N arcotic analgesics, also termed opioid analgesics, are widely prescribed to relieve mod- erate to severe pain. T hey are used in cases o acute pain, such as due to an injury or surgery, and in cases o chronic pain due to cancer, musculoskeletal conditions, and other illnesses. In cases o chronic pain, when the patient will most likely be on a narcotic anal- gesic or an extended period o time, the goal o therapy is usually to relieve the patient’s pain enough that he or she can continue a normal li estyle but without overmedicating the patient and causing unwanted side e ects o constant drowsiness, lethargy, and con- stipation. O nce a patient is established on a chronic narcotic analgesic therapy, changes o ten need to be made to manage the patient’s pain without overly sedating the patient.
Furthermore, the patient may be switched to a di erent narcotic analgesic medication i he or she has developed a tolerance to the current medication regimen, cannot tolerate the adverse e ects o the current medication, or desires a more convenient ormulation or dosing schedule. In these cases, an equianalgesic dosing chart, such as in Table 10.1, is used to determine the appropriate dose o the new medication to ensure that the patient receives adequate pain relie with minimal adverse e ects. An equianalgesic dosing chart is used to estimate the dose o the new narcotic analgesic to be used, and the patient should still be monitored or pain relie and presence o side e ects. Most o the pub- lished charts are limited to adult patients weighing greater than 50 kg, and recommend a reduced dosage or elderly patients and patients with renal or hepatic insu f ciency. In addition, clinicians may reduce the stated equivalent dose due to the potential or incom- plete cross-tolerance between opioid analgesics. To use the equianalgesic dosing chart, the daily dose o the current medication is determined rom the dose and dosage regimen, compared to the daily dose in the chart, and then converted to the dose and dosage regi- men or new medication.
W hereas Table 10.1 provides equianalgesic dosing or opioids acting as ull agonists at the mu opioid receptor, a di erent chart is utilized or opioid analgesics with di erent pharmacological pro iles (Table 10.2). T hese include buprenorphine (a partial agonist at mu opioid receptors), nalbuphine and butorphanol (opioid agonist–antagonists, which
CASE IN POINT 1 0.1a A 198-l ho p al zed pa en pla ed on hepar n herapy o rea a pulmonary em ol m. t he pa en requ re a olu nje on ollowed y a hepar n n u on. t he ho p al ollow he pro o ol hown n F gure 10.1.
t he ho p al pharma ha hepar n ava la le or olu do e on a n ng 5000 un /mL n 5-mL v al and hepar n or n ravenou n u on n 250-mL n u on ag ea h on a n ng 25,000 un o hepar n.
(a) How many m ll l er o he 5000 un /mL nje on hould he pharma re ommend a a olu do e?
( ) How many m ll l er per hour o he hepar n n u on hould he pharma n ru he nur e o del ver, a ed on he andard n u on pro o ol?
( ) i he n ravenou e programmed o del ver 60 drop per m ll l er, wha hould e he f ow ra e, n drop per m nu e, o del ver he mL/h requ red n an wer ( )?
(d) How long w ll he 250-mL n u on ag la , n hour ?
ac a e n Po n our e y o Flynn Warren, b hop, GA.
172 Pharma euti al c al ulations
block mu receptors and stimulate kappa opioid receptors), and pentazocine (an agonist at kappa receptors and weakly blocking at mu receptors). T he dosing chart for these opioids determines a dose equivalent to 10 mg of parenteral morphine. T he clinician may then use this morphine dose to convert to another opioid analgesic by consulting the equianalgesic dosing chart in Table 10.1.
Drug-specific conversion charts are available for certain opioid analgesics. For example, Table 10.3 provides equivalent dosing for conversion from an existing narcotic analgesic to the highly potent fentanyl transdermal system. Table 10.4 lists ratios to guide conversion from hydrocodone, oxycodone, methadone, or morphine to oxymorphone extended-release tablets. If a patient is changing to or from one of these narcotic analgesic medications, it is important for the clinician to consult these drug-specific charts to guide accurate and appropriate dosing.
