U.S. BRAND NAMES — Acephen™ [OTC]; Apra Children's [OTC]; Aspirin Free Anacin® Maximum Strength [OTC]; Cetafen Extra® [OTC]; Cetafen® [OTC]; Comtrex® Sore Throat Maximum Strength [OTC]; FeverALL® [OTC]; Genapap™ Children [OTC]; Genapap™ Extra Strength [OTC]; Genapap™ Infant [OTC]; Genapap™ [OTC]; Genebs Extra Strength [OTC]; Genebs [OTC]; Infantaire [OTC]; Mapap Children's [OTC]; Mapap Extra Strength [OTC]; Mapap Infants [OTC]; Mapap [OTC]; Nortemp Children's [OTC]; Pain Eze [OTC]; Silapap® Children's [OTC]; Silapap® Infants [OTC]; Tycolene Maximum Strength [OTC]; Tycolene [OTC]; Tylenol® 8 Hour [OTC]; Tylenol® Arthritis Pain [OTC]; Tylenol® Children's with Flavor Creator [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infants [OTC]; Tylenol® Junior [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin [OTC]
CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
SYNONYMS — APAP; N-Acetyl-P-Aminophenol; Paracetamol
THERAPEUTIC CATEGORY Analgesic, Non-narcoticAntipyretic
DOSING
(For additional information see "Acetaminophen: Drug information")Neonates: Oral, rectal: 10-15 mg/kg/dose every 6-8 hours as needed International Evidence-Based Group for Neonatal Pain recommendations (Anand, 2001; Anand, 2002): Preterm infants 28-32 weeks: Oral: 10-12 mg/kg/dose every 6-8 hours; maximum daily dose: 40 mg/kg/day Rectal: 20 mg/kg/dose every 12 hours; maximum daily dose: 40 mg/kg/day Preterm infants 32-36 weeks and term infants <10 days: Oral: 10-15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 15 mg/kg/dose every 8 hours; maximum daily dose: 60 mg/kg/day Term infants 10 days: Oral: 10-15 mg/kg/dose every 4-6 hours; maximum daily dose: 90 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 20 mg/kg/dose every 6-8 hours; maximum daily dose: 90 mg/kg/day
Infants and Children: Oral: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours; alternatively, the following doses may be used.
Alternative Acetaminophen Dosing (Oral)1: 6-11 lbs: 0-3 months: 40 mg 12-17 lbs: 4-11 months: 80 mg 18-23 lbs: 1-2 years: 120 mg 24-35 lbs: 2-3 years: 160 mg 36-47 lbs: 4-5 years: 240 mg 48-59 lbs: 6-8 years: 320 mg 60-71 lbs: 9-10 years: 400 mg 72-95 lbs: 11 years: 480 mg 1Manufacturer's recommendations; use of weight to select dose is preferred; if weight is not available, then use age Rectal: 10-20 mg/kg/dose every 4-6 hours as needed. Note: Although the perioperative use of high-dose 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; further studies are needed (see Buck, 2001).
Children 12 years and Adults: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 500 mg Cetafen Extra® Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Tycolene Maximum Strength, Tylenol® Extra Strength: 500 mg
Caplet, extended release: Tylenol® 8 Hour, Tylenol® Arthritis Pain: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) Apra Children's: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) [alcohol free; contains benzoic acid; cherry and grape flavors] Mapap Children's: 160 mg/5 mL (120 mL) [alcohol free; contains benzoic acid and sodium benzoate; cherry flavor]
Gelcap: Mapap Extra Strength, Tylenol® Extra Strength: 500 mg
Geltab: Tylenol® Extra Strength: 500 mg
Geltab, extended release: Tylenol® 8 Hour: 650 mg [DSC]
Liquid, oral: 500 mg/15 mL (240 mL) Comtrex® Sore Throat Maximum Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; honey lemon flavor] Genapap™ Children: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry and grape flavors] Silapap®: 160 mg/5 mL (120 mL, 240 mL, 480 mL) [sugar free; contains sodium benzoate; cherry flavor] Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; cherry flavor]
Solution, oral: 160 mg/5 mL (120 mL, 480 mL)
Solution, oral [drops]: 80 mg/0.8 mL (15 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)] Genapap™ Infant: 80 mg/0.8 mL (15 mL) [fruit flavor] Infantaire: 80 mg/0.8mL (15 mL, 30 mL) Silapap® Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor]
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen™: 120 mg, 325 mg, 650 mg FeverALL®: 80 mg, 120 mg, 325 mg, 650 mg Mapap: 125 mg, 650 mg
Suspension, oral: Mapap Children's: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry flavor] Nortemp Children's: 160 mg/5 mL (120 mL) [alcohol free; contains sodium benzoate; cotton candy flavor] Tylenol® Children's: 160 mg/5 mL (120 mL, 240 mL) [contains sodium benzoate; bubble gum yum, cherry blast, dye free cherry, grape splash, and very berry strawberry flavors] Tylenol® Children's with Flavor Creator: 160 mg/5 mL (120 mL) [contains sodium 2 mg/5 mL and sodium benzoate; cherry blast flavor; packaged with apple (4), bubblegum (8), chocolate (4), & strawberry (4) sugar free flavor packets]
Suspension, oral [drops]: Mapap Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor] Tylenol® Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry, dye free cherry, and grape flavors]
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Pain Eze, Tylenol® Extra Strength, Valorin Extra: 500 mg Cetafen®, Genapap™, Genebs, Mapap, Tycolene, Tylenol®, Valorin: 325 mg
Tablet, chewable: 80 mg Genapap™ Children: 80 mg [contains phenylalanine 6 mg/tablet; fruit and grape flavors] Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; bubble gum, fruit, and grape flavors] Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways: 80 mg [bubble gum, grape, and watermelon flavors] Tylenol® Junior Meltaways: 160 mg [bubble gum and grape flavors]
GENERIC AVAILABLE — Yes: Excludes extended release products
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use; do not crush or chew extended release products
USE — Treatment of mild to moderate pain and fever; does not have antirheumatic or systemic anti-inflammatory effects
ADVERSE REACTIONS Dermatologic: Rash
Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Hepatic necrosis with overdose
Renal: Renal injury with chronic use
Miscellaneous: Hypersensitivity reactions (rare)
CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component
PRECAUTIONS — Some products (eg, chewable tablets) contain aspartame which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — May cause severe hepatic toxicity with overdose. Use with caution in patients with alcoholic liver disease. Chronic daily dosing in adults of 5-8 g of acetaminophen over several weeks or 3-4 g/day for 1 year have resulted in liver damage. Do not exceed maximum daily doses; consider acetaminophen content of combination products when evaluating the dose of acetaminophen.
Some elixir preparations contain benzoic acid; liquid preparations (ie, elixir, liquid, suspension, and drops) may contain sodium benzoate (see Dosage Forms); benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP1A2 substrate (minor), CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A3/4 isoenzyme substrate
Enzyme inducers (barbiturates, carbamazepine, phenytoin, rifampin), carmustine (with high dose acetaminophen), isoniazid, alcohol (especially chronic use) can increase hepatotoxicity; rifampin may decrease acetaminophen's therapeutic effect; anticholinergic agents (scopolamine) may effect GI absorption; acetaminophen may increase the clearance of lamotrigine; acetaminophen may increase zidovudine concentration and toxicity
FOOD INTERACTIONS — Rate of absorption may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — B (show table)
REFERENCE RANGE — Acute ingestions: Toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion of overdose
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center
PHARMACOKINETICS Protein binding: 20% to 50%
Metabolism: At normal therapeutic dosages the parent compound is metabolized in the liver to sulfate and glucuronide metabolites, while a small amount is metabolized by microsomal mixed function oxidases to a highly reactive intermediate (N-acetyl-imidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g in a single day) glutathione can become depleted, and conjugation becomes insufficient to meet the metabolic demand causing an increase in N-acetyl-imidoquinone concentration, which is thought to cause hepatic cell necrosis.
Half-life: Neonates: 2-5 hours Adults: 1-3 hours
Time to peak serum concentration: 10-60 minutes after normal oral doses, but may be delayed in acute overdoses
PATIENT INFORMATION — Avoid alcohol; do not take longer than 10 days without physician's advice
(For additional information see "Acetaminophen: Patient drug information")
ADDITIONAL INFORMATION — Drops may contain saccharin.
