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Drug Administration to Children
Stacy Cardy BSc Phm
The Hospital for Sick Children
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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
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Information Required to Evaluate Pediatric Prescriptions
Drug & dosePatient Information
• Weight & Age• Indication
Additional information:• Concomitant medications• Allergies/ ADRs• Previous therapies & response
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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
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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
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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
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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
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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)
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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)
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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 capsulesChange to a similar drug
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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….
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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
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FACTORS AFFECTING STABILITY/BIOAVAILABILITY
Viscosity•Vehicle
Preservatives
Flavouring agents
pH
Storage
• Temperature/container
Brand of Ingredients
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Capusules
Strength required can not be obtained by
manipulation of commercially availabledosage forms
There is no extemporaneous formulation for the drug in liquid form
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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?
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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
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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
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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
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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)
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Pharmacokinetic Considerations
Local effect medications
Sustained Release preparations
Enteric coated preparations
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Medication Administration through Gastrostomy Tubes
Oral route is preferred Tubes must be flushed with minimum 5ml
water after medication administration (10ml-20ml flush is preferred)
Tabs must be:• Crushed finely• Mixed and dissolved completely in water• Given immediately
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Blockage of Tubes
Certain medications known to block tubes should be avoided:
• Liquid iron• Ciprofloxacin• Clarithromycin• Kayexalate• Cholestyramine Resin• Magnesium Oxide
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Omeprazole Administration
Tablets are ENTERIC COATEDThey must be SWALLOWED WHOLEOnce the tablet is :
•SPLIT [5mg or 2.5mg]•CRUSHED [NG or G tube]
IT MUST BE PROTECTED FROM
STOMACH ACID
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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
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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
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Rectal Dosage Forms
Suppositories
Enemas
Ointments
Foams
Drug NOT intended for rectal use
•eg Lorazepam injection given rectally for seizures
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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
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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
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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.
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When Medicines Taste Bad
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CONCLUSION
Pediatric Population is unique
Special considerations are required with
respect to drug dosing and dosage forms
KNOW YOUR RESOURCES