Drugs for pain

Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Pain p 31 Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS Revised 4/24/13: See p 32 The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 11 (Issue 128) April 2013 www.medicalletter.org Tables Some Nonopioid Analgesics Some Opioid Analgesics Some Adjuvant Pain Medications Pages 32-33 Pages 36-37 Page 40 Drugs for Pain Related article(s) since publication RECOMMENDATIONS Nociceptive pain can be treated with nonopioid analgesics or opioids Neuropathic pain is less responsive to opioids and is often treated with adjuvant drugs such as antidepressants and antiepileptics Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects Mild to Moderate Pain – Nonopioid analgesics such as aspirin, acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are preferred for initial treatment of mild to moderate pain For moderate acute pain, most NSAIDs are more effective than aspirin or acetaminophen and some have shown equal or greater analgesic effect than an oral opioid combined with acetaminophen, or even injected opioids The selective COX-2 inhibitor celecoxib appears to cause less severe GI toxicity than nonselective NSAIDs Moderate pain that does not respond to nonopioids can be treated with a combination of opioid and nonopioid analgesics Severe Pain – For treatment of most types of severe pain, full opioid agonists are the drugs of choice Unlike NSAIDs, morphine and the other full agonists generally have no dose ceiling for their analgesic effectiveness except that imposed by adverse effects Patients who not respond to one opioid may respond to another Meperidine use should be discouraged because of the high rate of CNS toxicity and the availability of less toxic, longer-acting alternatives Tolerance to most of the adverse effects of opioids, including respiratory and CNS depression, develops at least as rapidly as tolerance to the analgesic effect; tolerance can usually be surmounted and adequate analgesia restored by increasing the dose When frequent dosing becomes impractical, long-acting opioids may be helpful Pain can be acute or chronic The two major types of chronic pain are nociceptive pain and neuropathic pain Nociceptive pain can be treated with nonopioid analgesics or opioids Neuropathic pain is less responsive to opioids and is often treated with adjuvant drugs such as antidepressants and antiepileptics Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects NONOPIOID ANALGESICS The maximum analgesic effect of acetaminophen and aspirin usually occurs with single doses between 650 and 1300 mg With nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin, the analgesic ceiling may be higher Tolerance does not develop to the analgesic effects of these drugs ACETAMINOPHEN — Acetaminophen has no clinically significant anti-inflammatory activity and is less effective than full doses of NSAIDs, but has fewer adverse effects It is available in multiple oral formulations, often in combination with other OTC and prescription drugs It is also available in rectal and intravenous formulations.1 Acetaminophen overdose can cause serious or fatal hepatotoxicity, and in some patients, such as those who are fasting, are heavy alcohol users, or are concurrently taking isoniazid (INH), zidovudine (Retrovir, and others) or a barbiturate, it can develop after moderate overdosage or even with high therapeutic doses Most healthy patients can take up to grams daily with no adverse effects,2 but in one study repeated use of such doses was associated with elevations in alanine aminotransferase (ALT).3 Continued use of acetaminophen may increase the anticoagulant effect of warfarin (Coumadin, and generics) in some patients.4 Acetaminophen at a dose of gram three Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines 31 Revised 4/24/13: The price for IV ibuprofen (Caldolor) has been revised Drugs for Pain Drugs for Pain Table Some Nonopioid Analgesics Some Available Formulations Usual Adult Analgesic Dosage Maximum Daily Dose See footnote 650 mg q6h or 1000 mg q8h 4000 mg 10 mg/mL IV soln 1 hr >1 hr >1 hr >1 hr hrs 2, 4, mg tabs; mg/5 mL PO soln mg q6-8h 4-6 hrs 8, 12, 16, 32 mg ER tabs mg tabs See footnote mg q6-8h 24 hrs 6-8 hrs 50, 75, 100, 150 mg tabs; 50 mg/5 mL PO soln 50 mg q3-4h9 3-4 hrs 5, 10, mg tabs; 5, 10 mg/5 mL PO soln, 10 mg/mL PO conc 5, 10 mg tabs 15, 30 mg tabs; 20 mg/mL, 10, 20, 100 mg/5 mL PO soln 15, 30, 60, 100, 200 mg ER tabs 2.5-10 mg q8-12h 8-12 hrs 15-30 mg q8-12h5 8-12 hrs 10, 20, 30, 40, 50, 60, 70, 80, 100, 130, 150, 200 mg ER caps 20, 30, 50, 60, 80, 100 mg ER caps 30, 45, 60, 75, 90, 120 mg ER caps 20/0.8, 30/1.2, 50/2, 60/2.4, 80/3.2, 100/4 mg caps See footnote 12 hrs 30 mg once/d5 See footnote 24 hrs 12-24 hrs II C 5-15 mg q4-6h 4-6 hrs II B 5-15 mg q4-6h 10 mg q12h5 4-6 hrs 12 hrs II C Fentanyl4 Transdermal – Duragesic (Janssen) generic Transmucosal – Abstral (ProStrakan) Actiq (Cephalon) generic Fentora (Cephalon) Lazanda (Archimedes) Onsolis (Meda) Subsys (Insys) Hydrocodone Hydromorphone4 Dilaudid (Purdue) generic Exalgo (Mallinckrodt) Levorphanol – generic Meperidine4 Demerol (Sanofi) generic Methadone4 – generic Dolophine (Roxane) Morphine4 – generic MS Contin (Purdue) generic Kadian (Actavis) generic Avinza (Pfizer) Morphine/naltrexone – Embeda (Pfizer) Oxycodone – generic Oxecta (Pfizer) OxyContin (Purdue) Oxymorphone4 Opana (Endo) generic Opana ER generic Agonist/Reuptake Inhibitors Tapentadol Nucynta (Janssen) Nucynta ER Tramadol Ultram (Janssen) generic Rybix (Shionogi) Ultram ER (Janssen) generic ConZip (Cipher)12 multiphase generic mg caps; 5, 10, 15, 20, 30 mg tabs; mg/5 mL, 20 mg/mL PO soln 5, 7.5 mg tabs 10, 15, 20, 30, 40, 60, 80 mg ER tabs 10-30 mg q4h 5, 10 mg tabs 5-15 mg q4-6h 4-6 hrs 5, 7.5, 10, 15, 20, 30, 40 mg ER tabs 10 mg q12h5 12 hrs 50, 75, 100 mg tabs 50, 100, 150, 200, 250 mg ER tabs 50-100 mg q4-6h 50 mg bid5 4-6 hrs 12 hrs 50 mg tabs 50-100 mg q4-6h 4-6 hrs 50 mg orally disintegrating tabs 100, 200, 300 mg ER tabs 50 mg q4-6h 100 mg