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1 PHARMACEUTICAL LEADERSHIP AND DECISION MAKING PHA-7002Y Time allowed: 2 hours Part ONE UNIVERSITY OF EAST ANGLIA School of Pharmacy Main Series UG Examination Answer ALL questions. For each question, select ONE answer. Use the answer grid provided for ALL your answers. Part TWO Answer ONE of the TWO questions. Answer ALL parts of the question you select. The marks distribution is shown for each section of each question. The mark allocation for the paper is: Part ONE carries 75% of the total mark. Part TWO carries 25% of the total mark. You are advised to spend no more than 90 min on Part ONE and 30 min on Part TWO. This paper consists of 20 pages in total. The following will be provided: Multiple choice answer grid. Artefact 1 - Summary of product characteristics (SPC) for Priadel Artefact 2 - Summary of product characteristics (SPC) for metoclopramide Dictionaries are not permitted in this examination. Notes are not permitted in this examination. Do not take this question paper out of the examination room. Do not turn over until you are told to do so by the invigilator. (PHA-7002Y) Module contact: Dr Jeremy Sokhi, PHA Copyright of the University of East Anglia Version 3

2 PART ONE SECTION A TYPE 1 MCQ (Single best answer) 2 Answer ALL questions. For each question, select ONE answer. Use the answer grid provided for ALL of your answers. 1. You are working as an independent prescriber working in an asthma clinic in a GP practice. Mr ST, a 25 year old man with a medical history of asthma, is currently prescribed beclomethasone 100 micrograms inhaler 1 puff BD and salbutamol 100 micrograms 2 puffs QDS PRN. He tells you that he has been experiencing more breathlessness in the last month, using his salbutamol inhaler 5-6 times a week. A recent review with the practice nurse confirmed he has good inhaler technique and good adherence. Which would be the most appropriate course of action? Increase his beclomethasone dose to 800 micrograms twice daily Add a salmeterol inhaler Add oral prednisolone Add theophylline Add ipratropium inhaler 2. Mr JK comes into your pharmacy to collect his repeat prescription. He tells you that he s noticed his hands and feet have been feeling colder and wonders if it could be caused by his medication? You see from the patients PMR they are taking the following medication Bisoprolol 5 mg OD Warfarin mdu according to INR Which would be the most appropriate advice for the patient? He s experiencing a side effect of bisoprolol and should see the GP urgently as the dose of bisoprolol needs to be reduced He s experiencing a side effect of warfarin, though safe to continue He s experiencing a side effect of bisoprolol and while safe to continue taking he should see the GP to be switched to an alternative He s is experiencing a side effect of the warfarin and should see the GP urgently as the dose of warfarin needs to be reduced The symptoms descried are NOT known to be caused by his medication (PHA-7002Y) Version 3

3 3. Which of the following statements regarding the fate of this prescription and record keeping is TRUE? 3 J. Herriot Flatplace Vets 37 The Street, Flatplace FL23 4JA Bouncer the dog owned by Mr Peter Daw 27 High Street Flatplace FL27 48J Prescribed under the cascade Felodipine 2.5 mg tablets 1 OD 28 Repeat J.Herriot RCVS 5 th May 2018 No entry in the POM register is legally required and the prescription should be sent to the NHSBSA for reimbursement at the end of the month No entry in the POM register is legally required and the prescription should be retained in the pharmacy for two years No entry in the POM register is legally required and the prescription should be returned to the patient or their representative An entry in the POM register is legally required and the prescription should be retained in the pharmacy for two years An entry in the POM register is legally required and the prescription should be returned to the patient or their representative 4. Miss AB has recently been informed by her manager that due to a change in company priorities she will not be funded to undertake an independent prescribing course next year. When you speak to Miss AB she tells you that she can t believe this decision and that she has written to the chief executive of the company for clarification. Which stage of the Kubler-Ross grief cycle is likely to represent Miss AB s emotions most closely? Anger Bargaining Denial Discovery Shock TURN OVER (PHA-7002Y) Version 3

4 4 5. Mrs JK is 55 years old and has been started on IV vancomycin 1g BD for an MRSA infection. The doctors asks your advice on her vancomycin levels. After 2 days of treatment her plasma vancomycin level is found to be 20mg /L (target = 10 15mg /L) Which recommendation is most appropriate? The vancomycin dose should be increased to 1.5g BD The vancomycin dose should be changed to 2g OD Stop the vancomycin and recheck levels after 2 days The vancomycin dose should be reduced to 1g OD The patient should be switched to oral vancomycin 6. Mrs AB has recently been diagnosed with a shingles infection. The GP asks you what would be an appropriate first line treatment. Aciclovir Doxycycline Mebendazole Metronidazole Rifampicin 7. Which of the following counselling points would be most appropriate for a patient collecting a prescription for tamoxifen? Take in the morning 30 minutes before food The dose may need to be adjusted if smoking stopped/started whilst taking treatment Do not take milk/indigestion remedies at the same time of day May cause increased urinary frequency If you experience any symptoms of thromboembolism e.g. breathlessness and pain in calf seek medical advice 8. Mrs CS has recently been started on rivaroxaban 20 mg daily for treatment of a pulmonary embolism. When collecting her repeat prescription she noticed that her gums have been bleeding a lot since starting her new medication. Which is the most appropriate advice for Mrs CS? The symptoms described are NOT known to be caused by rivaroxaban She should see the GP as the dose of rivaroxaban needs to be reduced She should see the GP as the dose of rivaroxaban needs to be increased She s experiencing a side effect of rivaroxaban and while safe to continue, she should see the GP to be switched to an alternative She s experiencing a side effect of rivaroxaban and should see the GP immediately to review stopping the rivaroxaban (PHA-7002Y) Version 3

5 Questions 9-11 relate to Artefact 1 Summary of Product Characteristics (SPC) for Priadel (lithium) 200 mg Prolonged Release Tablets Mr PL (aged 26 years) is started on Priadel (lithium) for the prophylactic treatment of bipolar affective disorders. He asks you how long the medication will take to work. Which of the following would be the most appropriate advice to give him? Prophylactic effect is established at 10 days after initiation of therapy Prophylactic effect may take 6-12 months to be fully established after initiation of therapy Treatment will be effective when Priadel (lithium) reaches steady state between 4-6 days after starting therapy. Treatment will be effective when Priadel (lithium) reaches peak concentration between hours after the first dose Treatment will be effective when Priadel (lithium) has been absorbed, 2 hours after taking the first dose. 10. Miss LF (aged 38 years) asks to speak to you as she is experiencing nausea, blurred vision, increased confusion and urinary incontinence. She is concerned that this may be a side effect of her Priadel lithium. Which of the following would be the most appropriate advice to give? She should increase her salt and water intake to reduce these symptoms She should halve the dose of Priadel (lithium) she is taking until the effects disappear She should see her doctor immediately for her serum levels to be checked as she may be experiencing lithium toxicity These are known side effects of lithium therapy, though safe to continue taking The symptoms described are NOT known to be caused by Priadel (lithium) 11. Miss KD (aged 71 years) is prescribed Priadel (lithium) for treatment of acute manic episodes. Her prescriber contacts you to discuss an appropriate starting dose and you establish that Miss KD s only other medication is paracetamol for headaches. Which ONE of the following doses would you recommend? Four tablets (800 mg) to be taken in the morning One tablet (200 mg) to be taken daily for 5 days, then increase to one twice a day Three tablets (600 mg) to be taken in the morning Two tablets (400 mg) to be taken twice daily You cannot recommend a dose because Priadel (lithium) is contraindicated for Miss KD TURN OVER (PHA-7002Y) Version 3