Acetaminophen (15 mg/kg/dose given orally every 6 hours for 24 hours) did not relieve the intraoperative or the immediate postoperative pain associated with neonatal circumcision; some benefit was seen 6 hours after circumcision (see Howard, 1994).
There is currently no scientific evidence to support alternating acetaminophen with ibuprofen in the treatment of fever (see Mayoral, 2000).
Thursday, January 31, 2008
Acetaminophen
U.S. BRAND NAMES — Acephen™ [OTC]; Apra Children's [OTC]; Aspirin Free Anacin® Maximum Strength [OTC]; Cetafen Extra® [OTC]; Cetafen® [OTC]; Comtrex® Sore Throat Maximum Strength [OTC]; FeverALL® [OTC]; Genapap™ Children [OTC]; Genapap™ Extra Strength [OTC]; Genapap™ Infant [OTC]; Genapap™ [OTC]; Genebs Extra Strength [OTC]; Genebs [OTC]; Infantaire [OTC]; Mapap Children's [OTC]; Mapap Extra Strength [OTC]; Mapap Infants [OTC]; Mapap [OTC]; Nortemp Children's [OTC]; Pain Eze [OTC]; Silapap® Children's [OTC]; Silapap® Infants [OTC]; Tycolene Maximum Strength [OTC]; Tycolene [OTC]; Tylenol® 8 Hour [OTC]; Tylenol® Arthritis Pain [OTC]; Tylenol® Children's with Flavor Creator [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infants [OTC]; Tylenol® Junior [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin [OTC]
CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
SYNONYMS — APAP; N-Acetyl-P-Aminophenol; Paracetamol
THERAPEUTIC CATEGORY Analgesic, Non-narcoticAntipyretic
DOSING
(For additional information see "Acetaminophen: Drug information")Neonates: Oral, rectal: 10-15 mg/kg/dose every 6-8 hours as needed International Evidence-Based Group for Neonatal Pain recommendations (Anand, 2001; Anand, 2002): Preterm infants 28-32 weeks: Oral: 10-12 mg/kg/dose every 6-8 hours; maximum daily dose: 40 mg/kg/day Rectal: 20 mg/kg/dose every 12 hours; maximum daily dose: 40 mg/kg/day Preterm infants 32-36 weeks and term infants <10 days: Oral: 10-15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 15 mg/kg/dose every 8 hours; maximum daily dose: 60 mg/kg/day Term infants 10 days: Oral: 10-15 mg/kg/dose every 4-6 hours; maximum daily dose: 90 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 20 mg/kg/dose every 6-8 hours; maximum daily dose: 90 mg/kg/day
Infants and Children: Oral: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours; alternatively, the following doses may be used.
Alternative Acetaminophen Dosing (Oral)1: 6-11 lbs: 0-3 months: 40 mg 12-17 lbs: 4-11 months: 80 mg 18-23 lbs: 1-2 years: 120 mg 24-35 lbs: 2-3 years: 160 mg 36-47 lbs: 4-5 years: 240 mg 48-59 lbs: 6-8 years: 320 mg 60-71 lbs: 9-10 years: 400 mg 72-95 lbs: 11 years: 480 mg 1Manufacturer's recommendations; use of weight to select dose is preferred; if weight is not available, then use age Rectal: 10-20 mg/kg/dose every 4-6 hours as needed. Note: Although the perioperative use of high-dose 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; further studies are needed (see Buck, 2001).
Children 12 years and Adults: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 500 mg Cetafen Extra® Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Tycolene Maximum Strength, Tylenol® Extra Strength: 500 mg
Caplet, extended release: Tylenol® 8 Hour, Tylenol® Arthritis Pain: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) Apra Children's: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) [alcohol free; contains benzoic acid; cherry and grape flavors] Mapap Children's: 160 mg/5 mL (120 mL) [alcohol free; contains benzoic acid and sodium benzoate; cherry flavor]
Gelcap: Mapap Extra Strength, Tylenol® Extra Strength: 500 mg
Geltab: Tylenol® Extra Strength: 500 mg
Geltab, extended release: Tylenol® 8 Hour: 650 mg [DSC]
Liquid, oral: 500 mg/15 mL (240 mL) Comtrex® Sore Throat Maximum Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; honey lemon flavor] Genapap™ Children: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry and grape flavors] Silapap®: 160 mg/5 mL (120 mL, 240 mL, 480 mL) [sugar free; contains sodium benzoate; cherry flavor] Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; cherry flavor]
Solution, oral: 160 mg/5 mL (120 mL, 480 mL)
Solution, oral [drops]: 80 mg/0.8 mL (15 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)] Genapap™ Infant: 80 mg/0.8 mL (15 mL) [fruit flavor] Infantaire: 80 mg/0.8mL (15 mL, 30 mL) Silapap® Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor]
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen™: 120 mg, 325 mg, 650 mg FeverALL®: 80 mg, 120 mg, 325 mg, 650 mg Mapap: 125 mg, 650 mg
Suspension, oral: Mapap Children's: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry flavor] Nortemp Children's: 160 mg/5 mL (120 mL) [alcohol free; contains sodium benzoate; cotton candy flavor] Tylenol® Children's: 160 mg/5 mL (120 mL, 240 mL) [contains sodium benzoate; bubble gum yum, cherry blast, dye free cherry, grape splash, and very berry strawberry flavors] Tylenol® Children's with Flavor Creator: 160 mg/5 mL (120 mL) [contains sodium 2 mg/5 mL and sodium benzoate; cherry blast flavor; packaged with apple (4), bubblegum (8), chocolate (4), & strawberry (4) sugar free flavor packets]
Suspension, oral [drops]: Mapap Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor] Tylenol® Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry, dye free cherry, and grape flavors]
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Pain Eze, Tylenol® Extra Strength, Valorin Extra: 500 mg Cetafen®, Genapap™, Genebs, Mapap, Tycolene, Tylenol®, Valorin: 325 mg
Tablet, chewable: 80 mg Genapap™ Children: 80 mg [contains phenylalanine 6 mg/tablet; fruit and grape flavors] Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; bubble gum, fruit, and grape flavors] Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways: 80 mg [bubble gum, grape, and watermelon flavors] Tylenol® Junior Meltaways: 160 mg [bubble gum and grape flavors]
GENERIC AVAILABLE — Yes: Excludes extended release products
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use; do not crush or chew extended release products
USE — Treatment of mild to moderate pain and fever; does not have antirheumatic or systemic anti-inflammatory effects
ADVERSE REACTIONS Dermatologic: Rash
Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Hepatic necrosis with overdose
Renal: Renal injury with chronic use
Miscellaneous: Hypersensitivity reactions (rare)
CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component
PRECAUTIONS — Some products (eg, chewable tablets) contain aspartame which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — May cause severe hepatic toxicity with overdose. Use with caution in patients with alcoholic liver disease. Chronic daily dosing in adults of 5-8 g of acetaminophen over several weeks or 3-4 g/day for 1 year have resulted in liver damage. Do not exceed maximum daily doses; consider acetaminophen content of combination products when evaluating the dose of acetaminophen.
Some elixir preparations contain benzoic acid; liquid preparations (ie, elixir, liquid, suspension, and drops) may contain sodium benzoate (see Dosage Forms); benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP1A2 substrate (minor), CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A3/4 isoenzyme substrate
Enzyme inducers (barbiturates, carbamazepine, phenytoin, rifampin), carmustine (with high dose acetaminophen), isoniazid, alcohol (especially chronic use) can increase hepatotoxicity; rifampin may decrease acetaminophen's therapeutic effect; anticholinergic agents (scopolamine) may effect GI absorption; acetaminophen may increase the clearance of lamotrigine; acetaminophen may increase zidovudine concentration and toxicity
FOOD INTERACTIONS — Rate of absorption may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — B (show table)
REFERENCE RANGE — Acute ingestions: Toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion of overdose
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center
PHARMACOKINETICS Protein binding: 20% to 50%
Metabolism: At normal therapeutic dosages the parent compound is metabolized in the liver to sulfate and glucuronide metabolites, while a small amount is metabolized by microsomal mixed function oxidases to a highly reactive intermediate (N-acetyl-imidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g in a single day) glutathione can become depleted, and conjugation becomes insufficient to meet the metabolic demand causing an increase in N-acetyl-imidoquinone concentration, which is thought to cause hepatic cell necrosis.