once/d5 4-6 hrs 24 hrs 100, 200, 300 mg ER caps 100, 200, 300 mg ER tabs13; 150 mg ER caps 100 mg once/d5 100 mg once/d5 24 hrs 24 hrs FDA Pregnancy Categories: B = no evidence of risk in humans; C = risk cannot be ruled out Wholesale acquisition cost (WAC) of a single dose at the lowest available strength $ource® Monthly (Selected from FDB MedKnowledge™) March 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Single-agent codeine is schedule II; fixed dose combinations containing acetaminophen are schedule III or V Also available parenterally Starting dose determined by previous opioid dosage Long-acting formulations are generally not recommended for opioid-naive patients Some patients need to change the patch every 48 hours to achieve adequate analgesia Cost of one bottle containing sprays 36 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 Controlled Substance Schedule Pregnancy Category1 II-V3 C II C Comments 60 mg PO equivalent to 650 mg of aspirin or acetaminophen; 10% of people lack the enzyme needed to make codeine active and others rapidly metabolize codeine to morphine increasing the risk of respiratory depression; also available in fixed-dose combinations with acetaminophen (Tylenol/Codeine No 3, others) for treatment of pain Not recommended for opioid-naïve patients; standard dose determined by previous opioid dosage Abstral, Actiq, Fentora, Lazanda, Onsolis and Subsys are indicated only for breakthrough pain Actiq may cause dental caries III C II C Currently only available for treatment of pain in fixed-dose combinations with acetaminophen (Vicodin, others) or ibuprofen (Vicoprofen, others), but awaiting FDA approval as an individual agent; 10 mg equivalent to codeine PO 60-80 mg Also available as a high potency injectable (Dilaudid-HP, generics) and as a suppository II II C C II C Accumulation may occur with chronic use More rapid onset of action than morphine; toxic metabolite with long half-life causes CNS excitation and convulsions; tissue irritation occurs with parenteral use; use should be limited to 48 hours Accumulation may occur with chronic use II C Also available for intrathecal and epidural use and as a suppository Taking Kadian or Avinza with alcohol can result in rapid release of morphine, which could be fatal; maximum dose of Avinza is 1600 mg due to renal toxicity of fumaric acid in the beads; chewing or crushing the beads can be fatal Naltrexone is only absorbed if the capsules are crushed, chewed or dissolved; taking Embeda with alcohol can result in increased plasma levels of morphine; currently unavailable due to voluntary recall Also available in a fixed-dose combination with acetaminophen (Percocet, others), aspirin (Percodan, others) or ibuprofen (Combunox); Oxecta and OxyContin have been reformulated to deter abuse of the drug by injection or snorting No CYP drug interactions Taking long-acting oral oxymorphone with alcohol can result in substantial increases in peak serum concentrations of the drug, which could be fatal II C None11 C Mu-receptor agonist and norepinephrine reuptake inhibitor; fewer GI adverse effects, but similar CNS effects compared to some other opioid agonists; less potent than morphine Weak agonist/norepinephrine and serotonin reuptake inhibitor; variable response and threshold for nausea and vomiting; tolerability may be improved by starting with 25 mg/day and slowly titrating to usual dose over a few weeks; 50 mg equivalent to codeine 60 mg; 100 mg comparable to aspirin 650 mg plus codeine 60 mg; maximum dose 400 mg/d for IR and 300 mg/d for ER; also available in a fixed-dose combination with acetaminophen (Ultracet, others) Cost2 $0.34 21.65 13.64 14.00 45.40 13.08 28.79 280.007 20.58 27.92 0.238 1.03 0.12 10.29 1.56 1.84 0.28 0.13 0.10 0.20 1.77 0.36 4.8810 4.18 4.81 4.15 0.18 2.67 2.13 3.00 2.48 1.89 1.45 2.23 2.55 1.95 0.11 2.72 4.92 2.77 6.45 3.47 10 11 Cost of one dose of hydrocodone mg/acetaminophen 325 mg Oral meperidine is not recommended for treatment of acute or chronic pain Cost of 20 mg ER cap Tramadol is not a federally controlled substance in the US, but many states and the US military have it classified as a schedule IV controlled substance under state law 12 Mixture of immediate-release (IR) and extended-release (ER) tramadol: 100 mg contains 25 mg IR and 75 mg ER, 200 mg contains 50 mg IR and 150 mg ER, 300 mg contains 50 mg IR and 250 mg ER 13 Generic equivalent of Ryzolt (Purdue), which has been discontinued Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 37 Drugs for Pain Methadone – Methadone is used parenterally and orally for treatment of chronic pain.26-28 In one study of first-line treatment of cancer pain, methadone was similar to long-acting morphine.29 The plasma half-life of methadone is variable and can be as long as days; repeated doses can lead to accumulation and CNS depression without close monitoring during the titration period Methadone is not fully cross-tolerant with other opioid agonists Switching from another opioid agonist to methadone should be done cautiously; the equianalgesic dose of methadone is not well established in opioid-tolerant patients Methadone has no active metabolites, which may be advantageous in patients with renal insufficiency Dose-related QT interval prolongation, torsades de pointes and death have been reported with methadone use.30,31 Levorphanol – Oral levorphanol is used to treat chronic pain It has a long half-life (16-18 hours) and can accumulate with repeated dosing Like methadone, levorphanol also exhibits incomplete cross-tolerance when converting from other opioids and requires careful dose titration Meperidine – Meperidine should only be used for short-term (24-48 hours) treatment of moderate to severe acute pain It has a more rapid onset of action than morphine, but is shorter acting It is highly irritating to tissues when given subcutaneously, and when given IM, can cause muscle fibrosis Repeated doses of the drug can lead to accumulation of normeperidine, a toxic metabolite with a 15- to 30-hour half-life