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Principles of CMP Management | Analgesics | | References | |
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| Choline magnesium trisalicylate | Trilisate | 1,000 - 1,500 mg 3 x daily | Tablet: 500, 750, 1000 mg
Liquid: 500 mg/5 ml |
| Choline salicylate | Arthropan | 870 mg every 3-4 hours | Liquid: 870 mg/5 ml |
| Diflunisal | Dolobid | 500 mg every 12 hours | Tablet: 250, 500 mg |
| Etodolac | Lodine | 200-400 mg every 6-8 hours | Capsule: 200, 300 mg
Tablet: 400 mg XR*: 400, 600 mg |
| Fenoprofen calcium | Nalfon | 300-600 mg every 6 hours | Capsule: 200, 300 mg
Tablet: 600 mg |
| Ibuprofen | Motrin, Advil, Nuprin | 400-600 mg every 6 hours | Tablet: 50, 100, 200, 300, 400, 600, 800 mg
Suspension: 40 mg/ml, 100 mg/5 ml |
| Ketoprofen | Orudis,
Actron, Orudis KT, Oruvail |
25-60 mg every 6-8 hours | Capsule: 25, 50, 75 mg (Orudis); 12.5 mg (Actron, Orudis
KT)
XR: 100, 200 mg (Oruvail) |
| Ketorolac | Toradol | 10 mg every 4-6 hours, max 40 mg/day | Tablet: 10 mg
Injection: 15 mg/ml, 30 mg/ml |
| Magnesium salicylate | Doan's Magan, Mobidin, others | 650 mg every 4 hours | Tablet: 325 mg |
| Meclofenamate sodium | Meclomen | 50-100 mg every 6 hours | Capsule: 50, 100 mg |
| Mefenamic acid | Ponstel | 250 mg every 6 hours | Capsule: 250 mg |
| Naproxen,
Naproxen sodium |
Naprosyn,
Anaprox, Aleve, Naprelan |
250-275 mg every 6-8 hours | Tablet: 220, 275, 550 mg (Anaprox); 200 mg (Aleve); 250,
375, 500 mg (Naprosyn)
XR: 375, 500 mg (Naprelan) Suspension: 125 mg/5 ml |
| Sodium salicylate | 325-650 mg every 3-4 hours | Tablet: 325 mg |
Pharmacology
NSAIDs exert their analgesic effect by inhibiting the enzyme cyclooxygenase and thereby decreasing the synthesis of pain and inflammatory mediators: prostaglandins (P) and leukotrienes (L). Decreasing the production of P and L prevents the nerve endings from becoming sensitized to painful stimuli.
Precautions/Adverse Drug Reactions (ADRs)
The adverse effects of NSAIDs that may occur with chronic use include: fluid retention, renal failure, liver dysfunction, bleeding, and gastric ulceration. Bleeding and stomach ulcers may occur at any time without warning and the risk for these complications increase with high doses, prolonged use, previous history of stomach ulcers, excessive alcohol intake, and advanced age. The risk for GI distress may be lessened by taking the drug with food or milk. Patients who are susceptible to renal failure include the elderly, patients with dehydration, patients with congestive heart failure and patients with decreased renal function.
What to do when these ADRs occur
Should any of these signs or symptoms become suspected in the patient, a health care professional (doctor, pharmacist, nurse) should be immediately notified. Careful assessment of the ADR may lead to a dosage adjustment, drug switch, discontinuation of the drug, or an addition of another kind of drug to prevent further damaging effects.Acetaminophen (APAP), the active drug in Tylenol is also used to relieve mild pain for patients with chronic malignant pain. As with the NSAIDs, APAP is commonly combined with other opioid analgesics for an additive pain relief effect. The main advantage of APAP over NSAIDs is that APAP has a milder toxicity profile. APAP is gentler on the stomach (does not cause or worsen existing stomach ulcers) and unlike the opioid analgesics, it does not have the addiction liability.
APAP - adapted from AHCPR Clinical Practice Guideline No. 9
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| Acetaminophen (APAP) | Tylenol | 650 mg every 4 hours,
975 mg every 6 hours |
Tablet: 80 mg (chewable); 325, 500, 650 mg
Liquid: 160 mg/5 ml, 500 mg/15 ml Others: elixir, suppository, suspension... |
Pharmacology
Acetaminophen (APAP) works similarly to NSAIDs in that it decreases the synthesis of prostaglandins and other pain mediators, and has a "ceiling" on the analgesic effect.
Precautions/Adverse Drug Reactions (ADRs)
Serious and sometimes fatal liver failure has occurred in some patients taking large overdoses of APAP. The patients who are most susceptible to this kind of adverse effect are alcoholics, patients who are fasting, or patients who are concurrently taking other drugs which increase the toxicity of APAP. Examples of such drugs are barbiturates and anti-seizure medications (carbamazepine, hydantoins). To prevent this toxicity from occurring, the recommended daily dose of APAP should not exceed more than 4 grams per day. In most cases, however, patients are able to safely handle higher doses of APAP.
