Dosing schedule/ Dosage Regimen ¢ The schedule of doses of a therapeutic agent per unit of time, including: the time between doses (ex. Every 6 hours) or the time when the dose (s) are to be given ( ex. At 8am and 4 pm daily), and the amount of medicine ( ex. Number of capsules) to be given at each specific time.Standard Dosing schedule by Brown ¢ Standard “bid” = 10 am and 10 pm ¢ Standard “tid”= 9am-ipm-5pm ¢ Q6h= 9am-3pm-9pm-3am ¢ Qid= 9am- 1pm-5pm-9pm ° Hs- 9 pmDosing schedule according to Drug and Therapy Bulletin, University of Florida STANDARDIZED DOSING TIMES Standard Times Interval Daily 2 times a day (BID) 3 times a day (TID) 4 times a day (QID) 5 times a day Every 3 hours Every 4 hours Every 6 hours Every 8 hours Every 12 hours Every 24 hours Bedtime With meals 0900 0900, 0900, 0800, 0900, 0500, 0000, 0100, 0600, 0800, 0900, 2100 1400, 2100 1200, 1700 (52 Psych) 1300, 1700, 2100 0900, 1300, 1700, 2100 0300, 0600, 0900, 1200, 1500, 1800, 2100 0500, 0900, 1300, 1700, 2100 1200, 1800, 2400 1600, 2400 2100 Time will default to hour profiled (ie, 1* order processed) 2100 0800, 1200, 1700 With meals and at bedtime 0800, 1200, 1700, 2100 Times determined by the time the 1“ dose is processed Injectable antibioticsEXTEMPORANEOUS HO) ele) PINEObjectives: To define extemporaneous compounding + To discuss the risks associated with extemporaneous compounding + To discuss importance of extemporaneous compoundingUnited States Pharmacopeia (USP 795) define compounding as: “The preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug-delivery device, or device in accordance with a licensed practitioner’s prescription, medication order, or initiative based on the practitioner-patient- pharmacist-compounder relationship in the course of professional practice”Extemporaneous compounding ¢ Describes the use of traditional compounding techniques to manipulate chemical ingredients to produce appropriate dosage forms when no commercial medicine form is available.Extemporaneous Compounding “The timely preparation of a drug product according to the physician’s prescription, in which the amounts of the ingredients are calculated to meet the needs of a particular patient or a group of patients according to Good Manufacturing Practice”Compounding On-demand preparation of a drug product. According to a physician’s prescription. Meets the unique needs of an individual patient. The production or processing of a drug ina LARGE tity by various mechanism¢ In compounding, an individualized medicine is prepared at the request of a prescriber on a small scale basis. ¢ They are not required to report adverse events to FDA. ¢ Drugs, Dosage forms, equipments and techniques are the variablesWhy Compound? Pediatric patients requiring diluted adult strengths of drugs. Patients needing an oral solution or suspension of a product burl eee ANC] Mel me ett Patients with sensitivity to dyes, preservatives, or flavoring agents found in commercial formulations. Dermatological formulations with fortified (strengthened) or diluted concentrations of commercially available products. ® Specialized dosages for therapeutic drug monitoring. Care for hospice patients in pain management. eolelletieiy eee uurUnpreserved Circe (erg hypersensitive feos elie) Serer Retr Orphan drugs eee Pree eaeit ie drugs rc) diorders/ rel T tty Higher dose requiements Region Brel requirements Endogenous ftetenetey Changing ceo existing drugWORK FLOW CHART 2: HANDLING OF PRESCRIPTIONS WITH EXTEMPORANEOUS PREPARATION MEDICINES IN THE PHARMACYPrescription Analysis Compounding Considerations: 1. 2. a Always consider the use of commercially available products as far as possible. If no suitable commercial product exists, consider a therapeutic alternative that is available in a suitable dosage form. This must be discussed with the physician. Extemporaneous preparations should be done based on evidence-based references. Always check for the suitability of the product/brand for extemporaneous preparations. Preparations should be done according to what is stated as far as possible unless stated otherwise in the product leaflet. When no information is available, compound an oral medication by dispensing a tablet and/or capsule and directing the caregiver to mix just prior to administration. Stability for shelf storage in the pharmacy is applicable without opening. Once opened, the stability of the preparation should be no longer than 30 days. Maximum quantity of the extemporaneous preparations to be dispensed should eed ; hhupa.d/nemnphacmacy gox.em/2/iten/ deta fies/ dos not exceed one month: upload/ertemporanequs-formulation-2015.pdPrescription Analysis Compounding Considerations 8. Refrain assumptions on the therapeutic equivalence in the case of suggesting alternative agents as the possibilities and supporting data may be limited. 9. Techniques in compounding preparations and manipulations should always be in line with the standard Good Preparation Practice as delivering an accurate dose is paramount. 10. Staff and facilities are challenged to undertake intermittent competency assessments in order to achieve the standards requirement. 11. Documentation after each preparation should include details on the materials used, processes involved and the responsible personnel in- charge.CONSIDERATIONS FOR PREPARING EXTEMPORANEOUS COMPOUNDS 1. Pharmacy personnel are reminded not to empirically change flavourings or suspending agents because they can affect the pH and stability of the product and result in an unstable product. 2. Please consider ingredients in the formulations that require special precautions in neonates. 3. Mixing of a compounded formulation should always be in line with the following principles: a. Ensure that all ingredients used are within the expiry date. b. Ensure that all utensils are clean; including mortar and pestle, graduates, pill cutters and stirring rods. Ps Eroduct should be labelled clearly and stored as recommended within the mula. d. For solution or suspension products, emphasise on the importance of thorough shaking before administration. eesstaneanmhiinnltdad oltre ietiements fodCONSIDERATIONS FOR PREPARING EXTEMPORANEOUS COMPOUNDS 4. If compounding a preparation using contents from an ampoule, remember to withdraw the solution (medication) from the ampoule using a filter needle to ensure no glass particles are incorporated into the compound. 5. Place tablet(s) within mortar and pestle to grind tablets to a fine powder. For film-coated tablets, it may be necessary to add a small amount of diluents such as water, to soften the coating prior to grinding the tablets. This will ensure that the compound will not have an eggshell appearance from the film coating floating throughout the suspension. If you are using capsules, open the capsule and empty the powder into the mortar and discard the capsule shell. 6. Solutions will have a clearer appearance versus a compounded suspension.Considerations before compounding: ¢ Commercially available of drug in dosage form, strength and packaging + Ingredients, intended use, dosage and method of administration concern ¢ Education, skill and expertise to drug compounding ¢ Proper equipment, supplies, chemicals and the guidelines set in USP¢ Safety of the compounded product ¢ Storage facility ° Necessary calculations ° Necessary documentation + Literature references (use, preparation, stability and administration)¢ Expected duration of therapy * Quality control checks ( weight variation, pH) + Ingredient identity, quality and Purity ¢ Physico-chemical incompatibilitiesSources of Formulae *Compendia e.g. BP, Martindale 28'"/ USP/NF etc *Hospital-often continuation of treatment in primary care *GP’s own e.g. Dr Ives wart paint etc. *Published literature/journal articles available on internet. Often American/ EuropeanQuality control ¢ Oral and topical liquids ( solutions, suspensions and emulsions)- pH, sp. Gravity, assays, theological properties, physical observation, physical stability ¢ Hard gelatin capsules- weight variation, dissolution and disintegration¢ Ointments, creams and Gels- pH, sp. Gravity, assay, rheological properties ¢ Suppositories, Trouches- melting points, dissolution test, physical stability ¢ Parenteral Preparation- pH, sp. Gravity, osmolality, color, clarity, particulate matter, sterilityTraining and Experience ¢ Provide knowledge and _ skills in good extemporaneous practice, assessment of risk and medication error potential, formulation, quality assurance Demonstrate competency in the necessary extemporaneous' preparation skills and pharmaceutical calculations and dilutionsEquipments ¢ Laminar flow hoods ¢ Weighing balance ¢ Ointment slabs along with spatulas ¢ Mortar and pestle ¢ Volumetric glassware ( chips, cracks, leveling lines) ¢ Calibrated and ValidatedEnvironment ¢ Clean, Neat, well-lit and quiet working area ¢ If aseptic compounding is considered , a clean air environment is needed ¢ Measures must be taken to avoid cross contamination ¢ Environmental conditions such as temperature, humidity and lighting to limit degradation of product¢ Areas and equipment should be cleaned before and after use * Critical surfaces should be sanitized with 70% alcohol « Adequate pest control measures should be takenFormulas ¢ Should be developed or obtained ¢ Methods used, ingredients added and order of steps is documented.1. Provides methodology for each person involved or requested to provide such service the info. Necessary to do so properly. 2. It provides consistency from batch to batch 3. If the product does not turn out the way expected, a stepwise methodology exists for reviewing and determining what happened and if revisions and improvement are needed.Chemical and Supplies ¢ Proper dispensing container for the medications ¢ Pharmaceutical-grade chemical is necessary ¢ Pharmacist use different chemicals from reliable sourcesAvailability of Raw Materials 1, Need to obtain a Pharmaceutical Grade, BP, PhEur or USP 2. Laboratory Grades AnalaR may be all that’s available. 