Normeperidine can cause dysphoria, irritability, tremors, myoclonus and, occasionally, seizures, particularly with patient-controlled analgesia or in elderly patients or those with impaired renal function In patients who are taking or have recently stopped taking a monoamine oxidase inhibitor, meperidine can cause severe encephalopathy and death Codeine – Codeine is an oral opioid agonist with a long history of use as an analgesic and cough suppressant Codeine is converted to morphine, its active form, by the hepatic enzyme CYP2D6 Some patients are considered CYP2D6 “ultra-metabolizers” and rapidly convert codeine to higher than usual levels of morphine, resulting in toxicity There is emerging evidence that significant side effects, including death, can occur even at usual doses, particularly in children with genetic variations in drug metabolism Codeine is now contraindicated for use in children undergoing tonsillectomy and/or adenoidectomy.32 Patients who are CYP2D6 poor metabolizers (up to 10% of the population) or are taking drugs that inhibit CYP2D6, such as fluoxetine (Prozac, and generics), cannot convert codeine to morphine and may not experience any analgesic effect 38 Hydrocodone – Hydrocodone is a synthetic opioid that is metabolized to hydromorphone after oral administration For treatment of pain, this widely prescribed opioid is available only in combination with acetaminophen or ibuprofen; it is currently under review by the FDA for approval as a single agent The efficacy of the combination of hydrocodone and acetaminophen is similar to that of codeine plus acetaminophen FULL AGONIST/REUPTAKE INHIBITORS — Tapentadol – Tapentadol is an oral opioid receptor agonist and a norepinephrine reuptake inhibitor.33 The extended-release formulation of the drug appears to provide analgesic efficacy similar to that of extendedrelease oxycodone for osteoarthritis and low back pain with fewer adverse GI effects.34 Although it does not appear to have significant serotonergic activity, the drug’s labeling carries a warning about the possibility of serotonin syndrome when used concurrently with serotonergic drugs Due to its adrenergic effects, it should not be used with or within 14 days of taking a monoamine oxidase inhibitor Tramadol – An oral centrally-acting opioid agonist that blocks reuptake of norepinephrine and serotonin, tramadol is used to treat moderate to moderately severe pain Its effectiveness in combination with acetaminophen for treatment of chronic pain is comparable to that of combinations of acetaminophen with codeine or oxycodone The need for slow-dose titration to improve tolerability when initiating tramadol limits its use for treatment of acute pain Tramadol is also effective for treatment of neuropathic pain.35 Seizures have been reported with tramadol; according to the manufacturer, patients with a history of seizures and those concomitantly taking a tricyclic antidepressant or selective serotonin reuptake inhibitor, an MAO inhibitor, other opioids or an antipsychotic drug may be at increased risk As with codeine, much of tramadol’s analgesic efficacy is due to its active metabolite, and inhibition of CYP2D6 may decrease its efficacy Concurrent use of tramadol with drugs that inhibit CYP2D6 or 3A4 can decrease tramadol clearance and increase seizure risk The labeling warns of a possible increased risk of suicide in patients who are suicidal, emotionally disturbed or prone to addiction Tramadol is not federally classified as a controlled substance, but in many states it is classified as a schedule IV controlled substance, as psychological and physical dependence have occurred OTHERS — The partial agonist buprenorphine and the mixed agonist/antagonists pentazocine, butorphanol and nalbuphine all have a ceiling on their analgesic effects and can precipitate withdrawal symptoms in patients physically dependent on full Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 Drugs for Pain agonists All are less likely than full agonists to cause physical dependence, but none is entirely free of dependence liability Buprenorphine is available in a transdermal patch (Butrans) for treatment of chronic pain In some studies, application of one patch every days was effective in reducing pain in patients with chronic back pain Erythema and pruritus at the site of patch application, nausea, headache, dizziness and somnolence are common adverse effects Doses >20 mcg/hr are not recommended due to the risk of QT prolongation.36 Due to the low maximum dose, the patch is not useful for treatment of severe cancer pain Patients maintained on buprenorphine may require higher than normal doses of full opioid agonists during and for up to 48 hours following discontinuation of the patch Buprenorphine is also available parenterally (Buprenex, and generics) for treatment of pain and as sublingual tablets alone and in combination with naloxone (Suboxone) for treatment of opioid dependence.37 OPIOID ADVERSE EFFECTS — Sedation, dizziness, nausea, vomiting, pruritus, sweating and constipation are the most common adverse effects of opioids; respiratory depression is the most serious Usual doses of opioids, including the mixed agonist/antagonists, may decrease respiratory drive and cause apnea in opioid-naive acute-pain patients, particularly those who have chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve or pre-existing respiratory depression The addition of general anesthetics, phenothiazines, sedative-hypnotics such as benzodiazepines or barbiturates, tricyclic antidepressants, or other CNS depressants increases the risk of respiratory depression Patients who take opioids chronically are often tolerant to the respiratory depressant effect Persistent opioid-induced sedation that limits activity can be ameliorated by giving small oral doses of stimulants such as methylphenidate (Ritalin, and generics) in the morning and early afternoon The narcolepsy drug modafinil (Provigil, and generics) has also been shown to be beneficial in opioid-induced sedation.38 