Preparations: Pediatric powder for oral solution (when
reconstituted as
solution containing antacid): 10 mg/mL; Chewable tablets with
buffers: 25,
50, 100, and 150 mg; Buffered powder for oral solution: 100, 167,
and 250
mg
Dosage
Neonatal dose (infants aged <90 days): 50 mg per m2 of body surface area every 12 hours.
Pediatric usual dose: In combination with other
antiretrovirals: 90 mg
per m2 of body surface area every 12 hours.
Pediatric dosage range: 90 to 150 mg per m2 of body surface
area every
12 hours. (Note: may need higher dose in patients with central
nervous
system disease.)
Adolescent/Adult dose: Body weight >=60 kg: 200 mg twice daily.
Body
weight <60 kg: 125 mg twice daily.
Major toxicities
Most frequent: Diarrhea, abdominal pain, nausea, and vomiting.
Unusual (more severe): Peripheral neuropathy (dose related),
electrolyte abnormalities, and hyperuricemia.
Uncommon: Pancreatitis (dose related, less common in children
than
adults), increased liver enzymes, and retinal depigmentation.
Drug interactions
Possible decrease in absorption of ketoconazole, itraconazole,
and
dapsone; administer at least 2 hours before or 2 hours after
ddI.
Tetracycline and fluoroquinolone antibiotic absorption
significantly
decreased (chelation of drug by antacid in pediatric powder and
tablets); administer 2 hours before or 2 hours after ddI.
Concomitant administration of ddI and delavirdine may decrease
the
absorption of these drugs; separate dosing by at least 2 hours.
Administration with protease inhibitors: indinavir should be
administered at least 1 hour before or after ddI on an empty
stomach.
Ritonavir should be administered at least 2 hours before or
after ddI.
Special instructions
ddI formulation contains buffering agents or antacids.
Food decreases absorption; administer ddI on an empty stomach
(1 hour
before or 2 hours after a meal). Further evaluation in children
regarding administration with meals is under study.
For oral solution: shake well and keep refrigerated; admixture
is
stable for 30 days.
When administering chewable tablets, at least two tablets
should be
administered to ensure adequate buffering capacity (e.g., if
the
child's dose is 50 mg, administer two 25-mg tablets and not one
50-mg
tablet).
Lamivudine (3TC), EPIVIR (R)
Preparations: Solution: 10 mg/mL; Tablets: 150 mg
Dosage
Neonatal dose (infants aged <30 days): 2 mg per kg of body weight twice daily.
Pediatric dose: 4 mg per kg of body weight twice daily.
Adolescent/Adult dose: Body weight >=50 kg: 150 mg twice daily.
Body
weight <50 kg: 2 mg per kg body weight twice daily.
Major toxicities
Most frequent: Headache, fatigue, nausea, diarrhea, skin rash,
and
abdominal pain.
Unusual (more severe): Pancreatitis (primarily seen in children
with
advanced HIV infection receiving multiple other medications),
peripheral
neuropathy, decreased neutrophil count, and increased liver
enzymes.
When used with zidovudine (ZDV) may prevent emergence of ZDV
resistance, and for ZDV-resistant virus, revision to phenotypic
ZDV
sensitivity may be observed.
Special instructions
Can be administered with food.
For oral solution: store at room temperature.
Decrease dosage in patients with impaired renal function.
Drugs that decrease renal function could decrease clearance.
Should not be administered in combination with zidovudine (poor
antiretroviral effect).
Special instructions
Can be administered with food.
Need to decrease dose in patients with renal impairment.
For oral solution: shake well and keep refrigerated; solution
stable
for 30 days.
Zalcitabine (ddC), HIVID (R)
Preparations: Syrup: 0.1 mg/mL (investigational); Tablets:
0.375 and
0.75 mg
Dosage
Neonatal dose: Unknown.
Pediatric usual dose: 0.01 mg per kg of body weight every 8
hours.
Pediatric dosage range: 0.005 to 0.01 mg per kg of body weight
every 8
hours.
Adolescent/Adult dose: 0.75 mg three times a day.
