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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