Tolerance usually develops rapidly to the sedative and emetic effects of opioids, but not to constipation; a stimulant laxative with or without a stool softener should be started early in treatment The selective opioid antagonist methylnaltrexone (Relistor) is FDAapproved for treatment of opioid-induced constipation.39,40 Transdermal fentanyl may cause less constipation than sustained-release oral morphine Opioids can increase prolactin levels and reduce levels of sex hormones resulting in reduced sexual function, decreased libido, infertility, mood disturbances and bone loss.41 DOSAGE — Opioid dose requirements vary widely from one patient to another, but 10 mg of oral morphine per 70 kg body weight, or its equivalent, is a reasonable starting dose For most opioids, there is generally no maximum dose except when limited by the dose of aspirin, acetaminophen or ibuprofen in fixeddose combination preparations The dose required to maintain optimum pain relief with tolerable side effects should be used After initial titration with a short-acting opioid and determination of the 24-hour dose requirement, around-the-clock dosing with a long-acting formulation is recommended for persistent chronic pain Rapid-onset opioids should be made available every 2-3 hours for breakthrough pain TOLERANCE TO OPIOIDS — Tolerance can develop with chronic use of opioids; the patient first notices a reduction in adverse effects and a shorter duration of analgesia followed by a decrease in the effectiveness of each dose Tolerance to most of the adverse effects of opioids develops at least as rapidly as tolerance to the analgesic effect; it can usually be surmounted and adequate analgesia restored by increasing the dose Cross-tolerance exists among all full agonists, but is not complete; when switching to another opioid, starting with half of the customary equianalgesic dose is recommended Switching opioid-tolerant patients to methadone may improve pain relief, but should only be done by those prescribers who are familiar with use of methadone PHYSICAL DEPENDENCE — Patients being treated with opioids will develop physical dependence and withdrawal symptoms will occur if the drug is discontinued suddenly or an opioid antagonist is given Clinically significant dependence develops only after several weeks of chronic treatment with an opioid OPIOID-INDUCED HYPERALGESIA — Opioidinduced hyperalgesia is a controversial condition in which patients treated with high doses of opioids experience worsening pain that cannot be overcome simply by increasing the dose (as is the case in tolerance), but rather only by reducing the dose or completely discontinuing the opioid, or changing to another opioid.42 ABUSE — Opioids have the potential for addiction and abuse and are frequently diverted for non-medical use To reduce opioid abuse, misuse and diversion, the FDA has required the manufacturers of long-acting opioids to implement risk evaluation and mitigation strategies (REMs), including a medication guide for patients and training for prescribers Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 39 Drugs for Pain Table Some Adjuvant Pain Medications1 Drug Formulations Usual Daily Dosage for Pain 10, 25, 50, 75, 100, 150 mg tabs 10, 25, 50 mg tabs 25-100 mg once 50-100 mg once or divided 75, 100, 125, 150 mg caps 75-100 mg once 10, 25, 50, 75 mg caps; 10 mg/5 mL PO soln 25, 37.5, 50, 75, 100 mg tabs 37.5, 75, 150 tabs and caps; 225 mg tabs 37.5, 75, 150 mg caps 20, 30, 60 mg caps 12.5, 25, 50, 100 mg tabs 75 mg once or divided Cost2 Antidepressants Amitriptyline – generic Imipramine HCL – generic Tofranil (Mallinckrodt) Imipramine pamoate – generic Tofranil PM (Mallinckrodt) Nortriptyline – generic Pamelor (Mallinckrodt) Venlafaxine – generic extended-release – generic Effexor XR (Pfizer) Duloxetine – Cymbalta (Lilly) Milnacipran – Savella (Forest) 75 mg once-tid 75-150 mg once 60 mg once 50 mg bid $1.30 9.60 174.60 348.00 548.85 6.90 699.71 21.30 14.70 173.95 198.45 144.02 Antiepileptics Gabapentin – generic Neurontin (Pfizer) extended-release Gralise (Depomed) Horizant (GlaxoSmithKline) Pregabalin – Lyrica (Pfizer) Carbamazepine – generic Tegretol (Novartis) extended-release – generic Tegretol XR (Novartis) generic Carbatrol (Shire) Oxcarbazepine – generic Trileptal (Novartis) extended-release Oxtellar XR (Supernus) 100, 300, 400 mg caps; 600, 800 mg tabs; 250 mg/5 mL PO soln 1800-3600 mg divided tid 64.80 395.83 300, 600 mg ER tabs 600 mg ER tabs 25, 50, 75, 100, 150, 200, 225, 300 mg caps; 20 mg/mL PO soln 200 mg tabs; 100 mg chewable tabs; 100 mg/5 mL PO susp 200, 400 mg ER tabs 100, 200, 400 mg ER tabs 100, 200, 300 mg ER caps 100, 200, 300 mg ER caps 150, 300, 600 mg tabs; 300 mg/5 mL PO susp 1800 mg once 600 mg bid 150-600 mg divided bid or tid 226.80 228.75 220.76 400-800 mg divided bid 3.00 78.59 46.20 79.96 88.20 106.36 54.60 261.04 150, 300, 600 mg ER tabs 600-2400 mg once 400-800 mg divided bid 600-1200 mg divided bid 227.40 Some of the drugs listed here are not FDA-approved for use in treatment of pain Wholesale acquisition cost of 30 days’ treatment at the lowest usual dosage and/or longest dosing interval $ource® Monthly (Selected from FDB MedKnowledge™) March 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher ADJUVANT PAIN MEDICATIONS Antidepressants and antiepileptics are the mainstay of treatment for a variety of neuropathic pain syndromes, including postherpetic neuralgia, diabetic neuropathy, fibromyalgia, complex regional pain syndrome and phantom limb pain, even though most of them are not approved by the FDA for these indications Combining an antidepressant and an antiepileptic may produce a synergistic analgesic effect in neuropathic pain syndromes.43 ANTIDEPRESSANTS — Tricyclic antidepressants such as amitriptyline, nortriptyline and imipramine can relieve many types of neuropathic pain, including diabetic neuropathy, postherpetic neuralgia, polyneuropathy, and nerve injury or infiltration with cancer They are also effective for fibromyalgia pain.44 The