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ACEBUTOLOL
Dosage Forms Excipient information presented when
Warnings/Precautions Limit acetaminophen dose from
available (limited, particularly for generics); consult specific
product labeling.
Capsule, oral, as hydrochloride: 200 mg, 400 mg
Sectral®: 200 mg, 400 mg
all sources (prescription and OTC) to <4 g/day. May cause
severe hepatotoxicity on acute overdose; in addition,
chronic daily dosing in adults has resulted in liver damage
in some patients; hepatotoxicity is usually associated with
excessive acetaminophen intake (>4 g/day). Use with
caution in patients with alcoholic liver disease; consuming
≥3 alcoholic drinks/day may increase the risk of liver
damage. Use caution in patients with hepatic impairment
or active liver disease. Use of intravenous formulation is
contraindicated in patients with severe hepatic impairment
or severe active liver disease. Use caution in patients with
known G6PD deficiency; rare reports of hemolysis have
occurred. Use caution in patients with chronic malnutrition
and hypovolemia (intravenous formulation). Use caution in
patients with severe renal impairment; consider dosing
adjustments. Hypersensitivity and anaphylactic reactions
have been reported; discontinue immediately if symptoms
of allergic or hypersensitivity reactions occur.
^ Acebutolol Hydrochloride see Acebutolol on page 27
^ Aceon® see Perindopril Erbumine on page 1457
^ Acephen™ [OTC] see Acetaminophen on page 28
^ Acerola [OTC] see Ascorbic Acid on page 158
^ Acetadote® see Acetylcysteine on page 35
^ Aceta-Gesic® see Acetaminophen and Diphenhydr-
amine on page 32
Acetaminophen
(a seet a MIN oh fen)
Brand Names: U.S. Acephen™ [OTC]; APAP 500 [OTC];
Aspirin Free Anacin® Extra Strength [OTC]; Cetafen®
Extra [OTC]; Cetafen® [OTC]; Excedrin® Tension Headache [OTC]; Feverall® [OTC]; Infantaire [OTC]; Little
Fevers™ [OTC]; Mapap® Arthritis Pain [OTC]; Mapap®
Children's [OTC]; Mapap® Extra Strength [OTC]; Mapap®
Infant's [OTC]; Mapap® Junior Rapid Tabs [OTC]; Mapap®
[OTC]; Non-Aspirin Pain Reliever [OTC]; Nortemp Children's [OTC]; Ofirmev™; Pain & Fever Children's [OTC];
Pain Eze [OTC]; Q-Pap Children's [OTC]; Q-Pap Extra
Strength [OTC]; Q-Pap Infant's [OTC]; Q-Pap [OTC]; RapiMed® Children's [OTC]; RapiMed® Junior [OTC]; Silapap
Children's [OTC]; Silapap Infant's [OTC]; Triaminic™
Children's Fever Reducer Pain Reliever [OTC]; Tylenol®
8 Hour [OTC]; Tylenol® Arthritis Pain Extended Relief
[OTC]; Tylenol® Children's Meltaways [OTC]; Tylenol®
Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol®
Infant's Concentrated [OTC] [DSC]; Tylenol® Jr. Meltaways [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin
[OTC]
Brand Names: Canada Abenol®; Apo-Acetaminophen®;
Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
Index Terms APAP (abbreviation is not recommended); NAcetyl-P-Aminophenol; Paracetamol
Pharmacologic Category Analgesic, Miscellaneous
Use Treatment of mild-to-moderate pain and fever (analgesic/antipyretic)
I.V.: Additional indication: Management of moderate-tosevere pain when combined with opioid analgesia
Pregnancy Risk Factor C (intravenous)
Pregnancy Considerations Animal reproduction studies
have not been conducted with intravenous acetaminophen, therefore, acetaminophen I.V. is classified as pregnancy category C. Acetaminophen crosses the placenta
and can be detected in cord blood, newborn serum, and
urine immediately after delivery. An increased risk of
teratogenic effects has not been observed following maternal use of acetaminophen during pregnancy. Prenatal
constriction of the ductus arteriosus has been noted in
case reports following maternal use during the third trimester. The use of acetaminophen in normal doses during
pregnancy is not associated with an increased risk of
miscarriage or still birth; however, an increase in fetal
death or spontaneous abortion may be seen following
maternal overdose if treatment is delayed. Frequent maternal use of acetaminophen during pregnancy may be
associated with wheezing and asthma in early childhood.
The absorption may be delayed and the bioavailability of
acetaminophen may be decreased in some women during
pregnancy due to delayed gastric emptying.
