Zanmbeel

Sunday, May 16, 2010

Acetaminophen (paracetamol)

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Acephen® may be confused with AcipHex®
FeverALL® may be confused with Fiberall®
Tylenol® may be confused with atenolol, timolol, Tuinal®, Tylenol® PM, Tylox®

International issues:
Paralen® [Czech Republic] may be confused with Aralen® which is a brand name for chloroquine in the U.S.
Duorol® may be confused with Diuril® which is a brand name for chlorothiazide in the U.S.

Duplicate therapy issues: This product contains acetaminophen, which may be a component of combination products. Do not exceed the maximum recommended daily dose of acetaminophen.

SPECIAL ALERTS
Acetaminophen Concentrated Drops (16 ounce) Recall Due to Potential For Overdosing - July 2009

Brookstone Pharmaceuticals, with awareness of the U.S. Food and Drug Administration (FDA), has issued a voluntary recall of all lots of concentrated acetaminophen drops (80 mg/0.8 mL) in 16 ounce bulk containers. The manufacturer states this is a cautionary measure to minimize confusion between this bulk container of the concentrated acetaminophen preparation and the bulk container of the regular strength acetaminophen liquid preparations (160 mg/15 mL), and to limit the risk of potential dosing errors.

For additional information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm172252.htm

U.S. BRAND NAMES — Acephen™ [OTC]; APAP 500 [OTC]; Apra [OTC] [DSC]; Aspirin Free Anacin® Extra Strength [OTC]; Cetafen® Extra [OTC]; Cetafen® [OTC]; Excedrin® Tension Headache [OTC]; FeverALL® [OTC]; Genapap™ Extra Strength [OTC]; Genapap™ Infant [OTC] [DSC]; Genapap™ [OTC] [DSC]; Genebs Extra Strength [OTC]; Genebs [OTC] [DSC]; Infantaire [OTC]; Little Fevers™ [OTC]; Mapap Children's [OTC]; Mapap Extra Strength [OTC]; Mapap Infants [OTC]; Mapap Jr. Strength [OTC]; Mapap [OTC]; Nortemp Children's [OTC]; Pain Eze [OTC]; Silapap Children's [OTC]; Silapap Infant's [OTC]; Tycolene Maximum Strength [OTC]; Tycolene [OTC] [DSC]; Tylenol® 8 Hour [OTC]; Tylenol® Arthritis Pain Extended Relief [OTC]; Tylenol® Children's Meltaways [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infant's Concentrated [OTC]; Tylenol® Jr. Meltaways [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin [OTC]

PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous

DOSING: ADULTS — Pain or fever: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day.

DOSING: PEDIATRIC — Pain or fever: Oral, rectal: Children <12 years: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses (2.6 g) in 24 hours; alternatively, the following age-based doses may be used; see table.

(For additional information see "Acetaminophen (paracetamol): Pediatric drug information")

Acetaminophen Dosing 0-3 months: 40 mg 4-11 months: 80 mg 1-2 years: 120 mg 2-3 years: 160 mg 4-5 years: 240 mg 6-8 years: 320 mg 9-10 years: 400 mg 11 years: 480 mg

Note: Higher rectal doses have been studied for use in preoperative pain control in children. However, specific guidelines are not available and dosing may be product dependent. The safety and efficacy of alternating acetaminophen and ibuprofen dosing has not been established.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr 10-50 mL/minute: Administer every 6 hours.

Clcr <10 mL/minute: Administer every 8 hours (metabolites accumulate).

Moderately dialyzable (20% to 50%)

DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis. However, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Caplet, oral: 500 mg
Cetafen® Extra: 500 mg
Genapap™ Extra Strength: 500 mg [DSC]
Genebs Extra Strength: 500 mg
Mapap Extra Strength: 500 mg
Pain Eze: 650 mg
Tycolene Maximum Strength: 500 mg [DSC]
Tylenol®: 325 mg
Tylenol® Extra Strength: 500 mg

Caplet, extended release, oral:
Tylenol® 8 Hour: 650 mg
Tylenol® Arthritis Pain Extended Relief: 650 mg

Captab, oral: 500 mg

Elixir, oral:
Apra: 160 mg/5 mL (118 mL) [ethanol free; contains benzoic acid, propylene glycol, sodium benzoate, sucrose; grape flavor] [DSC]
Apra: 160 mg/5 mL (118 mL, 473 mL, 3785 mL) [ethanol free; contains propylene glycol, sodium benzoate, sucrose; cherry flavor] [DSC]
Mapap Children's: 160 mg/5 mL (118 mL, 480 mL) [ethanol free; contains benzoic acid, propylene glycol, sodium benzoate; cherry flavor]

Gelcap, oral:
Tylenol® Extra Strength: 500 mg [contains benzyl alcohol]

Geltab, oral:
Excedrin® Tension Headache: 500 mg [contains caffeine 65 mg/geltab]
Tylenol® Extra Strength: 500 mg [contains benzyl alcohol]

Liquid, oral:
APAP 500: 500 mg/5 mL (237 mL) [ethanol free, sugar free; cherry flavor]
Silapap Children's: 160 mg/5 mL (118 mL, 237 mL, 473 mL) [ethanol free, sugar free; contains propylene glycol, sodium benzoate; cherry flavor]
Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [ethanol free; contains propylene glycol, sodium benzoate; cherry flavor]

Solution, oral: 160 mg/5 mL (5 mL, 10 mL, 20 mL, 118 mL, 473 mL)

Solution, oral [drops]: 80 mg/0.8 mL (15 mL)
Genapap™ Infant: 80 mg/0.8 mL (15 mL) [ethanol free; contains propylene glycol; fruit flavor] [DSC]
Infantaire: 80 mg/0.8mL (15 mL, 30 mL)
Little Fevers™ : 80 mg/1 mL (30 mL) [dye free, ethanol free, gluten free; contains propylene glycol, sodium benzoate; berry flavor]
Silapap Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [ethanol free; contains propylene glycol, sodium benzoate; cherry flavor]

Suppository, rectal: 120 mg (12s, 50s, 100s); 325 mg (12s); 650 mg (12s, 50s, 100s)
Acephen™ : 120 mg (6s [DSC], 12s, 50s, 100s); 325 mg (6s, 12s, 50s, 100s); 650 mg (12s, 50s, 100s, 500s)
FeverALL®: 120 mg (6s, 12s, 50s); 325 mg (6s, 12s, 50s); 650 mg (12s, 50s, 500s); 80 mg (6s, 50s)
Mapap: 125 mg (12s)