Half-life: Neonates: 2-5 hours Adults: 1-3 hours
Time to peak serum concentration: 10-60 minutes after normal oral doses, but may be delayed in acute overdoses
PATIENT INFORMATION — Avoid alcohol; do not take longer than 10 days without physician's advice
(For additional information see "Acetaminophen: Patient drug information")
ADDITIONAL INFORMATION — Drops may contain saccharin.
Acetaminophen (15 mg/kg/dose given orally every 6 hours for 24 hours) did not relieve the intraoperative or the immediate postoperative pain associated with neonatal circumcision; some benefit was seen 6 hours after circumcision (see Howard, 1994).
There is currently no scientific evidence to support alternating acetaminophen with ibuprofen in the treatment of fever (see Mayoral, 2000).
CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
SYNONYMS — APAP; N-Acetyl-P-Aminophenol; Paracetamol
THERAPEUTIC CATEGORY Analgesic, Non-narcoticAntipyretic
DOSING
(For additional information see "Acetaminophen: Drug information")Neonates: Oral, rectal: 10-15 mg/kg/dose every 6-8 hours as needed International Evidence-Based Group for Neonatal Pain recommendations (Anand, 2001; Anand, 2002): Preterm infants 28-32 weeks: Oral: 10-12 mg/kg/dose every 6-8 hours; maximum daily dose: 40 mg/kg/day Rectal: 20 mg/kg/dose every 12 hours; maximum daily dose: 40 mg/kg/day Preterm infants 32-36 weeks and term infants <10 days: Oral: 10-15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 15 mg/kg/dose every 8 hours; maximum daily dose: 60 mg/kg/day Term infants 10 days: Oral: 10-15 mg/kg/dose every 4-6 hours; maximum daily dose: 90 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 20 mg/kg/dose every 6-8 hours; maximum daily dose: 90 mg/kg/day
Infants and Children: Oral: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours; alternatively, the following doses may be used.
Alternative Acetaminophen Dosing (Oral)1: 6-11 lbs: 0-3 months: 40 mg 12-17 lbs: 4-11 months: 80 mg 18-23 lbs: 1-2 years: 120 mg 24-35 lbs: 2-3 years: 160 mg 36-47 lbs: 4-5 years: 240 mg 48-59 lbs: 6-8 years: 320 mg 60-71 lbs: 9-10 years: 400 mg 72-95 lbs: 11 years: 480 mg 1Manufacturer's recommendations; use of weight to select dose is preferred; if weight is not available, then use age Rectal: 10-20 mg/kg/dose every 4-6 hours as needed. Note: Although the perioperative use of high-dose 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; further studies are needed (see Buck, 2001).
Children 12 years and Adults: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 500 mg Cetafen Extra® Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Tycolene Maximum Strength, Tylenol® Extra Strength: 500 mg
Caplet, extended release: Tylenol® 8 Hour, Tylenol® Arthritis Pain: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) Apra Children's: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) [alcohol free; contains benzoic acid; cherry and grape flavors] Mapap Children's: 160 mg/5 mL (120 mL) [alcohol free; contains benzoic acid and sodium benzoate; cherry flavor]
Gelcap: Mapap Extra Strength, Tylenol® Extra Strength: 500 mg
Geltab: Tylenol® Extra Strength: 500 mg
Geltab, extended release: Tylenol® 8 Hour: 650 mg [DSC]
Liquid, oral: 500 mg/15 mL (240 mL) Comtrex® Sore Throat Maximum Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; honey lemon flavor] Genapap™ Children: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry and grape flavors] Silapap®: 160 mg/5 mL (120 mL, 240 mL, 480 mL) [sugar free; contains sodium benzoate; cherry flavor] Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; cherry flavor]
Solution, oral: 160 mg/5 mL (120 mL, 480 mL)
Solution, oral [drops]: 80 mg/0.8 mL (15 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)] Genapap™ Infant: 80 mg/0.8 mL (15 mL) [fruit flavor] Infantaire: 80 mg/0.8mL (15 mL, 30 mL) Silapap® Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor]
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen™: 120 mg, 325 mg, 650 mg FeverALL®: 80 mg, 120 mg, 325 mg, 650 mg Mapap: 125 mg, 650 mg
Suspension, oral: Mapap Children's: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry flavor] Nortemp Children's: 160 mg/5 mL (120 mL) [alcohol free; contains sodium benzoate; cotton candy flavor] Tylenol® Children's: 160 mg/5 mL (120 mL, 240 mL) [contains sodium benzoate; bubble gum yum, cherry blast, dye free cherry, grape splash, and very berry strawberry flavors] Tylenol® Children's with Flavor Creator: 160 mg/5 mL (120 mL) [contains sodium 2 mg/5 mL and sodium benzoate; cherry blast flavor; packaged with apple (4), bubblegum (8), chocolate (4), & strawberry (4) sugar free flavor packets]
Suspension, oral [drops]: Mapap Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor] Tylenol® Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry, dye free cherry, and grape flavors]
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Pain Eze, Tylenol® Extra Strength, Valorin Extra: 500 mg Cetafen®, Genapap™, Genebs, Mapap, Tycolene, Tylenol®, Valorin: 325 mg
Tablet, chewable: 80 mg Genapap™ Children: 80 mg [contains phenylalanine 6 mg/tablet; fruit and grape flavors] Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; bubble gum, fruit, and grape flavors] Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways: 80 mg [bubble gum, grape, and watermelon flavors] Tylenol® Junior Meltaways: 160 mg [bubble gum and grape flavors]
GENERIC AVAILABLE — Yes: Excludes extended release products
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use; do not crush or chew extended release products
USE — Treatment of mild to moderate pain and fever; does not have antirheumatic or systemic anti-inflammatory effects
ADVERSE REACTIONS Dermatologic: Rash
Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Hepatic necrosis with overdose
Renal: Renal injury with chronic use
Miscellaneous: Hypersensitivity reactions (rare)
CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component
PRECAUTIONS — Some products (eg, chewable tablets) contain aspartame which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — May cause severe hepatic toxicity with overdose. Use with caution in patients with alcoholic liver disease. Chronic daily dosing in adults of 5-8 g of acetaminophen over several weeks or 3-4 g/day for 1 year have resulted in liver damage. Do not exceed maximum daily doses; consider acetaminophen content of combination products when evaluating the dose of acetaminophen.
Some elixir preparations contain benzoic acid; liquid preparations (ie, elixir, liquid, suspension, and drops) may contain sodium benzoate (see Dosage Forms); benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP1A2 substrate (minor), CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A3/4 isoenzyme substrate
Enzyme inducers (barbiturates, carbamazepine, phenytoin, rifampin), carmustine (with high dose acetaminophen), isoniazid, alcohol (especially chronic use) can increase hepatotoxicity; rifampin may decrease acetaminophen's therapeutic effect; anticholinergic agents (scopolamine) may effect GI absorption; acetaminophen may increase the clearance of lamotrigine; acetaminophen may increase zidovudine concentration and toxicity
FOOD INTERACTIONS — Rate of absorption may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — B (show table)
REFERENCE RANGE — Acute ingestions: Toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion of overdose
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center
PHARMACOKINETICS Protein binding: 20% to 50%
Metabolism: At normal therapeutic dosages the parent compound is metabolized in the liver to sulfate and glucuronide metabolites, while a small amount is metabolized by microsomal mixed function oxidases to a highly reactive intermediate (N-acetyl-imidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g in a single day) glutathione can become depleted, and conjugation becomes insufficient to meet the metabolic demand causing an increase in N-acetyl-imidoquinone concentration, which is thought to cause hepatic cell necrosis.
Half-life: Neonates: 2-5 hours Adults: 1-3 hours
Time to peak serum concentration: 10-60 minutes after normal oral doses, but may be delayed in acute overdoses
PATIENT INFORMATION — Avoid alcohol; do not take longer than 10 days without physician's advice
(For additional information see "Acetaminophen: Patient drug information")
ADDITIONAL INFORMATION — Drops may contain saccharin.