Major toxicities
Most frequent: Headache, gastrointestinal disturbances, and
malaise.
Unusual (more severe): Peripheral neuropathy, pancreatitis,
hepatic
toxicity, oral ulcers, esophageal ulcers, hematologic toxicity, and
skin
rashes.
Drug interactions
Cimetidine, amphotericin, foscarnet, and aminoglycosides may
decrease
renal clearance of ddC.
Antacids decrease absorption of ddC.
Concomitant use with ddI is not recommended because of the
increased
risk of peripheral neuropathy.
Intravenous pentamidine increases the risk for pancreatitis; do
not use
concurrently.
Special instructions
Administer on an empty stomach (1 hour before or 2 hours after
a meal).
Decrease dosage in patients with impaired renal function.
Dose for premature infants: (Standard neonatal dose may be
excessive in
premature infants.) Under study in Pediatric AIDS Clinical Trial
Group
protocol 331: 1.5 mg per kg of body weight every 12 hours from
birth to 2
weeks of age; then increase to 2 mg per kg of body weight every 8
hours
after 2 weeks of age.
Neonatal dose: Oral: 2 mg per kg of body weight every 6 hours.
Intravenous: 1.5 mg per kg of body weight every 6 hours.
Pediatric usual dose: Oral: 160 mg per m2 of body surface area
every 8
hours. Intravenous (intermittent infusion): 120 mg per m2 of body
surface
area every 6 hours. Intravenous (continuous infusion): 20 mg per m2
of body
surface area per hour.
Pediatric dosage range: 90 mg per m2 of body surface area to
180 mg per
m2 of body surface area every 6-8 hours.
Adolescent/Adult dose: 200 mg three times a day or 300 mg twice
daily.
Major toxicities
Most frequent: Hematologic toxicity, including granulocytopenia
and
anemia, and headache.
Unusual: Myopathy, myositis, and liver toxicity.
Drug interactions
Increased toxicity may be observed with concomitant
administration of
the following drugs (therefore, more intensive toxicity
monitoring may
be warranted): ganciclovir, interferon-alpha, TMP/SMX,
acyclovir, and
other drugs that can be associated with bone marrow
suppression.
The following drugs may increase ZDV concentration (and
therefore
potential toxicity): probenecid, atovaquone, methadone,
valproic acid,
and fluconazole.
Decreased renal clearance may be observed with
co-administration of
cimetidine (may be significant in patients with renal
impairment).
ZDV metabolism may be increased with co-administration of
rifampin and
rifabutin (clinical significance unknown); clarithromycin may
decrease
concentrations of ZDV probably by interfering with absorption
(preferably administer 4 hours apart).
Ribavirin decreases the intracellular phosphorylation of ZDV
(conversion to active metabolite).
Phenytoin concentrations may increase or decrease.
Should not be administered in combination with d4T (poor
antiretroviral
effect).
Special instructions
Can be administered with food (although the manufacturer
recommends
administration 30 minutes before or 1 hour after a meal).
Decrease dosage in patients with severe renal impairment.
Substantial granulocytopenia or anemia may necessitate
interruption of
therapy until marrow recovery is observed; use of
erythropoietin,
filgrastim, or reduced ZDV dosage may be necessary in some
patients.
Reduced dosage may be indicated in patients with substantial
hepatic
dysfunction.
Infuse intravenous loading dose or intermittent infusion dose
over 1
hour.
For intravenous solution: dilute with 5% dextrose injection
solution to
concentration <=4 mg/mL; refrigerated diluted solution is stable for 24 hours.
Some experts in pediatric HIV infection use a dose of 180 mg
per m2 of
body surface area every 12 hours when using in drug
combinations with
other antiretroviral compounds, but data on this dosing in
children is
limited.
Neonatal dose: Unknown.
Pediatric dose: Unknown.
Adolescent/Adult dose: 400 mg three times a day.
Major toxicities
Most frequent: Headache, fatigue, gastrointestinal complaints,
and rash
(may be severe).
Drug interactions
Metabolized in part by hepatic cytochrome P450 3A (CYP3A).
There could
potentially be multiple drug interactions. ***
Before administration, the patient's medication profile should
be
carefully reviewed for potential drug interactions.