6 12. Mr OR comes in to the pharmacy with a prescription for the following: 6 Morphine Sulphate 10 mg M/R Capsules (60) Take ONE capsule morning and night You notice that the prescriber hasn t stipulated the quantity to supply in words. Which is the most appropriate course of action? Amend the prescription to include the quantity in words and endorse with your initials and the date Dispense the full amount and return the prescription to the prescriber for amendment at a later date Dispense the item, there are no issues with this prescription Return the prescription to the prescriber as the quantity must be in words and figures and the prescriber must make the amendment Loan 5 day s supply and request a new correctly written prescription Questions relate to Artefact 2 Summary of Product Characteristics (SPC) for Metoclopramide 10mg Tablets. 13. Miss MT is prescribed metoclopramide 10 mg THREE times a day for acute vomiting in migraines. She tells you that she vomited ½ hour after taking her metoclopramide and that was the first dose she had taken that day. She asks you for your advice What would be the most appropriate recommendation? Advise her to take another 10 mg dose immediately Advise her to take 5 mg (half a tablet) after 2 hours have passed Advise her to take 5 mg (half a tablet) immediately Advise her to wait at least 2 hours before taking another dose Advise her to wait at least 6 hours before taking another dose 14. Mr TD (aged 67 years) presents in your pharmacy with a new prescription for metoclopramide. You notice on his Patient Medication Record (PMR) that he is prescribed regular co-beneldopa. Which of the following would be the MOST appropriate course of action? Contact the prescriber to discuss an alternative due to the mutual antagonistic interaction with co-beneldopa Contact the prescriber as the metabolism of co-beneldopa will be increased, therefore an increase in dose may be required Contact the prescriber as the metabolism of co-beneldopa will be reduced, therefore a reduction in dose may be required Dispense the metoclopramide, there are no issues Explain to Mr TD that he should leave at least one hour between taking the metoclopramide and the co-beneldopa, to prevent interactions (PHA-7002Y) Version 3

7 7 15. Mrs KD has been commenced on a dose of metoclopramide 10 mg THREE times a day for nausea and vomiting. Her creatinine clearance is 28 ml/min. Which of the following would be the appropriate recommendation to the prescriber? The dose should be given once daily to preserve her renal function The dose should be increased by 50% due to her renal function The dose should be increased by 75% due to her renal function The dose should be reduced by 50% due to her renal function The dose should be reduced by 75% due to her renal function 16. You are interviewing candidates for a healthcare assistant post. The current interviewee asks you several questions about the people he will be working with and what the induction process will entail if he is offered the position. Which personality type best describes this interviewee? Analytical Pragmatic Relater Manager Extrovert 17. The latest Biochemistry / Haematology Results for Mr AB show the following: Reference range Today s result Serum calcium (mmol/l) He is taking the following medication: Bendroflumethiazide 2.5 mg daily Ferrous Sulphate 200 mg twice daily Ispaghula sachets ONE daily Tamsulosin 400 mcg daily Simvastatin 40 mg at night Which is the most likely drug cause of the abnormal blood results? Bendroflumethiazide Ferrous Sulphate Ispaghula Tamsulosin Simvastatin TURN OVER (PHA-7002Y) Version 3

8 8 18. Miss HF comes into your pharmacy and requests something for the treatment of her nasal congestion and sneezing. She says that she has been suffering for two weeks and that it seems to be worse in the mornings and evenings. On questioning, Miss HF says that she also has itchy eyes. She tells you that she has a regular prescription of hydrocortisone cream and Oilatum emollient to treat her eczema. Miss HF is currently working outside on a farm as a fruit picker. Which of the following is the most likely diagnosis? Allergic rhinitis Asthma Infective rhinitis Rhinitis medicamentosa Viral conjunctivitis 19. You are the manager of a community pharmacy which has just relocated into a new premises. The two full-time dispensers and one part-time counter assistant who were with you at the former site have all transferred to the new location, which has a robotic dispensing unit. The pharmacy s owners have stated that you must introduce a range of advanced and locally commissioned services whilst still maintaining prescription volumes. There is no budget for extra staffing. Which of the following actions would NOT be of use in helping the staff adjust to the proposed changes? Emphasising the opportunities presented by the changes being introduced Minimising additional changes to avoid further disruption Planning for a reduction in productivity during major change Setting a clear vision of the benefits of the changes Setting short term goals to support the transition through change 20. A Randomised Controlled Trial (RCT) considered the effects of simvastatin therapy given for 5 years for the primary prevention of cardiovascular disease. 6% of patients receiving simvastatin suffered peripheral neuropathy compared with 2% in the control arm who were given a placebo Which of the following represents the NNH for peripheral neuropathy in these patients? (PHA-7002Y) Version 3

9 9 21. The management team at the hospital pharmacy where you work as a band 7 pharmacist have decided to change the supplier of their electronic healthcare records system. You have used this system at another hospital and prefer the current one. Which conflict mode style would be the most appropriate to adopt? Accommodating Avoiding Collaborating Competing Compromising 22. You are an independent prescriber working in a pain management clinic in a GP practice, Mrs ST a 60 year old female has a previous medical history of osteoarthritis and a previous duodenal ulcer. She has been prescribed paracetamol 1g four times a day for the past 6 months for her osteoarthritis, though her pain is still not effectively managed. On discussion she is taking her medication regularly and following lifestyle advice. Which is the most appropriate treatment choice? Add in codeine 30 mg four times a day when necessary Add in diazepam 2 mg twice daily when necessary Add in methotrexate 5 mg weekly Change her treatment to fentanyl patch 25mcg 72hrly Change her treatment to ibuprofen 400 mg three times daily 23. A Cochrane review considered the effects of taking zinc for the common cold. 20% more patients receiving zinc saw a reduction in their symptoms after 7 days compared with those who were given a placebo Which of the following represents the NNT for reducing cold symptoms after 7 days in these patients? TURN OVER (PHA-7002Y) Version 3

10 The hospital pharmacy where you work provides a pharmacy service to the elective admissions ward. You wish to establish the extent to which the service meets user needs. Which of the following would be the most appropriate method to use? Clinical audit Cohort study Patient satisfaction survey Service evaluation Systematic review 25. FG is branch manager of a pharmacy within the area you are responsible for within a large pharmacy chain. The last time you visited his branch he mentioned he was unclear about his place within the company s future plans. Which level of Maslow s Hierarchy of Needs best represents where you should target your efforts to improve FG s motivation? Esteem/ego Physiological Safety Self-actualisation Social 26. Your Area Manager has given you feedback that your team appear reluctant to contribute their own ideas about how the pharmacy is run. Which conflict mode style are you most likely to be overusing? Accommodating Avoiding Collaborating Competing Compromising (PHA-7002Y) Version 3

11 Medicines supplied in accordance with a prescription must be labelled with a Dispensed Medicinal Product label. The label must legally contain which one of the following pieces of information? Cautions for the medicine dispensed Patient address Quantity of medicine dispensed Strength of medicine dispensed The wording Keep out of the reach and sight of children 28. You receive the following request from a local prescriber. He does not have a requisition form (FP10 CDF) available and so handwrites the request. He would like to collect the ampoules tomorrow. Which would be the most appropriate course of action? Please supply for general use in my medical bag. 5 Diamorphine 5 mg Ampoules. Dr A Thompson AT General Practitioner Flatplace Medical Practice, Flatplace, Flatshire Make the supply as you have a legal signed order Refuse the request as this medication is a CD schedule 2 drug and therefore you cannot legally supply Refuse supply as it is not dated Refuse supply as there is no patient name Refuse supply as the request must be on the correct FP10 CDF TURN OVER (PHA-7002Y) Version 3

12 Mr DF is a regular patient at your community pharmacy. He calls in to explain that he has run out of the lansoprazole capsules (POM) which he takes once daily to control his gastro-oesophageal reflux disease (GORD) symptoms. He asked the surgery to send through a prescription but it will not be ready for three days. Which is the most appropriate course of action? Inform Mr DF that you must speak to the surgery before you can make the supply Loan Mr DF three capsules and deduct them from his next prescription Supply Mr DF three capsules, charge him for the medication and make a record in the POM register Supply Mr DF with a box of 30 capsules, charge him for the medication and make a record in the POM register Refuse the supply, you must have a prescription to supply a POM Questions relate to the following scenario: Mr PT a 34 year old male, is admitted to hospital with an exacerbation of his asthma. The medication on his drug chart is listed below: Drug Name Dose Route Frequency Salbutamol 2.5 mg Nebulised QDS Ipratropium 500 mcg Nebulised QDS Dalteparin 5000 units Subcutaneously OD Prednisolone 40 mg Oral OD Seretide 250 inhaler 2 puffs Inhaled BD 30. Mr PT tells you that since he has been admitted he has been experiencing a dry mouth. Which of the following drugs is the most likely cause of his dry mouth? Dalteparin Ipratropium Prednisolone Salbutamol Seretide (PHA-7002Y) Version 3