Lactation Enters breast milk/use caution (AAP rates "compatible"; AAP 2001 update pending)
Contraindications Hypersensitivity to acetaminophen or
any component of the formulation; severe hepatic impairment or severe active liver disease (Ofirmev™)
OTC labeling: When used for self-medication, patients
should be instructed to contact healthcare provider if used
for fever lasting >3 days or for pain lasting >10 days in
adults or >5 days in children. OTC labeling limits the
maximum daily dose to ≤3250 mg (dosage form specific).
Adverse Reactions Oral, Rectal: Frequency not defined:
Dermatologic: Rash
Endocrine & metabolic: May increase chloride, uric acid,
glucose; may decrease sodium, bicarbonate, calcium
Hematologic: Anemia, blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Bilirubin increased, alkaline phosphatase
increased
Renal: Ammonia increased, nephrotoxicity with chronic
overdose, analgesic nephropathy
Miscellaneous: Hypersensitivity reactions (rare)
I.V.:
>10%: Gastrointestinal: Nausea (adults 34%; children
≥5%), vomiting (adults 15%; children ≥5%)
1% to 10%:
Cardiovascular: Edema (peripheral), hypervolemia, hypo/
hypertension, tachycardia
Central nervous system: Headache (adults 10%; children
≥1%), insomnia (adults 7%; children ≥1%), agitation
(children ≥5%), anxiety, fatigue
Dermatologic: Pruritus (children ≥5%), rash
Endocrine & metabolic: Hypoalbuminemia, hypokalemia,
hypomagnesemia, hypophosphatemia
Gastrointestinal: Constipation (children ≥5%), abdominal
pain, diarrhea
Hematologic: Anemia
Hepatic: Transaminases increased
Local: Infusion site pain
Neuromuscular & skeletal: Muscle spasms, pain in
extremity, trismus
Ocular: Periorbital edema
Renal: Oliguria (children ≥1%)
Respiratory: Atelectasis (children ≥5%), breath sounds
abnormal, dyspnea, hypoxia, pleural effusion, pulmonary edema, stridor, wheezing
All formulations: <1% (Limited to important or life-threatening): Anaphylaxis (rare), hypersensitivity reactions
Drug Interactions
Metabolism/Transport Effects Substrate of CYP1A2
(minor), CYP2A6 (minor), CYP2C9 (minor), CYP2D6
(minor), CYP2E1 (minor), CYP3A4 (minor); Note:
Assignment of Major/Minor substrate status based on
clinically relevant drug interaction potential; Inhibits
CYP3A4 (weak)
Avoid Concomitant Use
Avoid concomitant use of Acetaminophen with any of the
following: Pimozide
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ACETAMINOPHEN
Adults: ~2 hours (range: 2-3 hours); may be slightly
prolonged in severe renal insufficiency (Clcr<30 mL/
minute): 2-5.3 hours
Time to peak, serum: Oral: Immediate release: 10-60
minutes (may be delayed in acute overdoses); I.V.: 15
minutes
Excretion: Urine (<5% unchanged; 60% to 80% as glucuronide metabolites; 20% to 30% as sulphate metabolites;
~8% cysteine and mercapturic acid metabolites)
Dosage Note: No dose adjustment required if converting
between different acetaminophen formulations. Limit acetaminophen dose from all sources (prescription and OTC)
to <4 g daily.
Increased Effect/Toxicity
Acetaminophen may increase the levels/effects of: ARIPiprazole; Busulfan; Dasatinib; Imatinib; Lomitapide;
Pimozide; Prilocaine; SORAfenib; Vitamin K Antagonists
The levels/effects of Acetaminophen may be increased
by: Dasatinib; Imatinib; Isoniazid; Metyrapone; Probenecid; SORAfenib
Decreased Effect
The levels/effects of Acetaminophen may be decreased
by: Anticonvulsants (Hydantoin); Barbiturates; CarBAMazepine; Cholestyramine Resin; Peginterferon Alfa-2b
Ethanol/Nutrition/Herb Interactions
Ethanol: Excessive intake of ethanol may increase the risk
of acetaminophen-induced hepatotoxicity. Avoid ethanol
or limit to <3 drinks/day.
Food: Rate of absorption may be decreased when given
with food.
Herb/Nutraceutical: St John's wort may decrease acetaminophen levels.
Oral: Note: OTC dosing recommendations may vary by
product and/or manufacturer.
Infants and Children <12 years: 10-15 mg/kg/dose every
4-6 hours as needed; do not exceed 5 doses (2.6 g) in
24 hours; alternatively, the following age-based doses
may be used; see table.
Children ≥12 years, Adolescents, and Adults:
Regular release: 325-650 mg every 4-6 hours or
1000 mg 3-4 times daily (maximum: 4 g daily)
Extended release: 1300 mg every 8 hours (maximum:
3.9 g daily)
Stability
Injection: Store intact vials at room temperature of 20°C to
25°C (68°F to 77°F); do not refrigerate or freeze. Injectable solution may be administered directly from the vial
without further dilution. Use within 6 hours of opening vial
or transferring to another container. Discard any unused
portion; single use vials only.
Doses <1000 mg (<50 kg): Withdraw appropriate dose
from vial and place into and transfer to a separate sterile
container (eg, glass bottle, plastic I.V. container,
syringe) for administration. Small volume pediatric
doses (up to 60 mL) may be placed in a syringe and
infused over 15 minutes via syringe pump.
Doses of 1000 mg (≥50 kg): Insert vented I.V. set through
vial stopper.
Oral formulations: Store at controlled room temperature.
Suppositories: Store at <27°C (80°F); do not freeze.
Mechanism of Action Although not fully elucidated,
believed to inhibit the synthesis of prostaglandins in the
central nervous system and work peripherally to block pain
impulse generation; produces antipyresis from inhibition of
hypothalamic heat-regulating center
Acetaminophen Pediatric Dosing
(Oral)1
Dosage
(mg)
Weight
(kg)
Weight
(lbs)
Age
2.7-5.3
6-11
0-3 mo
40
5.4-8.1
12-17
4-11 mo
80
8.2-10.8
18-23
1-2 y
120
10.9-16.3
24-35
2-3 y
160
16.4-21.7
36-47
4-5 y
240
21.8-27.2
48-59
6-8 y
320
27.3-32.6
60-71
9-10 y
400
32.7-43.2
72-95
11 y
480
1
Manufacturer's recommendations; use of weight to select
dose is preferred; if weight is not available, then use age.
Manufacturer’s recommendations are based on weight in
pounds (OTC labeling); weight in kg listed here is derived
from pounds and rounded; kg weight listed also is
adjusted to allow for continuous weight ranges in kg. OTC
labeling instructs consumer to consult with physician for
dosing instructions in children under 2 years of age.
Pharmacodynamics/Kinetics
Onset of action:
Oral: <1 hour
I.V.: Analgesia: 5-10 minutes; Antipyretic: Within 30
minutes
Peak effect: I.V.: Analgesic: 1 hour
Duration:
I.V., Oral: Analgesia: 4-6 hours
I.V.: Antipyretic: ≥6 hours
Absorption: Primarily absorbed in small intestine (rate of
absorption dependent upon gastric emptying); minimal
absorption from stomach; varies by dosage form
Distribution: ~1 L/kg at therapeutic doses
Protein binding: 10% to 25% at therapeutic concentrations;
8% to 43% at toxic concentrations
Metabolism: At normal therapeutic dosages, primarily hepatic metabolism to sulfate and glucuronide conjugates,
while a small amount is metabolized by CYP2E1 to a
highly reactive intermediate, N-acetyl-p-benzoquinone
imine (NAPQI), which is conjugated rapidly with glutathione and inactivated to nontoxic cysteine and mercapturic acid conjugates. At toxic doses (as little as 4 g daily)
glutathione conjugation becomes insufficient to meet the
metabolic demand causing an increase in NAPQI concentrations, which may cause hepatic cell necrosis. Oral
administration is subject to first pass metabolism.
Half-life elimination: Prolonged following toxic doses
Neonates: 7 hours (range: 4-10 hours)
Infants: ~4 hours (range: 1-7 hours)
Children: 3 hours (range: 2-5 hours)
Adolescents: ~3 hours (range: 2-4 hours)
Rectal:
Infants and Children <12 years: 10-20 mg/kg/dose every
4-6 hours as needed; do not exceed 5 doses (2.6 g) in
24 hours. Note: Although the perioperative use of highdose rectal acetaminophen (eg, 25-45 mg/kg/dose) has
been investigated in several studies, its routine use
remains controversial; optimal doses and dosing frequency to ensure efficacy and safety have not yet been
established (Buck, 2001).
Children ≥12 years, Adolescents, and Adults:
325-650 mg every 4-6 hours or 1000 mg 3-4 times daily
(maximum: 4 g daily)
I.V.:
Children 2-12 years: 15 mg/kg every 6 hours or
12.5 mg/kg every 4 hours; maximum single dose:
15 mg/kg/dose; maximum daily dose: 75 mg/kg/day
(≤3.75 g daily)
Adolescents and Adults:
<50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4
hours; maximum single dose: 750 mg/dose; maximum
daily dose: 75 mg/kg/day (≤3.75 g daily)
≥50 kg: 650 mg every 4 hours or 1000 mg every 6 hours;
maximum single dose: 1000 mg/dose; maximum daily
dose: 4 g daily
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