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PubMed1973

[Socialist management science in drug and pharmaceutical organizations. 30. Specialty-specific drug assortments in stationary health facilities as a factor in scientifically based drug therapy and as an hypothesis for the evaluation of drug requirements by means of automatic data processing. 2. Initial experiences in the elaboration and testing of specialty specific drug assortments, which can be evaluated using ADP].

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Costs and Cost Analysis↗
PubMedDate not supplied

Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions.

Recent surveys suggest that the abuse of drugs, often in combination, is pervasive throughout society. Adverse consequences of drug abuse tend to be attributed to the single drug "most likely" to be responsible. This is frequently seen in fatality cases, particularly those involving opioids. However, it is difficult to determine the specific cause of death when multiple drugs are involved. Although enhanced toxicity of alcohol and other centrally acting drugs with opioids has been well established in animal studies, there is a paucity of data in well-controlled human studies. We evaluated 1014 fatality cases involving oxycodone (OXC) for evidence of enhanced toxicity associated with multiple drug-drug interactions. We previously reported on these cases, and we classified them by a standardized method into groups that distinguished cases unrelated to drug abuse from those related to drug abuse, cases that involved only OXC from cases involving multiple drugs, drug-induced fatalities from drug-related fatalities, and cases in which the specific drug product OxyContin (oxycodone HCl controlled-release) tablets were identified from cases where OxyContin was not identified. Our working hypothesis was that OXC in combination with other centrally acting drugs is more toxic than OXC alone, evidenced by the finding of lower mean blood concentrations of OXC in multiple drug-induced deaths compared to single (OXC only) drug-induced deaths. Assessment of blood levels determined by specific assay methodology (primarily gas chromatography-mass spectrometry) in these cases provided the following mean postmortem concentrations of OXC: multiple drug-induced deaths, OxyContin identified, 0.93 mg/mL (N = 167); multiple drug-induced deaths, OxyContin not identified, 0.73 mg/mL (N = 579); single (OXC) drug-induced deaths, OxyContin identified, 1.55 mg/mL (N = 12); and single (OXC) drug-induced deaths, OxyContin not identified, 1.70 mg/mL (N = 15). Overall, mean OXC concentration trends were as follows: single (OXC), drug-induced, drug abuse deaths > multiple, drug-induced drug abuse deaths > drug-related drug abuse deaths approximately deaths unrelated to drug abuse; and deaths in which OxyContin was identified approximately deaths in which OxyContin was not identified, whether the deaths involved oxycodone alone or multiple drugs. Drug abuse patterns in the multiple drug-induced cases were complex. Over 135 drugs that were considered to be plausibly contributory to enhanced toxicity were identified in body fluids and tissues. Evaluation of mean OXC blood concentrations in cases that contained one, two, three, four, five, and six or more contributory drugs in combination demonstrated consistently lower mean OXC concentrations than those cases in which OXC was the only drug identified. A smaller number of cases were evaluated in the multiple drug-induced groups in which OXC was paired with a single other contributory drug. The overall mean OXC concentration for these cases was 0.71 mg/mL (N = 90) as compared to 1.64 mg/mL (N = 27) for the cases in the single drug-induced groups. The consistent finding of lower mean OXC blood levels associated with multiple drug-induced fatalities supports the stated hypothesis that OXC in combination with other centrally active drugs is more toxic than when OXC was the only drug involved. It was concluded that in cases of multiple drug fatalities, cause of death (COD) should not be attributed to any single drug. Rather, the unique combination of drugs, the pattern of drug use/abuse, and individual factors, such as tolerance to the respiratory depressant effects of opioids, must be taken into account in arriving at a valid COD statement.

Cause of Death↗
PubMed2004

Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions.

