3-year period was in 2007 - 3.61 DDDs/1000 inhabitants/day. Its consumption increased 12.81% during analyzed period.

Table 4. The calculated data of combined analgesic drugs (solid oral form) consumption in 2005*

No Analgesics Drug quantity, mg DDD U Drug quantity/ DDD DDDs/1000 inhabitants/day 1. Acetylsalicylic acid 9053876920 3000 mg 3017958.97 3.204 2. Paracetamol 8286237530 3000 mg 2762079.18 2.932 3. Diclofenac 64160500 100 mg 641605.00 0.681 Total: 6.817

DDD – defined daily dose. * 275 days (2005 04 - 12). 3425.3 thousand inhabitants

Paracetamol in combinations with other medicines usage did not differ from pure paracetamol consumption: 2.93 and 2.95 DDDs/1000 inhabitants/day in 2005 respectively, 3.30 and 3.94 DDDs/1000 inhabitants/day in 2007 respectively. Only the small changes (12.63%) were in paracetamol utilization during three - year period.

No Analgesics Drug quantity, mg DDD U Drug quantity/ DDD DDDs/1000 inhabitants/ day 1. Acetylsalicylic acid 10577879180 3000 mg 3525959.73 2.838 2. Paracetamol 11544537580 3000 mg 3848179.19 3.098 3. Diclofenac 103543500 100 mg 1035435.00 0.834 Total: 6.770

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The last drug on the list is diclofenac, which also is used in combinations with other medical substances. In 2005 it had the meaning of 0.68 DDDs/1000 inhabitants/day, though in the next year the value increased 22.65% - 0.83 DDDs/1000 inhabitants/day. The situation changed, when diclofenac consumption from 2006 to 2007 increased only 11.93%. Besides, pure diclofenac was used more often than in combinations during 2005 - 2007.

No Analgesics Drug quantity, mg DDD U Drug quantity/ DDD DDDs/1000 inhabitants/ day 1. Acetylsalicylic acid 13340959530 3000 mg 4446986.51 3.609 2. Paracetamol 12193089460 3000 mg 4064363.15 3.299 3. Diclofenac 114427000 100 mg 1144270.00 0.929 Total: 7.837

DDD – defined daily dose. * 365 days. 3375.7 thousand inhabitants.

6.3. Analysis of pain relievers for injections in DDD

The calculated data of analgesics for injections (ATC NO2B and M01A) consumption over a 3-year period (2005–2007) are shown in Tables 7–9. In 2005 metamizole sodium value was 0.57 DDDs/1000 inhabitants/day but the next year its consumption decreased 26.32% and had the meaning of 0.42 DDDs/1000 inhabitants/day, that became stable. Thus metamizole sodium utilization was the same in 2007. In apposition, ketorolac showed different tendency of consumption in 3-year period: its value decreased from 0.61 in 2005, to 0.54 DDDs/1000 inhabitants/day in 2006, but the next year ketorolac showed great increase (25.93%) and reached the meaning of 0.68 DDDs/1000 inhabitants/day. The following medicine - diclofenac utilization value showed stable increase during analyzed period - about 13.50% growth every next year.

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Table 7. The calculated data of pain relievers (injection form) consumption in 2005.

No Analgesics Drug quantity, mg DDD U Drug quantity/ DDD DDDs/1000 inhabitants/ day 1. Metamizole sodium 1598590000 3000 mg 532863.33 0.566 2. Ketorolac 17154750 30 mg 571825.00 0.607 3. Diclofenac 113162100 100 mg 1131621.00 1.201 4. Piroxicam 425500 20 mg 21275.00 0.023 5. Lornoxicam 333656 12 mg 27804.67 0.030 6. Meloxicam 3095805 15 mg 206387.00 0.219 7. Ketoprofen 45056600 150 mg 300377.33 0.319 Total: 2.964

Table 8. The calculated data of pain relievers (injection form) consumption in 2006.