13 The nurse tells you Mr PT s blood glucose levels have increased since starting the prednisolone and asks what do you recommend? Reference range Day 1 Day 2 Day 3 Blood glucose (mmol/l) Which would be the most appropriate response? Recommend no prednisolone dose adjustment and monitor blood glucose levels more frequently Recommend that prednisolone is not associated with hyperglycaemia Recommend that the prednisolone should be stopped and the patient switched to hydrocortisone Recommend that the dose of prednisolone should be reduced to 20 mg daily Recommend that the dose of prednisolone should be increased to 60 mg daily 32. Which of the following would NOT be an appropriate monitoring parameter for efficacy of Mr PT prescribed medication? Oxygen saturation Peak flow Pulse Respiratory rate Temperature 33. A female comes into your pharmacy with her 6 year old daughter. Her daughter has a red itchy rash on her trunk of her body, present for the past few days. On questioning you find that the mum has recently changed her brand of washing powder. Her daughter has no other medical conditions and takes no medication. Which is the most appropriate recommended treatment? Diprobase cream Chlorphenamine liquid Hydrocortisone cream Clotrimazole cream Paracetamol suspension TURN OVER (PHA-7002Y) Version 3

14 A woman comes into your pharmacy with her 3 year old daughter. She would like to purchase something for her daughter, who has had a red itchy right eye for the past few days with her eye lashes stuck together in the morning. On questioning you find that it is not painful and she has no aversion to light. She has no other medical conditions and takes no medication. Which is the most likely diagnosis and accompanying recommendation? Allergic conjunctivitis; give sodium cromoglicate eye drops Allergic conjunctivitis; refer to GP Grit in eye: eye bath to wash eye Infective conjuctivitis; give chloramphenicol eye drops Infective conjunctivitis; refer to GP 35. Mrs JH has recently been started on amiodarone and warfarin for atrial fibrillation. She comes to your community pharmacy and tells you that since starting on the medication, she has been experiencing increased sensitivity to sunlight and wants to know if it is due to her medication. Which would be the most appropriate recommendation for this patient? She s experiencing a side effect of amiodarone though safe to continue taking she should see the GP to be switched to an alternative She s experiencing a side effect of warfarin and though safe to continue taking she should see the GP to be switched to an alternative. She should see the GP as her dose of amiodarone needs to be reduced She should see the GP as her dose of warfarin needs to be reduced The symptoms described are NOT known to be caused by amiodarone or warfarin. 36. Mr AC, a 44 year old man, is admitted to hospital with nausea and vomiting, tachycardia and confusion. His medication on admission is: Theophylline 250mg MR tablets ONE twice daily Beclomethasone 100mcg inhaler TWO puffs twice daily Salbutamol 100mcg inhaler TWO puffs when needed On admission his theophylline plasma level is found to be 30 mg/l (target reference range 5 to 15 mg/l). Which of the following would be the most appropriate course of action? Double the dose of theophylline Halve the dose of theophylline Stop the theophylline for 2 weeks and then restart at a lower dose Stop the theophylline for 1-2 days and then restart at a lower dose Switch the patient to IV aminophylline (PHA-7002Y) Version 3

15 Mrs KL, a 73 year old female has been prescribed gentamicin for urosepsis. Which of the following would be an appropriate monitoring parameter for gentamicin toxicity? Platelet count Creatinine clearance Creatine Kinase Liver function tests Thyroid function 38. Mrs SS is admitted into hospital with a suspected gastrointestinal bleed. Her medication on admission is as follows: Amlodipine 5 mg OD Atorvastatin 20 mg OD Codeine 30 mg QDS PRN Ibuprofen 400 mg TDS PRN Rivaroxaban 20 mg ON Zopiclone 3.75 mg ON PRN The doctors ask if any of her medication could have contributed to the development of a gastrointestinal (GI) bleed. Which would be the most appropriate response? None of her medication could have contributed to development of a GI bleed Both ibuprofen and rivaroxaban are associated with a GI bleed Ibuprofen only is associated with a GI bleed They all could have contributed to development of GI bleed Atorvastatin, ibuprofen and rivaroxaban are associated with a GI bleed TURN OVER (PHA-7002Y) Version 3

16 16 SECTION B TYPE 2 MCQ (Extended matching questions) Contraindications (F) (G) (H) Addison s disease Myasthenia gravis Narrow angle glaucoma Parkinson s Peptic Ulcer Prostatic enlargement Severe respiratory depression Uncontrolled epilepsy For each of the following patients, identify which of the above would be a contraindication to the use of the prescribed drug. Each option may be used once, more than once, or not at all. 39. Miss ST has schizophrenia and she is to be started on clozapine. 40. Mr DE has been prescribed enoxaparin following a pulmonary embolism. 41. Mrs AG is to be given gentamicin for a biliary tract infection. Treatment of infections (F) (G) (H) Amoxicillin Azithromycin Cefalexin Flucloxacillin Metronidazole Oxytetracycline Phenoxymethylpenicillin Rifampicin For each of the following patients, select the most appropriate treatment from the list above. Each option may be used once, more than once, or not at all. 42. Mr FR has been diagnosed with an uncomplicated chlamydia infection 43. Miss CJ is allergic to penicillin. She has a confirmed helicobacter pylori infection and her doctor wishes to prescribe eradication therapy to include lansoprazole, clarithromycin and one other medicine. 44. TA is an 8 year old boy diagnosed with impetigo. (PHA-7002Y) Version 3

17 17 Leadership styles (F) (G) (H) Affiliative Authoritative Coaching Coercive Democratic Pacesetting Relational Situational For the scenarios described, select the most appropriate leadership style to adopt from the list above. Each option may be used once, more than once, or not at all. 45. Several of the nurses at the GP practice where you work have commented that you are better at reaching agreement when the Practice Manager makes unreasonable demands. 46. You and two of your colleagues have been asked by your line manager at the pharmaceutical company you all work for to produce a new patient information leaflet within a short timeframe. Everyone on the team is as competent and motivated as you are, however your line manager has asked you to take the lead on this for her. 47. It is 3pm on a Friday afternoon in the community pharmacy you manage when a pipe bursts flooding the dispensary. You need to quickly organise your staff so that you are able to ensure patients remain your first concern without compromising health and safety. TURN OVER (PHA-7002Y) Version 3

18 18 Monitoring for efficacy (F) (G) (H) Bone Mineral Density C-Reactive Protein (CRP) Creatine Kinase Myopathy Neutrophils Platelets Prothrombin time Total cholesterol For each of the following patients, select the most appropriate monitoring parameter for efficacy. Each option may be used once, more than once, or not at all. 48. A 60 year old male has been newly prescribed simvastatin 40 mg daily for hypercholesteraemia. 49. A 54 year old male, with rheumatoid arthritis started on methotrexate 5mg weekly. 50. A 48 year old male prescribed Filgrastim (granulocyte-colony stimulating factor) in response to the adverse effects of a cycle of chemotherapy. END OF PART ONE (PHA-7002Y) Version 3

19 19 PART TWO Answer ONE of the TWO questions. 51. You are working an out of hours shift at a community pharmacy. At pm, a female aged in her 20s says that she would like to speak to the pharmacist. She tells you that 10 hours ago she had unprotected intercourse and would therefore like to buy the morning after pill (levonorgestrel). She tells you that she has used it once before several years ago. On that occasion it was prescribed by her doctor who told her to take two tablets at once instead of the usual one tablet because of her epilepsy medication. She shows you the packet of her usual medication which is carbamazepine 400 mg tablets twice daily. With reference to criminal, civil, administrative and employment law, professional competence, professional guidance and support networks, provide arguments both for and against making the supply. [100%] TURN OVER (PHA-7002Y) Version 3