DLV decreases the metabolism of certain drugs, resulting in
increased
drug levels and potential toxicity. DLV is not recommended for
concurrent use with antihistamines (e.g., astemizole or
terfenadine);
sedative-hypnotics (e.g., alprazolam, midazolam, or triazolam);
calcium
channel blockers (e.g., nifedipine); ergot alkaloid
derivatives;
amphetamines; cisapride; or warfarin.
DLV clearance is increased, resulting in substantially reduced
concentrations of DLV, with concurrent use of rifabutin,
rifampin, or
anticonvulsants (e.g., phenytoin, carbamazepine, or
phenobarbital).
Concurrent use is not recommended.
Absorption of DLV is decreased if given with antacids or
histamine2
receptor antagonists.
Increased trough concentrations of DLV if given with
ketoconazole or
fluoxetine; increased levels of both drugs if DLV is given with
clarithromycin.
DLV increases levels of dapsone and quinidine.
Administration with protease inhibitors: decreases metabolism
of
saquinavir and indinavir, resulting in a significant increase
in
saquinavir and indinavir concentrations and a slight decrease
in DLV
concentrations.
Special instructions
Can be administered with food.
Should be taken 1 hour before or 1 hour after ddI or antacids.
Tablets can be dissolved in water and the resulting dispersion
taken
promptly.
Neonatal dose (through age 3 months): Under study in Pediatric
AIDS
Clinical Trial Group protocol 356: 5 mg per kg of body weight once
daily
for 14 days, followed by 120 mg per m2 of body surface area every
12 hours
for 14 days, followed by 200 mg per m2 of body surface area every
12 hours.
Pediatric dose: 120 to 200 mg per m2 of body surface area every
12
hours. Note: Initiate therapy with 120 mg per m2 of body surface
area
administered once daily for 14 days. Increase to full dose
administered
every 12 hours if there are no rash or other untoward effects.
Adolescent/Adult dose: 200 mg every 12 hours. Note: Initiate
therapy at
half dose for the first 14 days. Increase to full dose if there is
no rash
or other untoward effects.
Major toxicities
Most frequent: Skin rash (some severe and life-threatening,
including
Stevens-Johnson syndrome), sedative effect, headache, diarrhea, and
nausea.
Induces hepatic cytochrome P450 3A (CYP3A); autoinduction of
metabolism
occurs in 2-4 weeks with a 1.5-fold to twofold increase in
clearance.
There could potentially be multiple drug interactions. ***
Before administration, the patient's medication profile should
be
carefully reviewed for potential drug interactions.
Drugs having suspected interactions and should be used only
with
careful monitoring: rifampin and rifabutin; oral contraceptives
(alternative or additional methods of birth control should be
used if
co-administering with hormonal methods of birth control);
sedative-
hypnotics (e.g., triazolam or midazolam); oral anticoagulants;
digoxin;
phenytoin; or theophylline.
Administration with protease inhibitors: indinavir and
saquinavir
concentrations are decreased significantly, and ritonavir
concentration
may be decreased. Whether increased doses of protease
inhibitors are
needed is unknown.
Special instructions
Can be administered with food.
May be administered concurrently with ddI.
NVP-associated skin rash usually occurs within the first 6
weeks of
therapy. If rash occurs during the initial 14-day lead-in
period, do
not increase dose until rash resolves. NVP should be
discontinued
immediately in patients who develop severe rash or a rash
accompanied
by constitutional symptoms (i.e., fever, oral lesions,
conjunctivitis,
or blistering).
For investigational suspension: Must be shaken well; store at
room
temperature.
Protease Inhibitors* ** ****
Indinavir , CRIXIVAN (R)
Preparations: Capsules: 200 and 400 mg
Dosage
Neonatal Dose: Unknown. Due to side effect of
hyperbilirubinemia,
should not be given to neonates until further information is
available.
Pediatric Dose: Under study in clinical trials: 500 mg per m2
of body
surface area every 8 hours.
Adolescent/Adult dose: 800 mg every 8 hours.