Suspension, oral: 160 mg/5 mL (5 mL, 10 mL, 20 mL)
Mapap Children's: 160 mg/5 mL (118 mL) [ethanol free; contains propylene glycol, sodium benzoate; cherry flavor]
Nortemp Children's: 160 mg/5 mL (118 mL) [ethanol free; contains propylene glycol, sodium benzoate; cotton candy flavor]
Tylenol® Children's Suspension: 160 mg/5 mL (120 mL) [ethanol free; contains propylene glycol, sodium benzoate; bubblegum, strawberry, grape flavors]
Tylenol® Children's Suspension: 160 mg/5 mL (60 mL, 120 mL, 240 mL [DSC]) [ethanol free; contains propylene glycol, sodium benzoate; cherry flavor]
Tylenol® Children's Suspension: 160 mg/5 mL (120 mL) [dye free; ethanol free; contains propylene glycol, sodium benzoate; cherry flavor]

Suspension, oral [drops]:
Mapap Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [ethanol free; contains propylene glycol, sodium benzoate; cherry flavor]
Tylenol® Infant's Concentrated: 80 mg/0.8 mL (15 mL, 30 mL) [ethanol free; contains sodium benzoate; cherry, grape flavors]
Tylenol® Infant's Concentrated: 80 mg/0.8 mL (30 mL) [dye free; ethanol free; contains propylene glycol; cherry flavor]

Tablet, oral: 325 mg, 500 mg
Aspirin Free Anacin® Extra Strength: 500 mg
Cetafen®: 325 mg
Genapap™ : 325 mg [DSC]
Genapap™ Extra Strength: 500 mg
Genebs: 325 mg [DSC]
Genebs Extra Strength: 500 mg
Mapap: 325 mg
Tycolene: 325 mg [DSC]
Tylenol®: 325 mg
Valorin Extra®: 500 mg [sugar free]
Valorin®: 325 mg [sugar free]

Tablet, chewable, oral: 80 mg
Mapap Children's: 80 mg [bubblegum flavor] [DSC]
Mapap Children's: 80 mg [fruit flavor]
Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; grape flavor] [DSC]
Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]

Tablet, orally disintegrating, oral: 80 mg, 160 mg, 325 mg, 500 mg
Tylenol® Children's Meltaways: 80 mg [bubblegum, grape flavors]
Tylenol® Jr. Meltaways: 160 mg [bubblegum, grape flavors]

DOSAGE FORMS: CONCISE
Caplet, oral: 500 mg
Cetafen® Extra [OTC], Genebs Extra Strength [OTC], Mapap Extra Strength [OTC], Tylenol® Extra Strength [OTC]: 500 mg
Pain Eze [OTC]: 650 mg
Tylenol® [OTC]: 325 mg

Caplet, extended release, oral:
Tylenol® 8 Hour [OTC], Tylenol® Arthritis Pain Extended Relief [OTC]: 650 mg

Captab, oral: 500 mg

Elixir, oral:
Mapap Children's [OTC]: 160 mg/5 mL (118 mL, 480 mL)

Gelcap, oral:
Tylenol® Extra Strength [OTC]: 500 mg

Geltab, oral:
Excedrin® Tension Headache [OTC], Tylenol® Extra Strength [OTC]: 500 mg

Liquid, oral:
APAP 500 [OTC]: 500 mg/5 mL
Silapap Children's [OTC]: 160 mg/5 mL
Tylenol® Extra Strength [OTC]: 500 mg/15 mL

Solution, oral: 160 mg/5 mL

Solution, oral [drops]: 80 mg/0.8 mL
Infantaire [OTC], Silapap Infant's [OTC]: 80 mg/0.8mL
Little Fevers™ [OTC]: 80 mg/1 mL

Suppository, rectal: 120 mg (12s, 50s, 100s); 325 mg (12s); 650 mg (12s, 50s, 100s)
Acephen™ [OTC]: 120 mg (12s, 50s, 100s); 325 mg (6s, 12s, 50s, 100s); 650 mg (12s, 50s, 100s, 500s)
FeverALL® [OTC]: 120 mg (6s, 12s, 50s); 325 mg (6s, 12s, 50s); 650 mg (12s, 50s, 500s); 80 mg (6s, 50s)
Mapap [OTC]: 125 mg (12s)

Suspension, oral: 160 mg/5 mL
Mapap Children's [OTC], Nortemp Children's [OTC], Tylenol® Children's Suspension [OTC]: 160 mg/5 mL

Suspension, oral [drops]:
Mapap Infant's [OTC], Tylenol® Infant's Concentrated [OTC]: 80 mg/0.8 mL

Tablet, oral: 325 mg, 500 mg
Aspirin Free Anacin® Extra Strength [OTC], Genapap™ Extra Strength [OTC], Genebs Extra Strength [OTC], Valorin Extra® [OTC]: 500 mg
Cetafen® [OTC], Mapap [OTC], Tylenol® [OTC], Valorin® [OTC]: 325 mg

Tablet, chewable, oral: 80 mg
Mapap Children's [OTC]: 80 mg
Mapap Junior Strength [OTC]: 160 mg

Tablet, orally disintegrating, oral: 80 mg, 160 mg, 325 mg, 500 mg
Tylenol® Children's Meltaways [OTC]: 80 mg
Tylenol® Jr. Meltaways [OTC]: 160 mg

GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release products

ADMINISTRATION
Suppositories: Do not freeze.

Suspension, oral: Shake well before pouring a dose.

USE — Treatment of mild-to-moderate pain and fever (analgesic/antipyretic); does not have antirheumatic or anti-inflammatory effects

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.

Dermatologic: Rash

Endocrine & metabolic: May increase chloride, uric acid, glucose; may decrease sodium, bicarbonate, calcium

Hematologic: Anemia, blood dyscrasias (neutropenia, pancytopenia, leukopenia)

Hepatic: Bilirubin increased, alkaline phosphatase increased

Renal: Ammonia increased, nephrotoxicity with chronic overdose, analgesic nephropathy

Miscellaneous: Hypersensitivity reactions (rare)

CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component of the formulation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients.

Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency.

Other warnings/precautions: Dosage limit: Limit dose to <4>3 days or for pain lasting >10 days in adults or >5 days in children.

METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)

DRUG INTERACTIONS
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification

Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification

Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.

Food: Rate of absorption may be decreased when given with food.

Herb/Nutraceutical: St John's wort may decrease acetaminophen levels.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Acetaminophen crosses the placenta. It is generally considered to be safe for use during pregnancy when used at therapeutic doses for short periods of time.

LACTATION — Enters breast milk/compatible

BREAST-FEEDING CONSIDERATIONS — Acetaminophen is found in breast milk. The AAP considers acetaminophen to be "compatible" with breast-feeding.

DIETARY CONSIDERATIONS — Chewable tablets may contain phenylalanine (amount varies, ranges between 3-12 mg/tablet); consult individual product labeling.

PRICING — (data from drugstore.com)
Tablet, controlled release (Tylenol 8 Hour)
650 mg (50): $15.99

Tablet, controlled release (Tylenol Arthritis Pain)
650 mg (100): $19.99

Tablets (Acetaminophen)
500 mg (700): $38.99

Tablets (Tylenol)
325 mg (100): $16.99

MONITORING PARAMETERS — Relief of pain or fever

REFERENCE RANGE
Therapeutic concentration (analgesic/antipyretic): 10-30 mcg/mL

Toxic concentration (acute ingestion) with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion

CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®

INTERNATIONAL BRAND NAMES — A-Mol (TH); Acamol (CN, IL); Acamol To-Go (IL); Acamoli Baby (IL); Acamoli Forte suppositories for Kids (IL); Acenol (PL); Acet (PH); ACET suppositories (SG); Acetalgin (CH); Acetamol (IT); Adinol (MX); Adorem (CO); Afebrin (HK); Afebryl (LU); Alcocin (IN); Alvedon (SE); Amol (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Anadin (PL); Anadin dla dzieci (PL); Analgiser (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Analphen (MX); Antidol (PL, TW); APAP (PL); Aptamol (IN); Arfen (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Atamel (PE); Avadol (MY); ben-u-ron (HU); Ben-U-Ron (PT); Benuron (JP, PL); Biogesic (ID, PH, SG); Biogesic Suspension (HK); Biopain (PH); Calapol (ID); Calpol (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IE, IL, IQ, IR, JO, JP, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, PL, PR, QA, SA, SC, SD, SL, SN, SY, TH, TN, TZ, UG, YE, ZA, ZM, ZW); Causalon (AR); Cemol (TH); Children's S Tylenol (KP); Christamol (HK); Claradol (MA); Codipar (PL); Cotemp (TH); Croix Blanche (LU); Curpol (LU); Dafalgan (BE, LU, PL); Dafalgan odis (LU); Daga (TH); Denamol (TH); Dirox (AR); Dismifen (MX); Dol-Stop (LU); Dolex (UY); Dolgesic (ES); Doliprane (FR, IN, MA, PL); Dolitabs (FR); Dolomol (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Dolorol (ZA); Dolprone (LU); Doluvital (MX); Dolviran (MX); Dymadon (AU); Efferalgan (HU, LU, PL); Efferalgan 500 (CR, DO, EE, GT, HN, NI, PA, SV); Efferalganodis (FR); Enelfa (LU); Etoran (PL); Europain (HK); Febridol (AU); Fervex (BR); Filanc (MX); Gelocatil (ES); Geluprane 500 (FR); Grippostad (PL); Hedex (IE); Hoemal (MY); Itamol (ID); Itamol Forte (ID); Lekadol (HR, PL); Lemgrip (BE, LU); Lexalgin (PH); Lonarid mono (LU); Lotemp (TH); Lupocet (HR); Maganol (ID); Mebinol (PE); Mejoralito Junior (MX); Mejoralito Pediatrico (MX); Metagesic (PH); Mexalen (AT, CZ, HN, HU); Minopan (KP); Momentum (LU); Mypara (TH); Nalgesik (ID); Napafen (EC); Napamol (ZA); Napran (PH); Naprex (ID); NEBS (JP); Neuridon (LU); Nordinet Infantil (MX); Novo-Gesic (PL); Pacimol (IN); Pamol (DK); Panadol (AE, AU, BE, BF, BG, BH, BJ, CH, CI, CN, CY, EE, EG, ET, FI, FR, GB, GH, GM, GN, GR, HK, HU, ID, IE, IL, IQ, IR, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, PK, PL, QA, SA, SC, SD, SL, SN, SY, TH, TN, TW, TZ, UG, UY, YE, ZA, ZM, ZW); Panadol Actifast (MY, SG); Panadon (HR); Panamax (AU); Panodil (DK, NO, SE); Paracemol (PL); Paracenol (PL); Paracet (NO); Paracetamol (HR, PL); Paracetamol Pharmavit (HU); Paracetamol-ratiopharm (LU); Parafizz (MY); Parageniol (PY); Paragin (TH); Parahexal (AU); Paramidol (PE); Paramol (IL, PL, TW); Parapaed (DE); Parapaed Junior (NZ); Parapaed Six Plus (NZ); Parcemol (HK); Parcemol Forte (HK); Parvid (PH); Paximol (SG); Pe-Tam (LU); Pedipan (KP); Penral-Night (KP); Perdolan Mono (LU); Perfalgan (PL); Pharmacen-M (MX); Pinex (NO); Plicet (HR, PL); Poro (MY, PH, SG); Puernol (IT); Raperon (KP); Rapidol (CN); Reliv (SE); Remedol (PR); Revanin (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Rhinapen elixir (KP); Rubophen (HU); Salzone (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Saridon (CO); Sedalito (MX); Selegesic (PH); Sensamol (IL); Serimol (HK); Setopain (KP); Setopain ER (KP); Sinedol (MX); Supadol mono (LU); Suspen ER (KP); Tabcin (PL); Tamifen (EC); Tasmen (KP); Tazamol (PL); Tempra (EC, GR, ID, JP, LU, MX, TH); Tempte (TW); Teramol (PH); Teramol Forte (PH); Turpan (ID); Tylenol (AT, BR, CH, DE, FR, JP, KP, MX, PH, PT, TH, VE); Tylenol 8-hour (TH); Tylenol Acetaminophen Extended Relief (CL); Tylenol Extra Fuerte (PY); Tylenol Forte (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, PL, QA, SA, SY, YE); Tylex (BB, BM, BS, BZ, CR, DO, GT, GY, HN, JM, MX, NI, NL, PA, SR, SV, TT); Winadol (CO, VE); Xebramol (TH); XL-Dol Infantil (MX)

MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center

PHARMACODYNAMICS / KINETICS
Onset of action: <1 hour

Duration: 4-6 hours

Absorption: Incomplete; varies by dosage form

Protein binding: 8% to 43% at toxic doses

Metabolism: At normal therapeutic dosages, hepatic to sulfate and glucuronide metabolites, while a small amount is metabolized by CYP to a highly reactive intermediate (acetylimidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g daily) glutathione conjugation becomes insufficient to meet the metabolic demand causing an increase in acetylimidoquinone concentration, which may cause hepatic cell necrosis

Half-life elimination: Prolonged following toxic doses
Neonates: 2-5 hours
Adults: 1-3 hours (may be increased in elderly; however, this should not affect dosing)

Time to peak, serum: Oral: 10-60 minutes; may be delayed in acute overdoses

Excretion: Urine (2% to 5% unchanged; 55% as glucuronide metabolites; 30% as sulphate metabolites)

Acenocoumarol

MEDICATION SAFETY ISSUES — Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

PHARMACOLOGIC CATEGORY
Anticoagulant, Coumarin Derivative

DOSING: ADULTS — Note: Dosage must be individualized. The following information is based on the manufacturer's labeling in Canada.

Oral: Initial: 8-12 mg on day 1, followed by 4-8 mg on day 2. Subsequent dosage should be based on PT/INR measurements. Usual range of maintenance doses: 1-10 mg/day. Tapering of dosage is recommended prior to discontinuation.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name

Tablet:
Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]

DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name

Tablet:
Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Administer at the same time each day.

USE — Prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders; atrial fibrillation with risk of embolism; adjunct in the prophylaxis of coronary occlusion and transient ischemic attacks

ADVERSE REACTIONS SIGNIFICANT — As with all anticoagulants, bleeding is the major adverse effect of acenocoumarol. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility.

Frequency not defined.
Cardiovascular: Hemorrhagic shock
Central nervous system: Fever, headache, stroke (hemorrhagic)
Dermatologic: Rash, urticaria, skin necrosis
Skin necrosis/gangrene, due to paradoxical local thrombosis, is a known but rare risk of oral anticoagulant therapy. Its onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis. The risk of this effect is increased in patients with protein C or S deficiency.

Additional adverse reactions associated with warfarin, but likely to also occur with indanediones, include priapism and skin necrosis ("purple toe" syndrome or cutaneous gangrene).
Gastrointestinal: Gastrointestinal bleeding, melena
Genitourinary: Hematuria
Hematologic: Hemorrhage, retroperitoneal hematoma, unrecognized bleeding sites (eg, colon cancer) may be uncovered by anticoagulation. Other hematologic reactions reported with coumarin derivatives include agranulocytosis, red cell aplasia, anemia, thrombocytopenia, eosinophilia.
Hepatic: Hepatitis, hepatotoxicity, hematobilia
Ocular: Ocular hemorrhage
Respiratory: Epistaxis, hemoptysis, pulmonary hemorrhage
Miscellaneous: Hypersensitivity/allergic reactions

CONTRAINDICATIONS — Hypersensitivity to acenocoumarol or any component of the formulation; hemorrhagic tendencies; hemophilia; thrombocytopenia purpura; leukemia; recent or potential surgery of the eye or CNS; major regional lumbar block anesthesia or surgery resulting in large, open surfaces; bleeding from the GI, respiratory, or GU tract; threatened abortion; aneurysm; prolonged dietary insufficiencies (vitamin K deficiency); ascorbic acid deficiency; history of bleeding diathesis; prostatectomy; continuous tube drainage of the small intestine; polyarthritis; diverticulitis; emaciation; malnutrition; cerebrovascular hemorrhage; eclampsia/pre-eclampsia; blood dyscrasias; severe uncontrolled or malignant hypertension; severe hepatic disease; pericarditis or pericardial effusion; subacute bacterial endocarditis; visceral carcinoma; following spinal puncture and other diagnostic or therapeutic procedures with potential for significant bleeding; history of warfarin-induced necrosis; an unreliable, noncompliant patient; alcoholism; patient who has a history of falls or is a significant fall risk; pregnancy

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity: May cause hypersensitivity reactions, including anaphylaxis; use with caution in patients with anaphylactic disorders. Bleeding: May cause major or fatal bleeding. Risk factors for bleeding include high intensity anticoagulation (INR >4), age (>65 years), variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wound, history of PUD, indwelling catheters, menstruating and postpartum women, drug-drug interactions and long duration of therapy. Patient must be instructed to report bleeding, accidents, or falls as well as any new or discontinued medications, herbal or alternative products used, significant changes in smoking or dietary habits. Skin necrosis/gangrene: Necrosis or gangrene of the skin and other tissues can occur (rarely) due to early hypercoagulability; risk is increased in patients with protein C deficiency. "Purple toe" syndrome, due to cholesterol microembolization, has been described with coumarin-type anticoagulants.

Disease-related concerns: Infection: Use with caution in patients with acute infection or active TB; antibiotics and fever may alter response to acenocoumarol. Renal impairment: Use with caution in patients with renal impairment. Thyroid disease: Use with caution in patients with thyroid disease.

Special populations: Elderly: The elderly may be more sensitive to anticoagulant therapy. Ovulating women: May be at risk of developing ovarian hemorrhage at the time of ovulation. Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Patient selection: Use care in the selection of patients appropriate for this treatment; ensure patient cooperation especially from the alcoholic, illicit drug user, demented, or psychotic patient.

RESTRICTIONS — Not available in U.S.