20 FP10 HNC You are working in a community pharmacy and receive a handwritten hospital outpatient prescription for Miss Etta Stone that reads: Miss Etta Stone 14 Sunny Crescent Flatplace FL23 4HR Prednisolone liquid 15 mg for three days then taper Aly Barker Dr A Barker GMC: Flatplace General Hospital, Flatplace 5/6/18 On speaking with Etta s father, he tells you that his daughter was admitted after having an asthma attack. She was discharged this evening and the hospital pharmacy said that he would have to wait for at least two hours to get her medication dispensed. The doctor therefore kindly wrote him a prescription so that he could take Etta home and collect the medicine from a community pharmacy. You do not have any prednisolone liquid in stock but you do have prednisolone soluble tablets. With reference to criminal, civil, administrative and employment law, professional competence, professional guidance and support networks, provide arguments both for and against making the supply. [100%] END OF PAPER (PHA-7002Y) Version 3

21 1 PHARMACEUTICAL LEADERSHIP AND DECISION MAKING PHA-7002Y Main Series UG Examination Artefact 1: Summary of product characteristics (SPC) for Priadel sections Questions 9-11 relate to Artefact 1

22 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Priadel 200mg Prolonged Release Tablets 1. Name of the medicinal product Priadel 200mg prolonged release tablets. 2. Qualitative and quantitative composition Each tablet contains 200mg of the active substance lithium carbonate. 3. Pharmaceutical form Prolonged release tablet White, scored, capsule-shaped tablets engraved P200 on one side, in a prolonged release formulation. 4. Clinical particulars 4.1 Therapeutic indications 1. In the management of acute manic or hypomanic episodes. 2. In the management of episodes of recurrent depressive disorders where treatment with other antidepressants has been unsuccessful. 3. In the prophylaxis against bipolar affective disorders. 4. Control of aggressive behaviour or intentional self-harm. 4.2 Posology and method of administration Dosage must be individualised depending on serum lithium levels and clinical response. The dosage necessary to maintain serum lithium levels within the therapeutic range varies from patient to patient. The minimum effective dose should be sought and maintained. As a general rule, the following dosing schedule is recommended. Please refer also to the specific recommendations for the different indications as listed below: 1. In patients of average weight (70kg) an initial dose of 400-1,200mg of Priadel may be given as a single daily dose in the morning or on retiring. Alternatively, the dose may be divided and given morning and evening. The tablets should not be crushed or chewed. When changing between lithium preparations serum lithium levels should first be checked, then Priadel therapy started at a daily dose as close as possible to the dose of the other form of lithium. As bioavailability varies from product to product (particularly with regard to retard or slow release preparations), a change of product should be regarded as initiation of new treatment. 2. Four to a maximum of seven days after starting treatment, serum lithium levels should be measured. Optimal maintenance serum levels may vary from patient to patient. 3. Blood samples should be taken 12 or 24 hours after the previous dose of lithium, just before the next dose is due, to measure the serum lithium level at its trough. The serum level should not exceed 1.5 mmol/l. The objective is to adjust the Priadel dose so as to maintain the Target serum lithium concentrations at 12 and 24 hours as shown in the table below. Target serum lithium concentration (mmol/l) At 12 hours At 24 hours Once daily dosage Twice daily dosage Both strengths have break lines therefore they can be divided accurately to provide dosage requirements as small as 100mg. Serum lithium levels should be monitored weekly until stabilisation is achieved. The serum level should not exceed 1.5 mmol/l. The tablets should be taken at the same time every day. A double dose to make up for a dose that has been missed should not be taken.

23 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Lithium therapy should not be initiated unless adequate facilities for routine monitoring of serum concentrations are available. Following stabilisation of serum lithium levels, the period between subsequent measurements can be increased gradually, but should not normally exceed two to three months. Additional measurements should be made following alteration of dosage, on development of intercurrent disease, signs of manic or depressive relapse, following significant change in sodium or fluid intake, or if signs of lithium toxicity occur (see Section 4.9). 5. Whilst a high proportion of acutely ill patients may respond within three to seven days of the commencement of Priadel therapy, Priadel should be continued through any recurrence of the affective disturbance. This is important as the full prophylactic effect may not occur for 6 to 12 months after the initiation of therapy. 6. In patients who show a positive response to Priadel therapy, treatment is likely to be long term. Careful clinical appraisal of the patient should be exercised throughout medication (see precautions). 7. If lithium is to be discontinued, particularly in cases of high doses, the dose should be reduced gradually. Prophylactic treatment of bipolar affective disorders and control of aggressive behaviour or intentional self-harm: It is recommended that the described treatment schedule is followed. The dosage needed may vary from patient to patient. As a general rule, serum lithium levels should be maintained within the range of 0.5 to 1.0 mmol/l, and should not exceed 1.5mmol/L. Optimal maintenance serum lithium levels may vary from patient to patient. Treatment of acute manic or hypomanic episodes and recurrent depressive disorders: It is likely that a higher than normal Priadel intake may be necessary during an acute phase and divided doses would be required here. As a general rule the monitoring should maintain serum levels at mmol/l until acute symptoms have been controlled. In all other details the described treatment schedule is recommended. The dosage needed may vary from patient to patient. Serum lithium levels should be monitored (see above) and should not exceed 1.5 mmol/l. Once clinical control is achieved, dosage should be reduced to the prophylactic dose. Elderly: Elderly patients or those below 50kg in weight, often require lower lithium dosage to achieve therapeutic serum lithium levels. Starting doses of 200mg to 400mg are recommended. Dosage increments of 200 to 400mg every 3 to 5 days are usual. Total daily doses of 800 to 1800mg may be necessary to achieve effective blood lithium levels of 0.8 to 1.0 mmol/l. For prophylaxis, the dosage necessary to reach a blood lithium level of 0.4 to 0.8 mmol/l is generally in the range of 600 to 1200 mg/day. Children and adolescents: Not recommended. Renal impairment In patients with mild and moderate renal insufficiency treated with lithium, serum lithium levels must be closely monitored and the dose should be adjusted accordingly to maintain serum lithium levels within the recommended range (see Section 4.4). Lithium is contraindicated in patients with severe renal insufficiency (see Section 4.3).

24 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Contraindications Hypersensitivity to lithium or to any of the excipients. Cardiac disease. Cardiac insufficiency. Severe renal impairment. Untreated hypothyroidism. Breast-feeding. Patients with low body sodium levels, including for example dehydrated patients or those on low sodium diets. Addison's disease. Brugada syndrome or family history of Brugada syndrome. 4.4 Special warnings and precautions for use General When considering Priadel therapy, it is necessary to ascertain whether patients are receiving lithium in any other form. If so, check serum levels before proceeding. The minimum clinically effective dose of lithium should always be used (see Section 4.2). Clear instructions regarding the symptoms of impending toxicity should be given by the physician to patients receiving long-term lithium therapy (see Section 4.9). They should be warned of the urgency of immediate action should these symptoms appear, and also of the need to maintain a constant and adequate salt and water intake. At the first sign of toxicity, the patient should consult a physician and lithium levels should be checked. Treatment should be discontinued immediately on the first signs of toxicity (see Section 4.9). Monitoring recommendations Before starting treatment with lithium, renal function, cardiac function and thyroid function should be evaluated. Patients should be euthyroid before initiation of lithium therapy. Lithium therapy is contraindicated in patients with severe renal insufficiency or cardiac insufficiency (see Section 4.3). Renal, cardiac and thyroid functions should be re-assessed regularly during treatment with lithium. For monitoring recommendations of lithium serum levels see Section 4.2. Renal Impairment Since lithium is primarily excreted via the renal route, significant accumulation of lithium may occur in patients with renal insufficiency. Therefore, if patients with mild or moderate renal impairment are being treated with lithium, serum lithium levels should be closely monitored (see Section 4.2) and the dose should be adjusted accordingly. If very regular and close monitoring of serum lithium levels and plasma creatinine levels is not possible, lithium should not be prescribed in this population. Lithium is contraindicated in patients with severe renal insufficiency (see Section 4.3). The possibility of hypothyroidism and renal dysfunction arising during prolonged treatment should be borne in mind and periodic assessments made. Patients should be warned to report if polyuria or polydipsia develop. In patients who develop polyuria and/or polydipsia (see Section 4.8), renal function should be monitored in addition to the routine serum lithium assessment. Renal tumours: Cases of microcysts, oncocytomas and collecting duct renal carcinoma have been reported in patients with severe renal impairment who received lithium for more than 10 years (see section 4.8).

25 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Fluid/electrolyte balance If episodes of nausea, vomiting, diarrhoea, excessive sweating, and/or other conditions leading to salt/water depletion (including severe dieting) occur, lithium dosage should be closely monitored and dosage adjustments made as necessary. Drugs likely to upset electrolyte balance such as diuretics should also be reported. Indeed, sodium depletion increases the lithium plasma concentration (due to competitive reabsorption at the renal level). In these cases, lithium dosage should be closely monitored and reduction of dosage may be necessary. Caution should be exercised to ensure that diet and fluid intake are normal in order to maintain a stable electrolyte balance. This may be of special importance in very hot weather or work environment. Infectious diseases including colds, influenza, gastro-enteritis and urinary infections may alter fluid balance and thus affect serum lithium levels. Treatment discontinuation should be considered during any intercurrent infection. Risk of convulsions The risk of convulsions may be increased in case of co-administration of lithium with drugs that lower the epileptic threshold, or in epileptic patients (see sections 4.5 and 4.8). Benign intracranial hypertension There have been case reports of benign intracranial hypertension (see Section 4.8). Patients should be warned to report persistent headache and/or visual disturbances. QT prolongation As a precautionary measure, lithium should be avoided in patients with congenital long QT syndrome, and caution should be exercised in patients with risk factors such as QT interval prolongation (e.g. uncorrected hypokalaemia, bradycardia), and in patients concomitantly treated with drugs that are known to prolong the QT interval (see Sections 4.5 and 4.8). Brugada syndrome Lithium may unmask or aggravate Brugada syndrome, a hereditary disease of the cardiac sodium channel with characteristic electrocardiographic changes (right bundle branch block and ST segment elevation in right precordial leads), which may lead to cardiac arrest or sudden death. Lithium should not be administered to patients with Brugada Syndrome or a family history of Brugada Syndrome (see Section 4.3). Caution is advised in patients with a family history of cardiac arrest or sudden death. Elderly patients Elderly patients are particularly liable to lithium toxicity and may exhibit adverse reactions at serum levels ordinarily tolerated by younger patients. Caution is also advised since lithium excretion may be reduced in the elderly due to age related disease in renal function (see Sections 4.2 and 5.2). Children The use in children is not recommended.

26 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Interaction with other medicinal products and other forms of interaction Interactions which increase lithium concentrations: Serum lithium levels may be increased if one of the following drugs is co-administered. When appropriate, either lithium dosage should be adjusted or concomitant treatment stopped. Metronidazole may reduce lithium renal clearance. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase (COX) 2 inhibitors (monitor serum lithium concentrations more frequently if NSAID therapy is initiated or discontinued). Angiotensin-converting enzyme (ACE) inhibitors. Angiotensin II receptor antagonists. Diuretics (thiazides show a paradoxical antidiuretics effect resulting in possible water retention and lithium intoxication). If a thiazide diuretic has to be prescribed for a lithium-treated patient, lithium dosage should first be reduced and the patient re-stabilised with frequent monitoring. Similar precautions should be exercised on diuretic withdrawal. Loop diuretics seem less likely to increase lithium levels. Other drugs affecting electrolyte balance, e.g. steroids, may alter lithium excretion and should therefore be avoided. Tetracyclines. Interactions which decrease serum lithium concentrations: Serum lithium levels may be decreased due to an increase in lithium renal clearance in case of concomitant administration of one of the following drugs: Xanthines (theophylline, caffeine). Sodium bicarbonate containing products. Diuretics (osmotic and carbonic anhydrase inhibitors). Urea Calcitonin Interactions causing neurotoxicity: Co-administration of the following drugs may increase the risk of neurotoxicity: Antipsychotics (particularly haloperidol at higher dosages), flupentixol, diazepam, thioridazine, fluphenazine, chlorpromazine and clozapine may lead in rare cases to severe neurotoxicity with symptoms such as confusion, disorientation, lethargy, tremor, extra-pyramidal symptoms and myoclonus. Increased lithium levels were present in some of the reported cases. Coadministration of antipsychotics and lithium may increase the risk of Neuroleptic Malignant Syndrome, which may be fatal. Discontinuation of both drugs is recommended at the first signs of neurotoxicity. Methyldopa. Triptan derivatives and/or serotonergic antidepressants such as Selective Serotonin Re-uptake Inhibitors (e.g. fluvoxamine and fluoxetine) as this combination may precipitate a serotoninergic syndrome *, which justifies immediate discontinuation of treatment. Calcium channel blockers may lead to neurotoxicity with symptoms such as ataxia, confusion and somnolence. Lithium concentrations may be increased. Carbamazepine may lead to dizziness, somnolence, confusion and cerebellar symptoms such as ataxia.

27 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Other Caution is advised if lithium is co-administered with other drugs that prolong the QT interval (see Sections 4.4 and 4.8), e.g. Class IA (e.g. quinidine, disopyramide), or Class III (e.g. amiodarone) antiarrhythmic agents, cisapride, antibiotics such as erythromycin, antipsychotics such as thioridazine or amisulpride. The list is not comprehensive. Caution is advised if lithium is co-administered with drugs that lower the epileptic threshold (see Section 4.4), e.g. antidepressants such as SSRIs, tricyclic antidepressants, antipsychotics, anaesthetics, theophylline. The list is not comprehensive Lithium may prolong the effects of neuromuscular blocking agents. There have been reports of interaction between lithium and phenytoin, indomethacin and other prostaglandin-synthetase inhibitors. * Serotonin syndrome Serotonin syndrome is a potentially life-threatening adverse reaction, with is caused by an excess of serotonin (e.g. from overdose or concomitant use of serotonergic drugs), necessitating hospitalisation and even causing death. Symptoms may include: - Mental status changes (agitation, confusion, hypomania, eventually coma) - Neuromuscular abnormalities (myoclonus, tremor, hyperreflexia, rigidity, akathisia) - Autonomic hyperactivity (hypo or hypertonia, tachycardia, shivering, hyperthermia, diaphoresis) - Gastrointestinal symptoms (diarrhoea) Strict adherence to the recommended doses is an essential factor for the prevention of the occurrence of this syndrome. 4.6 Fertility, pregnancy and lactation Pregnancy Lithium therapy should not be used during pregnancy, especially during the first trimester, unless considered essential. There is epidemiological evidence that it may be harmful to the foetus in human pregnancy. Lithium crosses the placental barrier. In animal studies lithium has been reported to interfere with fertility, gestation and foetal development. Cardiac especially Ebstein anomaly, and other malformations have been reported. Therefore, a pre-natal diagnosis such as ultrasound and electrocardiogram examination is strongly recommended. In certain cases where a severe risk to the patient could exist if treatment were stopped, lithium has been continued during pregnancy. If it is considered essential to maintain lithium treatment during pregnancy, serum lithium levels should be closely monitored and measured frequently since renal function changes gradually during pregnancy and suddenly at parturition. Dosage adjustments are required. It is recommended that lithium be discontinued shortly before delivery and reinitiated a few days post-partum. Neonates may show signs of lithium toxicity including symptoms such as lethargy, flaccid muscle tone, or hypotonia. Careful clinical observation of the neonate exposed to lithium during pregnancy is recommended and lithium levels may need to be monitored as necessary. Women of child-bearing potential Women of child-bearing potential should use effective contraceptive methods during treatment with lithium. Lactation Lithium is secreted in breast milk and there have been case reports of neonates showing signs of lithium toxicity. Therefore lithium should not be used during breast-feeding (see Section 4.3). A decision should be made whether to discontinue lithium therapy or to discontinue breast-feeding, taking into account the importance of the drug to the mother and the importance of breast-feeding to the infant. 4.7 Effects on ability to drive and use machines Lithium may cause disturbances of the CNS. Since lithium may slow reaction time, and considering the adverse reactions profile of lithium (see Section 4.8), patients should be warned of the possible hazards when driving or operating machinery.

28 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Undesirable effects Side effects are usually related to serum lithium concentration and are less common in patients with plasma lithium concentrations below 1.0 mmol/l. The adverse reactions usually subside with a temporary reduction or discontinuation of lithium treatment. Mild gastrointestinal effects such as nausea, a general discomfort and vertigo, may occur initially, but frequently disappear after the first few days of lithium administration. Fine hand tremors, polyuria and mild thirst may persist. Blood and lymphatic system disorders Leucocytosis. Endocrine disorders Long-term adverse effects may include thyroid function disturbances such as euthyroid goitre and/or hypothyroidism and thyrotoxicosis. Lithium-induced hypothyroidism may be managed successfully with concurrent thyroxine. Hypercalcaemia, hypermagnesaemia, hyperparathyroidism have been reported. Metabolism and nutrition disorders Weight increase, hyperglycaemia. Psychiatric disorders Confusion, delirium Nervous system disorders Ataxia, hyperactive deep tendon reflexes, slurred speech, dizziness, stupor, coma, myasthenia gravis, giddiness, dazed feeling, memory impairment. Tremor, especially fine hand tremors, dysarthria, myoclonus, benign intracranial hypertension (see Section 4.4). Vertigo, impaired consciousness, abnormal reflexes, convulsions (see Sections 4.4 and 4.5), extrapyramidal disorders, encephalopathy, cerebellar syndrome (usually reversible), nystagmus. The above symptoms may result in fall. Peripheral neuropathy may occur on long-term treatment and is usually reversible at cessation of lithium. Cardiac disorders Cardiac arrhythmia, mainly bradycardia, sinus node dysfunction, peripheral circulatory collapse, hypotension, ECG changes such as reversible flattening or inversion of T-waves and QT prolongation (see Sections 4.4 and 4.5), AV block, cardiomyopathy. Gastrointestinal disorders Abdominal discomfort, taste disorder, nausea, vomiting, diarrhoea, gastritis, salivary hypersecretion, dry mouth, anorexia. Skin and subcutaneous tissue disorders Folliculitis, pruritus, papular skin disorders, acne or acneform eruptions, aggravation or occurrence of psoriasis, allergic rashes, alopecia, cutaneous ulcers. Musculoskeletal and connective tissue disorders Muscle weakness, rhabdomyolysis Renal and urinary disorders Polydipsia and/or polyuria and nephrogenic diabetes insipidus, histological renal changes with interstitial fibrosis after long term treatment have been reported (see Section 4.4). This is usually reversible on lithium withdrawal. Long-term treatment with lithium may result in permanent changes in kidney histology, and impairment of renal function. High serum concentrations of lithium including episodes of acute lithium toxicity may aggravate these changes. Rare cases of nephrotic syndrome have been reported. Frequency unknown: Microcysts, oncocytoma and collecting duct renal carcinoma (in long-term therapy) (see Section 4.4). General disorders and administration site conditions Peripheral oedema. Urticaria and angioedema, attributed to some excipients such as acacia powder (or Arabic gum) Reproductive Sexual dysfunction. Senses Dysgeusia, blurred vision, scotomata. If any of the above symptoms appear, treatment should be stopped immediately and arrangements made for serum lithium measurement.

29 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: Overdose In patients with a raised lithium concentration, the risk of toxicity is greater in those with the following underlying medical conditions: hypertension, diabetes, congestive heart failure, chronic renal failure, schizophrenia, Addison's disease. Acute A single acute overdose usually carries low risk and patients tend to show mild symptoms only, irrespective of their serum lithium concentration. However more severe symptoms may occur after a delay if lithium elimination is reduced because of renal impairment, particularly if a slow-release preparation has been taken. The fatal dose, in a single overdose, is probably over 5g. If an acute overdose has been taken by a patient on chronic lithium therapy, this can lead to serious toxicity occurring even after a modest overdose as the extravascular tissues are already saturated with lithium. Chronic Lithium toxicity can also occur in chronic accumulation for the following reasons: Acute or chronic overdosage; dehydration e.g. due to intercurrent illness, deteriorating renal function, drug interactions, most commonly involving a thiazide diuretic or a non-steroidal anti-inflammatory drug (NSAID). Symptoms The onset of symptoms may be delayed, with peak effects not occurring for as long as 24 hours, especially in patients who are not receiving chronic lithium therapy or following the use of a sustained release preparation. Symptoms of lithium intoxication include: Mild: Nausea, diarrhoea, blurred vision, polyuria, light headedness, fine resting tremor, muscular weakness and drowsiness. Moderate: Increasing confusion, blackouts, fasciculation and increased deep tendon reflexes, myoclonic twitches and jerks, choreoathetoid movements, urinary or faecal incontinence, increasing restlessness followed by stupor. Hypernatraemia. Severe: Coma, convulsions, cerebellar signs, cardiac dysrythmias including sinoatrial block, sinus and junctional bradycardia and first degree heart block. Hypotension or rarely hypertension, circulatory collapse and renal failure. Others: Gastrointestinal disorders: increasing anorexia and vomiting. Nervous system disorders: Encephalopathy, cerebellar syndrome with symptoms such as muscle weakness, lack of coordination, drowsiness or lethargy, giddiness, ataxia, nystagmus, coarse tremor. Tinnitus, dysarthria, twitching, myoclonus, extrapyramidal disorders. ECG changes (flat or inverted T waves, QT prolongation), AV block, dehydration and electrolyte disturbances. At blood levels above 2-3 mmol/l, there may be a large output of dilute urine and renal insufficiency, with increasing confusion, convulsions, coma and death.

30 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions 9-11 Artefact 1 - Summary of product characteristics (SPC) for Priadel sections Management There is no specific antidote to lithium. In the event of lithium overdose, lithium should be discontinued and lithium serum levels monitored closely. Supportive treatment should be initiated, which includes correction of fluid and electrolyte balance, if necessary. Diuretics should not be used (see Section 4.5). All patients should be observed for a minimum of 24 hours. ECG should be monitored in symptomatic patients. Steps should be taken to correct hypotension. Consider gastric lavage for non-sustained-release preparations if more than 4 g has been ingested by an adult within 1 hour or definite ingestion of a significant amount by a child. Slow-release tablets do not disintegrate in the stomach and most are too large to pass up a lavage tube. Gut decontamination is not useful for chronic accumulation. Activated charcoal does not adsorb lithium. Haemodialysis is the treatment of choice for severe lithium intoxication (especially in patients manifesting with severe nervous system disorders), or in cases of overdose accompanied by renal impairment. Haemodialysis should be continued until there is no lithium in the serum or dialysis fluid. Serum lithium levels should be monitored for at least another week to take account of any possible rebound in serum lithium levels as a result of delayed diffusion from the body tissues. In cases of acute on chronic overdose or in cases of chronic lithium toxicity if the lithium concentration is >4.0 mmol/l, discuss with your local poisons service. Clinical improvement generally takes longer than reduction of serum lithium concentrations regardless of the method used. 5. Pharmacological properties 5.1 Pharmacodynamic properties Mood-stabilising agent Pharmacotherapeutic group: Psycholeptics; Lithium, ATC code: N05AN01 Lithium is an alkali metal available for medical use as lithium carbonate or lithium citrate. The exact mechanism of action of lithium in the treatment of bipolar disorders is not known. The mode of action of lithium is still not fully understood. However, lithium modifies the production and turnover of certain neurotransmitters, particularly serotonin, and it may also block dopamine receptors. It modifies concentrations of some electrolytes, particularly calcium and magnesium, and it may reduce thyroid activity. 5.2 Pharmacokinetic properties Time to peak serum level for prolonged release Priadel tablets is about 2 hours and approximately 90% bioavailability would be expected. Absorption Lithium is rapidly absorbed from the gastrointestinal tract. Steady-state lithium levels may not be obtained until 4-6 days. Distribution Lithium has a low volume of distribution (0.7 to 0.9 L/kg). It is not bound to plasma proteins. Lithium crosses the placenta and is excreted in breast milk. Metabolism Lithium is not metabolised in the liver. Elimination Lithium is primarily excreted by the kidneys (>95% of the dose). Elimination half-life ranges from 18 to 36 hours. Lithium can be eliminated by haemodialysis. Special populations Elimination half-life may be increased in elderly patients due to age related decrease in renal function and also in patients with renal impairment (see Sections 4.2 and 4.4). 5.3 Preclinical safety data Nothing of therapeutic relevance.

