Initiating Opioid Therapy

Chapter outline

INITIATION of the opioid treatment plan is individualized to meet each patient’s unique characteristics and condition. After the opioid and route of administration are determined, multiple factors, including the patient’s age, previous exposure to opioids, and pain intensity are considered in selection of the initial dose. The initial dose is then titrated up or down based on the patient’s response (pain relief and adverse effects).

Selecting an Analgesic and Route of Administration

As a rule, treatment of moderate-to-severe cancer pain and persistent noncancer pain is started with just one opioid analgesic at a time by one route of administration. For example, the same drug and route are usually used for the short-acting opioid for breakthrough pain and for the around-the-clock (ATC) long-acting opioid. Starting with one drug and route at a time allows for simpler interpretation of adverse effects, if they occur, and presumably lowers the risk for additive toxicity. Notwithstanding those considerations, there are circumstances that may support the initiation of opioid therapy with more than one drug or route concurrently. For example, the emerging role of the oral transmucosal, rapid-onset fentanyl formulations for breakthrough pain was discussed in Chapter 14; these are often administered with transdermal or oral opioids for persistent pain. With close monitoring, the concomitant administration of a parenteral opioid for breakthrough pain may ensure very rapid onset of relief while a baseline drug is administered orally.

During planned long-term therapy, opioid selection is highly individualized, and treatment is usually initiated with a short-acting opioid, which can be titrated to effective analgesia more rapidly than a long-acting opioid (Fine, Mahajan, McPherson, 2009). As discussed in previous chapters, patients with persistent pain are commonly switched to a long-acting opioid to provide consistent pain relief and improve sleep and function. Initiating an opioid regimen in addition to an adjuvant analgesic is often warranted. For example, it may be necessary to use an opioid initially to control moderate to severe pain associated with a persistent noncancer pain syndrome for which the appropriate mainstay analgesic is an adjuvant that requires gradual titration over days or weeks before becoming effective (see Section V). In this case, it would be inhumane to expect the patient to endure severe pain while the adjuvant analgesic takes effect. As soon as the moderate to severe pain is resolved, the opioid can be tapered and discontinued if thought to be unnecessary to the treatment plan.

In contrast to the planned long-term management of persistent pain, the treatment of acute pain often requires beginning with more than one route and more than one analgesic. This is because there is not enough time to evaluate patients’ responses to one analgesic at a time. Therefore, decisions about postoperative analgesics are made on the basis of research findings and clinical experience. The intensity of pain is anticipated, and multimodal analgesic regimens are planned preoperatively whenever possible. For example, in addition to an ATC oral or intravenous (IV) nonsteroidal anti-inflammatory drug (NSAID) and acetaminophen for some major surgeries, an epidural catheter may be placed preoperatively for continuous infusion of opioid and local anesthetic to control anticipated severe postoperative pain.

Occasionally, two different routes of administration at the same time may be appropriate for postoperative pain. For example, continuous peripheral nerve blockade is often administered in conjunction with oral opioid analgesics or IV patient-controlled analgesia (PCA) (see Chapter 26 for continuous peripheral nerve blockade); however, the practice of using two different parenteral routes of administration at the same time or parenteral and intraspinal routes at the same time to administer opioids must be carried out with caution and appropriate monitoring. In particular, the administration of intramuscular (IM) opioids to opioid-naïve patients receiving IV or intraspinal analgesia can result in excessive sedation and clinically significant respiratory depression (see Chapter 19).

Selecting an Opioid Dose

Traditionally, age and weight have been used to determine opioid dose; however, studies have shown that there is no correlation between weight and analgesic requirements (Burns, Hodsman, McLintock, et al., 1989; Ginsberg, Cohen, Ossey, et al., 1989; Monk, Parker, White, 1990). A study comparing remifentanil pharmacokinetics in 12 obese and 12 lean patients undergoing surgery demonstrated no significant differences between the two groups (Egan, Huizinga, Gupta, et al., 1998). The researchers preferred dosing regimens based on ideal body weight, or lean body mass, as opposed to those based on total body weight.