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (major), 2C19 (minor)

DRUG INTERACTIONS
Acetaminophen: May enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy

Allopurinol: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Aminoglutethimide: May increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification

Amiodarone: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Androgens: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Anticoagulants: May enhance the anticoagulant effect of other Anticoagulants. Risk C: Monitor therapy

Antineoplastic Agents: May enhance the anticoagulant effect of Vitamin K Antagonists. Antineoplastic Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Exceptions: Alitretinoin; Altretamine; Aminoglutethimide; Anastrozole; Asparaginase; AzaCITIDine; Bleomycin; Capecitabine; CARBOplatin; Carmustine; Chlorambucil; CISplatin; Cladribine; Cytarabine; Cytarabine (Liposomal); Dacarbazine; DACTINomycin; DAUNOrubicin Citrate (Liposomal); DAUNOrubicin Hydrochloride; Denileukin Diftitox; Docetaxel; DOXOrubicin (Liposomal); Epirubicin; Estramustine; Etoposide Phosphate; Exemestane; Fludarabine; Goserelin; Hydroxyurea; IDArubicin; Irinotecan; Letrozole; Leuprolide; Lomustine; Mechlorethamine; Megestrol; Mitomycin; Mitoxantrone; Nilutamide; Paclitaxel; Pegaspargase; Pentostatin; Polyestradiol; Porfimer; RiTUXimab; Streptozocin; Tamoxifen; Temozolomide; Teniposide; Thioguanine; Thiotepa; Topotecan; Toremifene; Tretinoin (Oral); Valrubicin; VinBLAStine; Vinorelbine. Risk C: Monitor therapy

Antiplatelet Agents: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Antithyroid Agents: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

AzaTHIOprine: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification

Bicalutamide: May increase the serum concentration of Vitamin K Antagonists. Specifically, free concentrations of the vitamin K antaogonists may be increased. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Vitamin K Antagonists. Risk C: Monitor therapy

Bosentan: May increase the metabolism of Vitamin K Antagonists. Risk C: Monitor therapy

Capecitabine: May increase the serum concentration of Vitamin K Antagonists. Risk D: Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Vitamin K Antagonists. Risk D: Consider therapy modification

Cephalosporins: May enhance the anticoagulant effect of Vitamin K Antagonists. Exceptions: Cefaclor; Cefadroxil; Cefdinir; Cefepime; Cefixime; Cefonicid; Cefotaxime; Cefpodoxime; Cefprozil; Ceftazidime; Ceftibuten; Ceftizoxime; Ceftobiprole; Cefuroxime; Cephalexin; Cephradine [Off Market]. Risk C: Monitor therapy

Cimetidine: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Coenzyme Q-10: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Contraceptive (Progestins): May diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Risk D: Consider therapy modification

CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy

CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification

CYP2C9 Inducers (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy

CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Dicloxacillin: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Disulfiram: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Dronedarone: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Drotrecogin Alfa: Vitamin K Antagonists may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification

Efavirenz: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Esomeprazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Etoposide: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Fenugreek: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Fibric Acid Derivatives: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Fluconazole: May increase the serum concentration of Vitamin K Antagonists. Risk D: Consider therapy modification

Fluorouracil: May increase the serum concentration of Vitamin K Antagonists. Risk D: Consider therapy modification

Gefitinib: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Ginkgo Biloba: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Glucagon: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Glutethimide: May increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification

Green Tea: May enhance the adverse/toxic effect of Vitamin K Antagonists. Particularly, the risk of bleeding may be increased due to possible antiplatelet effects of green tea. Green Tea may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Griseofulvin: May increase the metabolism of Vitamin K Antagonists. Risk C: Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk D: Consider therapy modification

HMG-CoA Reductase Inhibitors: May enhance the anticoagulant effect of Vitamin K Antagonists. Exceptions: Atorvastatin. Risk C: Monitor therapy

Ifosfamide: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Itraconazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Ivermectin: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Ketoconazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Lansoprazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Leflunomide: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Macrolide Antibiotics: May increase the serum concentration of Vitamin K Antagonists. Exceptions: Dirithromycin [Off Market]; Spiramycin. Risk C: Monitor therapy

Mercaptopurine: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

MetroNIDAZOLE: May decrease the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification

Miconazole: May increase the serum concentration of Vitamin K Antagonists. Risk D: Consider therapy modification

Nafcillin: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

NSAID (COX-2 Inhibitor): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

NSAID (Nonselective): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Omeprazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Oral Contraceptive (Estrogens): May diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Risk D: Consider therapy modification

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates (High risk). Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Pentoxifylline: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Phenytoin: May enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Phenytoin. Risk D: Consider therapy modification

Phytonadione: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Posaconazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Propafenone: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Propoxyphene: May decrease the metabolism of Vitamin K Antagonists. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy

QuiNIDine: May enhance the anticoagulant effect of Vitamin K Antagonists. Note that the prothrombin time might be unchanged in the face of increased bleeding. Risk C: Monitor therapy

Quinolone Antibiotics: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Rifamycin Derivatives: May increase the metabolism of Vitamin K Antagonists. Risk C: Monitor therapy

Salicylates: May enhance the anticoagulant effect of Vitamin K Antagonists. Exceptions: Salsalate. Risk D: Consider therapy modification

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

St Johns Wort: May increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification

Sucralfate: May diminish the anticoagulant effect of Vitamin K Antagonists. Sucralfate may decrease the serum concentration of Vitamin K Antagonists. Specifically, sucralfate may decrease the absorption of Vitamin K Antagonists. Management: Administer vitamin K antagonists at least 2 hours before or at least 6 hours after sucralfate. Risk D: Consider therapy modification

Sulfinpyrazone [Off Market]: May decrease the metabolism of Vitamin K Antagonists. Sulfinpyrazone [Off Market] may decrease the protein binding of Vitamin K Antagonists. Risk D: Consider therapy modification

Sulfonamide Derivatives: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Tamoxifen: May increase the serum concentration of Vitamin K Antagonists. Risk X: Avoid combination

Tetracycline Derivatives: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Thyroid Products: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Tricyclic Antidepressants: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Vitamin A: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Vitamin E: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Voriconazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Vorinostat: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Zafirlukast: May decrease the metabolism of Vitamin K Antagonists. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Avoid ethanol. Acute ethanol ingestion (binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR. Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR.

Food: The anticoagulant effects of acenocoumarol may be decreased if taken with foods rich in vitamin K. Vitamin E may increase anticoagulant effect.

Herb/Nutraceutical: St John's wort may decrease oral anticoagulant levels. Alfalfa contains large amounts of vitamin K as do many enteral products. Coenzyme Q10 may decrease response to oral anticoagulants. Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, and ginkgo (all have additional antiplatelet activity).

PREGNANCY IMPLICATIONS — Oral anticoagulants cross the placenta and produce fetal abnormalities. Fatal hemorrhage in the fetus has been reported even when the mother's acenocoumarol levels were in the therapeutic range. Acenocoumarol should not be used during pregnancy because of significant risks. Adjusted-dose heparin can be given safely throughout pregnancy in patients with venous thromboembolism. Women of childbearing potential are advised to use effective contraception during treatment.

LACTATION — Enters breast milk/not recommended (per manufacturer)

DIETARY CONSIDERATIONS — Foods high in vitamin K (eg, beef liver, pork liver, green tea, and leafy green vegetables) inhibit anticoagulant effect. Do not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. Avoid large amounts of alfalfa, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress; these decrease efficacy of oral anticoagulants. It is recommended that the diet contain a CONSISTENT vitamin K content of 70-140 mcg/day. Check with healthcare provider before changing diet. Avoid using multivitamins that contain vitamin K.

MONITORING PARAMETERS — PT/INR; hepatic function, CBC, urinalysis (for albuminuria/proteinuria)

CANADIAN BRAND NAMES — Sintrom®

INTERNATIONAL BRAND NAMES — Acenocoumarol (PL); Acenocumarol (PL); Acenox (CN); Acitrom (IN); Neo-Sintrom (CN); Sinthrome (GB); Sintrom (AR, BE, BG, CH, FR, GR, IL, IT, MX, NL, PL, PT, PY); Syncumar (PL)

MECHANISM OF ACTION — Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)

PHARMACODYNAMICS / KINETICS
Onset of action: Peak anticoagulant effect: Oral: 36-48 hours

Absorption: Oral: 60%

Protein binding: 99%

Metabolism: Hepatic, via oxidation (possibly by CYP1A2, 2C9, and 2C19) to inactive metabolites

Half-life elimination: 8-11 hours

Time to peak, plasma: 1-3 hours

Excretion: Urine (60%) and feces (29%) as metabolites

Acenocoumarol

Acebutolol

Acebutolol: Drug information
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Sectral® may be confused with Factrel®, Seconal®, Septra®

U.S. BRAND NAMES — Sectral®

PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class II
Beta Blocker With Intrinsic Sympathomimetic Activity

DOSING: ADULTS
Angina, ventricular arrhythmia: Oral: 400 mg/day in divided doses; maintenance: 600-1200 mg/day in divided doses; maximum: 1200 mg/day

Hypertension: Oral: 400-800 mg/day (larger doses may be divided); maximum: 1200 mg/day; usual dose range (JNC 7): 200-800 mg/day in 2 divided doses

Chronic stable angina (unlabeled use): 400 mg/day in divided doses; maintenance: 600-1200 mg/day in divided doses; maximum: 1200 mg/day

DOSING: ELDERLY — Oral: Initial: 200-400 mg/day; dose reduction due to age-related decrease in Clcr will be necessary; do not exceed 800 mg/day.

DOSING: RENAL IMPAIRMENT
Clcr 25-49 mL/minute: Reduce dose by 50%.

Clcr <25 mL/minute: Reduce dose by 75%.

DOSING: HEPATIC IMPAIRMENT — Use with caution.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, as hydrochloride: 200 mg, 400 mg
Sectral®: 200 mg, 400 mg

DOSAGE FORMS: CONCISE
Capsule, as hydrochloride: 200 mg, 400 mg
Sectral®: 200 mg, 400 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — To discontinue therapy, taper dose gradually over a period of 2 weeks. May be administered without regard to meals.

USE — Treatment of hypertension; management of ventricular arrhythmias

USE - UNLABELED / INVESTIGATIONAL — Treatment of chronic stable angina

ADVERSE REACTIONS SIGNIFICANT
>10%: Central nervous system: Fatigue (11%)

1% to 10%:
Cardiovascular: Chest pain (2%), edema (2%), bradycardia, hypotension, CHF
Central nervous system: Headache (6%), dizziness (6%), insomnia (3%), depression (2%), abnormal dreams (2%), anxiety, hyper-/hypoesthesia
Dermatologic: Rash (2%), pruritus
Gastrointestinal: Constipation (4%), diarrhea (4%), dyspepsia (4%), nausea (4%), flatulence (3%), abdominal pain, vomiting
Genitourinary: Micturition frequency (3%), dysuria, impotence, nocturia
Neuromuscular & skeletal: Myalgia (2%), back pain, joint pain
Ocular: Abnormal vision (2%), conjunctivitis, dry eyes, eye pain
Respiratory: Dyspnea (4%), rhinitis (2%), cough (1%), pharyngitis, wheezing

Postmarketing and/or case reports: Alkaline phosphatase increased, anorexia, AV block, bilirubin increased, cold extremities, drug-induced lupus-like syndrome, exacerbate pre-existing renal insufficiency, facial edema, hepatotoxic reaction, lichen planus, palpitation, pleurisy, pneumonitis, pulmonary granulomas, systemic lupus erythematosus, transaminases increased, urinary retention, ventricular arrhythmia, xerostomia

Potential adverse effects (based on experience with other beta-blocking agents) include agranulocytosis, allergic reactions, alopecia, catatonia, claudication, depression (reversible), disorientation, emotional lability, erythematous rash, ischemic colitis, laryngospasm, mesenteric artery thrombosis, Peyronie's disease, purpura, respiratory distress, short-term memory loss, slightly clouded sensorium, thrombocytopenia

CONTRAINDICATIONS — Overt cardiac failure; cardiogenic shock; persistently-severe bradycardia or second- and third-degree heart block (except in patients with a functioning artificial pacemaker)

WARNINGS / PRECAUTIONS
Concerns related to adverse events: Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

Disease-related concerns: Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; for patients with bronchospastic disease who do not respond to or cannot tolerate other therapies, initial low doses of acebutolol may be employed and used cautiously with close monitoring. Ensure patient has an inhaled beta2-agonist immediately available. Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating. Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms. Heart failure (HF): Beta-blockers with intrinsic sympathomimetic activity (eg, acebutolol) are likely to worsen survival in patients with HF and should be avoided. Beta-blockers shown to improve survival in clinical trials should be used in these patients. Hepatic impairment: Use with caution in patients with hepatic impairment. Mesenteric vascular disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with mesenteric vascular disease. Use with caution in these patients. Observe closely for progression of arterial obstruction. Myasthenia gravis: Use with caution in patients with myasthenia gravis. Peripheral vascular disease (PVD): Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD. Use with caution in these patients. Observe closely for progression of arterial obstruction. Pheochromocytoma (untreated): Adequate alpha1-receptor blockade is required prior to use of any beta-blocker. Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established. Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression. Raynaud's disease: Use with caution in these patients with Raynaud's disease; may precipitate symptoms of Raynaud's. Renal impairment: Use with caution in patients with renal impairment, especially the elderly. Elimination of the metabolite, diacetolol, is reduced resulting in a two- to threefold increase in its half-life. Thyrotoxicosis: Beta-blockade may mask signs of hyperthyroidism (eg, tachycardia). Abrupt discontinuation may also induce a thyroid storm.