31 1 PHARMACEUTICAL LEADERSHIP AND DECISION MAKING PHA-7002Y Main Series UG Examination Artefact 2: Summary of product characteristics (SPC) for metoclopramide sections Questions relate to Artefact 2

32 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions Artefact 2 - Summary of product characteristics (SPC) for metoclopramide sections Metoclopramide 10mg Tablets 1. Name of the medicinal product Metoclopramide 10mg Tablets 2. Qualitative and quantitative composition Each tablet contains Metoclopramide Hydrochloride, equivalent to 10mg anhydrous metoclopramide hydrochloride. Excipient with known effects: Lactose monohydrate. Each tablet contains 85mg Lactose monohydrate. For the full list of excipients, see section Pharmaceutical form Tablet. White, circular, biconvex uncoated tablets impressed C on one face and the identifying letters M and P on either side of a central division line on the reverse. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses. 4. Clinical particulars 4.1 Therapeutic indications Adult population Metoclopramide is indicated in adults for: - Prevention of delayed chemotherapy induced nausea and vomiting (CINV) - Prevention of radiotherapy induced nausea and vomiting (RINV). - Symptomatic treatment of nausea and vomiting, including acute migraine induced nausea and vomiting. Metoclopramide can be used in combination with oral analgesics to improve the absorption of analgesics in acute migraine. Paediatric population Metoclopramide 10mg tablets are indicated in children (aged years) for: - Prevention of delayed chemotherapy induced nausea and vomiting (CINV) as a second line option 4.2 Posology and method of administration All indications (adult patients) The recommended single dose is 10 mg, repeated up to three times daily. The maximum recommended daily dose is 30 mg or 0.5mg/kg body weight. The maximum recommended treatment duration is 5 days. Paediatric patients aged years Prevention of delayed chemotherapy induced nausea and vomiting (CINV) The recommended dose is 0.1 to 0.15 mg/kg body weight, repeated up to three times daily by oral route. The maximum dose in 24 hours is 0.5 mg/kg body weight. Dosing table Age Body Weight Dose Frequency years Over 60kg 10mg Up to 3 times daily The maximum treatment duration is 5 days for prevention of delayed chemotherapy induced nausea and vomiting (CINV). Tablets are not suitable for use in children weighing less than 61kg. Other pharmaceutical forms/strengths may be more appropriate for administration to this population. Method of administration: A minimal interval of 6 hours between two administrations is to be respected, even in case of vomiting or rejection of the dose (see section 4.4).

33 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions Artefact 2 - Summary of product characteristics (SPC) for metoclopramide sections Special population Elderly In elderly patients a dose reduction should be considered, based on renal and hepatic function and overall frailty. Renal impairment: In patients with end stage renal disease (Creatinine clearance 15 ml/min), the daily dose should be reduced by 75%. In patients with moderate to severe renal impairment (Creatinine clearance ml/min), the dose should be reduced by 50% (see section 5.2). Hepatic impairment: In patients with severe hepatic impairment, the dose should be reduced by 50% (see section 5.2). Paediatric population Metoclopramide is contraindicated in children aged less than 1 year (see section 4.3). 4.3 Contraindications - Hypersensitivity to the active substance or to any of the excipients listed in section Gastrointestinal haemorrhage, mechanical obstruction or gastro-intestinal perforation for which the stimulation of gastrointestinal motility constitutes a risk - Confirmed or suspected pheochromocytoma, due to the risk of severe hypertension episodes - History of neuroleptic or metoclopramide-induced tardive dyskinesia - Epilepsy (increased crises frequency and intensity) - Parkinson's disease - Combination with levodopa or dopaminergic agonists (see section 4.5) - Known history of methaemoglobinaemia with metoclopramide or of NADH cytochrome-b5 deficiency. - Use in children less than 1 year of age due to an increased risk of extrapyramidal disorders (see section 4.4) 4.4 Special warnings and precautions for use Neurological Disorders Extrapyramidal disorders may occur, particularly in children and young adults, and/or when high doses are used. These reactions occur usually at the beginning of the treatment and can occur after a single administration. Metoclopramide should be discontinued immediately in the event of extrapyramidal symptoms. These effects are generally completely reversible after treatment discontinuation, but may require a symptomatic treatment (benzodiazepines in children and/or anticholinergic anti-parkinsonian medicinal products in adults). The time interval of at least 6 hours specified in the section 4.2 should be respected between each metoclopramide administration, even in case of vomiting and rejection of the dose, in order to avoid overdose. Prolonged treatment with metoclopramide may cause tardive dyskinesia, potentially irreversible, especially in the elderly. Treatment should not exceed 3 months because of the risk of tardive dyskinesia (see section 4.8). Treatment must be discontinued if clinical signs of tardive dyskinesia appear. Neuroleptic malignant syndrome has been reported with metoclopramide in combination with neuroleptics as well as with metoclopramide monotherapy (see section 4.8). Metoclopramide should be discontinued immediately in the event of symptoms of neuroleptic malignant syndrome and appropriate treatment should be initiated. Special care should be exercised in patients with underlying neurological conditions and in patients being treated with other centrally-acting drugs (see section 4.3) Symptoms of Parkinson's disease may also be exacerbated by metoclopramide. Methaemoglobinemia Methemoglobinemia which could be related to NADH cytochrome b5 reductase deficiency has been reported. In such cases, metoclopramide should be immediately and permanently discontinued and appropriate measures initiated (such as treatment with methylene blue).

34 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions Artefact 2 - Summary of product characteristics (SPC) for metoclopramide sections Cardiac Disorders There have been reports of serious cardiovascular undesirable effects including cases of circulatory collapse, severe bradycardia, cardiac arrest and QT prolongation following administration of metoclopramide by injection, particularly via the intravenous route (see section 4.8). Special care should be taken when administering metoclopramide, particularly via the intravenous route to the elderly population, to patients with cardiac conduction disturbances (including QT prolongation), patients with uncorrected electrolyte imbalance, bradycardia and those taking other drugs known to prolong QT interval. Intravenous doses should be administered as a slow bolus (at least over 3 minutes) in order to reduce the risk of adverse effects (e.g. hypotension, akathisia). Renal and Hepatic Impairment In patients with renal impairment or with severe hepatic impairment, a dose reduction is recommended (see section 4.2). Contains lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. 4.5 Interaction with other medicinal products and other forms of interaction Contraindicated combination Levodopa or dopaminergic agonists and metoclopramide have a mutual antagonism (see section 4.3). Combination to be avoided Alcohol potentiates the sedative effect of metoclopramide. Combination to be taken into account Due to the prokinetic effect of metoclopramide, the absorption of certain drugs may be modified. Anticholinergics and morphine derivatives Anticholinergics and morphine derivatives may have both a mutual antagonism with metoclopramide on the digestive tract motility. Central nervous system depressants (morphine derivatives, anxiolytics, sedative H1 antihistamines, sedative antidepressants, barbiturates, clonidine and related) Sedative effects of Central Nervous System depressants and metoclopramide are potentiated. Neuroleptics Metoclopramide may have an additive effect with other neuroleptics on the occurrence of extrapyramidal disorders. Serotonergic drugs The use of metoclopramide with serotonergic drugs such as SSRIs may increase the risk of serotonin syndrome. Digoxin Metoclopramide may decrease digoxin bioavailability. Careful monitoring of digoxin plasma concentration is required. Cyclosporine Metoclopramide increases cyclosporine bioavailability (Cmax by 46% and exposure by 22%). Careful monitoring of cyclosporine plasma concentration is required. The clinical consequence is uncertain. Mivacurium and suxamethonium Metoclopramide injection may prolong the duration of neuromuscular block (through inhibition of plasma cholinesterase). Strong CYP2D6 inhibitors Metoclopramide exposure levels are increased when co-administered with strong CYP2D6 inhibitors such as fluoxetine and paroxetine. Although the clinical significance is uncertain, patients should be monitored for adverse reactions.