Recent surveys suggest that the abuse of drugs, often in combination, is pervasive throughout society. Adverse consequences of drug abuse tend to be attributed to the single drug "most likely" to be responsible. This is frequently seen in fatality cases, particularly those involving opioids. However, it is difficult to determine the specific cause of death when multiple drugs are involved. Although enhanced toxicity of alcohol and other centrally acting drugs with opioids has been well established in animal studies, there is a paucity of data in well-controlled human studies. We evaluated 1014 fatality cases involving oxycodone (OXC) for evidence of enhanced toxicity associated with multiple drug-drug interactions. We previously reported on these cases, and we classified them by a standardized method into groups that distinguished cases unrelated to drug abuse from those related to drug abuse, cases that involved only OXC from cases involving multiple drugs, drug-induced fatalities from drug-related fatalities, and cases in which the specific drug product OxyContin (oxycodone HCl controlled-release) Tablets were identified from cases where OxyContin was not identified. Our working hypothesis was that OXC in combination with other centrally acting drugs is more toxic than OXC alone, evidenced by the finding of lower mean blood concentrations of OXC in multiple-drug-induced deaths compared to single (OXC only)-drug-induced deaths. Assessment of blood levels determined by specific assay methodology (primarily gas chromatography-mass spectrometry) in these cases provided the following mean postmortem concentrations of OXC: multiple-drug-induced deaths, OxyContin identified, 0.93 microg/mL (N = 167); multiple-drug-induced deaths, OxyContin not identified, 0.73 microg/mL (N = 579); single (OXC)-drug-induced deaths, OxyContin identified, 1.55 microg/mL (N = 12); and single (OXC)-drug-induced deaths, OxyContin not identified, 1.70 microg/mL (N = 15). Overall, mean OXC concentration trends were as follows: single (OXC)-drug-induced, drug-abuse deaths > multiple-drug-induced drug-abuse deaths > drug-related drug-abuse deaths approximately deaths unrelated to drug abuse; and deaths in which OxyContin was identified approximately deaths in which OxyContin was not identified, whether the deaths involved oxycodone alone or multiple drugs. Drug abuse patterns in the multiple-drug-induced cases were complex. Over 135 drugs that were considered to be plausibly contributory to enhanced toxicity were identified in body fluids and tissues. Evaluation of mean OXC blood concentrations in cases that contained one, two, three, four, five, and six or more contributory drugs in combination demonstrated consistently lower mean OXC concentrations than those cases in which OXC was the only drug identified. A smaller number of cases were evaluated in the multiple-drug-induced groups in which OXC was paired with a single other contributory drug. The overall mean OXC concentration for these cases was 0.71 microg/mL (N = 90) as compared to 1.64 microg/mL (N = 27) for the cases in the single drug-induced groups. The consistent finding of lower mean OXC blood levels associated with multiple-drug-induced fatalities supports the stated hypothesis that OXC in combination with other centrally active drugs is more toxic than when OXC was the only drug involved. It was concluded that in cases of multiple-drug fatalities, cause of death (COD) should not be attributed to any single drug. Rather, the unique combination of drugs, the pattern of drug use/abuse, and individual factors, such as tolerance to the respiratory depressant effects of opioids, must be taken into account in arriving at a valid COD statement.

Cause of Death↗
PubMedDate not supplied

Drug information systems, early warning, and new drug trends: can drug monitoring systems become more sensitive to emerging trends in drug consumption?

Drug Information Systems (DIS) are called upon to provide an early warning of emerging trends in drug use. However, little theoretical attention is directed toward exploring conceptual issues in this area. In this paper a typology of existing DIS is offered. Among the features that distinguish DIS are their structure (human network or organization systems) and the range of information sources used. Indicators of drug use can be placed on a continuum of sensitivity ranging from leading edge indicators to lagged indicators. Sensitivity implies volatility as sensitive indicators also react to fluctuations that do not become trends. DIS conventionally are largely reliant upon lagged indicators. What is required are DIS that combine a critical information processing function with the ongoing systematic collection of data from a range of data sources.