Acetaminophen (15 mg/kg/dose given orally every 6 hours for 24 hours) did not relieve the intraoperative or the immediate postoperative pain associated with neonatal circumcision; some benefit was seen 6 hours after circumcision (see Howard, 1994).
There is currently no scientific evidence to support alternating acetaminophen with ibuprofen in the treatment of fever (see Mayoral, 2000).
Acarbose
U.S. BRAND NAMES — Precose®
CANADIAN BRAND NAMES — Prandase®
THERAPEUTIC CATEGORY Antidiabetic Agent, Alpha-glucosidase InhibitorAntidiabetic Agent, Oral
DOSING — Oral:
(For additional information see "Acarbose: Drug information")
Adolescents and Adults: Dosage must be individualized on the basis of effectiveness and tolerance; do not exceed the maximum recommended dose (use slow titration to prevent or minimize GI effects): Initial: 25 mg 3 times/day; increase in 25 mg/day increments in 2-4 week intervals to maximum dose Maximum dose: Patients 60 kg: 50 mg 3 times/day Patients >60 kg: 100 mg 3 times/day
Dosing adjustment in renal impairment: See Warnings
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 25 mg, 50 mg, 100 mg
GENERIC AVAILABLE — No
ADMINISTRATION — Oral: Administer with first bite of each main meal
USE — Management of type II diabetes mellitus (noninsulin-dependent, NIDDM) when hyperglycemia cannot be managed by diet alone; may be used concomitantly with metformin, a sulfonylurea, or insulin to improve glycemic control
ADVERSE REACTIONS Central nervous system: Headache, vertigo, drowsiness
Dermatologic: Urticaria, erythema
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Abdominal pain, diarrhea, flatulence
Hepatic: Elevated liver enzymes
Neuromuscular & skeletal: Weakness
CONTRAINDICATIONS — Hypersensitivity to acarbose or any component; diabetic ketoacidosis; cirrhosis; patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or patients predisposed to intestinal obstruction; patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption; patients who have conditions that may deteriorate as a result of increased gas formation in the intestine
PRECAUTIONS — Hypoglycemia may occur when used in combination with sulfonylureas or insulin; oral glucose (absorption is not affected by acarbose) should be used instead of sucrose (table sugar) for the treatment of mild to moderate hypoglycemia
WARNINGS — Dose-related elevations in serum transaminases occurred in 15% of acarbose-treated patients in long-term studies; these elevations were asymptomatic, reversible, more common in females, and not associated with other evidence of liver dysfunction; acarbose serum levels are proportionately higher in patients with renal dysfunction (Scr >2 mg/dL); until long term clinical studies are completed, use in renally-compromised patients is not recommended
DRUG INTERACTIONS — Drugs that produce hyperglycemia (eg, diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, rifampin, and isoniazid) may lead to a loss of glycemic control; intestinal adsorbents; digestive enzyme preparations; decreases bioavailability of digoxin resulting in decreased serum levels
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Fasting blood glucose; hemoglobin A1c; liver enzymes every 3 months for the first year of therapy and periodically thereafter
REFERENCE RANGE — Target range:
Blood glucose: Fasting and preprandial: 80-120 mg/dL; bedtime: 100-140 mg/dL
Glycosylated hemoglobin (hemoglobin A1c): <7%
MECHANISM OF ACTION — Competitive inhibitor of pancreatic alpha-glucosidases, resulting in delayed hydrolysis of ingested complex carbohydrates and disaccharides and absorption of glucose; dose-dependent reduction in postprandial serum insulin and glucose peaks; inhibits the metabolism of sucrose to glucose and fructose
PHARMACODYNAMICS — Average decrease in fasting blood sugar: 20-30 mg/dL
PHARMACOKINETICS Absorption: <2% absorbed as active drug
Metabolism: Metabolized exclusively within the GI tract, principally by intestinal bacteria and by digestive enzymes; 13 metabolites have been identified
Bioavailability: Low systemic bioavailability of parent compound
Elimination: Fraction absorbed as intact drug is almost completely excreted in urine
ADDITIONAL INFORMATION — Acarbose has been used successfully to treat postprandial hypoglycemia in children with Nissen fundoplications. Six children (4-25 months) initially received 12.5 mg before each bolus feeding of formula containing complex carbohydrates. The dosage was increased in 12.5 mg increments (dosage range: 12.5-50 mg per dose) until postprandial serum glucose was stable 60 mg/dL. Most commonly reported side effects were flatulence, abdominal distension, and diarrhea (Ng, 2001).
CANADIAN BRAND NAMES — Prandase®
THERAPEUTIC CATEGORY Antidiabetic Agent, Alpha-glucosidase InhibitorAntidiabetic Agent, Oral
DOSING — Oral:
(For additional information see "Acarbose: Drug information")
Adolescents and Adults: Dosage must be individualized on the basis of effectiveness and tolerance; do not exceed the maximum recommended dose (use slow titration to prevent or minimize GI effects): Initial: 25 mg 3 times/day; increase in 25 mg/day increments in 2-4 week intervals to maximum dose Maximum dose: Patients 60 kg: 50 mg 3 times/day Patients >60 kg: 100 mg 3 times/day
Dosing adjustment in renal impairment: See Warnings
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 25 mg, 50 mg, 100 mg
GENERIC AVAILABLE — No
ADMINISTRATION — Oral: Administer with first bite of each main meal
USE — Management of type II diabetes mellitus (noninsulin-dependent, NIDDM) when hyperglycemia cannot be managed by diet alone; may be used concomitantly with metformin, a sulfonylurea, or insulin to improve glycemic control
ADVERSE REACTIONS Central nervous system: Headache, vertigo, drowsiness
Dermatologic: Urticaria, erythema
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Abdominal pain, diarrhea, flatulence
Hepatic: Elevated liver enzymes
Neuromuscular & skeletal: Weakness
CONTRAINDICATIONS — Hypersensitivity to acarbose or any component; diabetic ketoacidosis; cirrhosis; patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or patients predisposed to intestinal obstruction; patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption; patients who have conditions that may deteriorate as a result of increased gas formation in the intestine
PRECAUTIONS — Hypoglycemia may occur when used in combination with sulfonylureas or insulin; oral glucose (absorption is not affected by acarbose) should be used instead of sucrose (table sugar) for the treatment of mild to moderate hypoglycemia
WARNINGS — Dose-related elevations in serum transaminases occurred in 15% of acarbose-treated patients in long-term studies; these elevations were asymptomatic, reversible, more common in females, and not associated with other evidence of liver dysfunction; acarbose serum levels are proportionately higher in patients with renal dysfunction (Scr >2 mg/dL); until long term clinical studies are completed, use in renally-compromised patients is not recommended
DRUG INTERACTIONS — Drugs that produce hyperglycemia (eg, diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, rifampin, and isoniazid) may lead to a loss of glycemic control; intestinal adsorbents; digestive enzyme preparations; decreases bioavailability of digoxin resulting in decreased serum levels
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Fasting blood glucose; hemoglobin A1c; liver enzymes every 3 months for the first year of therapy and periodically thereafter
REFERENCE RANGE — Target range:
Blood glucose: Fasting and preprandial: 80-120 mg/dL; bedtime: 100-140 mg/dL
Glycosylated hemoglobin (hemoglobin A1c): <7%
MECHANISM OF ACTION — Competitive inhibitor of pancreatic alpha-glucosidases, resulting in delayed hydrolysis of ingested complex carbohydrates and disaccharides and absorption of glucose; dose-dependent reduction in postprandial serum insulin and glucose peaks; inhibits the metabolism of sucrose to glucose and fructose
PHARMACODYNAMICS — Average decrease in fasting blood sugar: 20-30 mg/dL
PHARMACOKINETICS Absorption: <2% absorbed as active drug
Metabolism: Metabolized exclusively within the GI tract, principally by intestinal bacteria and by digestive enzymes; 13 metabolites have been identified
Bioavailability: Low systemic bioavailability of parent compound
Elimination: Fraction absorbed as intact drug is almost completely excreted in urine
ADDITIONAL INFORMATION — Acarbose has been used successfully to treat postprandial hypoglycemia in children with Nissen fundoplications. Six children (4-25 months) initially received 12.5 mg before each bolus feeding of formula containing complex carbohydrates. The dosage was increased in 12.5 mg increments (dosage range: 12.5-50 mg per dose) until postprandial serum glucose was stable 60 mg/dL. Most commonly reported side effects were flatulence, abdominal distension, and diarrhea (Ng, 2001).