analgesic effects of these drugs are likely due to their inhibition of norepinephrine and serotonin reuptake; their antagonism of cholinergic and histaminergic systems causes sedation, urinary retention and hypotension SSRIs appear to be less effective than tricyclic antidepressants for treatment of neuropathic pain.45 40 Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), has been reported to be effective in neuropathic pain and has also been used to treat headache, fibromyalgia, and postmastectomy pain syndrome.46 It can cause a slight increase in diastolic blood pressure and discontinuation symptoms may be troublesome Duloxetine, another SNRI, is FDA-approved for treatment of pain associated with diabetic peripheral neuropathy and fibromyalgia, and for chronic musculoskeletal pain.47-49 In patients with chronic low back pain or osteoarthritis, it was modestly more effective than placebo Duloxetine appears to provide many of the analgesic benefits of older antidepressants with fewer adverse effects Milnacipran, an SNRI approved by the FDA only for use in fibromyalgia,50 appears to be moderately effective in decreasing pain and improving function It exhibits more selectivity for inhibition of norepinephrine reuptake than for that of serotonin How it compares to venlafaxine or duloxetine remains to be established ANTIEPILEPTICS — In controlled trials, gabapentin has been effective in reducing pain in postherpetic neuralgia (an FDA-approved use) and diabetic neuropathy.51 In one study in patients with Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 Drugs for Pain neuropathic pain, taking lower doses of gabapentin and morphine together provided better analgesia than taking either drug alone.52 Gabapentin can cause dizziness, somnolence, edema and weight gain Pregabalin, which is similar in structure to gabapentin, is approved for treatment of neuropathic pain associated with postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia The dose of pregabalin can be titrated more rapidly than that of gabapentin.53,54 Like gabapentin, it can cause dizziness, somnolence and peripheral edema; significant weight gain has been reported in some patients Because of some reports of euphoria, pregabalin is classified as a Schedule V controlled substance Carbamazepine is FDA-approved for treatment of pain due to trigeminal neuralgia Oxcarbazepine, which is related to carbamazepine, has been shown to provide similar analgesia, and may have fewer adverse effects OTHER DRUGS — Ziconotide (Prialt), a synthetic neuronal N-type calcium channel blocker, is administered intrathecally via a programmable microinfusion device for treatment of severe chronic pain The drug has been effective, both as monotherapy and when added to standard therapy, for treatment of refractory severe chronic pain, including neuropathic pain Severe psychiatric effects (paranoid reactions, psychosis) and CNS toxicity (confusion, somnolence, unresponsiveness) can occur Unlike opioids, ziconotide does not cause tolerance, dependence or respiratory depression, and is not a controlled substance.55 Caffeine in doses of 65-200 mg may enhance the analgesic effect of acetaminophen, aspirin or ibuprofen Hydroxyzine in doses of 25-50 mg given parenterally may add to the analgesic effect of opioids in postoperative and cancer pain while reducing the incidence of nausea and vomiting Corticosteroids can produce analgesia in some patients with inflammatory diseases or tumor infiltration of nerves The oral and transdermal patch formulation of the alpha2-adrenergic agonist clonidine may improve pain and hyperalgesia in sympathetically maintained pain Botulinum toxin type A administered intradermally appeared to be effective in one study for diabetic peripheral neuropathy pain.56 Although controversial, marijuana, delta9-tetrahydrocannabinol (Dronabinol), and a mixture of delta9tetrahydrocannabinol and cannabidiol (Sativex, not approved in the US) have been shown to be effective in multiple sclerosis patients with central neuropathic pain and spasticity; data supporting their efficacy for intractable cancer pain are limited.57,58 Topical Analgesics for Local Treatment – A 5% lidocaine patch (Lidoderm) is FDA-approved for treatment of postherpetic neuralgia.59 It is widely used off-label for other types of pain despite a lack of clinical trials supporting its efficacy Skin irritation can occur at the site of application An 8% capsaicin patch (Qutenza), available only by prescription, is FDA-approved for treatment of postherpetic neuralgia.60 Application of the patch for one hour was modestly effective in reducing pain associated with postherpetic neuralgia for up to months An increase in pain is common during, and for a few days after, application of the patch The patch is applied during an office visit Topical analgesics containing menthol, methylsalicylate or capsaicin are available over the counter for the relief of mild muscle and joint pain While generally well-tolerated, there have been rare reports of severe skin burns requiring treatment or hospitalization.61 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Intravenous acetaminophen (Ofirmev) Med Lett Drugs Ther 2011; 53:26 Acetaminophen safety - Deja vu Med Lett Drugs Ther 2009; 51:53 PB Watkins et al Aminotransferase elevations in healthy adults receiving grams of acetaminophen daily: a randomized controlled trial JAMA 2006; 296:87 Addendum: warfarin-acetaminophen interaction Med Lett Drugs Ther 2008; 50:45 In brief: does acetaminophen increase blood pressure? Med Lett Drugs Ther 2011; 53:29 PL McCormack Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis Drugs 2011; 71:2457 Primary prevention of ulcers in patients taking aspirin or NSAIDs Med Lett Drugs Ther 2010; 52:17 Naproxen/esomeprazole (Vimovo) Med Lett Drugs Ther 2010; 52:74 A fixed-dose combination of ibuprofen and famotidine (Duexis) Med Lett Drugs Ther 2011; 53:85 S Trelle et al Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis BMJ 2011; 342:c7086 P McGettigan and D Henry Cardiovascular