3, May be using a licensed medicine e.g. crushing tablets, diluting a steroid cream such as Betnovate 4. Difficult to obtain small quantities of pure drug powders 5, Need to consider TSE-Transmissible Spongiform Encephalopathy e.g. Lanolin 6. Good practice to obtain a Certificate of Analysis 7. May need to use another unlicensed medicine e.g. imported tablets. Need to be assured of QualityLabeling The label of an extermporaneously prepared product should include (in the exceptional circumstances of batch manufacture some Information may not be relevant): Name of the patient Name, address and telephone number of the pharmacy Date of preparation Date on which the product was dispensed Name of the product. if applicable. or a description of the product Generic name of the active substance(s). strength and quantity Name. strength and quantity of any other ingredient Total quantity of the final product to be supplied Directions for the appropriate use of the product Route of administration Relevant cautionary and advisory labels Warning “Keep out of the reach of children” Expiry date (including an in-use expiry date a@s appropriate) or information about limits for use Special storage or handling requirements ]©-g- for certain liquid preparations ‘Shake well before use Batch number, if applicableDocumentation - It gives processing, packaging and release instructions. + For products regularly prepared, master documents should be prepared and checked ¢ It should be clear and detailed * Worksheets: name and formula of the product, source of formula, unique ID number, manufacturer, batch number of each starting material, date of preparationRecord Keeping The following must be recorded each time a medicine is extemporaneously prepared for supply to a patient: Patient’s name Pt.’s address and contact details . Name and address of the patient’s prescriber . Date of preparation Formulation used and source aaRwPe5. Calculations 6. Details of each preparation step 7. Name, strength and quantity of each ingredient of material used 8. Source of starting ingredients or materials 9. Batch number and expiry date of each ingredients or material used 10. Storage conditions 11. Expiry date of finished product 12. Identity of the pharmacist 13. Results of QC test conductedCHECKLIST 2: HANDLING OF PRESCRIPTIONS WITH EXTEMPORANEOUS PREPARATION MEDICINES IN THE PHARMACY | Receive prescription Check availability of medicine 3. | Discuss with medical practitioner on alternative medicine 4, | Check commercially avaitable status at retail pharmacy outlet | , 4 5. | Search for evidence-based reference to prepare extemporaneous oe | Instruct patient/caregiveron how | | to prepare prior to administration | of medicine, if needed to prepare stat each time } } + 7. | Dispense medicine and counsel | Patient/caregiver accordinglyRisks associated with extemporaneous compounding: 1. Formulation Failure - Validated and stability data - Occurs when a formulation has not been adequately validated > toxicity and therapeutic incompatibilites - Overdose and Underdose may occur - Example: Suspension2. Microbial contamination - by-products of microbial degradation can lead to physical and chemical changes in the preparation - Microbial growth can lead to spoilage and producing foul odor3. Calculation errors - pose greatest risk of serious patient harm - @complexity of calculations, 7. risk of an error - Should be documented in worksheet - Common errors such as conversion of units4. Starting materials - risk of using ingredients that are no longer suitable - Some ingredients are age-specific, unsuitable for religious groups - List down all excipients used5. Patient Accessibility issues - Palatibility and presentation of oral liquid medicines6. Health and Safety Risk - Risk to the operator should be considered - When handling hazardous substances, it should be equipped suitable container and system should be implemented to avoid cross contamination7. Therapeutic risks and clinical consequences -It is important to review both inherent properties of drug and the patient’s clinical condition. - Risk assessment of the patient is very importantManaging the risk 1. a. aces rho Clinical Risk Reduction Identify extemporaneous compounding as high- risk therapy . Carry out a risk assessment Consider alternative therapies . Review all the available evidence to support the use of preparation Evaluate drug toxicity Monitor patient for clinical effect, toxicity and ADR . Documentation2. Technical Risk Reduction 2.1 Formulation a. Use standard, validate formula b. Evaluate data using first principles c. Gather information on or evidence use d. Use of information resources e. Restrict the shelf —life to limit degradation and spoilage2.2 Preparation a. Ensure facilities comply with guidance and subject to audit b. Use QA approved worksheets and procedures c. Ensure facilities and equipments are validated/calibrated d. Ensure all operatives are trained e. Use license or approved starting materialsRole of Pharmacist ¢ There is a growing need to compound certain medications because they are not available through conventional manufacturing methods. ¢ Compounding pharmacist gives many options with regard to drug therapy, have appropriate resources and references to compound quality medications.¢ Pharmacist are responsible for ensuring that extemporaneous preparations are compounded according to compounding guidelines and standards with respect to purity, quality, stability, packing, and record keeping.Commonly Requested Dosage Forms- Non Sterile » For Application to the skin » Creams, Ointments, Pastes, Lotions, External Solutions » For Oral Ingestion-Liquids » Suspensions, Solutions, Mucilage > Traditional terms: Elixir, Mixture, Linctus » Now all referred to as Oral Solution/Suspension unless using a compendial title.Oral Liquids > |s drug soluble in vehicle at dose required? > |f not could a suspension be prepared > Crush tablets or use Powder > Use highest strength tablets to reduce overall excipients » Check tablet characteristics: Controlled Release, Sugar Coated, Film Coated, Enteric Coated > Good Practice: Always use same brand and strength. Care with generics. > Good Practice: Standardise to dose/Sml orMaking a Suspension From Tablets » Crushing, grinding 7 > Wetting and pasting ’ ) > These steps are vital to give homogeneous productEQUIPMENT FOR WEIGHING, MEASURING, AND COMPOUNDING Balances: An electronic balance is easier to learn and use and is more accurate than other types of balances. Forceps and Spatulas: Forceps should be used when picking up weights so that moisture and oils are not transferred to the weights. Spatulas are used in compounding tasks such as preparing ointments and creams or loosening material from the surfaces of a mortar and pestle.* Compounding Slab: This is an ideal surface for mixing compounds because of its nonabsorbent surface. ¢ Mortar and Pestle: The coarser the surface of the mortar and pestle, the finer the triturating, or grinding, that can be done. * Graduates and Pipettes: A pipette is used for measuring liquids with a volume less than 1.5 mL¢ Master Formula Sheet: Prepared by the pharmacist, this sheet indicates the amount of each ingredient needed, lists the procedures to follow, and provides the labeling instructions.TECHNIQUE FOR WEIGHING PHARMACEUTICAL INGREDIENTS ¢ Weighing of the product is one of the most essential parts of the compounding process. ¢ Weighing the exact amount prescribed is essential in compounds for several reasons: the product cannot be “checked” for content once mixed, the quantities weighed out are often very small, and a slight overage could mean a serious overdose for the patient.TECHNIQUE FOR MEASURING LIQUID VOLUMES ¢ A general rule of thumb is to always select the device that will give you the most accurate volume. Selecting a container that will be at least half full when measuring, or using the smallest device that will hold the required volume, is considered good practice.Compounding Issues Safety Note! * Use the smallest device that will hold the required volume when measuring a liquid.Compounding Issues Safely Note! * Always measure liquids on a solid, level surface at eye level.COMMINUTION AND BLENDING OF DRUGS ° Geometric Dilution Method: A way to combine drugs using a mortar and pestle. ¢ Examples of Compounding Preparations: solutions, suspensions, ointments and creams, powders, suppositories, and capsules.¢ Labeling, Record Keeping, and Cleanup: After compounding, the product must be labeled with a prescription label, and a careful record of the compounding operation should be kept. Once the compounding operation is finished, the equipment and area should be cleaned and everything should be returned to their proper places in storage.Compounding Issues Safety Note! * Compounding should never be rushed.2. ALLOPURINOL SUSPENSION 20MG/ML GenericName —; Allopurinol Indication : Gout or uric acid and calcium oxalate renal stones Dosage Form — Suspension Strength : 20me/mt Stability : 60 days Storage : Refrigerate (preferable) or at room temperature Plus® (1:1) or Sweet SF* : Ora-Plus"(1:1) or Blend* or Blend SF* or Cherry syrup or Equivalent vehicle to Ora-Sweet® : Ora-Plus® (1:1) Methylcellulose 1% : Simple Syrup (1:1) PROCEDURE: Crush tablets in a mortar to fine powder. Levigate the powder with small amount of vehicle until. smooth past Add more vehicle to the paste until liquid is formed and transfer the liquid into a container. a 2. \s formed. 3. 4. Use additional vehicle to rinse the remaining drug from the mortar and pour into 5. 6 the container. Make up to final volume with vehicle. Shake wellGeneric Name Alprazolam Indication Anxiety disorders Dosage Form Suspension Strength : img/mt Stability : 60days Storage 2 Room temperature and protect from light VEHICLE OF CHOICE: + X-Temp®* Oral Suspension System 1. 2. a 4. 5. 6. Crush tablets in a mortar to fine powder. Levigate the powder with small amount of vehicle until smooth paste is formed. Add more vehicle to the paste until liquid is formed and transfer the liquid into a container. Use additional vehicle to rinse the remaining drug from the mortar and pour into the container. Make up to final volume with vehicle, Shake well and label. NOTES:Generic Name Amlodipine Indication + Hypertension Dosage Form 5 Suspension Strength Lmg/ent. Stability 20 days Storage Refrigerate VEHICLE OF CHOICE, + X-Temp™ Oral Suspension Sy: PROCEDURE: 1, Crush tablets in a mortar to fine powder. 2 Hed water to disintegrate the tab ’ jer with amall amount of velicle until smooth paste ts forned. 4. Add more vehicle to the paste until liquid is formed and transfer the liquid into # 5. 6 7 container. Use additional vehicle to rinse the remaining drug from the mortar and pour into the container, Make up to final volume with vehicte, . Shake well and label,