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Servicio Navarro de Salud / OsasunbideaPlaza de la Paz, s/n - 31002 PamplonaT 848429047 - F [email protected] VOL 19, No 2 MARCH-APRIL 2011
Could it be your
medicine?
Objective: to offer the physician a list of common symptoms that de- tn rive from adverse drug reactions and a relationship between com- c mon drugs or classes of drugs that are most frequently implica - ted. Material and methods: clinical physicians, pharmacists and physicians working for the Department of Information Systems and s Clinical Management were asked to identify the most common pro- b blems encountered in their daily practice and in which medications could be at the root of these effects. This issue was also presented toan internet forum on Family Medicine and Primary Care. A bibliogra-phical search was carried out in UpToDate® and MEDLINE updated on April 2011. Only review articles were included. We also searched theTRIP database and BOT Plus database which registers informationon the Summary of Product Characteristics reports. Results andconclusions: we provide a list of common symptoms that can derivefrom adverse reactions to drugs, and a relationship between the JAVIER GARJÓNDrug Prescribing Service, Navarre Regional Health Service. Spain drugs or classes of drugs most frequently implicated. The listcould represent a helpful tool for the e-prescribing software of theelectronic medical record. Key words: adverse reactions, drug indu-ced symptoms, pharmacovigilance.
DRUG AND THERAPEUTICS BULLETIN OF NAVARRE. SPAIN Clinical case
While completing the study, the patient discontin-ued treatment with pregabalin on her own, as it In July 2009, a 78 year old woman presented at was the most recent novel therapy she had start- the consultancy with a 4-day history of sudden ca- ed. Symptoms disappeared once pregabalin was cosmia. She explained that she went to bed feel- stopped. To date she remains asymptomatic. ing fine and in the morning she woke up with asense of bad odour around. She cleaned up the The drug information leaflet of pregabalin indi- cates numerous undesirable effects on the nerv-ous system, among them ageusia. The alterationsin taste and in smell are related and can be pro- duced by different drugs from the class of antie -pileptic1. It is important to notify the Center for Hipothyroidism. Spondyloarthrosis. Episodes of Pharmacovigilance to enable a better comprehen- sciatic pain due to L4-L5 segment affectation.
sion of the safety profile of all medications. The problem
An important part of the population is under chronic treatments. We should not forget that when prescribing a drug to achieve clinical bene- fit, the treatment also affects the functioning of pa- Calcium+vitamin D: 1000 mg-880 IU b.i.d.
tient’s organism. It should therefore not be surpris- ing that adverse reactions represent an important Behind the undesirable effects, which are the ob-jective of warnings issued by regulating bodies and the characteristic reactions that appear in pharma-cological texts, there lies the danger of complica- A general and neurological examination was per- tions that produce symptoms that are frequently formed with no findings. Nasal corticoid and an- unclearly defined and can cause confusion with the timicrobial treatment was initiated with a suspicion underlying disease or simulate any other disease.
of acute sinusitis, and the patient was referred to a These reactions deteriorate the patients quality of neurologist and an otolaryngologist to rule out life, make diagnosis and management of the pa- cortex, hypophysis or sinus affectation. tient’s diseases difficult, and can lead to what isknown as “prescription cascade” that is, treatment The patient was examined by the otolaryngologist of the undesirable effect of a drug by another drug. who recommended clonazepam and intramuscu-lar betametasone. She presented poor tolerance To attribute the cause of a symptom to a drug can to clonazepam and it was discontinued. A sinus be difficult and often is not done until suspension CT scan was carried out which was normal. After of the drug produces improvement in health. It evaluation by a neurologist, where an electroen- should be taken into account that any symptom cephalogram was performed which was normal, a can be caused by medications even those symp- cranial MRI was carried out which also turned out toms which have yet not been documented as ad- COULD IT BE YOUR MEDICINE? COMMON SYMPTOMS THAT COULD BE CAUSED BY ADVERSE DRUG REACTIONS Special attention should be given to new medica- Management were asked to identify the problems tions because their safety profiles are often not they most frequently encountered in their daily known when they become available on the mar- practice and which could be caused by medica- ket. Medications are often commercialised with tion. The issue was also presented to a internet fo- identified adverse effects, but it is also admitted rum on Family Medicine and Primary Care (MED- that there is still information lacking. This is reflect- ed by the fact that new medications are accompa-nied by a risk management plan (that includes During a meeting of the Editorial Board of the Drug known and potential risks). To mark out new & Therapeutics Bulletin of Navarre, brainstorming drugs, and therefore to indicate the existence techniques were applied to propose symptoms.