Special populations: Elderly: Use reduced doses in elderly patients; concentrations of acebutolol and diacetolol are significantly higher in the elderly. Dose should not exceed 800 mg/day. Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.

METABOLISM / TRANSPORT EFFECTS — Inhibits CYP2D6 (weak)

DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Risk D: Consider therapy modification

Alpha1-Blockers: Beta-Blockers may enhance the orthostatic effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk D: Consider therapy modification

Alpha2-Agonists: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification

Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Beta2-Agonists: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Risk D: Consider therapy modification

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy

Lidocaine: Beta-Blockers may decrease the metabolism of Lidocaine. Risk C: Monitor therapy

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination

Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Propafenone: May decrease the metabolism of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy

Propoxyphene: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

QuiNIDine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy

RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification

Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy

Theophylline Derivatives: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. This is true at higher beta-blockers doses where cardioselectivity is lost. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Peak serum acebutolol levels may be slightly decreased if taken with food.

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid yohimbe, ginseng (may worsen hypertension).

PREGNANCY RISK FACTOR — B (show table) (manufacturer); D (2nd and 3rd trimesters - expert analysis)

PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acebutolol and its metabolite cross the human placenta. The neonatal half-life of acebutolol is 6-14 hours and diacetolol is 24-30 hours. Decreased birth weight, blood pressure, and heart rate have been observed in neonates following maternal use of acebutolol during pregnancy. Neonatal hypoglycemia has also been reported. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Monitoring of the newborn is recommended.

LACTATION — Enters breast milk/not recommended (AAP recommends "use with caution")

BREAST-FEEDING CONSIDERATIONS — Acebutolol and its metabolites are found in human breast milk; the milk/plasma ratio is 7.1 for acebutolol and 12.2 for diacetolol. Hypotension, bradycardia, and tachypnea have been reported in nursing infants.

DIETARY CONSIDERATIONS — May be taken without regard to meals.

PRICING — (data from drugstore.com)
Capsules (Acebutolol HCl)
200 mg (100): $54.98
400 mg (30): $21.99

Capsules (Sectral)
200 mg (60): $179.98
400 mg (30): $124.99

MONITORING PARAMETERS — Blood glucose; blood pressure, orthostatic hypotension, heart rate, CNS effects, ECG

CANADIAN BRAND NAMES — Apo-Acebutolol®; Gen-Acebutolol; Monitan®; Novo-Acebutolol; Nu-Acebutolol; Rhotral; Rhoxal-acebutolol; Sandoz-Acebutolol; Sectral®

INTERNATIONAL BRAND NAMES — Abutol (PL); ACB (NZ); Acebutolol (PL); Acecor (PL); Acepin (TW); Acetanol (JP); Beloc (CN); Butobloc (ZA); Cetolol (PL); Diasectral (DK, FI); Flebutol (VE); Grifobutol (CN); Prent (CH, DE, IT, PT); Rhodiasectral (AR); Sectral (AE, AT, BB, BE, BG, BH, BM, BR, BS, BZ, CH, CY, CZ, EG, ES, FR, GB, GY, HK, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KW, LB, LU, LY, NL, OM, PL, QA, SA, SR, SY, TT, TW, YE, ZA); Sectral LP (FR); Sincer (TW); Wesfalin (AR)

MECHANISM OF ACTION — Competitively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors except at high doses; exhibits membrane stabilizing and intrinsic sympathomimetic activity

PHARMACODYNAMICS / KINETICS
Onset of action: 1-2 hours

Duration: 12-24 hours

Absorption: Oral: 40%

Protein binding: ~26%

Metabolism: Extensive first-pass effect to equipotent and cardioselective diacetolol metabolite

Half-life elimination: Parent drug: 3-4 hours; Metabolite: 8-13 hours

Time to peak: 2-4 hours

Excretion: Feces (50% to 60%); urine (30% to 40%); diacetolol eliminated primarily in the urine

PATIENT INFORMATION — Do not discontinue abruptly. Consult pharmacist or prescriber before taking with other adrenergic drugs (eg, cold medications). Take at the same time each day. May be taken without regard to meals. Use with caution while driving or performing tasks requiring alertness. Notify prescriber if CHF symptoms become worse or if other side effects occur. May mask signs of hypoglycemia in diabetics.

Acebutolol

Acarbose:

EDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Precose® may be confused with PreCare®

International issues:
Precose® may be confused with Precosa® which is a brand name for Saccharomyces boulardii in Denmark, Finland, Norway, and Sweden

U.S. BRAND NAMES — Precose®

PHARMACOLOGIC CATEGORY
Antidiabetic Agent, Alpha-Glucosidase Inhibitor

DOSING: ADULTS — Type 2 diabetes: Oral:

Initial: 25 mg 3 times/day with the first bite of each main meal; to reduce GI effects, some patients may benefit from initiating at 25 mg once daily with gradual titration to 25 mg 3 times/day as tolerated

Maintenance dose: Should be adjusted at 4- to 8-week intervals based on 1-hour postprandial glucose levels and tolerance until maintenance dose is reached; maintenance dose: 50-100 mg 3 times/day. Dosage must be individualized on the basis of effectiveness and tolerance while not exceeding the maximum recommended dose.

Maximum:
≤ 60 kg: 50 mg 3 times/day
>60 kg: 100 mg 3 times/day

Patients receiving sulfonylureas or insulin: Acarbose given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea or insulin. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr <25 mL/minute: Peak plasma concentrations were 5 times higher and AUCs were 6 times larger than in volunteers with normal renal function.