Major toxicities
Most frequent: Nausea, abdominal pain, headache, metallic
taste,
dizziness, and asymptomatic hyperbilirubinemia (10%).
Unusual (more severe): Nephrolithiasis (4%) and exacerbation of
chronic
liver disease.
Rare: Spontaneous bleeding episodes in hemophiliacs,
hyperglycemia,
keto-acidosis, diabetes, and hemolytic anemia.
Drug interactions
Cytochrome P450 3A4 (CYP3A4) responsible for metabolism. There
could
potentially be multiple drug interactions. ***
Before administration, the patient's medication profile should
be
carefully reviewed for potential drug interactions.
Indinavir decreases the metabolism of certain drugs, resulting
in
increased drug levels and potential toxicity. Indinavir is not
recommended for concurrent use with antihistamines (e.g.,
astemizole or
terfenadine); cisapride; ergot alkaloid derivatives; or
sedative-
hypnotics (e.g., triazolam or midazolam).
Indinavir levels are significantly reduced with concurrent use
of
rifampin. Concurrent use is not recommended.
Rifabutin concentrations are increased, therefore a dose
reduction of
rifabutin to half the usual daily dose is recommended.
Ketoconazole and itraconazole cause an increase in indinavir
concentrations (consider reducing adolescent/adult indinavir
dose to
600 mg every 8 hours).
Co-administration of clarithromycin increases serum
concentration of
both drugs (dosing modification not needed).
Co-administration of nevirapine may decrease indinavir serum
concentration.
Administration with other protease inhibitors:
co-administration with
nelfinavir increases concentration of both drugs;
co-administration
with saquinavir increases concentration of saquinavir.
Special instructions
Administer on an empty stomach 1 hour before or 2 hours after a
meal
(or can take with a light meal).
Adequate hydration required to minimize risk of nephrolithiasis
(at
least 48 oz of fluid daily in adult patients).
If co-administered with ddI, give at least 1 hour apart on an
empty
stomach.
Decrease dose in patients with hepatic insufficiency.
Capsules are sensitive to moisture and should be stored in
original
container with desiccant.
Nelfinavir , VIRACEPT (R)
Preparations: Powder for oral suspension: 50 mg per 1 level
gram
scoopful (200 mg per 1 level teaspoon); Tablets: 250 mg tablet
Dosage
Neonatal dose: Under study in Pediatric AIDS Clinical Trial
Group
protocol 353: 10 mg per kg of body weight three times a day. (Note:
no
preliminary data available, investigational.)
Pediatric dose: 20 to 30 mg per kg of body weight three times a
day.
Adolescent/Adult dose: 750 mg three times a day.
Major toxicities
Most frequent: Diarrhea.
Less common: Asthenia, abdominal pain, rash, and exacerbation
of
chronic liver disease.
Rare: Spontaneous bleeding episodes in hemophiliacs,
hyperglycemia,
keto-acidosis, and diabetes.
Drug interactions
Nelfinavir is in part metabolized by cytochrome P450 3A4
(CYP3A4).
There could potentially be multiple drug interactions. ***
Before administration, the patient's medication profile should
be
carefully reviewed for potential drug interactions.
Nelfinavir decreases the metabolism of certain drugs, resulting
in
increased drug levels and potential toxicity. Nelfinavir is not
recommended for concurrent use with antihistamines (e.g.,
astemizole or
terfenadine); cisapride; ergot alkaloid derivatives; certain
cardiac
drugs (e.g., quinidine or amiodarone); or sedative-hypnotics
(e.g.,
triazolam or midazolam).
Nelfinavir levels are greatly reduced with concurrent use of
rifampin.
Concurrent use is not recommended.
Rifabutin causes less decline in nelfinavir concentrations; if
co-
administered with nelfinavir, rifabutin should be reduced to
one half
the usual dose.
Estradiol levels are reduced by nelfinavir, and alternative or
additional methods of birth control should be used if
co-administering
with hormonal methods of birth control.
Co-administration with delavirdine (DLV) increases nelfinavir
concentrations twofold and decreases DLV concentrations by 50%.