risk with non-steroidal antiinflammatory drugs: systematic review of population-based controlled observational studies PLoS Med 2011; 8:e1001098 ME Farkouh and BP Greenberg An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs Am J Cardiol 2009; 103:1227 WB White et al Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials Am J Cardiol 2007; 99:91 EM Antman et al Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association Circulation 2007; 115:1634 E Cho et al Prospective evaluation of analgesic use and risk of renal cell cancer Arch Intern Med 2011; 171:1487 CM Reid et al Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials Arch Intern Med 2006; 166:837 TJ Cicero et al Effect of abuse-deterrent formulation of OxyContin N Engl J Med 2012; 367:187 In brief: immediate-release oxycodone (Oxecta) for pain Med Lett Drugs Ther 2012; 54:20 Oral oxymorphone (Opana) Med Lett Drugs Ther 2007; 49:3 PA Sloan and R Barkin Oxymorphone and oxymorphone extended release: a pharmacotherapeutic review J Opioid Manag 2008; 4:131 Extended-release hydromorphone (Exalgo) for pain Med Lett Drugs Ther 2011; 53:62 H Binsfeld et al A randomized study to demonstrate noninferiority of once-daily OROS hydromorphone with twice-daily sustained-release oxycodone for moderate to severe chronic noncancer pain Pain Pract 2010; 10:404 In brief: heat and transdermal fentanyl Med Lett Drugs Ther 2009; 51:64 CYP3A and drug interactions Med Lett Drugs Ther 2005; 47:54 FDA FDA reminds the public about the potential for life-threatening Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 41 Drugs for Pain 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 42 harm from accidental exposure to fentanyl transdermal systems (“patches”) April 18, 2012 Available at www.fda.gov/Drugs/DrugSafety/ ucm300747.htm JS Morley et al Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial Palliat Med 2003; 17:576 MC Rowbotham et al Oral opioid therapy for chronic peripheral and central neuropathic pain N Engl J Med 2003; 348:1223 KM Foley Opioids and chronic neuropathic pain N Engl J Med 2003; 348:1279 E Bruera et al Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study J Clin Oncol 2004; 22:185 GB Ehret et al Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors Arch Intern Med 2006; 166:1280 MJ Krantz et al QTc interval screening in methadone treatment Ann Intern Med 2009; 150:387 FDA FDA Drug Safety Communication: safety review update of codeine use in children; new boxed warning and contraindication on use after tonsillectomy and /or adenoidectomy February 20, 2013 Available at www.fda.gov/Drugs/DrugSafety/ucm339112.htm Accessed March 7, 2013 Tapentadol (Nucynta) – a new analgesic Med Lett Drugs Ther 2009; 51:61 M Afilalo and B Morlion Efficacy of tapentadol ER for managing moderate to severe pain Pain Physician 2013; 16:27 RM Duhmke et al Tramadol for neuropathic pain (review) Cochrane Database Syst Rev 2004; (2):CD003726 Transdermal buprenorphone (Butrans) for chronic pain Med Lett Drugs Ther 2011; 53:31 Buprenorphine: an alternative to methadone Med Lett Drugs Ther 2003; 45:13 New indications for modafinil (Provigil) Med Lett Drugs Ther 2004; 46:34 Methylnaltrexone (Relistor) for opioid-induced constipation Med Lett Drugs Ther 2008; 50:63 J Thomas et al Methylnaltrexone for opioid-induced constipation in advanced illness N Engl J Med 2008; 358:2332 MJ Brennan The effect of opioid therapy on endocrine function Am J Med 2013; 126:S12 K Bannister and AH Dickenson Opioid hyperalgesia Curr Opin Support Palliat Care 2010; 4:1 I Gilron et al Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial Lancet 2009; 374:1252 W Häuser et al Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis JAMA 2009; 301:198 SH Sindrup et al Antidepressants in the treatment of neuropathic pain Basic Clin Pharmacol Toxicol 2005; 96:399 DR Grothe et al Treatment of pain syndromes with venlafaxine Pharmacotherapy 2004; 24:621 Duloxetine (Cymbalta) for diabetic neuropathic pain Med Lett Drugs Ther 2005; 47:67 Duloxetine (Cymbalta) for fibromyalgia Med Lett Drugs Ther 2008; 50:57 Duloxetine (Cymbalta) for chronic musculoskeletal pain Med Lett Drugs Ther 2011; 53:33 Milnacipran (Savella) for fibromyalgia Med Lett Drugs Ther 2009; 51:45 Gabapentin (Neurontin) for chronic pain Med Lett Drugs Ther 2004; 46:29 I Gilron et al Morphine, gabapentin, or their combination for neuropathic pain N Engl J Med 2005; 352:1324 Pregabalin (Lyrica) for neuropathic pain and epilepsy Med Lett Drugs Ther 2005; 47:75 W Häuser et al Treatment of fibromyalgia syndrome with gabapentin and pregabalin—a meta-analysis of randomized controlled trials Pain 2009; 145:69 Ziconotide (Prialt) for chronic pain Med Lett Drugs Ther 2005; 47:103 RY Yuan et al Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial Neurology 2009; 72:1473 Medical marijuana Med Lett Drugs Ther 2010; 52:5 M Karst et al Role of cannabinoids in the treatment of pain and (painful) spasticity Drugs 2010; 70:18 59 PS Davies and BS Galer Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia Drugs 2004; 64:937 60 Capsaicin patch (Qutenza) for postherpetic neuralgia Med Lett Drugs Ther 2011; 53:42 61 FDA FDA drug safety communication: rare cases of serious burns with the use of over-the-counter topical muscle and joint pain relievers Available at www.fda.gov/Drugs/DrugSafety/ucm318858.htm Accessed March 8, 2013 Treatment Guidelines ® from The Medical Letter EDITOR IN CHIEF: Mark Abramowicz, M.D EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pflomm, Pharm.D ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine Jane P Galiardi, M.D., M.H.S., F.A.C.P., Duke University School of Medicine Jules Hirsch, M.D., Rockefeller University David N Juurlink, BPhm, M.D., PhD, Sunnybrook Health Sciences Centre Richard B Kim, M.D., University of Western Ontario Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M Roden, M.D., Vanderbilt University School of Medicine Esperance A K Schaefer, M.D., M.P.H., Harvard Medical School F Estelle R Simons, M.D., University of Manitoba Neal