Significant renal dysfunction (Scr >2 mg/dL): Use is not recommended.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet: 25 mg, 50 mg, 100 mg
Precose®: 25 mg, 50 mg, 100 mg

DOSAGE FORMS: CONCISE
Tablet: 25 mg, 50 mg, 100 mg
Precose®: 25 mg, 50 mg, 100 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Should be administered with the first bite of each main meal.

USE — Adjunct to diet and exercise to lower blood glucose in patients with type 2 diabetes mellitus (noninsulin dependent, NIDDM)

ADVERSE REACTIONS SIGNIFICANT
>10%:
Gastrointestinal: Diarrhea (31%) and abdominal pain (19%) tend to return to pretreatment levels over time; frequency and intensity of flatulence (74%) tend to abate with time
Hepatic: Transaminases increased (≤ 4%)

Postmarketing and/or case reports: Edema, erythema, exanthema, hepatitis, ileus/subileus, jaundice, liver damage, rash, urticaria

CONTRAINDICATIONS — Hypersensitivity to acarbose or any component of the formulation; patients with diabetic ketoacidosis or cirrhosis; patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or in patients predisposed to intestinal obstruction; patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption, and in patients who have conditions that may deteriorate as a result of increased gas formation in the intestine

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Elevated serum transaminases: Treatment-emergent elevations of serum transaminases (AST and/or ALT) occurred in up to 14% of acarbose-treated patients in long-term studies. These serum transaminase elevations appear to be dose related. At doses >100 mg 3 times/day, the incidence of serum transaminase elevations greater than 3 times the upper limit of normal was 2-3 times higher in the acarbose group than in the placebo group. These elevations were asymptomatic, reversible, more common in females, and, in general, were not associated with other evidence of liver dysfunction. Fulminant hepatitis has been reported rarely.

Disease-related concerns: Renal impairment: Use not recommended in patients with significant impairment (Scr >2 mg/dL); use with caution in other patients with renal impairment. Stress-related states: It may be necessary to discontinue acarbose and administer insulin if the patient is exposed to stress (ie, fever, trauma, infection, surgery).

Concurrent drug therapy issues: Sulfonylureas/insulin: In combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea or insulin.

Special populations: Pediatrics: Safety and efficacy have not been established in children.

DRUG INTERACTIONS
Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy

Digoxin: Acarbose may decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy

Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy

Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy modification

Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Limit ethanol.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Adverse events have not been reported in animal reproduction studies; therefore, acarbose is classified as pregnancy category B. Low amounts of acarbose are absorbed systemically which should limit fetal exposure. Maternal hyperglycemia can be associated with adverse effects in the fetus, including macrosomia, neonatal hyperglycemia, and hyperbilirubinemia; the risk of congenital malformations is increased when the Hb A1c is above the normal range. Diabetes can also be associated with adverse effects in the mother. Poorly-treated diabetes may cause end-organ damage that may in turn negatively affect obstetric outcomes. Physiologic glucose levels should be maintained prior to and during pregnancy to decrease the risk of adverse events in the mother and the fetus. Acarbose has been studied for its potential role in treating GDM; however, only limited information is available describing pregnancy outcomes. Until additional safety and efficacy data are obtained, the use of oral agents is generally not recommended as routine management of GDM or type 2 diabetes mellitus during pregnancy. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — It is not known if acarbose is found in breast milk; however, low amounts of acarbose are absorbed systemically in adults, which may limit the amount that could distribute into breast milk. Breast-feeding is not recommended by the manufacturer.

DIETARY CONSIDERATIONS — Take with food (first bite of meal).

PRICING — (data from drugstore.com)
Tablets (Acarbose)
25 mg (100): $81.99
50 mg (100): $87.99
100 mg (100): $89.99

Tablets (Precose)
25 mg (90): $85.52
50 mg (90): $88.49
100 mg (90): $102.58

MONITORING PARAMETERS — Postprandial glucose, glycosylated hemoglobin levels, serum transaminase levels should be checked every 3 months during the first year of treatment and periodically thereafter, renal function (serum creatinine); blood pressure

REFERENCE RANGE — Recommendations for glycemic control in adults with diabetes:

Hb A1c: <7%

Preprandial capillary plasma glucose: 70-130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

CANADIAN BRAND NAMES — Glucobay™

INTERNATIONAL BRAND NAMES — Decarbay (TW); Deglu (TW); Dibose (MY); Glibose (TW); Glicobase (IT); Glucar (MY); Glucobay (AE, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, GB, GH, GM, GN, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PH, PK, PL, PT, PY, QA, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Gluconase (PH); Glucor (FR); Glumida (ES); Incardel (MX); Prandase (IL); Precose (MY); Rebose (IN); Sincrosa (MX)

MECHANISM OF ACTION — Competitive inhibitor of pancreatic alpha-amylase and intestinal brush border 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 / KINETICS
Absorption: <2% as active drug; ~35% as metabolites

Metabolism: Exclusively via GI tract, principally by intestinal bacteria and digestive enzymes; 13 metabolites identified (major metabolites are sulfate, methyl, and glucuronide conjugates)

Bioavailability: Low systemic bioavailability of parent compound; acts locally in GI tract

Half-life elimination: ~2 hours

Time to peak: Active drug: ~1 hour

Excretion: Urine (~34% as inactive metabolites, <2% parent drug and active metabolite); feces (~51% as unabsorbed drug)

PATIENT INFORMATION — Take this medication exactly as directed, with the first bite of each main meal. It is important to continue to adhere to dietary instructions, a regular exercise program, and regular testing of urine and/or blood glucose. The risk of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be well understood by patients and responsible family members. A source of glucose (dextrose) should be readily available to treat symptoms of low blood glucose when taking acarbose in combination with a sulfonylurea or insulin. If side effects occur, they usually develop during the first few weeks of therapy and are most often mild-to-moderate gastrointestinal effects, such as flatulence, diarrhea, or abdominal discomfort and generally diminish in frequency and intensity with time.

(For additional information see "Acarbose: Patient drug information")

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Sunday, May 16, 2010

Acetaminophen (paracetamol)

Acenocoumarol

Acenocoumarol

Acebutolol

Acebutolol

Acarbose: