Transcript Objectives
Drug Administration to Children Stacy Cardy BSc Phm The Hospital for Sick Children 1 Objectives To determine what information is required to evaluate pediatric prescriptions To discuss the process of establishing a pediatric dose without previous pediatric experience with a drug To discuss various extemporaneous compounds used in the pediatric population To discuss the “adaptation” of various traditional dosage forms to suite the needs of the pediatric patient 2 Information Required to Evaluate Pediatric Prescriptions Drug & dose Patient Information • Weight & Age • Indication Additional information: • Concomitant medications • Allergies/ ADRs • Previous therapies & response 3 Establishing a Pediatric Dose without Pediatric Experience with Drug Proportion of adult dose • mg/kg dose sometimes calculated based on 70kg average adult weight • assumes similar pharmacokinetics between adults and children • less likely to be valid with very young children 4 Establishing a Pediatric Dose (cont.) Extrapolate from other drugs in class if: • Pediatric experience with other members of class • Very similar pharmacology • Comparative “potency” known eg. opioids, calcium channel blockers 5 Establishing a Pediatric Dose (cont.) Dose titration by response • works best for drugs with quick, measurable response eg. inotropes, antihypertensives • start with very low dose in first patients--may be a delay in achieving therapeutic effect • base dosage increments on adult data re: half life or time to onset of effect • once optimal dose is established in a number of patients, it may be possible to calculate effective mg/kg dose 6 Example-Evaluation Process- for Amlodipine Therapeutic alternatives to amlodipine? • not suitable in all patients Urgency • not immediate • formal clinical trial planned, however some patients required earlier therapy 7 Evaluation Process (cont.) Assess risks & benefits • request for drug originated with staff physician • discussion between clinical pharmacy specialists & physician re: benefits • increased compliance with long-acting calcium channel blocker • increased flexibility in dosing compared with nifedipine in very small patients because solution could be prepared • other drugs from this class have been used with good results in children (eg. Nifedipine, felodipine)8 Evaluation Process (cont.) Estimate dose • Starting dose of 0.1mg/kg/day estimated from potency of amlodipine relative to other CCB and compared with known adult dose Administration • Drug is soluble in water but stability is unknown • Use DISSOLVE AND DOSE-make solution fresh each day Determine endpoints, monitoring • blood pressure (easy to monitor) 9 NONSTANDARD DOSE/DOSAGE FORMS Alter the dosage form • 1/4 or 1/2 tablet Round off the dose • Dose adjustments of 15% may be possible Alter the dosage regimen • Administer uneven doses throughout the day Crush tablets/open capsules Change to a similar drug 10 Extemporaneous Preparations HSC formulations are derived: • • Published formulations with adequate stability data with NO MODIFICATIONS If published formulations have not been fully studied or ingredients are unavailable: • Existing formulas are then modified, or • New formulas designed BUT…. 11 Extemporaneous Preparations Quality product can be ONLY be assured AFTER: • • • • Microbial studies Stability studies (physical & chemical) Bioavailability studies Taste tests OR • Clinical use for minimum of 6 months with positive clinical results 12 FACTORS AFFECTING STABILITY/BIOAVAILABILITY Viscosity • Vehicle Preservatives Flavouring agents pH Storage • Temperature/container Brand of Ingredients 13 Capusules Strength required can not be obtained by manipulation of commercially available dosage forms There is no extemporaneous formulation for the drug in liquid form 14 Capsules Considerations before proceeding with capsule making: • Is drug light sensitive? • Is drug rapidly oxidized? • Is drug a LA product? • Is drug sensitive to humidity or moisture? 