of less information on their safety profile, in Spain Once completed, all the information recollected it is compulsory to include in all advertising materi- was re-evaluated to prioritize those symptoms to al for health professionals the yellow pictogram ’), for a period of 5 years from the time of the Another problem was the enormous amount of in-formation to be managed. Our objective was to fo- Summaries of Product Characteristics contain a cus on commonly used drugs in primary care and lot of information on adverse reactions, but do not the most common and validated reactions. Med- always respond to the needs of the clinician. The ications restricted to hospital use including anti- data may derive from clinical trials carried out in neoplastic agents or HIV antiviral therapy were ex- controlled conditions, in selected populations and A bibliographical search was carried out in the Therefore, the real frequency of adverse reactions electronic book UpToDate® and MEDLINE using remains unknown in common daily conditions of the following strategy: “problem/chemically in- use. Moreover, it is necessary to review all the duced”[Mesh] or (“problem” [Mesh] AND “Diagno- drug information lists of all the medication a pa- sis, Differential” [Mesh].” Only review articles were tient may be taking which would take consider- selected. A search was also made in the TRIP database and the BOT Plus2 database which rec-ollects information on the Summary of Product Besides the symptoms caused by medications, Characteristics of all medications. As our selec- consideration should be given to those effects tion was reviews, recently marketed drugs were that result from the withdrawal of drugs, especially not included, and so the Summary Product Char- if withdrawal is sudden (table 2). Good communi- acteristics reports of the most commonly em- cation between doctors and patients is essential ployed medications marketed over the last 5 years to tackle the problem. If we want to detect drug- related symptoms, it is necessary to ask and lis-ten actively to our patients. Conclusion
Our objective
This article offers the physician a list of the com-mon symptoms that could cause adverse reac- The aim of this article is to provide the physician tions to drugs, and a relationship between drugs with a list of the most common symptoms that or classes of drugs that are most frequently impli- could be caused by adverse reactions, and a rela- cated. The result is only a starting point which can tionship between the drugs or classes of drugs be completed and updated, and even included as a helpful tool for the e-prescribing software of theelectronic medical record.
Methodology
Physicians require better information on drugsafety in real conditions of use. This can only The first difficulty encountered was to make a se- come through spontaneous notifications of the lection of symptoms. Practically any symptom suspicion of adverse reactions (Yellow Card that a patient could present can be caused by Scheme) and more and better pharmacoepidemi- medications. To address the problem, practising ological studies. The adequate codification of physicians, pharmacists, and physicians from the symptoms and treatments in the electronic med- Department of Information Systems and Clinical ical record is essential to carry out such studies. DRUG AND THERAPEUTICS BULLETIN OF NAVARRE. SPAIN Warning: as explained earlier we have focussed on the most common problems of the mostfrequently employed medications. We do not present a comprehensive list of medications thatcould produce an undesirable effect. Moreover, the sources do not always coincide whenattributing an adverse reaction to a class of drugs. There are much more relations betweenadverse reactions and drugs than those presented here. If there is any suspicion of an adverseeffect then the physician should consult the Summary of Product Characteristics or consult thePharmacovigilance Centre or the Drug Information Centre.
Acknowledgements
We thank Dr Clint Jean Louis, of the Emergency Department of the Navarre Regional Health Service in Spain, for
translating the original manuscript into English.
Table 1. Common symptoms (ordered according to ICPC or ICD-9 codes) and the medication implicated (ordered
according to therapeutic group ATC).