Data Collection↗
PubMed2000

Tricyclic and related drugs for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) is a socially unacceptable and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. OBJECTIVES: To assess the effects of tricyclic and related drugs on nocturnal enuresis in children, and to compare them with other interventions. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997. SELECTION CRITERIA: All randomised trials of tricyclic and related drugs for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive tricyclics compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were provided. Trials focused solely on daytime wetting were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: Twenty two randomised trials, involving 1100 children treated with tricyclic or related drugs, met the inclusion criteria. The quality of many of the trials was poor. Only single trials compared tricyclic or related drugs with each other, other drugs, desmopressin, alarms or other behavioural interventions. Treatment with tricyclic drugs (such as imipramine, amitriptyline, viloxazine, clomipramine and desipramine but not mianserin) were associated with a reduction of about one wet night per week while on treatment (eg using imipramine, WMD -0.99, 95% CI -1.27 to -0.71). Children were almost five times more likely to achieve 14 dry nights with the drugs (eg using imipramine, RR = 4.99, 95% CI 2.4 to 10.40). Desmopressin and tricyclics appeared equally effective while on treatment, but this effect was not sustained after treatment stopped. There was no detectable difference between imipramine and alarms while on treatment, but afterwards those who had used alarms had one fewer wet night per week (WMD 1.03, 95% CI 0. 19 to 1.87). REVIEWER'S CONCLUSIONS: Treatment with tricyclic drugs (imipramine, amitriptyline, viloxazine, clomipramine and desipramine but not mianserin) was associated with a reduction of about one wet night per week while on treatment, but long term effectiveness is unknown. Desmopressin and tricyclics appeared equally effective while on treatment, but this effect was not sustained after treatment stopped. Alarms may be more effective in the long term. Comparisons between drug and behavioural treatments are needed, and should include relapse rates after treatment is finished.

Antidepressive Agents, Tricyclic↗
PubMed1992

Low molecular weight proteins as carriers for renal drug targeting. Preparation of drug-protein conjugates and drug-spacer derivatives and their catabolism in renal cortex homogenates and lysosomal lysates.

Low molecular weight proteins (LMWPs) are known to be reabsorbed and catabolized primarily by the proximal tubular cells of the kidneys. As such, LMWPs might serve as drug carriers that release drugs site-specifically in the kidney. We tested this concept in vitro by coupling different drugs to the LMWP lysozyme both directly (amide bond) and via different spacers: oligopeptides (amide bond), (poly-)alpha-hydroxy acids (ester bond), and a pH sensitive cis-aconityl spacer (amide bond). The capability of the kidney to release the parent drug from such drug-spacer derivatives and drug-LMWP conjugates by enzymatic or chemical hydrolysis of the bond was tested by incubation experiments in renal cortex homogenates and lysosomal lysates. Directly coupled conjugates of terminal carboxyl group containing drugs and lysozyme were catabolized to single amino acids, but did not result in release of the parent drug. The amide bond between the drug and the final amino acid (lysine) appeared to be stable in the incubation milieu. Different oligopeptide spacers coupled to the drugs showed similar results: the oligopeptide itself was cleaved but the amide bond between the drug and different single amino acids remained untouched. Only amide bonds of derivatives of carboxylic drugs with peptide structures themselves were cleaved. Some of the directly coupled conjugates of terminal amino drugs and oligopeptides showed clear release of the parent drug whereas others were stable. Terminal amino drugs were rapidly released from an acid-sensitive cis-aconityl spacer. Terminal carboxyl group containing drugs were enzymatically released from their glycolic and lactic ester spacers at different rates. These kinds of drugs were also released as parent drug from LMWP conjugates with ester spacers like L-lactic acid. Increasing spacer length by intercalating a tetra(L-lactic acid) molecular between the drug and the protein further increased the extent and rate of drug release, indicating increased accessibility of the bond to the enzymes. Terminal amino group containing drugs were rapidly generated as parent drug from LMWP conjugates using an acid-sensitive spacer. In addition the conjugates were found to be adequately stable in plasma, considering their rapid clearance from the bloodstream. It is concluded that LMWPs may indeed be of use as carriers for specific renal delivery of drugs, since renal cortex homogenates and lysosomal lysates are able to catabolize the protein and generate the parent drug from drug-LMWP conjugates bearing suitable spacers. The option of enzymatic release is limited by the narrow specificity of the lysosomal enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed2006

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment.