15 Dissolve and Dose Administration Utilized as a quick and efficient method to administer small doses of some drugs using standard tablets or capsules and dissolve and dose container Only for water-soluble drugs 16 Considerations for Dissolve and Dose SOLUBILITY • Drug must be soluble in less than 15mL of water – Other ingredients in tablet may be insoluble and sink to bottom, or – Solution may be cloudy STABILITY • Solution must be administered immediately since stability cannot be guaranteed for longer than 20 minutes 17 Considerations for Using IV Orally Form of the drug (ie salt or base) • IV form = oral form? • If forms not =, bioavailablity? • – absorption – not destroyed by gastric contents Drug or excipient irritating/harmful to mucosal membranes? Pro-drugs have poor bioavailability and are not suitable for oral administration Excipients and adjuvants in injectables can be undesirable (eg. alcohol, preservatives) Cost Taste 18 Feeding Tubes Gastrostomy (= G-tube) and Jejunostomy (= J-tube) • Pass through the skin and into stomach or jejunum Nasoenteric Tubes • Tube placed nasally into oesophagus and beyond • Tube can terminate in the: • Stomach = nasogastric (NG) • Duodenum = nasoduodenal (ND) • Jejunum = nasojejunal (NJ) 19 Pharmacokinetic Considerations Local effect medications Sustained Release preparations Enteric coated preparations 20 Medication Administration through Gastrostomy Tubes Oral route is preferred Tubes must be flushed with minimum 5ml water after medication administration (10ml20ml flush is preferred) Tabs must be: • Crushed finely • Mixed and dissolved completely in water • Given immediately 21 Blockage of Tubes Certain medications known to block tubes should be avoided: • • • • • • Liquid iron Ciprofloxacin Clarithromycin Kayexalate Cholestyramine Resin Magnesium Oxide 22 Omeprazole Administration Tablets are ENTERIC COATED They must be SWALLOWED WHOLE Once the tablet is : • SPLIT [5mg or 2.5mg] • CRUSHED [NG or G tube] IT MUST BE PROTECTED FROM STOMACH ACID 23 Acid Neutralization Onset of omeprazole activity = 4 days Recommended to neutralize acid for the FIRST WEEK of therapy for patients receiving split or crushed tablets via PO/GT/NG routes • Extra Strength Antacids (Al & Mg Hydroxides) • Acid Neutralizing Agent is given 15-20 minutes prior to omeprazole administration • Exceptions – NJ or J tube administration – Patients who have achieved reasonable control of gastric acid with H2 antagonists 24 Rectal Administration Advantages • • • • • No venous access NPO status Nausea / vomiting Unconscious / seizure state For drugs not suitable for oral administration • local effect (eg laxatives) Disadvantages • Drug absorption may be poor or erratic • Drug absorption may be interrupted by defecation • Administration may be uncomfortable or unpleasant Local Effect Versus Systemic Effect 25 Rectal Dosage Forms Suppositories Enemas Ointments Foams Drug NOT intended for rectal use • eg Lorazepam injection given rectally for seizures 26 Splitting Suppositories Generally NOT done since drug is usually NOT uniformly distributed Exceptions: • company provides information to support that drug IS uniformly distributed • Drug with a wide therapeutic range 27 Opium and Bellodonna 1/4 or 1/2 Suppositories INGREDIENTS Mfgr Lot # Qty Msrd Chk’d 1. Opium & Bellodonna Whole Suppositories STORAGE: Refrigerate EXPIRY: 4 weeks 28 Nifedipine 1.25mg and 2.5mg Doses 1. Place one 10mg capsule in a small amount of water in a med cup. This will soften capsule. When capsule is soft (after about 90 seconds) pat dry with a tissue. 2. In a dry med cup, poke the capsule using the end of a dry 1mL oral syringe. 3. Push out the oil inside the capsule into a med cup. 4. For approximate dose of 1.25mg measure 0.04mL. For approximate dose of 2.5mg measure 0.08mL. 5. Nifedipine is light sensitive. Administer immediately after preparation. 29 When Medicines Taste Bad 30 CONCLUSION Pediatric Population is unique Special considerations are required with respect to drug dosing and dosage forms KNOW YOUR RESOURCES 31