There
are no data on co-administration with nevirapine, but some
experts use
higher doses of nelfinavir if used in combination with
nevirapine.
Administration with other protease inhibitors:
co-administration with
indinavir increases concentration of both drugs;
co-administration with
saquinavir increases concentration of saquinavir with little
change in
nelfinavir concentration; co-administration with ritonavir
increases
concentration of nelfinavir without change in ritonavir
concentration.
Special instructions
Administer with meal or light snack.
If co-administered with ddI, nelfinavir should be administered
2 hours
before or 1 hour after ddI.
For oral solution: powder may be mixed with water, milk,
pudding, ice
cream, or formula (for up to 6 hours).
Do not mix with any acidic food or juice because of resulting
poor
taste.
Do not add water to bottles of oral powder; a special scoop is
provided
with oral powder for measuring purposes.
Tablets readily dissolve in water and produce a dispersion that
can be
mixed with milk or chocolate milk; tablets also can be crushed
and
administered with pudding.
Neonatal dose: Under study in Pediatric AIDS Clinical Trial
Group
protocol 354 (single dose pharmacokinetics).
Pediatric usual dose: 400 mg per m2 of body surface area every
12
hours. To minimize nausea/vomiting, initiate therapy starting at
250 mg per
m2 of body surface area every 12 hours and increase stepwise to
full dose
over 5 days as tolerated.
Pediatric dosage range: 350 to 400 mg per m2 of body surface
area every
12 hours.
Adolescent/Adult dose: 600 mg twice daily. To minimize
nausea/vomiting,
initiate therapy starting at 300 mg twice daily and increase
stepwise to
full dose over 5 days as tolerated.
Major toxicities
Most frequent: Nausea, vomiting, diarrhea, headache, abdominal
pain,
and anorexia.
Less common: Circumoral paresthesias and increase in liver
enzymes.
Rare: Spontaneous bleeding episodes in hemophiliacs,
pancreatitis,
increased levels of triglycerides and cholesterol, hyperglycemia,
ketoacidosis, diabetes, and hepatitis.
Drug interactions
Ritonavir is extensively metabolized by hepatic cytochrome P450
3A
(CYP3A). There could potentially be multiple drug interactions.
***
Before administration, the patient's medication profile should
be
carefully reviewed for potential drug interactions.
Not recommended for concurrent use with analgesics (e.g.,
meperidine,
piroxicam, or propoxyphene); antihistamines (e.g., astemizole
or
terfenadine); certain cardiac drugs (e.g., amiodarone, bepridil
hydrochloride, encainide hydrochloride, flecainide acetate,
propafenone, or quinidine); ergot alkaloid derivatives;
cisapride;
sedative-hypnotics (e.g., alprazolam, clorazepate, diazepam,
estazolam,
flurazepam hydrochloride, midazolam, triazolam, or zolpidem
tartrate);
certain psychotropic drugs (e.g., bupropion hydrochloride,
clozapine,
or pimozide); rifampin; or rifabutin.
Estradiol levels are reduced by ritonavir, and alternative or
additional methods of birth control should be used if
co-administering
with hormonal methods of birth control.
Ritonavir increases metabolism of theophylline (levels should
be
monitored, and dose may need to be increased).
Ritonavir increases levels of clarithromycin (dose adjustment
may be
necessary in patients with impaired renal function);
desipramine (dose
adjustment may be necessary); and warfarin (monitoring of
anticoagulant
effect is necessary).
Ritonavir may increase or decrease digoxin levels (monitoring
of levels
is recommended).
Drugs that increase CYP3A activity can lead to increased
clearance and
therefore lower levels of ritonavir include carbamazepine,
dexamethasone, phenobarbital, and phenytoin (anticonvulsant
levels
should be monitored because ritonavir can affect the metabolism
of
these drugs as well).
Administration with other protease inhibitors:
co-administration with
saquinavir and nelfinavir increases concentration of these
drugs with
little change in ritonavir concentration.
Special instructions
Administration with food increases absorption.
If ritonavir is prescribed with ddI, there should be 2 hours
between
taking each of the drugs.
Oral solution must be kept refrigerated and stored in original
container; can be kept at room temperature if used within 30
days.