Acarbose
U.S. BRAND NAMES — Precose®
CANADIAN BRAND NAMES — Prandase®
THERAPEUTIC CATEGORY Antidiabetic Agent, Alpha-glucosidase InhibitorAntidiabetic Agent, Oral
DOSING — Oral:
(For additional information see "Acarbose: Drug information")
Adolescents and Adults: Dosage must be individualized on the basis of effectiveness and tolerance; do not exceed the maximum recommended dose (use slow titration to prevent or minimize GI effects): Initial: 25 mg 3 times/day; increase in 25 mg/day increments in 2-4 week intervals to maximum dose Maximum dose: Patients 60 kg: 50 mg 3 times/day Patients >60 kg: 100 mg 3 times/day
Dosing adjustment in renal impairment: See Warnings
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 25 mg, 50 mg, 100 mg
GENERIC AVAILABLE — No
ADMINISTRATION — Oral: Administer with first bite of each main meal
USE — Management of type II diabetes mellitus (noninsulin-dependent, NIDDM) when hyperglycemia cannot be managed by diet alone; may be used concomitantly with metformin, a sulfonylurea, or insulin to improve glycemic control
ADVERSE REACTIONS Central nervous system: Headache, vertigo, drowsiness
Dermatologic: Urticaria, erythema
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Abdominal pain, diarrhea, flatulence
Hepatic: Elevated liver enzymes
Neuromuscular & skeletal: Weakness
CONTRAINDICATIONS — Hypersensitivity to acarbose or any component; diabetic ketoacidosis; cirrhosis; patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or patients predisposed to intestinal obstruction; patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption; patients who have conditions that may deteriorate as a result of increased gas formation in the intestine
PRECAUTIONS — Hypoglycemia may occur when used in combination with sulfonylureas or insulin; oral glucose (absorption is not affected by acarbose) should be used instead of sucrose (table sugar) for the treatment of mild to moderate hypoglycemia
WARNINGS — Dose-related elevations in serum transaminases occurred in 15% of acarbose-treated patients in long-term studies; these elevations were asymptomatic, reversible, more common in females, and not associated with other evidence of liver dysfunction; acarbose serum levels are proportionately higher in patients with renal dysfunction (Scr >2 mg/dL); until long term clinical studies are completed, use in renally-compromised patients is not recommended
DRUG INTERACTIONS — Drugs that produce hyperglycemia (eg, diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, rifampin, and isoniazid) may lead to a loss of glycemic control; intestinal adsorbents; digestive enzyme preparations; decreases bioavailability of digoxin resulting in decreased serum levels
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Fasting blood glucose; hemoglobin A1c; liver enzymes every 3 months for the first year of therapy and periodically thereafter
REFERENCE RANGE — Target range:
Blood glucose: Fasting and preprandial: 80-120 mg/dL; bedtime: 100-140 mg/dL
Glycosylated hemoglobin (hemoglobin A1c): <7%
MECHANISM OF ACTION — Competitive inhibitor of pancreatic alpha-glucosidases, resulting in delayed hydrolysis of ingested complex carbohydrates and disaccharides and absorption of glucose; dose-dependent reduction in postprandial serum insulin and glucose peaks; inhibits the metabolism of sucrose to glucose and fructose
PHARMACODYNAMICS — Average decrease in fasting blood sugar: 20-30 mg/dL
PHARMACOKINETICS Absorption: <2% absorbed as active drug
Metabolism: Metabolized exclusively within the GI tract, principally by intestinal bacteria and by digestive enzymes; 13 metabolites have been identified
Bioavailability: Low systemic bioavailability of parent compound
Elimination: Fraction absorbed as intact drug is almost completely excreted in urine
ADDITIONAL INFORMATION — Acarbose has been used successfully to treat postprandial hypoglycemia in children with Nissen fundoplications. Six children (4-25 months) initially received 12.5 mg before each bolus feeding of formula containing complex carbohydrates. The dosage was increased in 12.5 mg increments (dosage range: 12.5-50 mg per dose) until postprandial serum glucose was stable 60 mg/dL. Most commonly reported side effects were flatulence, abdominal distension, and diarrhea (Ng, 2001).
CANADIAN BRAND NAMES — Prandase®
THERAPEUTIC CATEGORY Antidiabetic Agent, Alpha-glucosidase InhibitorAntidiabetic Agent, Oral
DOSING — Oral:
(For additional information see "Acarbose: Drug information")
Adolescents and Adults: Dosage must be individualized on the basis of effectiveness and tolerance; do not exceed the maximum recommended dose (use slow titration to prevent or minimize GI effects): Initial: 25 mg 3 times/day; increase in 25 mg/day increments in 2-4 week intervals to maximum dose Maximum dose: Patients 60 kg: 50 mg 3 times/day Patients >60 kg: 100 mg 3 times/day
Dosing adjustment in renal impairment: See Warnings
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 25 mg, 50 mg, 100 mg
GENERIC AVAILABLE — No
ADMINISTRATION — Oral: Administer with first bite of each main meal
USE — Management of type II diabetes mellitus (noninsulin-dependent, NIDDM) when hyperglycemia cannot be managed by diet alone; may be used concomitantly with metformin, a sulfonylurea, or insulin to improve glycemic control
ADVERSE REACTIONS Central nervous system: Headache, vertigo, drowsiness
Dermatologic: Urticaria, erythema
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Abdominal pain, diarrhea, flatulence
Hepatic: Elevated liver enzymes
Neuromuscular & skeletal: Weakness
CONTRAINDICATIONS — Hypersensitivity to acarbose or any component; diabetic ketoacidosis; cirrhosis; patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or patients predisposed to intestinal obstruction; patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption; patients who have conditions that may deteriorate as a result of increased gas formation in the intestine
PRECAUTIONS — Hypoglycemia may occur when used in combination with sulfonylureas or insulin; oral glucose (absorption is not affected by acarbose) should be used instead of sucrose (table sugar) for the treatment of mild to moderate hypoglycemia
WARNINGS — Dose-related elevations in serum transaminases occurred in 15% of acarbose-treated patients in long-term studies; these elevations were asymptomatic, reversible, more common in females, and not associated with other evidence of liver dysfunction; acarbose serum levels are proportionately higher in patients with renal dysfunction (Scr >2 mg/dL); until long term clinical studies are completed, use in renally-compromised patients is not recommended
DRUG INTERACTIONS — Drugs that produce hyperglycemia (eg, diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, rifampin, and isoniazid) may lead to a loss of glycemic control; intestinal adsorbents; digestive enzyme preparations; decreases bioavailability of digoxin resulting in decreased serum levels
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Fasting blood glucose; hemoglobin A1c; liver enzymes every 3 months for the first year of therapy and periodically thereafter
REFERENCE RANGE — Target range:
Blood glucose: Fasting and preprandial: 80-120 mg/dL; bedtime: 100-140 mg/dL
Glycosylated hemoglobin (hemoglobin A1c): <7%
MECHANISM OF ACTION — Competitive inhibitor of pancreatic alpha-glucosidases, resulting in delayed hydrolysis of ingested complex carbohydrates and disaccharides and absorption of glucose; dose-dependent reduction in postprandial serum insulin and glucose peaks; inhibits the metabolism of sucrose to glucose and fructose
PHARMACODYNAMICS — Average decrease in fasting blood sugar: 20-30 mg/dL
PHARMACOKINETICS Absorption: <2% absorbed as active drug
Metabolism: Metabolized exclusively within the GI tract, principally by intestinal bacteria and by digestive enzymes; 13 metabolites have been identified
Bioavailability: Low systemic bioavailability of parent compound
Elimination: Fraction absorbed as intact drug is almost completely excreted in urine
ADDITIONAL INFORMATION — Acarbose has been used successfully to treat postprandial hypoglycemia in children with Nissen fundoplications. Six children (4-25 months) initially received 12.5 mg before each bolus feeding of formula containing complex carbohydrates. The dosage was increased in 12.5 mg increments (dosage range: 12.5-50 mg per dose) until postprandial serum glucose was stable 60 mg/dL. Most commonly reported side effects were flatulence, abdominal distension, and diarrhea (Ng, 2001).
Abacavir, lamivudine, and zidovudine
U.S. BRAND NAMES — Trizivir®
SYNONYMS — 3TC, Abacavir, and AZT; 3TC, Abacavir, and ZDV; 3TC, Abacavir, and Zidovudine; 3TC, ABC, and AZT; 3TC, ABC, and ZDV; Abacavir, 3TC, and AZT; Abacavir, 3TC, and ZDV; Abacavir, Lamivudine, and Azidothymidine; Abacavir, Zidovudine, and Lamivudine; ABC, 3TC, and AZT; ABC, 3TC, and ZDV; Azidothymidine, Abacavir, and Lamivudine; Azidothymidine, Lamivudine and Abacavir; AZT, Abacavir, and 3TC; AZT, Abacavir, and Lamivudine; AZT, ABC, and 3TC; Compound S, Abacavir, and 3TC; Compound S, Abacavir, and Lamivudine; Compound S, ABC, and 3TC; Lamivudine, Abacavir, and Zidovudine; Lamivudine, Zidovudine, and Abacavir; ZDV, Abacavir, and 3TC; ZDV, Abacavir, and Lamivudine; ZDV, ABC, and 3TC; Zidovudine, Abacavir, and Lamivudine
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir, lamivudine, and zidovudine: Drug information")
Children: Not intended for pediatric use; product is a fixed-dose combination
Adolescents <40 kg: Not recommended; product is a fixed-dose combination
Adolescents 40 kg and Adults: 1 tablet twice daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended; data on the use of this triple NRTI combination regimen in patients with baseline viral loads >100,000 copies/mL is limited)
ADVERSE REACTIONS — See Abacavir, Lamivudine, and Zidovudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir, potentially fatal hypersensitivity reactions may occur (see Warnings)
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir, lamivudine, and zidovudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis) and GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Trizivir®, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir, Trizivir®, or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Trizivir®, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Trizivir® in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir, lamivudine, and zidovudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation, neutropenia, and anemia; consider discontinuation of abacavir, lamivudine, and zidovudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Zidovudine is associated with hematologic toxicity including granulocytopenia and severe anemia requiring transfusions; use with caution in patients with ANC <1000 cells/mm3 or hemoglobin <9.5 g/dL; discontinue treatment in children with an ANC <500 cells/mm3 until marrow recovery is observed; use of erythropoietin, or filgrastim may be necessary in some patients; prolonged use of zidovudine may cause myositis and myopathy; zidovudine has been shown to be carcinogenic in rats and mice.
Trizivir® contains abacavir, lamivudine, and zidovudine as a fixed-dose combination; do not use in patients weighing <40 kg, in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine and zidovudine dosage adjustment, or in patients with hepatic dysfunction (Note: Patients with mild to moderate hepatic dysfunction or liver cirrhosis require zidovudine dosage adjustment; abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Trizivir® with abacavir, lamivudine, emtricitabine, or zidovudine-containing products.
DRUG INTERACTIONS — See Abacavir, Lamivudine, and Zidovudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption (see Yuen, 2001).
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, anemia, bone marrow suppression, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, platelets, hemoglobin, MCV, reticulocyte count, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests. HIV patients should be screened for hepatitis B infection before starting lamivudine (see Warnings).
STABILITY — Store at room temperature 25ºC (77ºF)
MECHANISM OF ACTION — See Abacavir, Lamivudine, and Zidovudine
PHARMACOKINETICS — One Trizivir® tablet is bioequivalent, in the extent (AUC) and rate of absorption (peak concentration and time to peak concentration), to one abacavir 300 mg tablet, one lamivudine 150 mg tablet, plus one zidovudine 300 mg tablet; See Abacavir, Lamivudine, and Zidovudine
PATIENT INFORMATION — Trizivir® is not a cure for HIV. Take Trizivir® every day as prescribed; do not change dose or discontinue without physician's advice. If Trizivir® is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information")
Trizivir® contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reaction. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir, lamivudine, and zidovudine. Stop taking Trizivir® and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain), flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Trizivir® (or abacavir, Ziagen®, or Epzicom™), never take Trizivir®, abacavir, Ziagen®, or Epzicom™ again.
Trizivir® contains zidovudine which may cause a decrease in white blood cells or red blood cells (anemia); routine blood tests can help detect these blood problems. Zidovudine may also cause muscle weakness with prolonged use, which may be a serious problem; notify physician if muscle weakness occurs.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir, lamivudine, and zidovudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Trizivir®, inform your physician about your medical conditions, including any blood, kidney, or liver problems (including hepatitis B infection). Do not take Trizivir ® with Combivir ®, Emtriva™, Epivir®, Epivir-HBV®, Epzicom®, Retrovir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them
SYNONYMS — 3TC, Abacavir, and AZT; 3TC, Abacavir, and ZDV; 3TC, Abacavir, and Zidovudine; 3TC, ABC, and AZT; 3TC, ABC, and ZDV; Abacavir, 3TC, and AZT; Abacavir, 3TC, and ZDV; Abacavir, Lamivudine, and Azidothymidine; Abacavir, Zidovudine, and Lamivudine; ABC, 3TC, and AZT; ABC, 3TC, and ZDV; Azidothymidine, Abacavir, and Lamivudine; Azidothymidine, Lamivudine and Abacavir; AZT, Abacavir, and 3TC; AZT, Abacavir, and Lamivudine; AZT, ABC, and 3TC; Compound S, Abacavir, and 3TC; Compound S, Abacavir, and Lamivudine; Compound S, ABC, and 3TC; Lamivudine, Abacavir, and Zidovudine; Lamivudine, Zidovudine, and Abacavir; ZDV, Abacavir, and 3TC; ZDV, Abacavir, and Lamivudine; ZDV, ABC, and 3TC; Zidovudine, Abacavir, and Lamivudine
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir, lamivudine, and zidovudine: Drug information")
Children: Not intended for pediatric use; product is a fixed-dose combination
Adolescents <40 kg: Not recommended; product is a fixed-dose combination
Adolescents 40 kg and Adults: 1 tablet twice daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended; data on the use of this triple NRTI combination regimen in patients with baseline viral loads >100,000 copies/mL is limited)
ADVERSE REACTIONS — See Abacavir, Lamivudine, and Zidovudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir, potentially fatal hypersensitivity reactions may occur (see Warnings)
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir, lamivudine, and zidovudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis) and GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Trizivir®, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir, Trizivir®, or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Trizivir®, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Trizivir® in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir, lamivudine, and zidovudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation, neutropenia, and anemia; consider discontinuation of abacavir, lamivudine, and zidovudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Zidovudine is associated with hematologic toxicity including granulocytopenia and severe anemia requiring transfusions; use with caution in patients with ANC <1000 cells/mm3 or hemoglobin <9.5 g/dL; discontinue treatment in children with an ANC <500 cells/mm3 until marrow recovery is observed; use of erythropoietin, or filgrastim may be necessary in some patients; prolonged use of zidovudine may cause myositis and myopathy; zidovudine has been shown to be carcinogenic in rats and mice.
Trizivir® contains abacavir, lamivudine, and zidovudine as a fixed-dose combination; do not use in patients weighing <40 kg, in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine and zidovudine dosage adjustment, or in patients with hepatic dysfunction (Note: Patients with mild to moderate hepatic dysfunction or liver cirrhosis require zidovudine dosage adjustment; abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Trizivir® with abacavir, lamivudine, emtricitabine, or zidovudine-containing products.
DRUG INTERACTIONS — See Abacavir, Lamivudine, and Zidovudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption (see Yuen, 2001).
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, anemia, bone marrow suppression, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, platelets, hemoglobin, MCV, reticulocyte count, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests. HIV patients should be screened for hepatitis B infection before starting lamivudine (see Warnings).
STABILITY — Store at room temperature 25ºC (77ºF)
MECHANISM OF ACTION — See Abacavir, Lamivudine, and Zidovudine
PHARMACOKINETICS — One Trizivir® tablet is bioequivalent, in the extent (AUC) and rate of absorption (peak concentration and time to peak concentration), to one abacavir 300 mg tablet, one lamivudine 150 mg tablet, plus one zidovudine 300 mg tablet; See Abacavir, Lamivudine, and Zidovudine
PATIENT INFORMATION — Trizivir® is not a cure for HIV. Take Trizivir® every day as prescribed; do not change dose or discontinue without physician's advice. If Trizivir® is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information")
Trizivir® contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reaction. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir, lamivudine, and zidovudine. Stop taking Trizivir® and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain), flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Trizivir® (or abacavir, Ziagen®, or Epzicom™), never take Trizivir®, abacavir, Ziagen®, or Epzicom™ again.
Trizivir® contains zidovudine which may cause a decrease in white blood cells or red blood cells (anemia); routine blood tests can help detect these blood problems. Zidovudine may also cause muscle weakness with prolonged use, which may be a serious problem; notify physician if muscle weakness occurs.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir, lamivudine, and zidovudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Trizivir®, inform your physician about your medical conditions, including any blood, kidney, or liver problems (including hepatitis B infection). Do not take Trizivir ® with Combivir ®, Emtriva™, Epivir®, Epivir-HBV®, Epzicom®, Retrovir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them
Abacavir, lamivudine, and zidovudine
U.S. BRAND NAMES — Trizivir®
SYNONYMS — 3TC, Abacavir, and AZT; 3TC, Abacavir, and ZDV; 3TC, Abacavir, and Zidovudine; 3TC, ABC, and AZT; 3TC, ABC, and ZDV; Abacavir, 3TC, and AZT; Abacavir, 3TC, and ZDV; Abacavir, Lamivudine, and Azidothymidine; Abacavir, Zidovudine, and Lamivudine; ABC, 3TC, and AZT; ABC, 3TC, and ZDV; Azidothymidine, Abacavir, and Lamivudine; Azidothymidine, Lamivudine and Abacavir; AZT, Abacavir, and 3TC; AZT, Abacavir, and Lamivudine; AZT, ABC, and 3TC; Compound S, Abacavir, and 3TC; Compound S, Abacavir, and Lamivudine; Compound S, ABC, and 3TC; Lamivudine, Abacavir, and Zidovudine; Lamivudine, Zidovudine, and Abacavir; ZDV, Abacavir, and 3TC; ZDV, Abacavir, and Lamivudine; ZDV, ABC, and 3TC; Zidovudine, Abacavir, and Lamivudine
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir, lamivudine, and zidovudine: Drug information")
Children: Not intended for pediatric use; product is a fixed-dose combination
Adolescents <40 kg: Not recommended; product is a fixed-dose combination
Adolescents 40 kg and Adults: 1 tablet twice daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended; data on the use of this triple NRTI combination regimen in patients with baseline viral loads >100,000 copies/mL is limited)
ADVERSE REACTIONS — See Abacavir, Lamivudine, and Zidovudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir, potentially fatal hypersensitivity reactions may occur (see Warnings)
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir, lamivudine, and zidovudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis) and GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Trizivir®, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir, Trizivir®, or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Trizivir®, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Trizivir® in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir, lamivudine, and zidovudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation, neutropenia, and anemia; consider discontinuation of abacavir, lamivudine, and zidovudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Zidovudine is associated with hematologic toxicity including granulocytopenia and severe anemia requiring transfusions; use with caution in patients with ANC <1000 cells/mm3 or hemoglobin <9.5 g/dL; discontinue treatment in children with an ANC <500 cells/mm3 until marrow recovery is observed; use of erythropoietin, or filgrastim may be necessary in some patients; prolonged use of zidovudine may cause myositis and myopathy; zidovudine has been shown to be carcinogenic in rats and mice.
Trizivir® contains abacavir, lamivudine, and zidovudine as a fixed-dose combination; do not use in patients weighing <40 kg, in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine and zidovudine dosage adjustment, or in patients with hepatic dysfunction (Note: Patients with mild to moderate hepatic dysfunction or liver cirrhosis require zidovudine dosage adjustment; abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Trizivir® with abacavir, lamivudine, emtricitabine, or zidovudine-containing products.
DRUG INTERACTIONS — See Abacavir, Lamivudine, and Zidovudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption (see Yuen, 2001).
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, anemia, bone marrow suppression, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, platelets, hemoglobin, MCV, reticulocyte count, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests. HIV patients should be screened for hepatitis B infection before starting lamivudine (see Warnings).
STABILITY — Store at room temperature 25ºC (77ºF)
MECHANISM OF ACTION — See Abacavir, Lamivudine, and Zidovudine
PHARMACOKINETICS — One Trizivir® tablet is bioequivalent, in the extent (AUC) and rate of absorption (peak concentration and time to peak concentration), to one abacavir 300 mg tablet, one lamivudine 150 mg tablet, plus one zidovudine 300 mg tablet; See Abacavir, Lamivudine, and Zidovudine
PATIENT INFORMATION — Trizivir® is not a cure for HIV. Take Trizivir® every day as prescribed; do not change dose or discontinue without physician's advice. If Trizivir® is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information")
Trizivir® contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reaction. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir, lamivudine, and zidovudine. Stop taking Trizivir® and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain), flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Trizivir® (or abacavir, Ziagen®, or Epzicom™), never take Trizivir®, abacavir, Ziagen®, or Epzicom™ again.
Trizivir® contains zidovudine which may cause a decrease in white blood cells or red blood cells (anemia); routine blood tests can help detect these blood problems. Zidovudine may also cause muscle weakness with prolonged use, which may be a serious problem; notify physician if muscle weakness occurs.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir, lamivudine, and zidovudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Trizivir®, inform your physician about your medical conditions, including any blood, kidney, or liver problems (including hepatitis B infection). Do not take Trizivir ® with Combivir ®, Emtriva™, Epivir®, Epivir-HBV®, Epzicom®, Retrovir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them
SYNONYMS — 3TC, Abacavir, and AZT; 3TC, Abacavir, and ZDV; 3TC, Abacavir, and Zidovudine; 3TC, ABC, and AZT; 3TC, ABC, and ZDV; Abacavir, 3TC, and AZT; Abacavir, 3TC, and ZDV; Abacavir, Lamivudine, and Azidothymidine; Abacavir, Zidovudine, and Lamivudine; ABC, 3TC, and AZT; ABC, 3TC, and ZDV; Azidothymidine, Abacavir, and Lamivudine; Azidothymidine, Lamivudine and Abacavir; AZT, Abacavir, and 3TC; AZT, Abacavir, and Lamivudine; AZT, ABC, and 3TC; Compound S, Abacavir, and 3TC; Compound S, Abacavir, and Lamivudine; Compound S, ABC, and 3TC; Lamivudine, Abacavir, and Zidovudine; Lamivudine, Zidovudine, and Abacavir; ZDV, Abacavir, and 3TC; ZDV, Abacavir, and Lamivudine; ZDV, ABC, and 3TC; Zidovudine, Abacavir, and Lamivudine
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir, lamivudine, and zidovudine: Drug information")
Children: Not intended for pediatric use; product is a fixed-dose combination
Adolescents <40 kg: Not recommended; product is a fixed-dose combination
Adolescents 40 kg and Adults: 1 tablet twice daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended; data on the use of this triple NRTI combination regimen in patients with baseline viral loads >100,000 copies/mL is limited)
ADVERSE REACTIONS — See Abacavir, Lamivudine, and Zidovudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir, potentially fatal hypersensitivity reactions may occur (see Warnings)
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir, lamivudine, and zidovudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis) and GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Trizivir®, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir, Trizivir®, or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Trizivir®, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Trizivir® in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir, lamivudine, and zidovudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation, neutropenia, and anemia; consider discontinuation of abacavir, lamivudine, and zidovudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Zidovudine is associated with hematologic toxicity including granulocytopenia and severe anemia requiring transfusions; use with caution in patients with ANC <1000 cells/mm3 or hemoglobin <9.5 g/dL; discontinue treatment in children with an ANC <500 cells/mm3 until marrow recovery is observed; use of erythropoietin, or filgrastim may be necessary in some patients; prolonged use of zidovudine may cause myositis and myopathy; zidovudine has been shown to be carcinogenic in rats and mice.