H Steigbigel, M.D., New York University School of Medicine Arthur M.F Yee, M.D., Ph.D., F.A.C.R, Weill Medical College of Cornell University SENIOR ASSOCIATE EDITORS: Donna Goodstein, Amy Faucard ASSOCIATE EDITOR: Cynthia Macapagal Covey EDITORIAL FELLOW: Jennifer Y Lin, M.D., Harvard Medical School MANAGING EDITOR: Susie Wong ASSISTANT MANAGING EDITOR: Liz Donohue PRODUCTION COORDINATOR: Cheryl Brown EXECUTIVE DIRECTOR OF SALES: Gene Carbona FULFILLMENT AND SYSTEMS MANAGER: Cristine Romatowski DIRECTOR OF MARKETING COMMUNICATIONS: Joanne F Valentino VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy Founded in 1959 by Arthur Kallet and Harold Aaron, M.D Copyright and Disclaimer: The Medical Letter is an independent nonprofit organization that provides healthcare professionals with unbiased drug prescribing recommendations The editorial process used for its publications relies on a review of published and unpublished literature, with an emphasis on controlled clinical trials, and on the opinions of its consultants The Medical Letter is supported solely by subscription fees and accepts no advertising, grants or donations No part of the material may be reproduced or transmitted by any process in whole or in part without prior permission in writing The editors not warrant that all the material in this publication is accurate and complete in every respect The editors shall not be held responsible for any damage resulting from any error, inaccuracy or omission Subscription Services Subscriptions (US): Mailing Address: The Medical Letter, Inc 145 Huguenot Street, Ste 312 New Rochelle, NY 10801-7537 Customer Service: Call: 800-211-2769 or 914-235-0500 Fax: 914-632-1733 Web Site: www.medicalletter.org E-mail: custserv@medicalletter.org Permissions: To reproduce any portion of this issue, please e-mail your request to: permissions@medicalletter.org Subscriptions (US): - $189; year - $98; years years - $189; year years- -$98; $279 $49/yr for students, years residents - $279 $49/yr for students, interns, and fellows in the interns, US and residents Canada and fellows in the US and Canada E-mail site license inquiries to: E-mail site license inquiries info@medicalletter.org or call to: info@medicalletter.org 800-211-2769 x315 or call 800-211-2769 x315 Special fees for bulk subscriptions Special for bulk subscriptions Special fees classroom rates are availSpecial classroom rates areeach available Back issues are $12 able Back issues are $12 each Major credit cards accepted Major credit cards accepted Copyright 2012 ISSN 1541-2784 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 Treatment Guidelines: Online Continuing Medical Education Up to 24 credits included with your subscription medicalletter.org/cme Choose CME from Treatment Guidelines from The Medical Letter and earn up to 24 Category Credits per year: Free Individual Exams - Free to active subscribers of Treatment Guidelines from The Medical Letter Answer 12 questions per issue and submit answers online Earn up to credits/exam Paid Individual Exams - Available to non-subscribers Answer 12 questions per issue and submit answers online Earn up to credits/exam $12/exam ACCREDITATION INFORMATION: ACCME: The Medical Letter is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians The Medical Letter Inc designates this enduring material for a maximum of AMA PRA Category Credit(s)™ Physicians should claim only the credit commensurate with the extent of their participation in the activity This CME activity was planned and produced in accordance with the ACCME Essentials and Policies AAFP: This enduring material activity, Treatment Guidelines from the Medical Letter Continuing Medical Education Program, has been reviewed and is acceptable for up to 15 Prescribed credits by the American Academy of Family Physicians AAFP certification begins January 1, 2013 Term of approval is for one year from this date Each issue is approved for 1.25 Prescribed credits Credit may be claimed for one year from the date of each issue Physicians should claim only the credit commensurate with the extent of their participation in the activity ACPE: The Medical Letter is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education This exam is acceptable for 2.0 hour(s) of knowledge-based continuing education credit (0.2 CEU) ® AANP and AAPA: The American Academy of Nurse Practitioners (AANP) and the American Academy of Physician Assistants (AAPA) accept AMA Category Credit for the Physician’s Recognition Award from organizations accredited by the ACCME AOA: This activity, being ACCME (AMA) approved, is acceptable for Category 2-B credit by the American Osteopathic Association (AOA) Physician Assistants: The National Commission on Certification of Physician Assistants (NCCPA) accepts AMA PRA Category Credit(s)™ from organizations accredited by ACCME NCCPA also accepts AAFP Prescribed credits for recertification Treatment Guidelines is accredited by both ACCME and AAFP Physicians in Canada: Members of The College of Family Physicians of Canada residing in the US are eligible to receive Mainpro-M1 credits (equivalent to AAFP Prescribed credits), and members residing in Canada are eligible to receive Mainpro-M2 credits due to a reciprocal agreement with the American Academy of Family Physicians Treatment Guidelines CME activities are eligible for either Section or Section (when creating a personal learning project) in the Maintenance of Certification Program of the Royal College of Physicians and Surgeons of Canada (RCPSC) Physicians, nurse practitioners, pharmacists and physician assistants may earn credits with this exam MISSION: The mission of The Medical Letter's Continuing Medical Education Program is to support the professional development of healthcare professionals including physicians, nurse practitioners, pharmacists and physician assistants by providing independent, unbiased drug information and prescribing recommendations that are free of industry influence The program content includes current information and unbiased