To minimize nausea, therapy should be initiated at a low dose
and
increased to full dose over 5 days as tolerated.
Techniques to increase tolerance in children: a) mixing oral
solution
with milk, chocolate milk, or vanilla or chocolate pudding or
ice
cream; b) dulling the taste buds before administration by
chewing ice,
giving popsicles or spoonfuls of partially frozen orange or
grape juice
concentrates; c) coating the mouth by giving peanut butter to
eat
before the dose; or d) administration of strong-tasting foods
such as
maple syrup, cheese, or strong-flavored chewing gum immediately
after
dose.
Saquinavir , INVIRASE (TM) (TM) (hard gel capsule) and FORTOVASE
(TM)
(soft gel capsule)
Preparations: Hard gel capsules: 200 mg; Soft gel capsules: 200
mg
Dosage
Neonatal dose: Unknown.
Pediatric dose: Unknown (will be studied in Pediatric AIDS
Clinical
Trials Group protocol 397).
Adolescent/Adult dose: Hard gel capsules: 600 mg three times a
day;
Soft gel capsules: 1200 mg three times a day.
Major toxicities
Most frequent: Diarrhea, abdominal discomfort, headache,
nausea,
paresthesias, and skin rash.
Less common: Exacerbation of chronic liver disease.
Rare: Spontaneous bleeding episodes in hemophiliacs,
hyperglycemia,
keto-acidosis, and diabetes.
Drug interactions
Saquinavir is metabolized by the cytochrome P450 3A4 (CYP 3A4)
system
in the liver, and there are numerous potential drug
interactions. ***
Before administration, the patient's medication profile should
be
carefully reviewed for potential drug interactions.
Saquinavir decreases the metabolism of certain drugs, resulting
in
increased drug levels and potential toxicity. Saquinavir is not
recommended for concurrent use with antihistamines (e.g.,
astemizole or
terfenadine); cisapride; ergot alkaloid derivatives, or
sedative-
hypnotics (e.g., midazolam or triazolam).
Saquinavir levels are significantly reduced with concurrent use
of
rifampin (decreases saquinavir levels by 80%), rifabutin
(decreases
saquinavir levels by 40%), and nevirapine (decreases saquinavir
levels
by 25%).
Saquinavir levels are decreased by carbamazepine,
dexamethasone,
phenobarbital, and phenytoin.
Saquinavir levels are increased by delvirdine and ketoconazole.
Saquinavir may increase levels of calcium channel blockers,
clindamycin, dapsone, and quinidine. If used concurrently,
patients
should be closely monitored for toxicity.
Administration with other protease inhibitors:
co-administration with
indinavir, ritonavir, or nelfinavir increases concentration of
saquinavir with little change in concentration of the other
drug.
Special instructions
Administer within 2 hours of a full meal to increase
absorption.
Concurrent administration of grapefruit juice increases
saquinavir
concentration.
Sun exposure can cause photosensitivity reactions, therefore
sunscreen
or protective clothing is recommended.
* Information in this appendix is not all inclusive. Complete and
detailed
prescribing and toxicity information on these drugs is available
from the
drug companies and should be reviewed by the health-care provider
before
prescribing these drugs.
** Adolescents in early puberty (Tanner I-II) should be dosed using
pediatric schedules, whereas those in late puberty (Tanner Stage V)
should
be dosed using adult schedules. Youth who are in the midst of their
growth
spurt (Tanner III females and Tanner IV males) should be closely
monitored
for medication efficacy and toxicity when choosing adult or
pediatric
dosing guidelines.
*** Drugs metabolized by the hepatic cytochrome P450 enzyme system
have the
potential for significant interactions with multiple drugs, some of
which
may be life-threatening. These interactions are outlined in detail
in
prescribing information available from the drug companies. These
interactions will not be reiterated in this document, and the
health-care
provider should review those documents for detailed information.
Before
therapy with these drugs is initiated, the patient's medication
profile
should be carefully reviewed for potential drug interactions.
**** Data in children is limited, and doses may change as more
information
is obtained about the pharmacokinetics of these drugs in children.
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