OBJECTIVES: To determine the clinical and cost-effectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to, or having unacceptable side-effects from, their current medication. DESIGN: Two pragmatic, randomised controlled trials (RCTs) were undertaken. The first RCT (band 1) compared the class of older, inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders, whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects. The second RCT (band 2) compared the new (non-clozapine) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs. Both RCTs were four-centre trials with concealed randomisation and three follow-up assessments over 1 year, blind to treatment. SETTING: Adult mental health settings in England. PARTICIPANTS: In total, 227 participants aged 18-65 years (40% of the planned sample) were randomised to band 1 and 136 (98% of the planned sample) to band 2. INTERVENTIONS: Participants were randomised to a class of drug. The managing clinician selected the individual drug within that class, except for the clozapine arm in band 2. The new atypical drugs included risperidone, olanzapine, quetiapine and amisulpride. The conventional drugs included older drugs, including depot preparations. As in routine practice, clinicians and participants were aware of the identity of the prescribed drug, but clinicians were asked to keep their participating patient on the randomised medication for at least the first 12 weeks. If the medication needed to be changed, the clinician was asked to prescribe another drug within the same class, if possible. MAIN OUTCOME MEASURES: The primary outcome was the Quality of Life Scale (QLS). Secondary clinical outcomes included symptoms [Positive and Negative Syndrome Scale (PANSS)], side-effects and participant satisfaction. Economic outcomes were costs of health and social care and a utility measure. RESULTS: Recruitment to band 1 was less than anticipated (40%) and diminished over the trial. This appeared largely due to loss of perceived clinical equipoise (clinicians progressively becoming more convinced of the superiority of new atypicals). Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75% power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks. The recruitment to band 2 was approximately as planned. Follow-up assessments were completed at week 52 in 81% of band 1 and 87% of band 2 participants. Band 1 data showed that, on the QLS and symptom measures, those participants in the conventional arm tended towards greater improvements. This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample. Participants reported no clear preference for either class of drug. There were no statistically significant differential outcomes for participants entering band 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance. Net costs over the year varied widely, with a mean of 18,850 pounds sterling in the conventional drug group and 20,123 pounds sterling in the new atypical group, not a statistically significant difference. Of these costs, 2.1% and 3.8% were due to antipsychotic drug costs in the conventional and atypical group, respectively. There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year. The results for band 2 showed an advantage for commencing clozapine in quality of life (QLS) at trend level (p = 0.08) and in symptoms (PANSS), which was statistically significant (p = 0.01), at 1 year. Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects. Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals (p < 0.05). Net costs of care varied widely, but were higher than in band 1, with a mean of 33,800 pounds sterling in the clozapine group and 28,400 pounds sterling in the new atypical group. Of these costs, 4.0% and 3.3%, respectively, were due to antipsychotic drug costs. The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug. There was a trend towards higher mean participant utility scores in the clozapine group. CONCLUSIONS: For band 1, there is no disadvantage in terms of quality of life and symptoms, or associated costs of care, over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs. Conventional drugs were associated with non-significantly better outcomes and lower costs. Drug costs represented a small proportion of the overall costs of care (<5%). For band 2, there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs, but with increased associated costs of care. The results suggest that conventional antipsychotic drugs, which are substantially cheaper, still have a place in the treatment of patients unresponsive to, or intolerant of, current medication. Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance, valid measures of utility in serious mental illness, low-dose 'conventional' treatment in first episode schizophrenia, QLS validity and determinants of QLS score in schizophrenia, and into the possible financial and other mechanisms of rewarding clinician participation in trials.

Adolescent↗
PubMed2006

Prescription drug abuse: what is being done to address this new drug epidemic? Testimony before the Subcommittee on Criminal Justice, Drug Policy and Human Resources.

This comprehensive health policy review of the prescription drug abuse epidemic is based on the written and oral testimony of witnesses at a July 26, 2006 Congressional Hearing, including that of Laxmaiah Manchikanti, MD, the chief executive officer of the American Society of Interventional Pain Physicians and additions from review of the literature. Honorable Mark E. Souder, chairman of the Subcommittee on Criminal Justice, Drug Policy, and Human Resources, introduced the issue as follows: "Prescription drug abuse today is second only to marijuana abuse. In the most recent household survey, initiates to drug abuse started with prescription drugs (especially pain medications) more often than with marijuana. The abuse of prescription drugs is facilitated by easy access (via physicians, the Internet, and the medicine cabinet) and a perception of safety (since the drugs are FDA approved). In addition to the personal toll of drug abuse using prescription drugs, indirect costs associated with prescription drug abuse and diversion include product theft, commission of other crimes to support addiction, law enforcement costs, and encouraging the practice of defensive medicine." The Administration witnesses, Bertha Madras, Nora D. Volkow, MD, Sandra Kweder, MD, and Joe Rannazzisi reviewed the problem of drug abuse and discussed what is being done at the present time as well as future strategies to combat drug abuse, including prescription drug monitoring programs, reducing malprescriptions, public education, eliminating Internet drug pharmacies, and the development of future drugs which are not only tamper-resistant but also non-addictive. The second panel, consisting of consumers and advocates, included Misty Fetco, Linda Surks, and Barbara van Rooyan, all of whom lost their children to drugs, presented their stories and strategies to prevent drug abuse, focusing on education at all levels, development of resistant drugs, and non-opioid treatment of chronic pain. Mathea Falco, JD, and Stephen E. Johnson presented issues related to drug abuse and measures to curb drug abuse by various means. Stephen J. Pasierb presented startling statistics on teen drug abuse and various educational programs to deter abuse. Laxmaiah Manchikanti, MD presented an overview of prescription drug abuse, strategies to prevent drug abuse, including immediate funding and rapid implementation of NASPER, education at all levels and improving relations with the DEA and the provider community.

Analgesics, Opioid↗
PubMed2006

Poly(ethylene-co-vinyl acetate) copolymer matrix for delivery of chlorhexidine and acyclovir drugs for use in the oral environment: effect of drug combination, copolymer composition and coating on the drug release rate.

OBJECTIVES: This study utilizes a bio-compatible ethylene vinyl acetate (EVA) copolymer to deliver drugs at therapeutic levels over extended periods of time. The release rate of an anti-fungal and an anti-microbial drug namely acyclovir (ACY) and chlorhexidine diacetate (CDA) from EVA was investigated individually and as a mixture. The effect of drug combination, the composition of the copolymer and the coating of the matrix with a different polymer on the rate of drug release are presented. METHOD: Polymer casting solutions were prepared by homogeneously dissolving EVA copolymer and the drugs in the ratio (40:1) in dichloromethane. The drugs ACY and CDA were used individually as well as in three different weight ratios maintaining the total drug concentration in the polymer at 2.5%. Different concentrations of vinyl acetate (VA) 28, 32 and 40% in the EVA matrix were used to study the release of either ACY or CDA alone while 40% VA was used for the release study of the individual drug as well as their mixtures. Thin square films of 3cmx3cm with a thickness of 0.7mm were cut from the dry sheet obtained by solvent evaporation. Coated films were prepared by dipping ACY and CDA drug-loaded EVA films (VA 40%) into EVA copolymer of VA 32% and then dried. All of the drug-loaded samples were extracted at 37 degrees C in 10ml distilled water that was replaced daily. The rate of individual drug release was measured by UV-spectrophotometer while the mixtures of drugs were measured by high performance liquid chromatography (HPLC). RESULTS: The release rate of ACY is higher than that of CDA both individually and in the ACY/CDA 50/50 mixture. In the other mixtures, the release of the drug is proportional to its concentration in the mixture. Total release of ACY is higher than CDA in most compositions. The effect of increasing the vinyl acetate content of the EVA matrix increased the drug release rate (p=0.02) while coating of films resulted in a decrease of the release rate of the drugs. SIGNIFICANCE: Measurements of the in vitro rate of drug release showed that there was a sustained release of drug at an almost constant concentration over extended period of time, thus providing a basis for oral treatment modality. We show that it is possible to alter the rate of drug release in the EVA matrix to a desired value by: (1) changing the composition of the EVA copolymer, (2) altering the mixtures of drugs and (3) coating the matrix with additional polymer. The use of mixtures of drugs that can enhance or decrease the rate of drug release may prove more effective in treating persistent oral infections in immunocompromised patients.

Acyclovir↗
PubMed2005

Suboptimal prescribing in elderly outpatients: potentially harmful drug-drug and drug-disease combinations.

OBJECTIVES: To assess the prevalence and correlates of potentially harmful drug-drug combinations and drug-disease combinations prescribed for elderly patients at outpatient settings. DESIGN: Retrospective analysis of the 1995-2000 National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS). SETTING: Physician offices and hospital outpatient departments. PARTICIPANTS: Outpatient visits by patients aged 65 and older in the NAMCS and NHAMCS (n=70,203). MEASUREMENTS: Incidences of six drug-drug combinations and 50 drug-disease combinations that can place elderly patients at risk for adverse events according to expert consensus panels. RESULTS: Overall, 0.74% (95% confidence interval (CI)=0.65-0.83) of visits with two or more prescriptions had at least one inappropriate drug-drug combination, and 2.58% (95% CI=2.44-2.72) of visits with at least one prescription had one or more inappropriate drug-disease combinations. Of visits with a prescription of warfarin, 6.60% (95% CI=5.46-7.74) were prescribed a drug with potentially harmful interaction. Of patients with benign prostatic hypertrophy, 4.06% (95% CI=3.06-5.06) had at least one of six drugs that should be avoided. The number of drugs prescribed is most predictive of inappropriate drug-drug and drug-disease combinations. CONCLUSION: Potentially harmful drug-drug and drug-disease combinations occur in various degrees in outpatient care in the elderly population. Targeting combinations such as those involving warfarin that are high in prevalence and potential harm offers a practical approach to improving prescribing and patient safety.

Aged↗
PubMed2001

In human therapy, is the drug-drug interaction or the adverse drug reaction the issue?

In recent years, many publications in scientific journals have reported, in healthy volunteers, potential food-drug or drug-drug interactions. The lay press has frequently emphasized such interactions and extrapolated on the dangers of food-drug or drug-drug interactions. However, the clinical relevancy of these interactions has not always been substantiated in patients. The aim of the present review was to assess the clinical relevancy of drug-drug interactions occurring at the level of the biotransformation of the drug. For this purpose, the incidence of serious, life-threatening adverse drug reactions (ADRs) of drugs metabolized by different enzymes of cytochrome P450 found in the safety reports issued in megatrials were compared with those from placebo trials. It was concluded that serious ADRs secondary to drug-drug interactions are infrequent; drug-drug interactions including selected drugs with a narrow therapeutic index and eliciting life-threatening undesired effects occur; and serious ADRs secondary to drug-drug interactions are most frequent in elderly patients, in the presence of polypharmacy, in the psychiatric patient population, and in the presence of inappropriate prescriptions and of multiple prescriptors.

Adverse Drug Reaction Reporting Systems↗
PubMed2006

Drug related problems and off-label drug treatment in children as seen at a drug information centre.

The aim of this work was to analyse the characteristics of Questions and Answers (Q&As) at a drug information centre (DIC) regarding drug related problems and off-label drug treatment in children. All questions concerning children 15 years or younger at a DIC in Stockholm, Sweden during the years 1995-2004 were analysed with respect to the main drug related problem, drug/s and drug group/s, whether the drugs were licensed or not, pediatric labelling of the drug/s and age and sex of the patient. Q&As were classified as whether or not they included evaluated literature information, adding to the labelling of the drugs. We identified 249 Q&As concerning pediatric drug treatment. Each question addressed an average of 1.5 drugs. More than two-thirds of the Q&As concerned adverse drug reactions and pediatric drug choice or dosing. Every second question was classified as off-label, psychotropic drugs being the most common. In half of all off-label Q&As, pediatric documentation on drug efficacy and safety outside the Swedish catalogue of medical products was found. Most Q&As concerned newborns and infants. However, the off-label proportion among questions was highest in adolescence as well as the evaluated literature information, adding to the labelling of the drugs. It was thus found that off-label drug treatment is common among pediatric questions at a DIC. This service can provide additional literature based information contributing to a safer use of drugs in children. There is still, however, a substantial need for clinical documentation of drug use in children.

Adolescent↗
PubMed2006

Patterns of drug use among a sample of drug users and injecting drug users attending a General Practice in Iran.

AIM: This study aimed to examine drug use, drug treatment history and risk behaviour among a sample of Iranian drug users seeking treatment through a general practice clinic in Iran. METHODS: Review of medical records and an intake questionnaire at a large general practice in Marvdasht, Iran, with a special interest in drug dependence treatment. Records from a random sample of injecting drug users (IDU), non-injecting drug users (DU) and non-drug using patients were examined. RESULTS: 292 records were reviewed (34% IDU, 31% DU and 35% non-drug users). Eighty-three percent were males; all females were non-drug users. The mean age of the sample was 30 years. Of the IDU sample, 67% reported sharing a needle or syringe, 19% of these had done so in prison. Of those who had ever used drugs, being 'tired' of drug use was the most common reason for seeking help (34%). Mean age of first drug use was 20 years. The first drugs most commonly used were opium (72%), heroin (13%) and hashish/ other cannabinoids (13%). Three quarters reported having previously attempted to cease their drug use. IDU were more likely than DU to report having ever been imprisoned (41% vs 7%) and 41% to have used drugs in prison. CONCLUSION: This study has shown that there is a need for general practice clinics in Iran to treat drug users including those who inject and that a substantial proportion of those who inject have shared needles and syringes, placing them at risk of BBVI such as HIV and hepatitis C. The expansion of services for drug users in Iran such as needle and syringe programs and pharmacotherapies are likely to be effective in reducing the harms associated with opium use and heroin injection.

Journal Article↗
PubMed2005

Evaluation of drug-drug interaction in the hepatobiliary and renal transport of drugs.

Recent studies have revealed the import role played by transporters in the renal and hepatobiliary excretion of many drugs. These transporters exhibit a broad substrate specificity with a degree of overlap, suggesting the possibility of transporter-mediated drug-drug interactions with other substrates. This review is an overview of the roles of transporters and the possibility of transporter-mediated drug-drug interactions. Among the large number of transporters, we compare the Ki values of inhibitors for organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) and their therapeutic unbound concentrations. Among them, cephalosporins and probenecid have the potential to produce clinically relevant OAT-mediated drug-drug interactions, whereas cyclosporin A and rifampicin may trigger OATP-mediated ones. These drugs have been reported to cause drug-drug interactions in vivo with OATs or OATP substrates, suggesting the possibility of transporter-mediated drug-drug interactions. To avoid adverse consequences of such transporter-mediated drug-drug interactions, we need to be more aware of the role played by drug transporters as well as those caused by drug metabolizing enzymes.

Animals↗
PubMed2005

Injecting shared drugs: an observational study of the process of drug acquisition, preparation, and injection by Puerto Rican drug users.

The practice of injecting shared drugs, in which drug users prepare, divide and inject portions of a drug solution, is a means of transmitting HIV, HCV, and other blood-borne pathogens. This study examined the process of injecting shared drugs among drug users in San Juan, Puerto Rico, through detailed observations of 25 episodes of the injection of shared drugs, and by informal interviewing of episode participants. The ways in which price and packaging of drugs, access to drug preparation materials, and social and economic relations between drug-sharing "partners" influence the process of injecting shared drugs are explored. Because differential power relations, and in turn, injection drug users' exposure to HIV and HCV, are apparent in some drug-sharing partnerships, a key objective of this study was to extend our understanding of contributions or "investments" made by different drug-sharing partners, the benefits and costs that different partners experience, and the extent to which IDUs assume different partner roles. The findings of this small, in-depth qualitative study provide insight into drug users' motivations for injecting shared drugs, and suggest reasons why certain standardized, countrywide HIV/HCV intervention efforts have not been entirely successful in preventing the devastating illnesses that disproportionately affect injection drug users.

Adult↗
PubMed1996

Drug-drug and drug-disease interactions in the ED: analysis of a high-risk population.

A study was undertaken to determine the potential for adverse drug interactions (ADIs) and drug-disease interactions (DDIs) in a high-risk population of emergency department (ED) patients and to characterize drug-drug and drug-disease interactions in terms of percentage of patients at risk from existing drug regimens, percentage of patients at risk from ED treatment, relation between number of drugs and potential for interactions, types of drugs and diseases posing greatest potential for interaction, and the differences in a general versus community hospital population with respect to these parameters. Records of 205 consecutive patients, 111 from a general hospital teaching facility ED (Facility 1) and 94 from a community hospital ED (Facility 2) were retrospectively reviewed. The records of all patients receiving three or more medications and all patients older than 50 years of age receiving two or more medications were analyzed by two computer programs for the presence of potential drug-drug and drug-disease interactions. A total of 226 potential ADIs were found in 89 patients (47%), with 50% of ADIs being related to ED treatment. A total of 94 potential DDIs were found in 44 patients (21%), with 34% of DDIs being related to ED treatment. The risk of an ADI rose from 13% for patients taking 2 medications to 82% for patients taking 7 or more medications. Eleven medications and four disease categories were identified as having particular potential for interactions. No significant differences were found between the general and the community hospital populations in these respects. ED patients taking three or more medications and patients older than 50 years of age taking two or more medications are at substantial risk for adverse drug-drug and drug-disease interactions. The risk is increased in patients taking particular drugs or having particular disease states.

Adolescent↗
PubMed2005

Lack of drug interaction conformity in commonly used drug compendia for selected at-risk dermatologic drugs.

BACKGROUND: Systemic treatments that have significant efficacy for dermatologic conditions can often cause severe adverse reactions when improperly combined with interacting drugs. We have noted discrepancies in the reporting of such drug-drug interactions among major drug compendia used in hospitals and physicians' offices. OBJECTIVE: The aim of this study was to compare the consistency of drug-drug interaction listings among four of the most widely used English language drug compendia in the US. METHODS: Drug monographs from Mosby's GenRx, USP DI, AHFS Drug Information, and the Physicians' Desk Reference were compared. The respective drug-drug interactions provided by the various compendia for four systemic agents -- dapsone, erythromycin, methotrexate and prednisone -- commonly prescribed for dermatologic purposes were compiled. RESULTS: We found considerable discrepancies among the compendia with respect to the number of drug interactions listed. Agreement among the compendia was especially poor when more than two sources were compared. CONCLUSIONS: There is a need for a drug compendium that reconciles drug-drug interaction reporting discrepancies under standardized criteria based on the scientific literature and clinical significance.

Adverse Drug Reaction Reporting Systems↗