Trizivir® contains abacavir, lamivudine, and zidovudine as a fixed-dose combination; do not use in patients weighing <40 kg, in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine and zidovudine dosage adjustment, or in patients with hepatic dysfunction (Note: Patients with mild to moderate hepatic dysfunction or liver cirrhosis require zidovudine dosage adjustment; abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Trizivir® with abacavir, lamivudine, emtricitabine, or zidovudine-containing products.
DRUG INTERACTIONS — See Abacavir, Lamivudine, and Zidovudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption (see Yuen, 2001).
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, anemia, bone marrow suppression, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, platelets, hemoglobin, MCV, reticulocyte count, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests. HIV patients should be screened for hepatitis B infection before starting lamivudine (see Warnings).
STABILITY — Store at room temperature 25ºC (77ºF)
MECHANISM OF ACTION — See Abacavir, Lamivudine, and Zidovudine
PHARMACOKINETICS — One Trizivir® tablet is bioequivalent, in the extent (AUC) and rate of absorption (peak concentration and time to peak concentration), to one abacavir 300 mg tablet, one lamivudine 150 mg tablet, plus one zidovudine 300 mg tablet; See Abacavir, Lamivudine, and Zidovudine
PATIENT INFORMATION — Trizivir® is not a cure for HIV. Take Trizivir® every day as prescribed; do not change dose or discontinue without physician's advice. If Trizivir® is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information")
Trizivir® contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reaction. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir, lamivudine, and zidovudine. Stop taking Trizivir® and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain), flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Trizivir® (or abacavir, Ziagen®, or Epzicom™), never take Trizivir®, abacavir, Ziagen®, or Epzicom™ again.
Trizivir® contains zidovudine which may cause a decrease in white blood cells or red blood cells (anemia); routine blood tests can help detect these blood problems. Zidovudine may also cause muscle weakness with prolonged use, which may be a serious problem; notify physician if muscle weakness occurs.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir, lamivudine, and zidovudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Trizivir®, inform your physician about your medical conditions, including any blood, kidney, or liver problems (including hepatitis B infection). Do not take Trizivir ® with Combivir ®, Emtriva™, Epivir®, Epivir-HBV®, Epzicom®, Retrovir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them
Abacavir and lamivudine
U.S. BRAND NAMES — Epzicom™
CANADIAN BRAND NAMES — Kivexa™
SYNONYMS — 3TC and ABC; 3TC and Abacavir; Abacavir and 3TC; ABC and 3TC; Lamivudine and Abacavir
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir and lamivudine: Drug information")
Children and Adolescents <18 years of age: Not intended for pediatric use; product is a fixed-dose combination; safety and efficacy has not been established in pediatric patients
Adolescents 18 years of age and Adults: 1 tablet daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Epzicom™: Abacavir 600 mg and lamivudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regards to meals.
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended)
ADVERSE REACTIONS — See Abacavir and Lamivudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir; potentially fatal hypersensitivity reactions may occur (see Warnings).
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir and lamivudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis), GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Epzicom™, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, or reactions to other medications). If abacavir, Epzicom™ or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Epzicom™, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Epzicom™ in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir and lamivudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation; consider discontinuation of abacavir and lamivudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Epzicom™ contains abacavir and lamivudine as a fixed-dose combination; do not use in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine dosage adjustment or in patients with hepatic dysfunction (Note: Abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Epzicom™ with abacavir, lamivudine, or emtricitabine-containing products.
DRUG INTERACTIONS — See Abacavir and Lamivudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption; in a single dose study, a high-fat meal did not change bioavailability or peak concentrations.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, hemoglobin, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests; HIV patients should be screened for hepatitis B before starting lamivudine (see Warnings)
STABILITY — Store at room temperature 25ºC (77ºF).
MECHANISM OF ACTION — See Abacavir and Lamivudine
PHARMACOKINETICS — One Epzicom™ tablet is bioequivalent, in the extent (AUC) of absorption and peak concentration, to two abacavir 300 mg tablets and two lamivudine 150 mg tablets; see Abacavir and Lamivudine
PATIENT INFORMATION — Epzicom™ is not a cure for HIV. Take Epzicom™ every day as prescribed; do not change dose or discontinue without physician's advice. If Epzicom™ is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir and lamivudine: Patient drug information")
Epzicom™ contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reactions. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir and lamivudine. Stop taking Epzicom™ and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain); flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Epzicom™ (or abacavir, Ziagen®, or Trizivir®), never take Epzicom™, abacavir, Ziagen®, or Trizivir® again.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir and lamivudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Epzicom™, inform your physician about your medical conditions, including any kidney or liver problems (including hepatitis B infection). Do not take Epzicom™ with Combivir®, Emtriva™, Epivir®, Epivir-HBV®, Trizivir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them.
A high rate of early virologic failure in therapy-naive adult HIV patients has been observed with the once-daily three-drug combination therapy of abacavir, lamivudine, and tenofovir; this antiretroviral regimen is currently not recommended; any patient currently receiving this regimen should be closely monitored for virologic failure and considered for treatment modification
CANADIAN BRAND NAMES — Kivexa™
SYNONYMS — 3TC and ABC; 3TC and Abacavir; Abacavir and 3TC; ABC and 3TC; Lamivudine and Abacavir
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir and lamivudine: Drug information")
Children and Adolescents <18 years of age: Not intended for pediatric use; product is a fixed-dose combination; safety and efficacy has not been established in pediatric patients
Adolescents 18 years of age and Adults: 1 tablet daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Epzicom™: Abacavir 600 mg and lamivudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regards to meals.
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended)
ADVERSE REACTIONS — See Abacavir and Lamivudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir; potentially fatal hypersensitivity reactions may occur (see Warnings).
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir and lamivudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis), GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Epzicom™, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, or reactions to other medications). If abacavir, Epzicom™ or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Epzicom™, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Epzicom™ in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir and lamivudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation; consider discontinuation of abacavir and lamivudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Epzicom™ contains abacavir and lamivudine as a fixed-dose combination; do not use in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine dosage adjustment or in patients with hepatic dysfunction (Note: Abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Epzicom™ with abacavir, lamivudine, or emtricitabine-containing products.
DRUG INTERACTIONS — See Abacavir and Lamivudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption; in a single dose study, a high-fat meal did not change bioavailability or peak concentrations.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, hemoglobin, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests; HIV patients should be screened for hepatitis B before starting lamivudine (see Warnings)
STABILITY — Store at room temperature 25ºC (77ºF).
MECHANISM OF ACTION — See Abacavir and Lamivudine
PHARMACOKINETICS — One Epzicom™ tablet is bioequivalent, in the extent (AUC) of absorption and peak concentration, to two abacavir 300 mg tablets and two lamivudine 150 mg tablets; see Abacavir and Lamivudine
PATIENT INFORMATION — Epzicom™ is not a cure for HIV. Take Epzicom™ every day as prescribed; do not change dose or discontinue without physician's advice. If Epzicom™ is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir and lamivudine: Patient drug information")
Epzicom™ contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reactions. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir and lamivudine. Stop taking Epzicom™ and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain); flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Epzicom™ (or abacavir, Ziagen®, or Trizivir®), never take Epzicom™, abacavir, Ziagen®, or Trizivir® again.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir and lamivudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Epzicom™, inform your physician about your medical conditions, including any kidney or liver problems (including hepatitis B infection). Do not take Epzicom™ with Combivir®, Emtriva™, Epivir®, Epivir-HBV®, Trizivir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them.
A high rate of early virologic failure in therapy-naive adult HIV patients has been observed with the once-daily three-drug combination therapy of abacavir, lamivudine, and tenofovir; this antiretroviral regimen is currently not recommended; any patient currently receiving this regimen should be closely monitored for virologic failure and considered for treatment modification
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