What to do when these ADRs occur
Since toxic overdoses of APAP is difficult to detect until after the damage has already occurred, the best way to prevent liver toxicity is to avoid alcohol and not exceed the recommended maximum daily dosage - 4 grams/day. Patients and health care providers must be especially aware of the potential for double dosing when the patient is on a combination analgesic product such as Lorcet (hydrocodone/APAP) and APAP. In this case, the combined dose of APAP in both products limits further dose escalation.Examples of combination APAP products
Davrocet, Darvon - propoxyphene/APAP (not used in CMP management)
Vicodin, Lortab, Lorcet - hydrocodone bitartrate/APAP
Tylenol with Codeine - codeine phosphate/APAP
Percocet, Roxicet, Roxilox, Tylox, Endocet - oxycodone/APAP
These combination opioid/APAP products are used to relieve moderate to severe pain with the exception of oxycodone/APAP which is used in severe pain.
Opioid analgesics are divided into three categories depending on the nature of the drug's interaction with the pain receptors in the brain: full agonists, partial agonists, or mixed agonist-antagonists. For the purpose of treating CMP, full opioid agonists are used to relieve pain. The main reason for this is due to the fact that the other opioids, partial agonists and mixed agonist-antagonists, have a ceiling on the analgesic effect. Mixed agonist-antagonists also have the potential to elicit withdrawal syndrome and increase pain when patients are switched from full agonists to mixed agonist-antagonists or when an opioid is abruptly discontinued. The signs and symptoms of withdrawal syndrome include: yawning, teary eyes, runny nose, chills, goose-bumps, hyperventilation, hyperthermia, muscle aches, vomiting, diarrhea, anxiety, and hostility. Therefore, these agents would not be good choices to treat pain in the cancer patients due to the limited analgesic effects.
Partial Agonists
buprenorphine - BuprenexMixed Agonists
butorphanol tartrate - Stadol, dezocine - Dalgan, pentazocine - Talwin, nalbuphine hydrochloride - Nubain
Full Agonists
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| morphine | Ms Contin, Roxanol, Oramorph, MSIR, MS/L, OMS | Oral: 30 mg every 3-4 hours (repeat around-the-clock)
60 mg every 3-4 hours (single dose or intermittent dosing) |
Capsule: 15, 30 mg (MSIR); 20, 50, 100 mg (Kadian)
Tablet: 15, 30 mg (MSIR, generic); 15, 30, 60, 100, 200 mg (MS Contin); 30 mg (Roxanol); 10, 15, 30 mg (soluble); 30, 60, 100 mg (Oramorph SR Solution: 10 mg/5 ml, 20 mg/5 ml; 10 mg/5 ml, 20 mg/5 ml, 20 mg/ml (MSIR); 100 mg/5 ml, 20 mg/5 ml (MS/L); 20 mg/ml (OMS); 10 mg/2.5 ml, 20 mg/ml (Roxanol) Suppositories: 5, 10, 20, 30 mg (MS/S, RMS, Roxanol, generic) Injections: numerous |
| hydromorphone | Dilaudid, Dilaudid-HP | 6 mg every 3-4 hours |
Tablet: 1, 2, 3, 4, 8 mg
Liquid: 5 mg/5 ml Suppository: 3 mg Injection: 1 mg/ml, 2 mg/ml, 3 mg/ml, 4 mg/ml (Dilaudid); 10 mg/ml (Dilaudid-HP) |
| codeine | *combination | 60 mg every 3-4 hours |
Capsule: APAP 325 and Codeine phosphate 15 mg (#2); APAP 325 and Codeine phosphate 30 mg (#3); APAP 325 and Codeine phosphate 60 mg (#4)
Tablet: APAP 300 and Codeine phosphate 7.5 mg (#1); APAP 300 and Codeine phosphate 15 mg (#2); APAP 300 and Codeine phosphate 30 mg (#3); APAP 300 and Codeine phosphate 60 mg (#4); APAP 500 and Codeine phosphate 30 mg; APAP 650 and Codeine phosphate 30 mg Elixir: APAP 120 and Codeine phosphate 12 mg/5 ml with alcohol 7% Suspension: APAP 120 and Codeine phosphate 12 mg/5 ml alcohol free |
| oxycodone | OxyContin | 10 mg every 3-4 hours |
Capsule: 5 mg (OxyIR); APAP 500 and Oxycodone hydrochloride 5 mg
Tablet: 5 mg; controlled release 10, 20, 40, 80 (OxyContin); APAP 325 and Oxycodone hydrochloride 5 mg Liquid: 5 mg/5 ml, 20 mg/ml; APAP 325 and Oxycodone hydrochloride 5 mg per 5 ml |
| hydrocodone | *combination | 10 mg every 3-4 hours |
Capsule: APAP 500 mg and Hydrocodone bitartrate 5 mg
Tablet: APAP 500 mg and Hydrocodone bitartrate 2.5 mg; APAP 500 mg and Hydrocodone bitartrate 5 mg; APAP 500 mg and Hydrocodone bitartrate 7.5 mg; APAP 500 mg and Hydrocodone bitartrate 10 mg; APAP 650 mg and Hydrocodone bitartrate 10 mg (Lortab, Lorcet, Vicodin, Anexsia) |
| methadone | Dolophine | 20 mg every 6-8 hours |
Tablet: 5, 10, 40 mg
Solution: 5 mg/5 ml, 10 mg/5 ml, 10 mg/ml (concentrate) Injection: 10 mg/ml |
| levorphanol | Levo-Dromoran | 4 mg every 6-8 hours |
Tablet: 2 mg
Injection: 2 mg/ml |
| fentanyl | Duragesic, Sublimaze | 25 mcg/hr patch starting dose for opioid naive patients | Transdermal Patch: 25, 50, 75, 100 mcg/hour (Duragesic) |
| meperidine | Demerol | 100 mg every 3 hours - IV route only.
