sobre ventas totales
4.5.4.1.9 Evaluación de medianos y grandes proyectos como pequeños
& Other Serious Illness
A. Formulations and Regimens
For many patients, opioids are the mainstay of pain manage- ment. Opioids are appropriate for severe pain due to any cause, including neuropathic pain. Opioid medications are listed in Table 5–3. Full opioid agonists such as morphine, hydromorphone, oxycodone, methadone, fentanyl, hydro- codone, and codeine are used most commonly. Hydroco- done and codeine are typically combined with acetaminophen or an NSAID, although acetaminophen in these combina- tions is restricted to 325 mg per unit dose due to the risk of toxicity. Extended-release hydrocodone without acetamino- phen is FDA approved. Short-acting formulations of oral morphine sulfate (starting dosage 4–8 mg orally every 3–4 hours), hydromorphone (1–2 mg orally every 3–4 hours), or oxycodone (5 mg orally every 3–4 hours) are use- ful for acute pain not controlled with other analgesics. These same oral medications, or oral transmucosal fentanyl (200 mcg oralet dissolved in the mouth) or buccal fentanyl (100 mcg dissolved in the mouth), can be used for “rescue” or “breakthrough” treatment for patients experiencing pain that breaks through long-acting medications. Distribution is restricted in the United States, and management issues are complex for opioid agonist-antagonists, such as buprenor- phine. Its use as a short-acting analgesic generally should be reserved for specialists.
Table 5–2. Acetaminophen, COX-2 inhibitors, and useful nonsteroidal anti-inflammatory drugs.
Drug
Usual Oral Dose for Adults
≥ 50 kg
Usual Oral Dose for
Adults
< 50 kg1 Cost per Unit 30 DaysCost for 2 Comments3
Acetaminophen or paracetamol4 (Tylenol, Datril, etc) 325–500 mg every 4 hours or 750 mg every 6 hours, up to 2000–3000 mg/d 10–15 mg/kg every 4 hours (oral); 15–20 mg/kg every 4 hours (rectal), up to 2000– 3000 mg/d $0.02/500 mg (oral) OTC; $0.71/650 mg (rectal) OTC $3.60 (oral); $127.80 (rectal)
Not an NSAID because it lacks peripheral anti-inflammatory effects. Equivalent to aspirin as analgesic and antipyretic agent. Limit dose to 3000 mg/d and to 2000 mg/d in
older patients and those with liver disease. Be mindful of multiple sources of acetamin- ophen as in combination analgesics, cold remedies, and sleep aids.
Aspirin5 650 mg every 4 hours or 975 mg every 6 hours 10–15 mg/kg every 4 hours (oral); 15– 20 mg/kg every 4 hours (rectal) $0.02/325 mg OTC; $1.51/600 mg (rectal) OTC $7.20 (oral); $271.80 (rectal)
Available also in enteric-coated form that is more slowly absorbed but better tolerated.
Celecoxib4
(Celebrex) 200 mg once daily (osteoarthritis); 100–200 mg twice daily (RA)
100 mg once or
twice daily $4.62/100 mg; $7.58/200 mg $227.40 OA; $454.80 RA
Cyclooxygenase-2 inhibitor. No antiplatelet effects. Lower doses for elderly who weigh < 50 kg. Lower incidence of endo- scopic gastrointestinal ulceration. Not known if true lower incidence of gastroin- testinal bleeding. Possible link to cardio- vascular toxicity. Celecoxib is contraindicated in sulfonamide allergy. Choline
magnesium salicylate6
(Trilasate, others)
1000–1500 mg three times daily
25 mg/kg three times daily
$0.46/500 mg $124.20 Salicylates cause less gastrointestinal dis- tress and kidney impairment than NSAIDs but are probably less effective in pain management than NSAIDs. Diclofenac (Voltaren, Cataflam, others) 50–75 mg orally two or three times daily; 1% gel 2–4 g four times daily; 1.3% patch two times daily
$1.47/50 mg;
$1.77/75 mg $132.30; $159.30 May impose higher risk of hepatotoxicity. Enteric-coated product; slow onset. Topical formulations may result in fewer side effects than oral formulations. Diclofenac sustained release (Voltaren- XR, others) 100–200 mg once daily $2.81/100 mg $168.60 Diflunisal7 (Dolobid, others) 500 mg every 12 hours
$2.07/500 mg $124.20 Fluorinated acetylsalicylic acid derivative. Etodolac (Lodine,
others) 200–400 mg every 6–8 hours $1.32/400 mg $158.40 Fenoprofen calcium
(Nalfon, others) 300–600 mg every 6 hours $3.40/600 mg $408.00 Perhaps more side effects than others, including tubulointerstitial nephritis. Flurbiprofen
(Ansaid) 50–100 mg three or four times daily $0.83/50 mg; $1.25/100 mg $99.60; $150.00 Adverse gastrointestinal effects may be more common among elderly. Ibuprofen (Motrin, Advil, Rufen, others) 400–800 mg every 6 hours 10 mg/kg every 6–8 hours $0.28/600 mg Rx; $0.05/ 200 mg OTC $33.60; $9.00
Relatively well tolerated and inexpensive. Indomethacin
(Indocin, Indometh, others)
25–50 mg two to four times daily
$0.38/25 mg; $0.64/50 mg
$45.60; $76.80
Higher incidence of dose-related toxic effects, especially gastrointestinal and bone marrow effects.
Ketoprofen (Orudis,
Oruvail, others) 25–75 mg every 6–8 hours (max 300 mg/d)
$1.12/50 mg Rx; $1.24/75 mg Rx
$126.00;
$148.80 Lower doses for elderly.
Table 5–2. Acetaminophen, COX-2 inhibitors, and useful nonsteroidal anti-inflammatory drugs.
Drug
Usual Oral Dose for Adults
≥ 50 kg
Usual Oral Dose for
Adults
< 50 kg1 Cost per Unit 30 DaysCost for 2 Comments3
Ketorolac trometh-
amine (Toradol) 10 mg every 4–6 hours to a maxi- mum of 40 mg/d orally
$2.16/10 mg Not recom- mended
Short-term use (< 5 days) only; otherwise, increased risk of gastrointestinal side effects.
Ketorolac trometh-
amine8 (Toradol) 60 mg intramuscu-larly or 30 mg
intravenously ini- tially, then 30 mg every 6 hours intramuscularly or intravenously $1.45/30 mg Not recom- mended
Intramuscular or intravenous NSAID as alternative to opioid. Lower doses for elderly. Short-term use (< 5 days) only.
Magnesium salicy-
late (various) 467–934 mg every 6 hours $0.23/467 mg OTC $55.20 Meclofenamate
sodium9
(Meclomen)
50–100 mg every 6 hours
$7.74/100 mg $928.80 Diarrhea more common.
Mefenamic acid
(Ponstel) 250 mg every 6 hours $17.41/250 mg $2089.20 Nabumetone
(Relafen) 500–1000 mg once daily (max dose 2000 mg/d)
$1.30/500 mg;
$1.53/750 mg $91.80 May be less ulcerogenic than ibuprofen, but overall side effects may not be less. Naproxen
(Naprosyn, Anaprox, Aleve [OTC], others)
250–500 mg every
6–8 hours 5 mg/kg every 8 hours $1.29/500 mg Rx; $0.08/ 220 mg OTC
$154.80; $7.20 OTC
Generally well tolerated. Lower doses for elderly.
Oxaprozin (Daypro, others)
600–1200 mg once daily
$1.50/600 mg $90.00 Similar to ibuprofen. May cause rash, pruritus, photosensitivity. Piroxicam (Feldene,
others) 20 mg daily $2.64/20 mg $79.20 Not recommended in the elderly due to high adverse drug reaction rate. Single daily dose convenient. Long half-life. May cause higher rate of gastrointestinal bleeding and dermatologic side effects. Sulindac (Clinoril,
others) 150–200 mg twice daily $0.98/150 mg; $1.21/200 mg $58.80; $72.60 May cause higher rate of gastrointestinal bleeding. May have less nephrotoxic potential.
Tolmetin (Tolectin) 200–600 mg four
times daily $0.75/200 mg; $3.98/600 mg $90.00; $477.60 Perhaps more side effects than others, including anaphylactic reactions.
1Acetaminophen and NSAID dosages for adults weighing < 50 kg should be adjusted for weight.
2Average wholesale price (AWP, for AB-rated generic when available) for quantity listed. Source: Red Book Online, 2015, Truven Health
Analytics, Inc. AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions.
3The adverse effects of headache, tinnitus, dizziness, confusion, rashes, anorexia, nausea, vomiting, gastrointestinal bleeding, diarrhea,
nephrotoxicity, visual disturbances, etc, can occur with any of these drugs. Tolerance and efficacy are subject to great individual variations among patients. Note: All NSAIDs can increase serum lithium levels.
4Acetaminophen and celecoxib lack antiplatelet effects.
5May inhibit platelet aggregation for 1 week or more and may cause bleeding. 6May have minimal antiplatelet activity.
7Administration with antacids may decrease absorption. 8Has the same gastrointestinal toxicities as oral NSAIDs.
9Coombs-positive autoimmune hemolytic anemia has been associated with prolonged use.
COX-2, cyclooxygenase-2; OA, osteoarthritis; RA, rheumatoid arthritis; OTC, over the counter; Rx, prescription.
Data from Jacox AK et al. Management of Cancer Pain: Quick Reference Guide for Clinicians No. 9. AHCPR Publication No. 94–0593. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. March 1994.
Ch
APTER
5
CMD
T 2016
(compared to morphine 30 mg orally
or 10 mg IV/SC)1 Adults ≥ 50 kg Body Weight Adults < 50 kg Body Weight
Drug Oral Parenteral Oral Parenteral Oral Parenteral AdvantagesPotential DisadvantagesPotential
Opioid Agonists2 Buprenorphine
transdermal
Not available Not available Not available orally. Transdermal doses available: 5, 10, and 20 mcg/h. Initiate 5 mcg/h patch for opioid-naïve patients (may currently be using nonopioid analge- sics); $84.03/ 10 mcg/h
Not available Not available Not available 7-day analgesia; may
be initiated in opioid-naïve patients. Can titrate up dose
after 72 hours.
QT prolongation.
Fentanyl Not available 100 mcg
every hour Not available 50–100 mcg IV/IM every hour or 0.5–1.5 mcg/kg/h IV infusion $0.53/100 mcg Not available 0.5–1 mcg/kg IV every 1–4 hours or 1–2 mcg/kg IV × 1, then 0.5–1 mcg/kg/h infusion Possibly less neuroexcitatory effects, including in kidney failure. Fentanyl oral transmucosal (Actiq); buccal (Fentora)
Not available Not available 200 mcg transmuco-
sal; 100 mcg buccal; $18.80/ 200 mcg transmu- cosal; $55.80/ 200 mcg buccal
Not available Not available Not available For pain breaking
through long- acting opioid medication.
Transmucosal and buccal formulations are not bioequiva- lent; there is higher bioavailability in buccal formulation.