Tab e 1 0 .2 • OPIOId AGONIST–ANTAGONIST ANAl GESICS:
APPROxImATE Eq UIANAl GESIC d OSES FOR Ad Ul TSa
Agonist–Antagonist
d ose E uiva ent to 1 0 g Parentera morphine
Buprenorphine IM 0.3 mg
IV
Sublingual Transdermal
Butorphanol IM 2 mg
IV Nasal
Nalbuphine SC/IM 10 mg
IV
Pentazocine SC/IM 30 mg
IV
aAdapted with permission from Drug Facts & Comparisons. Facts & Comparisons eAnswers [database online]. St. Louis, MO: Clinical Drug Information LLC; 2015.
Tab e 1 0 .1 • OPIOId ANAl GESICS: APPROxImATE Eq UIANAl GESIC d OSES FOR Ad Ul TSa
Opioi
E uiana gesic d ose
Ora Parentera
Codeine 200 mg NA
Fentanyl NA 0.1 mg
Hydrocodone 30–45 mg NA
Hydromorphone 7.5 mg 1.5 mg
Levorphanol 4 mg (acute);
1 mg (chronic)
NA
Meperidine 300 mg 75 mg
Morphine 30 mg 10 mg
Oxycodone 20 mg NA
Oxymorphone 10 mg 1 mg
aAdapted with permission from Drug Facts & Comparisons. Facts & Comparisons eAnswers [database online]. St. Louis, MO: Clinical Drug Information LLC; 2015.
10 • s ele ted c lini al c al ulation 173
Example Calculations Using Equianalgesic Dosing Charts
(1) A patient is taking LORTAB 7.5-mg tablets containing 7.5 mg of hydrocodone bitar- trate and 325 mg of acetaminophen to manage his chronic back pain. His current dosage is two tablets every 6 hours, but his pain management doctor would like to switch him to hydromorphone hydrochloride tablets to better alleviate his pain. Hydromorphone hydrochloride tablets are available in strengths of 2, 4, and 8 mg and should be admin- istered every 4 to 6 hours. Determine the dose of hydromorphone hydrochloride for this patient.
7 5 2 4
. mg hydrocodone 60 tablet
tablets dose
doses
day mg hydrocod
× × = oone day/
According to the chart in Table 10.1, 30 mg of hydrocodone is equivalent to 7.5 mg of hydromorphone taken orally.
60 7 5
30 15
mg hydrocodone day
mg hydromorphone
mg hydrocodone mg h
× . =
yydromorphone day/
Ta e 1 0 .3 • FENTANyl TRANSd ERmAl d OSAGE CONvERSION GUId El INESa,b
Current Ana gesic d ai d osage ( g/ a )
Oral morphine 60–134 135–224 225–314 315–404
IM/IV morphine 10–22 23–37 38–52 53–67
Oral oxycodone 30–67 67.5–112 112.5–157 157.5–202
Oral codeine 150–447
Oral hydromorphone 8–17 17.1–28 28.1–39 39.1–51
IV hydromorphone 1.5–3.4 3.5–5.6 5.7–7.9 8–10
IM meperidine 75–165 166–278 279–390 391–503
Oral methadone 20–44 45–74 75–104 105–134
Recommended fentanyl transdermal system dose
Fentanyl transdermal system 25 mcg/h 50 mcg/h 75 mcg/h 100 mcg/h
aAdapted with permission from Drug Facts & Comparisons. Facts & Comparisons eAnswers [database online]. St. Louis, MO:
Clinical Drug Information LLC; 2015.
bThis table should not be used to convert fentanyl transdermal to other therapies because the conversion to fentanyl transder- mal is conservative. Use of this table for conversion to other analgesic therapies can overestimate the dose of the new agent.
Overdosage of the new analgesic agent is possible.
Ta e 1 0 .4 • CONvERSION FACTORS TO OxymORPh ONE ER TAb l ETSa
Prior Ora Opioi
Appro i ate Ora Con ersion Factor
Oxymorphone 1
Hydrocodone 0.5
Oxycodone 0.5
Methadone 0.5
Morphine 0.333
aAdapted with permission from Drug Facts & Comparisons.
Facts & Comparisons eAnswers [database online].
St. Louis, MO: Clinical Drug Information LLC; 2015.
174 Pharma euti al c al ulations
Since the patient is accustomed to taking the current medication every 6 hours, this dosage regimen would probably be most effective for him.
15 1
4 mg hydromorphone
day
day doses
× = 3 75 mg dose. /
T he patient should begin with hydromorphone hydrochloride 4-mg tablets every 6 hours and monitored for relief of pain symptoms as well as for adverse effects.
(2) CR is a 57-year-old male patient who is 6 feet 1 inch tall and weighs 212 lb. He is receiving a 20-mg intravenous injection of pentazocine lactate every 4 hours to control his pain after an injury due to a motorcycle accident. His physician wishes to switch him to an oral dose of meperidine hydrochloride so that he can move into a rehabilitation facility. W hat would be the equivalent dose of meperidine hydrochloride for this patient?
According to Table 10.2, a 30-mg injection of pentazocine is equivalent to a 10-mg injection of morphine; therefore, the amount of morphine represented by a 20-mg injection of pentazocine can be calculated as:
10
30 mg morphine 20 6 67
mg pentazocine × mg pentazocine = . mg morphine
According to Table 10.1, a 10-mg injection of morphine is equivalent to 300 mg of meperidine given orally. T he oral dose of meperidine for this patient can be calculated as:
300
10 mg meperidine 6 67
mg morphine × . mg morphine = 200 mg meperidine
T he patient can take two 100-mg meperidine hydrochloride tablets every 4 hours to manage his pain.
(3) A cancer patient is taking one 20-mg oxycodone tablet q.i.d. to manage her pain. (a) W hat is the total daily oxycodone dose for this patient? (b) The patient’s pain management physician decides to switch her to fentanyl transdermal patches. W hat strength of fentanyl patch should he prescribe?5 (a) 20 mg 4
tablet
tablets
× day = 80 mg day/
(b) According to Table 10.3, a patient receiving an oral oxycodone dose of 67.5 to 112 mg/day of oral oxycodone should begin with a 50 mcg/h fentanyl patch.
(4) A patient with a spinal injury is taking one 15-mg tablet of immediate-release morphine sulfate every 4 hours for pain. His physician wants to switch him to oxymorphone hydrochlo- ride extended-release tablets to better manage his pain, and reserve the immediate-release morphine tablets for breakthrough pain. T he oxymorphone hydrochloride extended-release (ER) tablets should be given every 12 hours. Calculate the appropriate dose for this patient.
First, the daily dose of morphine sulfate must be calculated:
15 6 mg 90 dose
doses
day mg day
× = /
According to Table 10.4, a conversion factor of 0.333 should be used to convert an oral dose of morphine to oxymorphone ER tablets.
90 mg morphine 0 333 29 97 30
day × . = . mg ≈ mg oxymorphone ER day/
10 • s ele ed c lini al c al ula ion 175 Since the oxymorphone ER tablets are to be given every 12 hours, the single dose can be calculated as:
30 1
2 mg oxymorphone ER
day
day doses
× =15 mg oxymorphone ER day/
T herefore, one 15-mg oxymorphone ER tablet should be given to this patient every 12 hours.
CASE IN POINT 10.26 t he u ual re ommended do e of bu orphanol ar ra e na al pray i one pray on aining 1 mg of drug, and he na al pray olu ion on ain he drug a a on en ra ion of 10 mg/mL. c al ula e (a) he volume of olu ion delivered wi h ea h do e; (b) he number of do e on ained in he 2.5-mL manufa urer’
on ainer; and ( ) he number of able , on aining 5 mg of hydro odone bi ar ra e and 300 mg of a e aminophen, needed o produ e he 1-mg do e of bu orphanol ar ra e.