No Analgesics Drug quantity, mg DDD U Drug quantity/ DDD DDDs/1000 inhabitants/ day 1. Metamizole sodium 1551060000 3000 mg 517020.00 0.416 2. Ketorolac 20250510 30 mg 675017.00 0.543 3. Diclofenac 166803675 100 mg 1668036.75 1.343 4. Piroxicam 472600 20 mg 23630.00 0.019 5. Lornoxicam 604160 12 mg 50346.67 0.041 6. Meloxicam 4796205 15 mg 319747.00 0.257 7. Ketoprofen 77233000 150 mg 514886.67 0.414 Total: 3.034

Table 9. The calculated data of pain relievers (injection form) consumption in 2007.

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The following two drugs in the table - lornoxicam and meloxicam (ATC M01A) demonstrated great increase in three years: 110% and 50% respectively. And the last painkiller ketoprofen did not showed great increase but it reached 28.13% growth between 2005 - 2006 and when became stable - showed the same meaning 0.41 DDDs/1000 inhabitants/day in the next two years.

The total consumption of painkillers in various drug forms (pure, combined and injections) in analyzed period (2005-2007) is shown in Figures 5-7.

Fig.5. The total consumption of analgesics in variuos drugs forms in 2005

The total consumption of analgesics in various drugs forms in 2006 11% 84% 5% Combined Plain Injections

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6.4. Analgesics consumption in various European countries

The calculated data of analgesics (ATC NO2B and M01A) in different countries consumption over a 3-year period (2005–2007) are shown in Fig. 8. The total consumption of analgesics in Lithuania increased by 16.55% in a 3-year period: from 58.37 DDDs/1000 inhabitants/day in 2005, to 68.03 DDDs/1000 inhabitants/day in 2007, while in Norway during analyzed period the meaning increased 8.85%, from 73.46 to 79.96 DDDs/1000 inhabitants/day. It is two times smaller increase than in our country. Finland had meaning of 97.29 DDDs/1000 inhabitants/day in 2005, but the next year the utilization decreased 9.93% and had the value of 87.63 DDDs/1000 inhabitants/day.

In addition, the situation changed in 2007 when painkillers consumption in Finland reached 99.48 DDDs/1000 inhabitants/day and showed 13.52% rise. In contrast, the status was totaly different in Denmark: the each previous year the utilization value showed little but stable decrease: 0.1% and 0.6% respectively. The peak of consumption was in 2005, when it achieved 124.50 DDDs/1000 inhabitants/day. Thus, analgesics consumption in Lithuania during mentioned time was two times smaller than in Denmark.

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73,46 58,37 124,5 97,29 124,4 87,63 75,86 62,81 123,7 99,48 79,96 68,03 0 20 40 60 80 100 120 140

Lithuania Norway Finland Denmark

D D D s /1 0 0 0 i n h a b it a n ts /d a y 2005 2006 2007

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7. DISCUSSION

7.1. Evaluation of analgesic drugs consumption in DDD

The consumption of analgesics (ATC N02B and M01A) was analyzed using the number of defined daily dose per 1000 inhabitants per day (DDD/1000 inhabitants/day). 10 mostly consumed medicines were taken into consideration and their DDDs/1000inhabitants/day values were compared with each other.

First of all, diclofenac (ATC M01A) seemed to be the most highly consumed analgesic drug in Lithuania in the three-year period. The peak of diclofenac value was 19.26 DDDs/1000 inhabitants/day in 2005. Diclofenac (M01A) price/DDD is only 0.28 Lt. For these reasons, diclofenac was more often used than other painkillers. In other European countries (i.e. Norway) the consumption of diclofenac was two times smaller: 9.60 DDDs/1000 inhabitants/day in 2007. In Finland the meaning was 5.38 DDDs/1000 inhabitants/day. Thus diclofenac usage is really huge in Lithuania.

