Drug Administration to Children

1
Drug Administration to Children

• Stacy Cardy BSc Phm
• The Hospital for Sick Children

2
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

3
Information Required to Evaluate Pediatric
Prescriptions

• Drug dose
• Patient Information
• Weight Age
• Indication
• Additional information
• Concomitant medications
• Allergies/ ADRs
• Previous therapies response

4
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

5
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

6
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

7
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

8
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)

9
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)

10
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

11
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.

12
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

13
FACTORS AFFECTING STABILITY/BIOAVAILABILITY

• Viscosity
• Vehicle
• Preservatives
• Flavouring agents
• pH
• Storage
• Temperature/container
• Brand of Ingredients

14
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

15
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?

16
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

17
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

18
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

19
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)

20
Pharmacokinetic Considerations

• Local effect medications
• Sustained Release preparations
• Enteric coated preparations

21
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

22
Blockage of Tubes

• Certain medications known to block tubes should
  be avoided
• Liquid iron
• Ciprofloxacin
• Clarithromycin
• Kayexalate
• Cholestyramine Resin
• Magnesium Oxide

23
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

24
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

25
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

26
Rectal Dosage Forms

• Suppositories
• Enemas
• Ointments
• Foams
• Drug NOT intended for rectal use
• eg Lorazepam injection given rectally for seizures

27
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

28
Opium and Bellodonna 1/4 or 1/2 Suppositories

• INGREDIENTS Mfgr Lot Qty Msrd Chkd
• 1. Opium Bellodonna
• Whole Suppositories
• STORAGE Refrigerate
• EXPIRY 4 weeks

29
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.

30

• When Medicines Taste Bad

31
CONCLUSION

• Pediatric Population is unique
• Special considerations are required with respect
  to drug dosing and dosage forms
• KNOW YOUR RESOURCES