Medication safety issue in pharmacivigilance centres Moroccan experience. L. ALJ, G. Benabdallah, R. Benkirane, R. Soulaymani Bencheikh

Transcription

1 Medication safety issue in pharmacivigilance centres Moroccan experience L. ALJ, G. Benabdallah, R. Benkirane, R. Soulaymani Bencheikh

2 Background It is now admitted that pharmacovigilance centres are involved in detecting medication errors Several publications revealed the input of pharmacovigilance centres in increasing patient safety No patient safety organization in Morocco PV Moroccan Centre receives ME ICSRs Poison Control Centre

3 Pharmacovigilance Scope The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems Medication errors Abuse Misuse Quality defect product counterfeit medical product

4 Medication safety activities Retrospective study Surveys (anesthetists, pediatricians) Awareness trainings Physicians Nurses All pharmacists in public hospitals Francophone training course for African countries Bulletins published monthly

5 Alerts triggered in Moroccan ME database Drug Medication error Taken actions Paracetamol in pediatric use Wrong drug Wrong dose Information of HCP Opioids Wrong dose Dear doctor letter Insulin Prescribing error Standardization of the therapeutic protocol Methotrexate Wrong frequency of administration Dear doctor letter Metoclopramid - Wrong frequency of administration - Inappropriate drug selection Dear doctor letter Azithromycin Wrong frequency of administration Dear doctor letter Methylergometrin - Patient error - Wrong drug Dear doctor letter Enoxaparine Poor quality drug Defective batch withdrawal Vitamin D Wrong dose Dear doctor letter Change of Vitamin D dosage

6 Methotrexate

7 Case 1 Female, 60 years old: rheumatoid arthritis and psoriasis Methotrexate 2.5mg tablet was prescribed Prescribed dose : 2 tablets / week Administered dose : 2 tablets / day during 1 week Adverse reactions: abdominal pain, stomatitis aphtous, arthritis Laboratory tests Normal renal function SGOT = 60 UI/l Hemoglobin = 10 g/100ml Platelets normal Medicine was discontinued Treatment of reaction: Antacid Favorable outcome

8 Case 2 Female, 64 years old: rheumatoid arthritis Treatment prescribed Prednisolone 20 mg, 1 tablet / day Methotrexate 2.5mg tablet prescribed dose : 4 tablets / week administered dose : 2 tablets / day during 15 days Adverse reactions fever, diarrhea, headache jaundice stupor cough, mucositis, epidermal necrolysis Laboratory tests Increase of hepatic enzymes: negative hepatic serologies NFS: Hemoglobin = 7.9g/100ml Red blood cell = 3.16M/µl Platelets = /µl White blood cell = 700/µl Renal failure

9 Case 2 Methotrexate and prednisolone were discontinued Treatment Calcium folinate (specific antidote) 15mg every 4 hours Alkaline hyperhydration Ceftriaxone 2g / day Gentamycine 160mg / day Metronidazole 500mg twice day Outcome: patient death following circulatory failure

10 Root Cause Analysis Proximal cause Daily administration of oral methotrexate instead of weekly administration

11 Root Cause Analysis Possible contributing factors Methotrexate 2.5mg tablet: not available in Morocco Delivering medicine by pharmacist was jumped Treatment schedule not clearly explained by the physician Misunderstanding the dosage schedule by the patient Most oral medicines are daily administered: weekly dosage regime is unusual for patient

12 Moroccan health authority decisions to prevent recurrence of this ME Explain patients the treatment: non standard dosage Stress on the weekly administration of oral methotrexate Provide patients with clear and legible handwritten instructions: including the form, strength, dose and directions for use Name a specific day of the week for taking the tablet with patient: to be indicated on the prescription to be written on the packaging when medicine is delivered by the pharmacist avoid choosing Monday since it could be misread as morning (in French speaking countries mardi/matin) Mention the indication for using methotrexate on the ordering form: useful information for health care professionals