reviews of FDA-approved and off-label uses of drugs, their mechanisms of action, clinical trials, dosage and administration, adverse effects and drug interactions The Medical Letter delivers educational content in the form of self-study material The expected outcome of the CME Program is to increase the participant’s ability to know, or apply knowledge into practice after assimilating, information presented in materials contained in Treatment Guidelines The Medical Letter will strive to continually improve the CME program through periodic assessment of the program and activities The Medical Letter aims to be a leader in supporting the professional development of healthcare professionals through Core Competencies by providing continuing medical education that is unbiased and free of industry influence The Medical Letter is supported solely by subscription fees and accepts no advertising, grants or donations GOAL: Through this program, The Medical Letter expects to provide the healthcare community with unbiased, reliable and timely educational content that they will use to make independent and informed therapeutic choices in their practice LEARNING OBJECTIVES: The objective of this activity is to meet the need of healthcare professionals for unbiased, reliable and timely information on treatment of major diseases The Medical Letter expects to provide the healthcare community with educational content that they will use to make independent and informed therapeutic choices in their practice Participants will be able to select and prescribe, or confirm the appropriateness of the prescribed usage of the drugs and other therapeutic modalities discussed in Treatment Guidelines with specific attention to clinical evidence of effectiveness, adverse effects and patient management Upon completion of this program, the participant will be able to: Explain the current approach to the management of patients with pain Discuss the pharmacologic agents available for treatment of pain and compare them based on their efficacy, dosage and administration, potential adverse effects and drug interactions Determine the most appropriate therapy given the clinical presentation of an individual patient Privacy and Confidentiality: The Medical Letter guarantees our firm commitment to your privacy We not sell any of your information Secure server software (SSL) is used for commerce transactions through VeriSign, Inc No credit card information is stored IT Requirements: Windows 98/NT/2000/XP/Vista/7, Pentium+ processor, Mac OS X+ w/ compatible process; Microsoft IE 6.0+, Mozilla Firefox 2.0+ or any other compatible Web browser Dial-up/high-speed connection Have any questions? Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org Questions start on next page Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 DO NOT FAX OR MAIL THIS EXAM To take CME exams and earn credit, go to: medicalletter.org/CMEstatus Issue 128 Questions Which of the following should be tried first for initial treatment of mild to moderate pain? a acetaminophen b fentanyl c ketorolac d tramadol Issue 128 Codeine: a is now contraindicated for use in children undergoing tonsillectomy and/or adenoidectomy b is metabolized to morphine c may be less effective if taken with fluoxetine d all of the above Issue 128 Aspirin should not be used in children with viral syndromes because of the risk of: a hepatotoxicity b gastric ulcer c Reye’s syndrome d thrombosis Issue 128 Which morphine formulation is limited in its maximum daily dose by its fumaric acid content? a generic tablets b MS Contin c Avinza d Kadian Issue 128 A 28-year-old patient asks you what the difference is between acetaminophen and ibuprofen You could tell her that, compared to NSAIDs such as ibuprofen, acetaminophen has: a no clinically significant anti-inflammatory activity b less risk of GI adverse effects c less risk of renal toxicity d all of the above Issue 128 Meperidine: a has a potentially toxic active metabolite b should only be used for short-term treatment of moderate to severe acute pain c should not be taken with a monoamine oxidase inhibitor d all of the above Issue 128 Patients at an increased risk for GI bleeding, ulceration and perforation with use of non-selective NSAIDs include those with: a previous peptic ulcer disease b excessive alcohol intake c advanced age d all of the above Issue 128 A 68-year-old man with chronic shoulder pain tells you he has heard favorable things from other patients about the lack of side effects with Celebrex You could tell him that compared to nonselective NSAIDs, celecoxib appears to cause: a less severe GI toxicity b an increase in bleeding time c more cardiac toxicity d more GI ulceration and perforation Issue 128 Strong full opioid agonists are generally used for treatment of: a mild pain b moderate to severe pain c high fever d all of the above Issue 128 10 Tramadol: a has a dual mechanism of action b needs slow dose titration to improve tolerability c can cause seizures d all of the above Issue 128 11 Tolerance usually develops rapidly to most of the adverse effects of opioids except: a respiratory depression b sedation c constipation d nausea Issue 128 12 Antidepressants and antiepileptics are commonly used to treat: a postherpetic neuralgia b diabetic neuropathy c fibromyalgia d all of the above ACPE UPN: 0379-0000-13-128-H01-P; Release: March 2013, Expire: March 2014 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 ... fines 31 Revised 4/24/13: The price for IV ibuprofen (Caldolor) has been revised Drugs for Pain Drugs for Pain Table Some Nonopioid Analgesics Some Available Formulations Usual Adult Analgesic... The Medical Letter • Vol 11 ( Issue 128) • April 2013 35 Drugs for Pain Drugs for Pain Table Some Opioid Analgesics Drug Oral/Topical Formulations Usual Adult Starting Oral Dosage Duration of... guide for patients and training for prescribers Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 128) • April 2013 39 Drugs for Pain Table Some Adjuvant Pain Medications1 Drug Formulations