The second most used agent for pain control was the analgesic - glucosamine (6.38 DDDs/1000 inhabitants/day in 2005), which popularity increased sharply. Its consumption grew by 29.80% and achieved 8.28 DDDs/1000 inhabitants/day in 2007. Glucosamine value (Price/DDD) is 1.39 Lt, while paracetamol - 0.59 Lt. Glucosamine is OTC drug so people can buy it easily without control. Maybe for this reasons the usage of glucosamine is too high in Lithuania. In other countries glucosamine consumption was quite different in 2007 (Norway - 5.00 DDDs/1000 inhabitants/day, Finland - 8.50 DDDs/1000 inhabitants/day, Denmark 13.00 DDDs/1000 inhabitants/day, Lithuania 8.28 DDDs/1000 inhabitants/day), but its utilization permanently grows each year, although in Denmark, where glucosamine consumption was two times bigger, the meaning showed 16.67% decrease (ANNEX 1).

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Nimesulide consumption increased dramatically and reached 4.91 DDDs/1000 inhabitants/day in 2007. Its value (price/DDD) was 1.69 Lt, while paracetamol and other analgesics (diclofenac, ibuprofen) price/DDD did not achieved 1.00 Lt. In other countries (i.e. Ireland) nimesulide was withdrawn from the market for its side effects (hepatotoxicity).

Acetaminophen is a commonly used drug in the Norway, Denmark and other countries (ANNEX 3). Its utilization demonstrated consistent increase during three years time. Paracetamol showed 33.56% growth in Lithuania and 21.52% increase in Finland. In Denmark paracetamol (plain) is one of the most used analgesic drugs: its consumption reached 60.80 DDDs/1000 inhabitants/day in 2007, while in Lithuania paracetamol (plain) consumption was only 3.94

DDDs/1000 inhabitants/day. Used correctly, acetaminophen is a safe drug. Unlike non-steroidal anti inflammatory drugs, acetaminophen is not thought to increase the risk of upper gastrointestinal complications.

Rational combinations of analgesic drugs offer a viable approach to managing persistent pain that involves multiple sites or pathways. This means that no single drug is likely to be completely effective in managing persistent pain for many patients; there are simply too many different pain mechanisms involved for a single agent to target them all. Another issue that can complicate prescribing analgesia for these patients is that persistent pain demands chronic treatment. Combined analgesics consumption was only 12% of all painkillers usage in Lithuania in 2007.

Paracetamol consumption is too low, glucosamine usage is so high, controversial nimesulide consumption - for these reasons, we can say that analgesics consumption is irrational in Lithuania.

7.2. NSAIDs utilization, effectiveness and safety

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently used medicines to treat osteoarthritis and mild to moderate pain. In Lithuania their costs (Price/DDD) vary from about 0.28 to about 3.43 Lt in 2007. For example: diclofenac 0.28 Lt (Price/DDD) and oxaprozin 3.43 Lt (Price/DDD) in 2007.

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NSAIDs are the most commonly used medicines to treat mild to moderate pain – from arthritis, bursitis, tendinitis, and sprains, as well as premenstrual cramps, headache, dental pain, back ache, and minor injuries. They are also used to reduce fever. NSAIDs are also the most frequently prescribed treatment for osteoarthritis, a degenerative joint disease that causes pain, stiffness and immobility.

For stomach bleeding, there’s a better sense of the magnitude of the risk, and the population that suffers problems. People with a family or personal history of stomach bleeding and/or ulcers are at higher risk.

Another problem is that blocking the Cox-2 enzyme may, over time, contribute to raising the risk of heart attack and stroke. Exactly how this occurs is not yet clear, but it has raised some troubling questions: (a) if all the NSAIDs (except aspirin, which is discussed below) could have this bad effect, at what dose and over what period of time do NSAIDs become unsafe, to the point that the dangers and ill effects outweigh the benefits; and (b) given that the various NSAIDs have differing effects on the Cox-2 enzyme, what does that mean for their safety? The short answer to these two questions is that no one knows. Definitive studies have not been done on the potential effects on the heart and blood vessels of most NSAIDs. The evidence strongly suggests, however, that lower doses of NSAIDs used for short periods by most people do not pose any risk of heart disease or stroke. So, if you use NSAIDs only occasionally for, say, headache relief or to ease sore muscle, there is very likely no reason to worry or stop using them.

NSAIDs are potent, valuable medicines. But even the nonprescription forms like ibuprofen can be dangerous when taken too often and/or in high doses regularly.

Some advices:

1. Take NSAIDs with more caution than you perhaps have up to now, especially if you use them fairly regularly.

2. Consider trying acetaminophen first.

3. Don’t take NSAIDs on a regular basis to treat osteoarthritis or chronic pain without seeing a doctor to assess your heart and gastrointestinal bleeding risk.

7.3. Consumption and safety of paracetamol

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of acetaminophen was disputed, but it is now thought to act by inhibiting cyclooxygenase 3. In the USA under the trade name Tylenol and in generic forms, it is now the leading analgesic that is available ‘over the counter’ (OTC) without medical supervision or a prescription. Studies of the analgesic efficacy of acetaminophen have reported variable efficacy. Of 76 published studies of acute pain, 14 reported that acetaminophen was better than placebo, 6 that it was equivalent to placebo, 3 that it was better than another drug, 27 that it was worse than another drug, 25 that it was equivalent to another drug, and 12 studies reported no effective analgesia. Thus, the analgesic benefits of acetaminophen are somewhat modest.

Used correctly, acetaminophen is a safe drug. Unlike non-steroidal anti inflammatory drugs, acetaminophen is not thought to increase the risk of upper gastrointestinal complications although one study has suggested some association in high dose. Acetaminophen can also be used safely in subjects with NSAID-induced asthma. It is also suitable for use in children. In addition, acetaminophen is quite inexpensive. In Lithuania, it is possible to purchase a packet of 10 paracetamol tablets manufactured by a generic supplier for 0.80 Lt. These properties make acetaminophen rather useful as an OTC analgesic. Used incorrectly and taken in excessive dose either accidentally or intentionally, acetaminophen is a very toxic drug, the most important complication being centrilobular hepatic necrosis. This can occasionally occur with modest overdose especially in susceptible individuals such as those with eating disorders, chronic alcohol abuse, or concurrent enzyme inducing drugs. This hepatic damage is due largely to the timedependent conversion of acetaminophen to the toxic metabolite N-acetyl-p-benzoquinoneimine. In serious poisoning, severe hepatic damage, renal failure, and death can be avoided in virtually 100% of subjects by the administration of the antidote N-acetylcysteine either orally or intravenously within 10 h of ingestion of the overdose. In the UK acetaminophen is a very common cause of poisoning and as a result it is the principle cause of poison-related deaths and liver transplants for acute hepatic failure. The estimated magnitude of this toxicity in the UK is daunting with deaths in England and Wales varying from between 127 for acetaminophen as the only overdose drug to 260 for death involving this drug and others taken in a cocktail. Acetaminophen also accounts for over 200 admissions to a liver unit and 20 or so liver transplants per year.

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8. CONCLUSIONS

• The total analgesic drugs consumption increased by 16.55% in a 3-year period (2005-2007): from 58.37 DDDs/1000 inhabitants/day to 68.03 DDDs/1000 inhabitants/day.

• In comparison with the data of similar studies in other European countries, it showed that the utilization of painkillers in Lithuania is low.

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SUMMARY

Trends in the consumption of analgesic drugs in Lithuania in 2005 – 2007

Objective: To evaluate the consumption of analgesics in Lithuania in the year 2005 – 2007. Material and methods: The data on sales of analgesics drugs in Lithuanian over a 3-year

period (2005 – 2007) were obtained from Softdent database. Data were calculated by defined daily dose (DDD) methodology and expressed in DDDs per 1000 inhabitants per day.

Results: The total analgesic drugs consumption increased by 16.55% in a 3-year period

(2005 – 2007): from 58.37 DDDs/1000 inhabitants/day to 68.03 DDDs/1000 inhabitants/day. Diclofenac (ATC M01A) seemed to be the most highly consumed drug in Lithuania in the three-year period. Diclofenac (M01A) price/DDD is only 0.28 Lt. For these reasons diclofenac was more often used than other painkillers. The second most used agent for pain control was glucosamine (6.38 DDDs/1000 inhabitants/day in 2005), which is used for the treatment of osteoarthritis and, along with new products, its popularity increased sharply. Its consumption grew by 29.80% and achieved 8.28 DDDs/1000 inhabitants/day in 2007. Glucosamine value (Price/DDD) is 1.39 Lt, while paracetamol - 0.59 Lt. Glucosamine is OTC drug so people can buy it easily without control. Maybe for this reasons the usage of glucosamine is enough high. Ibuprofen has regained its popularity after the problems with coxibs. In 2005, the consumption of ibuprofen (4.42 DDDs/1000 inhabitants/day) grew rapidly once again, reached 7.26 DDDs/1000 inhabitants/day in 2007 and showed 64.25% increase.

Nimesulide consumption increased dramatically and reached 4.91 DDDs/1000 inhabitants/day in 2007. Its value (price/DDD) was 1.69 Lt, while paracetamol and other analgesics (diclofenac, ibuprofen) price/DDD did not achieved 1.00 Lt. In other countries (i.e. Ireland) nimesulide was withdrawn from the market for its side effects (hepatotoxicity).

In Denmark paracetamol (plain) is one of the most used analgesic drugs: its consumption reached 60.80 DDDs/1000 inhabitants/day in 2007, while in Lithuania paracetamol (plain) consumption was only 3.94 DDDs/1000 inhabitants/day.

Combined analgesics consumption was only 12% of all painkillers usage in Lithuania in 2007.

Conclusions: The facts show that the consumption of painkillers continues to increase as

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SANTRAUKA

Analgetikų vartojimo tendencijos Lietuvoje 2005 – 2007 m.

Tikslas. Įvertinti analgetikų vartojimo tendencijas Lietuvoje 2005 – 2007 m.

Metodai. Duomenys apie analgetikų pardavimą Lietuvoje 2005 – 2007 metais rinkti iš

UAB „Softdent" duomenų baz÷s. Vaistai buvo klasifikuojami pagal anatominę terapinę cheminę (ATC) klasifikaciją. Vaistų suvartojimas buvo vertinamas pagal apibr÷žtos dienos doz÷s (DDD – angl. defined daily dose) metodiką, o duomenys pateikiami apibr÷žta dienos doze tūkstančiui gyventojų.

Rezultatai. Lietuvoje per trejus metus (2005 – 2007) analgetikų vartojimas padid÷jo

16.55%: nuo 58.37 iki 68.03 DDD/tūkstančiui gyventojų. Daugiausiai buvo suvartojama diklofenako (ATC grup÷ M01A), tai gal÷jo būtų d÷l tam tikrų priežasčių: diklofenako vieno DDD kaina tik 0.28 lito. Antroje vietoje pagal suvartojimą – gliukozaminas, kuris vartojamas osteoartritui gydyti. Jo suvartojimas išaugo 29.80% ir 2007 m. pasiek÷ 8.28 DDD/tūkstančiui gyventojų. Gliukozamino vieno DDD vert÷ 1.39 Lt, kai paracetamolio – 0.59 Lt. Gliukozaminas yra bereceptis vaistas, taigi žmon÷ms jis legvai prieinamas. Galbūt d÷l šių priežasčių gliukozamino suvartojama gana daug. Ibuprofenas susigrąžino savo populiarumą: 2005 metais jo suvartojimas prad÷jo v÷l sparčiai did÷ti, 2007 metais pasiek÷ 7.26 DDD/tūkstančiui gyventojų, ir parod÷ 64.25% augimą.

Nimesulido vartojimas dramatiškai išaugo ir 2007 metais pasiek÷ 4.91 DDD/tūkstančiui gyventojų. Jo vieno DDD vert÷ 1.69 Lt, kai paracetamolio ir kitų analgetikų ši vert÷ nesiek÷ 1 Lt. Airijoje nimesulidas buvo pašalintas iš rinkos d÷l neigiamų poveikių (hepatotoksinis poveikis).

Paracetamolis – vienas iš dažniausiai vartojamų analgetikų Vokietijoje (60.80 DDD/tūkstančiui gyventojų 2007m. ). Lietuvoje paracetamolio buvo suvartojama mažai – 3.94 DDD/tūkstančiui gyventojų 2007 m.

Kombinuoti analgetikai sudar÷ 12% visų suvartotų analgetikų 2007 metais.

Išvados. Analgetikų vartojimas did÷ja ir daugiausiai d÷l NVNU (nesteroidiniai vaistai nuo

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ANNEX 1

Table 1. Glucosamine consumption in DDDs/1000 inhabitants/day in different countries 2005 - 2007 DDDs/1000 inhabitants/day 2005 DDDs/1000 inhabitants/day 2006 DDDs/1000 inhabitants/day 2007 Lithuania 6.38 7.58 8.28 Finland 4.97 6.81 8.50 Denmark 15.60 14.3 13.00 Norway 3.79 5.21 5.00

DDD – defined daily dose.

ANNEX 2

Table 2. Diclofenac consumption in DDDs/1000 inhabitants/day in different countries 2005 - 2007

DDDs/1000 inhabitants/day 2005 DDDs/1000 inhabitants/day 2006 DDDs/1000 inhabitants/day 2007 Lithuania 19.26 19.10 18.58 Finland 5.55 5.50 5.38 Denmark 6.90 7.00 7.00 Norway 7.68 8.69 9.60

ANNEX 3

Table 3. Paracetamol consumption in DDDs/1000 inhabitants/day in different countries 2005 - 2007

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ANNEX 4

Table 4. Ibuprofen consumption in DDDs/1000 inhabitants/day in different countries 2005 - 2007

ANNEX 5

Table 5. Acetylsalicylic acid consumption in DDDs/1000inhabitants/day in different countries 2005 - 2007 DDDs/1000 inhabitants/day 2005 DDDs/1000 inhabitants/day 2006 DDDs/1000 inhabitants/day 2007 Lithuania 1.75 1.89 1.37 Finland 3.21 2.47 3.05 Denmark 1.00 0.80 0.70 Norway 0.49 0.43 0.38

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ANNEX 6

Table 6. The calculated data of plain analgesic drugs (solid oral form) consumption and expenditures in 2005*

No Analgesics Drug quantity, mg DDD/1000 inhabitants/ day Price, Lt Price/DDD, Lt 1. Diclofenac 1814513323 19.260 5159854.26 0.28 2. Glucosamine 9007093100 6.375 8553189.44 1.42 3. Ibuprofen 4997504000 4.421 3756266.55 0.90 4. Nimesulide 627669180 3.332 5776159.21 1.84 5. Ketorolac 85413000 3.023 2513441.42 0.88 6. Paracetamol 8338118080 2.951 1681240.69 0,60 7. Meloxicam 25977906,75 1.839 2757883.84 1.59 8. Indometacin 170120475 1.806 357612.55 0.21 9. Acetylsalicylic acid 4943304960 1.749 775371.18 0.47 10. Metamizole sodium 3664565000 1.297 332200.06 0.27 11. Lornoxicam 6704440 0.593 898860.96 1.61 12. Dexketoprofen 19758250 0.280 738837.30 2.80 13. Ketoprofen 37883500 0.268 174749.25 0.69 14. Celecoxib 49566000 0.263 468816.91 1.89 15. Piroxicam 2306200 0.122 39464.82 0.34 16. Nabumetone 94540000 0.100 224771.24 2.38 17. Oxaprozin 82374000 0.097 221697.92 2.42 18. Dexibuprofen 13086000 0.017 36782.58 2.25 19. Etoricoxib 890040 0.016 11983.60 0.81 Total: 47.812 34479183.77

Trends in the consumption of analgesic drugs in Lithuania in 2005 - 2007.