Oral route not recommended. |
Tablet: 50, 100 mg
Syrup: 50 mg/5 ml Injection: 10 mg/dose (5, 10, 30 ml), 25 mg/dose (0.5, 1 ml), 50 mg/dose (1 ml), 75 mg/dose, 100 mg/dose (1 ml) |
Pharmacology: No ceiling on analgesic effect.
Side Effects/Precautions: constipation, nausea/vomiting, urinary retention, confusion, sedation, respiratory depression.
Precautionary Measures:
The most common and yet preventable side effect of opioid treatment is constipation. Numerous prophylactic measures can be taken to prevent and treat this side effect. For patients who present with colicky abdominal pain, irritable bowel syndrome (IBS), cancer in the liver, confusion or encephalopathy with constipation, the drug of choice is sorbitol 30 - 150 mls (usual adult dose as 70% solution) if nausea is also present. If the patient has one of the above symptoms but does not feel nauseated, the drug of choice is lactulose 30 - 45 ml given 3-4 times a day (usual daily adult dose). For patients who do not have any of those symptoms, a prophylactic regimen of stool softeners and laxatives should be initiated.
Another common side effect patients experience is nausea/vomiting. Since this side effect can be due to a variety of problems (i.e. chemotherapy, altered taste, flu... etc.) a proper assessment of the cause should be made. Once the cause has been identified as opioid induced nausea/vomiting, the drug of choice for treatment is prochlorperazine (Compazine) 5 - 10 mg given 3 - 4 times a day.
Tolerance and Physical Dependence: This often misused term is a rare phenomena in patients being treated for cancer pain. Fear and misunderstanding of this phenomena frequently causes under treatment of cancer pain and needless suffering. Studies have shown that cancer patients rarely become addicted to the drugs they take for pain and they typically do not become tolerant to the drugs they take unless the pain increases due to worsening of the cancer itself.5,6 In this case, the dose of the drug remains the same, but the frequency of administration increases.
The following table lists the drugs used to treat neuropathic pain and other associated symptoms in the management of CMP.
Adjuvant Analgesics - adapted from AHCPR Clinical Practice Guideline No. 9
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| Corticosteroids | ||||
| Dexamethasone (Decadron) | 16-96 mg | oral, IV | Pain associated with brain metastases and spinal cord compression | weight gain, depression, increased blood sugar with prolonged use |
| Prednisone (Deltasone) | 40-100 mg | oral | ||
| Anticonvulsants | ||||
| Carbamazepine (Tegretol) | 200-1,600 mg | oral | Neuropathic pain | rash, nausea, vomiting, blurred vision, diarrhea |
| Phenytoin (Dilantin) | 300-500 mg | oral | ||
| Antidepressants | ||||
| Amitriptyline (Elavil) | 25-150 mg | oral | Neuropathic pain | dry mouth, blurred vision, constipation, urinary retention |
| Doxepin (Adapin, Sinequan) | 20-150 mg | oral | ||
| Imipramine (Tofranil) | 20-100 mg | oral | ||
| Trazodone (Deseryl) | 75-225 mg | oral | ||
| Neuroleptics | ||||
| Methotrimeprazine | 40-80 mg | intramuscular injection | Analgesia, sedation, nausea/vomiting | |
| Antihistamines | ||||
| Hydroxyzine (Atarax) | 300-450 mg | intramuscular injection | Adjuvant to opioids in post-operative and other types of pain; relief of complicating symptoms including anxiety, insomnia, nausea | drowsiness, headache, fatigue, dizziness, nausea, diarrhea |
| Local anesthetics/antiarrhythmics | ||||
| Lidocaine (Xylocaine, Solarcaine) | 5 mg/kg | IV, subcutaneous injection | Neuropathic pain | hypotension, headache, shivering |
| Mexiletine (Mexitil) | 450-600 mg | oral | ||
| Tocainide (Tonocard) | 20 mg/kg | oral | ||
| Psychostimulants | ||||
| Dextroamphetamine (Dexedrine) | 5-10 mg | oral | Improve opioid analgesia, decrease sedation | nervousness, restlessness, hypertension, nausea, diarrhea, arrhythmia |
| Methylphenidate (Ritalin) | 10-15 mg | oral |