(ICPC, ICD-9)*
Medication
Observations
Asthenia3,4
RanolazinAntihypertensive agents: betablockersmost frequently implicatedOpioidsBenzodiazepinesAntidepressantsH1 Antihistamine agents Diarrhoea5,6,7
H2 antihistamine agents MisoprostolProton pump inhibitorsMetforminAcarbose, miglitolExenatide, liraglutideCilostazoleDigoxinAntiarrythmic agents AliskirenNicotinic acid/laropiprantEzetimibeAntibioticsNSAIDsStrontium ranelateCarbamazepineSSRI, duloxetin, agomelatineTeophilineRoflumilast COULD IT BE YOUR MEDICINE? COMMON SYMPTOMS THAT COULD BE CAUSED BY ADVERSE DRUG REACTIONS (ICPC, ICD-9)*
Medication
Observations
Constipation5-7
H2 Antihistamine agents Proton pump inhibitorsSucralfateLaxatives (chronic use)Calcium supplementsIron supplementsAmiodaroneRanolazinDiuretic agentsBetablockersCalcium channel blockersCholestiramine, colestipolOral contraceptive agentsUrinary antispasmodic agents NSAIDsBisphosphonates Opioids Prescription should beaccompanied by preven-tive measures, includinglaxatives AntipsychoticsAnticholinergic agents for Parkinson diseaseLithiumTricyclic antidepressants, duloxetine, venlaxafin H1 Antihistamine agents Vertigo8
AminoglycosidesNSAIDsAcetylsalicylic acid Muscle cramps9
Dihydropiridine calcium channel blockers StatinsNicotinic acid/laropiprantRaloxifene, bazedoxifenePenicilamineAntipsychotics: phenothiazinesBeta 2 adrenergic agonists Muscular pain10,11
Evaluate risk of rhab-domyolysis. Precautionwith interactions.
CorticoidsQuinolonesColchicineBisphosphonates Quinine, chloroquin Cefalea12
DRUG AND THERAPEUTICS BULLETIN OF NAVARRE. SPAIN (ICPC, ICD-9)*
Medication
Observations
Due to acute exposure
CilostazoleNitroglicerineIvabradine, ranolazineBetablockers Calcium channel blockers Nicotinic acid/laropiprantSildenafil, vardenafilNSAIDsTheophyllineRoflumilast Due to abuse of
medication
Due to chronic use
CorticoidsThyroid hormoneIndomethacinLithium Acute dystonia13
Tremor14
domperidone. Watch forsigns of parkinsonism Consider hyperthyroi-dism, reduce dose to200 mg daily. Consider a betablocker Reduce dose. Change toanother antiepileptic drug Watch for signs of par-kinsonism (see table 4).
Withdraw. Change toanother of lower risk Precaution due to possi-ble serotoninergicsyndrome (see table 3) Adrenergic agonists: efedrine, phenyl-propanolamine, pseudoephedrineBeta 2 adrenergic agonists.
COULD IT BE YOUR MEDICINE? COMMON SYMPTOMS THAT COULD BE CAUSED BY ADVERSE DRUG REACTIONS (ICPC, ICD-9)*
Medication
Observations
Alterations in taste
(ageusia) or smell1,15
PropaphenoneAmiodarone, dronedaroneNitroglicerinDiuretics: acetazolamide, amyloride,hydrochlorothiazide, spironolactoneCalcium channel blockersACE inhibitor and ARBsStatinsAntifungal agents: terbinafine, griseofulvinCorticoidsThyroid therapy: levothyroxine, carbimazole, tiamazoleAntimicrobials: ampicillin, azithromycin,ciprofloxacin, clarithromycin, etambutol,metronidazole, ofloxacin, sulphametoxa-zole, ticarcillin, tetracyclineAntiviral agents: aciclovir, amantadine,interferon, osetalmivirPenicillamineColchicineTriptansAntiepileptic agentsAntiparkinson agentsLithiumSedatives and hipnotics: alprazolam, fluracepam, buspirone, zolpidemAntidepressants: tricyclic, SSRI, duloxetin, venlafaxine, bupropionH1 Antihistamine agents Dizziness/
unstability8,16
Ivabradin, ranolazineAntihypertensive agentsNicotinic agents/laropiprantAlpha blockersNSAIDsAntiepileptic agentsBenzodiazepinesAntidepressantsAntivertiginous agents (chronic use) Anxiety/agitation2,17
BenzodiazepinesAntidepressants: tricyclics, SSRI, dulo- Adrenergic agonist: ephedrine, phenyl-propanolamine, pseudoephedrineRoflumilast DRUG AND THERAPEUTICS BULLETIN OF NAVARRE. SPAIN (ICPC, ICD-9)*
Medication
Observations
Insomnia18
Calcium channel blockersCorticoidsAntidepressants: tricyclics, SSRI, dulo-xetin, venlafaxine, bupropion, agome-latineMethylphenidate, atomoxetineAdrenergic agonists: ephedrine, phenyl-propanolamine, pseudoephedrineBeta 2 adrenergic agonistsTheophylline Delirium19,20
Betablockers Urinary antispasmodic agents Anticholinergic effectsare an important cause of confusion in elderlypatients CorticoidsBetalactamicsQuinolonesNSAIDsOpiodsAntiepileptic agentsAntiparkinson agentsAntipsychotic agents Anticholinergic effectsare an important cause of confusion in elderlypatients BenzodiazepinesTricyclic antidepressants Anticholinergic effectsare an important cause of confusion in elderlypatients Precaution with possibleserotoninergic syndrome(see table 3) are an important cause of confusion in elderlypatients Hallucinations21,22
DigoxinBetablockersCorticoidsClarithromycinOpioidsDopaminergic antiparkinson agonists BenzodiazepinesAntidepressantsMethylphenidate Adrenergic agonist: ephedrine, phenyl-propanolamine, pseudoephedrine COULD IT BE YOUR MEDICINE? COMMON SYMPTOMS THAT COULD BE CAUSED BY ADVERSE DRUG REACTIONS (ICPC, ICD-9)*
Medication
Observations
Mania23,24
AntidepressantsMethylphenidate, atomoxetine Distimia23,25,26
BetablockersACE inhibitors, ARBsContraceptivesCorticoidsInterferonsNSAIDsAntiepileptic agentsBenzodiazepinesCalcium channel blockers: flunarizine Roflumilast Pruritus27
Sexual hormonesBetalactamicsMacrolidsQuinolonesTamoxifenNSAIDsAlopurinolOpiodsAntiepileptic agentsAntipsychotic agentsAntidepressants Antimalarial agents NSAIDs: Non steroidal anti-inflammatory drugs.
ACE: Angiotensin converting enzyme.
ARBs: Angiotensin II receptor blockers.
SSRI: Selective Serotonin Reuptake Inhibitors.
(*) These include ICPC and ICD-9 codes of diseases that can be related to an adverse reaction but may not necessarily be the correct code of the problem. DRUG AND THERAPEUTICS BULLETIN OF NAVARRE. SPAIN Table 2. Problems related with the abrupt withdrawal of commonly used drugs in primary care2,28.
MEDICATION
Rebound hypertension Symptoms of sympathetic hyperactivity Adrenal insufficiency: fatigue, anorexia, weight loss, gastrointestinal disorders, dizziness,hypotension, muscle pain Convulsions, anxiety, insomnia, pain, nausea, diarrhoea, flu-like syndrome, nervousness,depression, sweating and dizziness Flu like syndrome, insomnia, nausea, dizziness, anxiety, agitation sensory disorders, tremor RelapseCholinergic rebound: nausea, anxiety, insomnia, agitation, dyskinesia Table 3. Serotoninergic syndrome13,32.
SYMPTOMS
Autonomous
Tachypnea, dispnoeaDiarrhoeaHypotension or hypertension Neurological
Implicated medications
Antidepressants: SSRI, tricyclics, MAO inhibitor, bupropion, trazodone, nefazodone, venlafaxine, duloxetine, hypericum.
Triptans.
Opioids: fentanyl, tramadol, pentazocine, meperidine, dextrometorphan.
Selegiline, sibutramine, lithium, ondansetron, granisetron.
Frecuently this syndrome is caused by the interaction of various of these drugs.
Table 4. Main extrapiramidal reactions related to antipsychotic agents2,13.
YATROGENIC EPISODE
CHARACTERISTICS
Rigidity, bradikinesia, tremor, characteristic gait.
Muscle spasm in tongue, face, neck and back. More common in young patients. Motor agitation, without psychological symptoms Facial movements of mastication and sucking, involuntary movements in the legs, trunk dystonia. More common in elderly patients. COULD IT BE YOUR MEDICINE? COMMON SYMPTOMS THAT COULD BE CAUSED BY ADVERSE DRUG REACTIONS References
1. Doty RL, Shah M, Bromley SM. Drug-induced taste 20. Moore AR, O’Keeffe ST. Drug-induced cognitive disorders. Drug Saf 2008;31(3):199-215.