35 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions Artefact 2 - Summary of product characteristics (SPC) for metoclopramide sections Fertility, pregnancy and lactation Pregnancy A large amount of data on pregnant women (more than 1000 exposed outcomes) indicates no malformative toxicity nor foetotoxicity. Metoclopramide can be used during pregnancy if clinically needed. Due to pharmacological properties (as other neuroleptics), in case of metoclopramide administration at the end of pregnancy, extrapyramidal syndrome in newborn cannot be excluded. Metoclopramide should be avoided at the end of pregnancy. If metoclopramide is used, neonatal monitoring should be undertaken. Breastfeeding Metoclopramide is excreted in breast milk at low level. Adverse reactions in the breast-fed baby cannot be excluded. Therefore metoclopramide is not recommended during breastfeeding. Discontinuation of metoclopramide in breastfeeding women should be considered. 4.7 Effects on ability to drive and use machines Metoclopramide may cause drowsiness, dizziness, dyskinesia and dystonias which could affect the vision and also interfere with the ability to drive and operate machinery. 4.8 Undesirable effects Adverse reactions listed by System Organ Class. Frequencies are defined using the following convention: very common ( 1/10), common ( 1/100, <1/10), uncommon ( 1/1000, <1/100), rare ( 1/10000, <1/1000), very rare (<1/10000), not known (cannot be estimated from the available data). System Organ Class Frequency Adverse reactions Blood and lymphatic system disorders Not known Methaemoglobinaemia, which could be related to NADH cytochrome b5 reductase deficiency, particularly in neonates (see section 4.4) Sulfhaemoglobinaemia, mainly with concomitant administration of high doses of sulfur-releasing medicinal products Cardiac disorders Uncommon Bradycardia, particularly with intravenous formulation Not known Cardiac arrest, occurring shortly after injectable use, and which can be subsequent to bradycardia (see section 4.4); Atrioventricular block, Sinus arrest particularly with intravenous formulation; Electrocardiogram QT prolonged; Torsade de Pointes; Endocrine disorders* Gastrointestinal disorders Uncommon Rare Not known Common Amenorrhoea, Hyperprolactinaemia, Galactorrhoea Gynaecomastia Diarrhoea General disorders and administration site conditions Common Asthenia

36 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions Artefact 2 - Summary of product characteristics (SPC) for metoclopramide sections Immune system disorders Uncommon Not known Nervous system disorders Very common Common Uncommon Rare Not known Psychiatric disorders Common Uncommon Rare Vascular disorder Common Hypersensitivity Anaphylactic reaction (including anaphylactic shock particularly with intravenous formulation Somnolence Extrapyramidal disorders (particularly in children and young adults and/or when the recommended dose is exceeded, even following administration of a single dose of the drug) (see section 4.4), Parkinsonism, Akathisia Dystonia, Dyskinesia, Depressed level of consciousness Convulsion especially in epileptic patients Tardive dyskinesia which may be persistent, during or after prolonged treatment, particularly in elderly patients (see section 4.4), Neuroleptic malignant syndrome (see section 4.4) Depression Hallucination Confusional state Hypotension, particularly with intravenous formulation Not known Shock, syncope after injectable use Acute hypertension in patients with phaeochromocytoma (see section 4.3) Transient increase in blood pressure * Endocrine disorders during prolonged treatment in relation with hyperprolactinaemia (amenorrhoea, galactorrhoea, gynaecomastia). The following reactions, sometimes associated, occur more frequently when high doses are used: - Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonian syndrome, akathisia, even following administration of a single dose of the medicinal product, particularly in children and young adults (see section 4.4). - Drowsiness, decreased level of consciousness, confusion, hallucination. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: Overdose Symptoms Extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucination, and cardio-respiratory arrest may occur. Management In case of extrapyramidal symptoms related or not to overdose, the treatment is only symptomatic (benzodiazepines in children and/or anticholinergic anti-parkinsonian medicinal products in adults). A symptomatic treatment and a continuous monitoring of the cardiovascular and respiratory functions should be carried out according to clinical status.

37 Main Series UG Examination Additional Examination Material PHA-7002Y - Questions Artefact 2 - Summary of product characteristics (SPC) for metoclopramide sections Pharmacological properties 5.1 Pharmacodynamic properties Metoclopramide hydrochloride is an anti-emetic and an accelerator of gastric emptying. 5.2 Pharmacokinetic properties Renal impairment The clearance of metoclopramide is reduced by up to 70% in patients with severe renal impairment, while the plasma elimination half-life is increased (approximately 10 hours for a creatinine clearance of ml/minute and 15 hours for a creatinine clearance <10 ml/minute). Hepatic impairment In patients with cirrhosis of the liver, accumulation of metoclopramide has been observed, associated with a 50% reduction in plasma clearance. 5.3 Preclinical safety data Not applicable.

38 UNIVERSITY OF EAST ANGLIA School of Pharmacy UG Reassessment or Delayed First Sit Examination Registration Number PHA-7002Y PHARMACEUTICAL LEADERSHIP AND DECISION MAKING Answer Grid Question No. Answer Question No. Answer Question No. Answer Staff only No. correct: No. wrong: No. not attempted: Final: Signature and check signature: (PHA-7002Y) Version 1

39 School of Pharmacy Examination Feedback Summary Module Name Pharmaceutical Leadership and Decision Making Module Code PHA-7002Y Year Overall marks Mean mark: 65.5 Max. mark 78.5 Min. mark: Grade distribution: 1 st Fail % % % % % MCQ (Questions 1 to 50): Mean mark: 67.8% Max. mark : 82% Min. mark: 48% Comments: Overall students performed exceptionally well on this part of the paper. Less well answered questions included those covering OTC requests, information retrievable for interpretation from the SPC, and the extended matching type questions. Question: 51 No. of attempts 15 Comments: Some students chose to weave a story in response to the question by trying to embed the required elements into the prose. The result was that they omitted one or more of the components of the decision making process: criminal, civil, administrative and employment law, professional guidance, professional competence and support networks. Students are therefore advised to please assign a clear structure to the answer by using subheadings or even tabulating the answer. Some also did not explore both the argument for and against making the supply. Some also did not explore both the argument for and against making the supply. Students also often did not specify by whom the legislation/guidance was enforced, the potential outcomes and most likely outcomes in the given scenario. A small minority of students failed to identify that EHC is not an emergency supply at the request of a patient levonorgestrel is licensed as a P when sold according to the product license. Question: 52 No. of attempts 57 Comments: Some students chose to weave a story in response to the question by trying to embed the required elements into the prose. The result was that they omitted one or more of the components of the decision making process: criminal, civil, administrative and employment law, professional guidance, professional competence and support networks. Students are therefore advised to please assign a clear structure to the answer by using subheadings or even tabulating the answer. Some also did not explore both the argument for and against making the supply. Students also often did not specify by whom the legislation/guidance was enforced, the potential outcomes and most likely outcomes in the given scenario. School of Pharmacy Summative exam feedback (V1) January 2013 Page 1 of 1