13 Flucloxacillin

14 Tissular necrolysis Arterial thrombosis

15 RCA Step 1: Description of the adverse drug events 22 notifications related to loco regional reactions to intra venous Flucloxacillin (May June 2005) Paediatric department in the Teaching Hospital of Rabat 20 children: developed tissular necrosis at the site of injection 2 children: presented an arterial thrombosis following intra venous injection of the product Indication of the treatment: Staphylococcal infections Dosage regimen: 50mg/kg Preparation of the product: dilution of the powder in 5ml Nacl 9

16 RCA Step 2: Identification of the proximal causes Literature review Symptomatology: belongs to Nicolau syndrom (acute violent pain during or immediatly after injection, pallor, erythema, necrotic eschar) Drugs commonly involved: phenylbutazones, corticosteroids, local anaesthetics, antibiotics (flucloxacillin)

17 RCA Step 2: Identification of the proximal causes Underlined mechanisms Vessels occlusion by penicillin crystals resulting from inadequate dilution Arterial vasospasm Inadvertent intra-arterial injection

18 RCA Step 2: Identification of the proximal causes 2 proximal causes identified Inadvertent intra arterial injection for the 2 cases whose experienced arterial thrombosis Inadequate dilution of flucloxacillin that is responsible of tissue irritation regarding the penicillin particles size: Recommended dilution available in the SPC specified: 1g in 20ml water for IV injection or Na cl Whereas, nurses used to dilute the product with 5 ml of saline serum (water for IV injection not available in the box)

19 RCA Step 3 : 2 contributing factors identified Equipment and Resource Factors information on the dilution of the product is not available in the leaflet the sterile water for product dilution is not available in the drug box Individual factors good level of nurses training with IV the technique that led to bypass the preventive actions checking when administering intra venous product to avoid intra arterial injection

20 RCA Step 4: Taking action An alert was triggered by the Ministry of health Largely disseminated nearby pediatricians and nurses The manufacturer was informed to amend the leaflet To mention the risk of local necrolysis if the recommended dilution process is not respected To add the dilution process Assessment of the plan s outcomes : no more cases observed

21 Vitamin D

22 Background Vitamin D: plays a key role in the development of strong bones Deficiency in infants: rickets Excessive vitamin D nephrocalcinosis cardiac complications Moroccan program for preventing rickets (PHP) Established in doses: IU each at birth at 6 months old

23 Since 2012 Moroccan Pharmacovigilance Centre received 17 case reports related to vitamin D overdose 16 presented nephrocalcinosis Outcome was fatal for 2 newborns due to cardiac arrest terminal renal failure

24 Cases reported description (17 cases) Age Clinical and biological symptoms Explorations Treatment Seriousness Outcome 15 days to 6 months dehydration, somnolence, vomiting, convulsion, weight loss, tachycardia, hypotonia, hypotrophy, hyperglycemia Nephrocalcinosis in 16 cases IV Rehydration Diuretics (Furosemide) Corticoids Hospitalization : 17 cases Favorable: 11 cases Not recovering: 4 (renal impairments) Death: 2 cases

25 Literature review Similar cases reported Chronic overdoses: vitamin D intake daily

26 Overdose contributing factors Recommended dose ( IU): 3 times higher than the recommended one by international guidelines Lack of an adequate formulation of vitamin D for pediatric population vitamin D IU SPC: adult use only Administration of additional doses of vitamin D by parents Fortified milk with vitamin D for infants

27 CAPM proposal Reduce the recommended dose of vitamin D by the national program for preventing rickets: IU Provide pediatricians with a formulation of vitamin D adapted for pediatric population Draw up the attention of health care professionals to reduce dose prescribed when infants are fed with vitamin D fortified milk to know about the risks related to vitamin D overdoses Parents education: do not give supplementary doses of vitamin D

28 Thank you for your attention