impairment in the elderly. Drugs Aging 1999;15(1):15- 2. BOT Plus. Base de Datos del Conocimiento Sanita- rio. Consejo General de Colegios Farmacéuticos. Madrid; 21. Pelak , VS. Approach to the patient with visual hal- lucinations. In: UpToDate, Basow, DS (Ed), UpToDate, 3. Fosnocht KM, Ende J. Approach to the adult pa- tient with fatigue. In: UpToDate, Basow, DS (Ed), UpTo- 22. Mosholder AD, Gelperin K, Hammad TA, Phelan K, Johann-Liang R. Hallucinations and Other Psychotic 4. CKS (2009) Tiredness/fatigue in adults. Clinical Symptoms Associated With the Use of Attention- Knowledge Summaries. http://www.cks.nhs.uk/tired- Deficit/Hyperactivity Disorder Drugs in Children. Pedi- ness_fatigue_in_adults [Accessed: 30/3/2011].
5. Jain V, Pitchumoni CS. Gastrointestinal side effects 23. Substance-Induced Mood Disorders, Depression of prescription medications in the older adult. J Clin and Mania. eMedicine from WebMD. (Accessed Mar 24, 2011, at http://emedicine.medscape.com/article/2868 6. Triantafyllou K, Vlachogiannakos J, Ladas SD. Gas- trointestinal and liver side effects of drugs in elderly pa- 24. Peet M, Peters S. Drug-induced mania. Drug Saf tients. Best Pract Res Clin Gastroenterol 2010;24(2): 25. Kotlyar M, Dysken M, Adson DE. Update on drug- 7. Lat I, Foster DR, Erstad B. Drug-induced acute liver induced depression in the elderly. Am J Geriatr Pharma- failure and gastrointestinal complications. Crit Care 26. Patten SB, Barbui C. Drug-induced depression: a 8. Tusa RJ. Dizziness. Med Clin North Am 2009;93(2): systematic review to inform clinical practice. Psy- chother Psychosom 2004;73(4):207-15.
9. CKS (2008) Leg cramps - unknown cause. Clinical 27. Reich A, Stander S, Szepietowski JC. Drug-in- Knowledge Summaries. http://www.cks.nhs.uk/leg_ duced pruritus: a review. Acta Derm Venereol 2009;89 10. Bannwarth B. Drug-induced musculoskeletal dis- 28. Stopping Medicines. WeMeReC. 2010, Jan. (Ac- cessed jun 16, 2011, at http://www.wemerec.org/Docu- 11. U.S. Drug and Food Administration. Information ments/Bulletins/StoppingMedicinesBulletinOnline.pdf).
on Bisphosphonates (marketed as Actonel, Actonel+ 29. Kaplan NM, Rose BD . Withdrawal syndromes Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, with antihypertensive therapy. In: UpToDate, Basow, DS Reclast, Skelid, and Zometa) 2008. (Accessed 29 dic 2008, at http://www.fda.gov/cder/drug/infopage/bis- 30. Furst DE, Saag KG . Glucocorticoid withdrawal.
In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, 12. Butt TF, Evans B. Drug-induced headache. Ad- verse Drug Reaction Bulletin 2006(240):919-22.
31. Warner CH, Bobo W, Warner C, Reid S, Rachal J.
13. Grosset KA, Grosset DG. Prescribed drugs and Antidepressant discontinuation syndrome. Am Fam neurological complications. J Neurol Neurosurg Psychi- 32. Jackson N, Doherty J, Coulter S. Neuropsychi- 14. Morgan JC, Sethi KD. Drug-induced tremors.
atric complications of commonly used palliative care drugs. Postgraduate Medical Journal 2008;84(989): 15. Naik BS, Shetty N, Maben EV. Drug-induced taste disorders. Eur J Intern Med 2010;21(3):240-3.
16. Lee CA, Mistry D, Uppal S, Coatesworth AP. Oto- logic side effects of drugs. J Laryngol Otol 2005;119(4):267-71.
17. Ciechanowski P, Katon W. Generalized anxiety dis- order: Epidemiology, clinical manifestations, and diagno-sis. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham,MA, 2011. 18. Bonnet MH, Arand DL. Types of insomnia. In: Up- ToDate, Basow, DS (Ed), UpToDate, Waltham, MA,2011.
19. Alagiakrishnan K, Wiens CA. An approach to drug induced delirium in the elderly. Postgrad Med J 2004;80(945):388-93.
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