Age, on the other hand, is a valid consideration (Hanks, Cherny, Fallon, 2004; Keita, Tubach, Maalouli, et al., 2008; Mercadante, Ferrera, Villari, et al., 2006). Starting doses should be adjusted for patients at the extremes of the age spectrum, such as neonates and infants, who have incomplete organ development; and older adults, who have increased sensitivity to drug effects. For both the very young and the very old, initial doses are adjusted downward and a longer interval between doses is anticipated. For example, a common recommendation is to lower the recommended starting dose for adults in older individuals (older than 70 years) by 25% to 50% (American Pain Society [APS], 2003). It is important to remember, however, that numerous factors, including genetics (Argoff, 2010; Chou, Wang, Liu, et al., 2006; Fillingim, 2005; Landau, 2006; Nielsen, Stubhaug, Price, et al., 2008; Pasternak, 2005, 2010); underlying pathology and medical condition (Hanks, Cherny, Fallon, 2004; Soares, Martins, Uchoa, 2003); surgical procedure and incision site (Chang, Dai, Ger, et al., 2006); opioid tolerance (Davis, Johnson, Egan, et al., 2003; Hanks, Cherny, Fallon, 2004; Patanwala, Jarzyna, Miller, et al., 2008; Rozen, DeGaetano, 2006); and pain intensity (Dahmani, Dupont, Mantz, et al., 2001), also contribute to wide variability in pain reports and dose requirements among patients.

Although pain intensity is obviously a very important factor to consider, selecting a dose based on a specific pain intensity can be dangerous and is strongly discouraged (Blumstein, Moore, 2003; Gordon, Dahl, Phillips et al., 2004; Lucas, Vlahos, Ledgerwood, 2007; Vila, Smith, Augustyniak, et al., 2005). The most important principle is to select a safe starting dose and be prepared to titrate to individualize the dose while monitoring patient response. No matter what method is used to predict analgesic requirements, the starting doses of opioid treatments are merely estimates. When starting doses are given, they are titrated up or down according to patient response (Fine, Mahajan, McPherson, 2009).

The term equianalgesia means approximately equal analgesia and is used when referring to the doses of various opioid analgesics that provide approximately the same amount of pain relief. Using the equianalgesic chart in Table 16-1 as an example, note that the chart provides a list of analgesics at doses, both oral and parenteral (with other routes such as rectal as appropriate), that are approximately equal to each other and theoretically interchangeable in their ability to provide pain relief in opioid-naïve patients. These doses are also referred to as equianalgesic dose units. Most of the doses in equianalgesic charts are made on the basis of single-dose studies, commonly conducted in surgical patients and using morphine, 10 mg IM, for comparison (Knotkova, Fine, Portenoy, et al., 2009). The parenteral doses listed are typical of IM doses given approximately every 3 to 4 hours. Equianalgesic dose calculation provides a basis for selecting the appropriate starting dose when changing from one opioid drug or route of administration to another. However, these calculations are just estimates and vary with repeated dosing and with opioid rotation (Knotkova, Fine, Portenoy, 2009; Shaheen, Walsh, Lasheen, et al., 2009). The optimal dose for the patient is always determined by titration (Fine, Portenoy, 2007).

Table 16-1

Equianalgesic Dose Chart
A Guide to Using Equianalgesic Dose Charts *

ATC, Around-the-clock; h, hour; IM, intramuscular; IV, intravenous; MR, oral modified-release; ND, no data; NR, not recommended; NS, nasal spray; OT, oral transmucosal; PO, oral; R, rectal; SC, subcutaneous; SL, sublingual; TD, transdermal.

^*This table provides equianalgesic doses and pharmacokinetic information about selected opioid drugs. Characteristics and comments about selected mu opioid agonist drugs can be found in Table 13-1, pp. 326-327.

¹ An expert panel was convened for the purpose of establishing a new guideline for opioid rotation and recently proposed a two-step approach (Fine, Portenoy, Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation, 2009). The approach presented in the text for calculating the dose of a new opioid can be conceptualized as the panel’s Step One, which directs clinicians to calculate the equianalgesic dose of the new opioid based on the equianalgesic table. Step Two suggests that clinicians perform a second assessment of patients to evaluate the current pain severity (perhaps suggesting that the calculated dose be increased or decreased) and to develop strategies for assessing and titrating the dose as well as to determine the need for breakthrough doses and calculate those doses (see Box 16-2). The specific steps provided in the examples in the text reflect the panel’s two-step approach (see Fine, Portenoy, the Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation, 2009).

² Duration of analgesia is dose dependent; the higher the dose, usually the longer the duration.

³ As in, e.g., MS Contin and Oramorph (8 to 12 hours) and Avinza and Kadian (12 to 24 hours).

⁴ IV boluses may be used to produce analgesia that lasts nearly as long as IM or SC doses; however, of all routes of administration, IV produces the highest peak concentration of the drug, and the peak concentration is associated with the highest level of toxicity (e.g., sedation). To decrease the peak effect and lower the level of toxicity, IV boluses may be administered more slowly (e.g., 10 mg of morphine over a 15-min period); or smaller doses may be administered more often (e.g., 5 mg of morphine every 1 to 1.5 hours).

⁵ This is the ratio that is used clinically.

⁶ The delivery system for transmucosal fentanyl influences potency, e.g., buccal fentanyl is approximately twice as potent as oral transmucosal fentanyl (see Chapter 14).

⁷ At steady state, slow release of fentanyl from storage in tissues can result in a prolonged half-life (e.g., 4 to 5 times longer).

⁸ Equianalgesic data are not available.

⁹ The recommendation that 1.5 mg of parenteral hydromorphone is approximately equal to 10 mg of parenteral morphine is based on single-dose studies. With repeated dosing of hydromorphone (as during PCA), it is more likely that 2 to 3 mg of parenteral hydromorphone is equal to 10 mg of parenteral morphine (see Chapter 13).

¹⁰ As in, e.g., OxyContin.

¹¹ As in Opana ER.

¹² 65 to 130 mg = approximately 1/6 of all doses listed in this chart.

¹³ Used in combination with mu agonist opioids, this drug may reverse analgesia and precipitate withdrawal in opioid-dependent patients.

¹⁴ In opioid-naive patients who are taking occasional mu agonist opioids, such as hydrocodone or oxycodone, the addition of butorphanol nasal spray may provide additive analgesia. However, in opioid-tolerant patients such as those receiving ATC morphine, the addition of butorphanol nasal spray should be avoided because it may reverse analgesia and precipitate withdrawal.

From Pasero, C., & McCaffery, M. Pain assessment and pharmacologic management, pp. 444-446, St. Louis, Mosby. Data from American Pain Society (APS). (2003). Principles of analgesic use in the treatment of acute pain and chronic cancer pain. Glenview, IL, APS; Breitbart, W., Chandler, S., Eagel, B., et al. (2000). An alternative algorithm for dosing transdermal fentanyl for cancer-related pain. Oncology, 14(5), 695-705. See discussion in same issue, pp. 705, 709-710, 712, 17; Coda, B. A., Tanaka, A., Jacobson, R. C., et al. (1997). Hydromorphone analgesia after intravenous bolus administration. Pain, 71(1), 41-48; Donner, B., Zenz, M., Tryba, M., et al. (1996). Direct conversion from oral morphine to transdermal fentanyl: A multicenter study in patients with cancer pain. Pain, 64(3), 527-534; Dunbar, P. J., Chapman, C. R., Buckley, F. P., et al. (1996). Clinical analgesic equivalence for morphine and hydromorphone with prolonged PCA. Pain, 68, 226-270; Fine, P. G., Portenoy, R. K., & Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. (2009). Establishing best practices for opioid rotation: Conclusions of an expert panel. J Pain Symptom Manage, 38(3), 418-425; Gutstein, H. B., & Akil, H. (2006). Opioid analgesics. In L. L. Brunton, J. S. Lazo, & K. L. Parker (Eds.), Goodman & Gilman’s The pharmacological basis of therapeutics, ed 11, New York, McGraw-Hill; Hanks, G., Cherny, N. I., Fallon, M. (2004). Opioid analgesic therapy. In D. Doyle, G. Hanks, N. I. Cherny, et al (Eds.), Oxford textbook of palliative medicine, ed 3, New York, Oxford Press; Johnson, R. E., Fudala, P. J., & Payne, R. (2005). Buprenorphine: Considerations for pain management. J Pain Symptom Manage, 29(3), 297-326; Kaiko, R. F., Lacouture, P., Hopf, K., et al. (1996). Analgesic onset and potency of oral controlled release (CR) oxycodone CR and morphine. Clin Pharmacol Ther, 59(2), 130-133; Knotkova, H., Fine, P. G., & Portenoy, R. K. (2009). Opioid rotation: The science and limitations of the equianalgesic dose table. J Pain Symptom Manage, 38(3), 426-439; Lawlor, P., Turner, K., Hanson, J., et al. (1997). Dose ratio between morphine and hydromorphone in patients with cancer pain: A retrospective study. Pain, 72(1, 2), 79-85; Manfredi, P. L., Borsook, D., Chandler, S. W., et al. (1997). Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: Clinical observations. Pain, 70, 99-101; Portenoy, R. K. (1996). Opioid analgesics. In R. K. Portenoy, & R. M. Kanner (Eds.), Pain management: Theory and practice, Philadelphia, FA Davis; Sittl, R., Likar, R., & Nautrup, B. P. (2005). Equipotent doses of transdermal fentanyl and transdermal buprenorphine in patients with cancer and noncancer pain: Results of a retrospective cohort study. Clin Ther, 27(2), 225-237; Skaer, T. L. (2004). Practice guidelines for transdermal opioids in malignant pain. Drugs, 64(23), 2629-2638; Skaer, T. L. (2006). Transdermal opioids for cancer pain. Health Qual Life Outcomes, 4, 24; Vogelsang, J., & Hayes, S. R. (1991). Butorphanol tartrate (Stadol). A review. J Post Anesthes Nurs, 6(2), 129-135; Weinberg, D. S., Inturrisi, C. E., Reidenberg, B., et al. (1988). Sublingual absorption of selected opioid analgesics. Clin Pharmacol Ther, 44, 335-342; Wilson, J. M., Cohen, R. I., Kezer, E. A., et al. (1995). Single and multiple-dose pharmacokinetics of dezocine in patients with acute and chronic pain. J Clin Pharmacol, 35, 395-403. Pasero C, McCaffery M. May be duplicated for use in clinical practice.

A patient’s pain intensity (see previous discussion) and the equianalgesic chart are practical tools that can be used to determine an appropriate opioid dose for an opioid-naïve patient. To become familiar with the equianalgesic chart, note that it has several columns. The first column lists the common opioid analgesics. Morphine is listed first because it has been the standard for comparison, and the others follow in alphabetical order. The remaining doses are equianalgesic to the doses listed for morphine. The second column lists the equianalgesic doses of opioids by the oral route. The third column lists the equianalgesic doses of opioids by the parenteral (IM, subcutaneous [SC], and IV) routes. The last four columns provide pharmacokinetic information about specific opioids.

Guidelines

Box 16-1 Selection of an Opioid Starting Dose

1. Use an equianalgesic chart and your patient’s pain intensity (among other factors ¹) to determine an appropriate opioid dose.

2. Locate the prescribed opioid in column one in the equianalgesic chart (e.g., morphine).

3. Move horizontally from column one to column two if the opioid is to be given by the oral route or to column three if by the parenteral route.

4. This is the appropriate starting dose for an opioid-naïve patient with severe pain (e.g., 30 mg of PO morphine every 3 to 4 hours).

5. If the patient has moderate pain, calculate a dose that is 50% of the dose for severe pain: Severe pain dose × 0.5 (50%) = appropriate starting dose for patient with moderate pain (e.g., 15 mg of PO morphine every 3 to 4 hours).

6. If the patient has mild pain, calculate a dose that is 25% of the dose for severe pain: Severe pain dose × 0.25 (25%) = appropriate starting dose for patient with mild pain (e.g., 7.5 mg of PO morphine every 3 to 4 hours).

Note: A patient’s pain intensity and the equianalgesic chart are practical tools to use to determine an appropriate opioid starting dose for an opioid-naïve patient. This box demonstrates how to combine these two tools to determine starting doses for opioid-naive patients with mild, moderate, or severe pain intensity. The initial opioid dose is merely an estimate. At all times, the opioid dose is titrated up or down based on patients’ responses (pain relief and adverse effects).

PO, Oral.

¹ The appropriateness of an opioid dose is considered after careful assessment of other factors, such as the patient’s co-morbidities, previous exposure to opioids, and sedation and respiratory status. A dose is never selected based solely on a specific pain intensity (see text for discussion).

From Pasero, C., & McCaffery, M. Pain assessment and pharmacologic management, p. 446, St. Louis, Mosby. Pasero C, McCaffery M. May be duplicated for use in clinical practice.

All of the opioid doses listed in the equianalgesic chart were developed in controlled trials that were conducted in opioid-naïve postoperative patients or in cancer patients with little or no prior exposure to opioids. For this reason, they may be considered a starting point for determining appropriate initial doses given about every 4 hours for opioid-naïve adults with severe pain. Percentages of these doses are used to determine the appropriate starting dose for moderate and mild pain, pain in patients at the extremes of age, and pain in patients who are medically frail or otherwise predisposed to the adverse effects of opioids. For example, the European Association for Palliative Care (EAPC) has recommended a starting dose of 5 mg of short-acting oral morphine every 4 hours in opioid-naïve patients and 10 mg in patients already being treated with “weak” opioids (Hanks, De Conno, Cherny, et al., 2001). This recommendation is more conservative than the dose that would be calculated from the equianalgesic dose table, but it recognizes the medical frailty of patients with advanced illness.

In contrast to the patient who is medically compromised, a healthy patient with severe pain who is to receive parenteral morphine might be prescribed as much as 10 mg of morphine parenterally every 4 hours. If, instead of severe pain, the patient has moderate pain, the starting dose would be 50% of 10 mg (5 mg) of morphine, and for mild pain, 25% of 10 mg (2.5 mg) (Box 16-1). When administered by the IV route, the total dose is given in smaller boluses over the 4-hour interval. Bolus doses over a 4-hour period are usually calculated by dividing the 4-hour dose by 4. In other words, the bolus dose is one-fourth of the 4-hour dose.

As discussed earlier in this section, mild pain may not require an opioid. A nonopioid, such as ibuprofen or acetaminophen, may be appropriate. If an opioid is indicated, mild pain can be treated with a low dose of any of the opioids or with an opioid-nonopioid combination, such as hydrocodone or oxycodone compounded with acetaminophen. In opioid-tolerant patients, these doses may be used as starting doses with the awareness that the dose will probably have to be titrated upward quickly.

Patient Example: PACU IV Starting Dose

Three opioid-naïve patients have just been admitted to the PACU. All three will be managed with IV boluses of hydromorphone (Dilaudid). Pain intensity and the equianalgesic chart are used to determine appropriate starting doses for each patient (see text for other factors to consider). Pain intensity is assessed by using a 0-to-10 numeric rating scale. The following steps are taken to determine appropriate starting doses.

Patient no. 1

1. Hydromorphone is located in the first column of the equianalgesic chart.

2. Moving horizontally from hydromorphone to column 3 (parenteral route), the appropriate dose for severe pain is located (1.5 mg).

3. Patient No. 1 reports a pain rating of 8/10, or severe pain.

4. The appropriate starting dose for patient No. 1 is 1.5 mg of IV hydromorphone over 4 hours.

5. The calculation for the first bolus is 1.5 mg ÷ 4 (1/4 of the 4-h dose) = approximately 0.4 mg (0.375 mg), titrating up or down using larger or smaller doses depending on the patient’s responses (pain intensity and adverse effects).

Patient no. 2

1. Steps 1 and 2 outlined for patient No. 1 are followed.

2. Patient No. 2 reports a pain rating of 5/10, or moderate pain.

3. The appropriate starting dose for moderate pain is 50% of the starting dose for severe pain. The calculation is 1.5 mg × 0.50 (50%) = 0.75 mg.

4. The appropriate starting dose for patient No. 2 is 0.75 mg of hydromorphone by the IV route over 4 hours.

5. The calculation for the first bolus is 0.75 mg ÷ 4 (1/4 of the 4-h dose) = approximately 0.2 mg, titrating up or down using larger or smaller boluses depending on the patient’s responses (pain intensity and adverse effects).

Patient no. 3

1. Steps 1 and 2 outlined for patient No. 1 are followed.

2. Patient No. 3 reports a pain rating of 3/10, or mild pain.

3. The appropriate starting dose for mild pain is 25% of the starting dose for severe pain. The calculation is 1.5 mg × 0.25 (25%) = 0.375 mg.

4. The appropriate starting dose for patient No. 3 is approximately 0.4 mg of hydromorphone by the IV route over 4 hours.

5. The calculation for the first bolus is 0.4 mg ÷ 4 (1/4 of the 4-h dose) = approximately 0.1 mg, titrating up or down using larger or smaller boluses depending on the patient’s responses (pain intensity and adverse effects).

As mentioned, the doses in the equianalgesic chart are made on the basis of a 4-hour dosing schedule. To determine the appropriate starting dose when the dosing schedule is other than every 4 hours, different calculations are necessary.

Patient Example: Cancer Pain

Mr. H. has cancer pain. Until now he has been controlling his pain with two Percocet (oxycodone, 5 mg, plus acetaminophen, 325 mg per tablet) q 4 h ATC. He reports that his pain has been increasing. He rates his pain as 6/10. The decision is made to begin treatment with oral modified-release oxycodone. Mr. H.’s starting dose is calculated as follows:

10 mg oxycodone (2 Percocet) × 6 doses/day = 60 mg/day

60 mg ÷ 2 (number of doses/24 h with 12-h dosing) = 30 mg

Mr. H. is started on 30 mg modified-release oxycodone q 12 h. Acetaminophen is continued ATC. This will provide the same analgesia at more convenient dosing intervals for the opioid. Percocet 1 to 2 tablets can be taken every 4 hours for breakthrough pain (see Box 16-2 for how to calculate breakthrough doses). Mr. H. should be assessed regularly for the need for an increase in the oxycodone dose, which is based on the amount of breakthrough analgesic he requires over 24 hours.

Note: This approach to managing Mr. H.’s pain is logical and conservative. Other approaches may be used (e.g., starting at a higher dose [40 mg] of modified-release oxycodone).

Continuous Infusions

In patients with cancer pain and in opioid-naive postoperative or trauma patients in the intensive care unit (ICU) who require parenteral opioids, a maintenance continuous infusion is initiated after pain is controlled by IV or SC boluses (Coyle, Cherny, Portenoy, 1995). As mentioned, additional boluses offered every 15 to 30 minutes may be prescribed for the management of breakthrough pain (see Breakthrough Doses, discussed next, and Chapter 17 for continuous infusions in opioid-naïve patients outside of the ICU).

Patient Example: ICU Continuous Infusion

Ms. D. has been admitted directly to the ICU after an automobile accident and emergency abdominal surgery. In addition to abdominal surgery, she has deep face, neck, and chest cuts and contusions. She is opioid-naïve, is on a ventilator, and is somewhat disoriented and restless. She is unable to provide self-reports of pain yet but, based on Ms. D.’s pathology, the nurse assumes that she has moderate to severe pain. Her pain is to be controlled with a continuous IV infusion of morphine. The following calculation of the starting dose is necessary:

• Morphine is located in the first column of the equianalgesic chart.

• Moving horizontally from morphine to column 3 (parenteral route), the appropriate starting dose for severe pain is located (10 mg over a 4-hour period).

Because Ms. D. is opioid naïve and is expected to have moderate to severe pain, an appropriate conservative starting dose for her is 5 mg (50% of 10 mg) of morphine IV over a 4-hour period.

Ms. D. is to receive a continuous IV infusion, so an hourly dose must be calculated: 5 mg ÷ 4 h = approximately 1.3 mg/h.

The nurse suspects that Ms. D.’s restlessness may be related to unrelieved pain, so she administers a loading IV bolus equal to the starting hourly dose (1.3 mg) and begins the opioid infusion immediately. Within 45 minutes, Ms. D. is no longer restless, and her vital signs are stable.

Breakthrough Doses

The term breakthrough dose is used interchangeably with the terms supplemental dose or rescue dose. It is now conventional practice to offer all patients with pain related to active cancer or other serious illnesses who are receiving ATC opioid analgesics access to doses of a fast-acting mu agonist opioid analgesic to treat breakthrough pain (see Chapter 12 for a detailed discussion of breakthrough pain). The use of these short-acting supplemental doses for breakthrough pain should not be considered conventional practice in the large and heterogeneous population with persistent noncancer pain. In this population, the decision to provide such a treatment should be made after a careful risk-to-benefit analysis that assesses both the risk of pharmacologic adverse effects such as peak concentration sedation and the risk of problematic drug-related behaviors that may be consistent with abuse or addiction. Well-controlled research is needed to inform decisions on breakthrough pain in this diverse population (Devulder, Jacobs, Richarz, et al., 2009; Fine, Portenoy, 2007).

For patients taking oral opioids, the recommended amount of opioid for breakthrough doses is within a range of approximately 5% to 15% of the total daily dose of the ATC opioid analgesic; however, some clinicians prefer to use 10% to 15% unless there are circumstances that suggest a conservative calculation (5%) should be made, for example, in the case of a frail patient or a patient older than 70 years (Box 16-2). This calculation is used consistently, regardless of the total daily dose of opioid. For example, the range of a given breakthrough dose for a patient receiving a total daily dose of 8000 mg of modified-release morphine would be 800 mg (10%) to 1200 mg (15%).

Patient Example: Oral Breakthrough Dose

Mr. H. is receiving 30 mg of modified-release oxycodone twice daily. The breakthrough dose range is determined by calculating 10% to 15% of the total daily dose. The calculation is as follows: