Mild Pain

Use one of the following:

ASA

• 325-650 mg po q4h; enteric coated
• Good mild analgesic but use limited by side-effects (nausea, tinnitus, GI irritation, bleeding, etc.)

Acetaminophen

• 325-650 mg po q4h
• Weaker anti-inflammatory effect than ASA but fewer side-effects and safer; liver toxicity rare

Non-steroid anti-inflammatories ("NSAIDs")

• Effective for bone and soft tissue pain but have many side-effects, some of which are dangerous (e.g. G.I. bleeding, ulceration, fluid retention)
• Expensive
• Many types available but two which are fairly well tolerated are:
  • Diclofenac (Voltaren) 50-100 mg po bid, or 75 mg slow release (SR) or 50-100 mg suppositories hs
  • Naproxen (Naprosyn) 250-500 mg once or twice daily po
• Slow release forms, taken 1-2 hours before bedtime, often control pain through the night

Note: ASA + NSAIDs can precipitate acute asthma, with severe bronchospasm.

Mild to Moderate Pain

Non-narcotic analgesic combined with mild narcotic

• Many preparations containing either ASA or acetaminophen and Codeine are available; most also contain caffeine to aid GI absorption of drug
• Dose - one to two tabs po q4h
• E.g. Tylenol 1, 2, 3 or 4 (contains 300 mg acetaminophen, with 8, 15, 30, or 60 mg codeine respectively and 15 mg caffeine except Tylenol 4 which has no caffeine)

or Atasol 8, 15 or 30

(with 325 mg acetaminophen and 8, 15, or 30 mg codeine respectively, and 30 mg caffeine)

or Empracet 30 or 60

(with 300 mg acetaminophen and 30 or 60 mg codeine)

Note: no caffeine in Empracet, which may be useful when insomnia or agitation are prominent

or Frosst 222, 282, 292 Tablets

• With 375 mg ASA
• With 8, 15 or 30 mg codeine respectively
• With 30 mg caffeine

Fiorinal is probably best avoided in treatment of chronic pain of cancer because of barbiturate content which may aggravate depression and confusion.

Some patients are unable to tolerate codeine, not because of allergy, but because of intolerable nausea and constipation (which may be less when other narcotics are used).

NSAID

May continue NSAID (e.g. diclofenac or other) along with codeine-containing preparation provided it is well tolerated.

Moderate Pain

More than 60 mg codeine per dose is usually poorly tolerated, mainly because of nausea; therefore, if two tabs Tylenol 3 or one tab Tylenol 4 or two tabs Empracet 30 q4h fail to control pain, move to moderate strength narcotic; continue plain ASA 325-650 mg q4h or acetaminophen 325-650 mg q4h along with narcotic as follows:

Percocet

• 325 mg acetaminophen and 5 mg oxycodone
• Dose: one to two tabs po q4h
• Or Percodan
• 325 mg ASA and 5 mg oxycodone
• Dose: one to two tabs po q4h

or

Anileridine (Leritine)

• 25-75 mg po q4h; higher dose usually poorly tolerated because of nausea and confusion
• Continue plain ASA, acetaminophen or NSAID, if tolerated

or

Levorphanol (Levo-dromeran)

• 2 to 4 mg q6h
• Note: this drug has longer half-life and duration of analgesic effect than many other narcotics, hence use q6h
• If pain poorly controlled on above dose it is usually best to move to stronger narcotic because of intolerable side-effects on higher dose of levorphanol
• Continue plain ASA or acetaminophen q6h along with levorphanol

Severe Pain

• Choose either Morphine;
• or Hydromorphone (Dilaudid);
• or Methadone;
• and continue ASA, acetaminophen or NSAID, if tolerated.

Morphine solution

The most widely used strong narcotic analgesic because it is effective, inexpensive, readily available and usually well tolerated. Usual starting dose in adult is 5-10 mg po q4h; however, if switching from moderate strength narcotic such as Percocet tabs two q4h, a higher dose of morphine solution will be required - 20-30 mg po q4h; refer to chart of equianalgesic doses (Section 7.2) and titrate up or down as required to achieve good pain control.

If solution is irritating to mouth, consult with pharmacist about base used; some use alcohol which can be very irritating to mouth especially after irradiation to head and neck, chemotherapy, or with candidiasis. Aqueous base is preferable.

If pain is poorly controlled, increase dose (not frequency); note that by giving morphine solution q2-3h (rather than q4h) intolerable side-effects are much more likely to occur.

If pain control is good, it may be possible to give 1 1/2-2 times usual dose hs; this may allow uninterrupted sleep through the night; morphine suppositories of 10, 20 or 30 mg may be used rectally q6-8h and are often useful hs.

Immediate Release Morphine Tablets

Morphine tablets are available in various strengths (e.g. morphine immediate release) and may be preferred. Morphine tablets are available in 10, 20, 30 mg strengths.

How to Increase Dose of Morphine Solution

• Between 5 and 40 mg per dose - by 5 mg
• E.g. 10-15-20-25-30-35-40 mg po q4h
• Between 40 and 80 mg per dose - by 10 mg
• E.g. 40-50-60-70-80 mg po q4h
• Between 100 and 200 mg per dose - by 20 mg
• E.g. 100-120-140-160-180-200 mg po q4h
• Between 200 and 400 mg per dose - by 40 mg
• E.g. 200-240-280-320-360-400 mg po q4h
• Over 400 mg po q4h - by 50 mg per dose
• E.g. 400-450-500 mg po q4h

These dose increments can be made safely at least every 24 hours; if pain control is poor dose can be increased more rapidly.

Sustained release morphine preparations

MS Contin and MOS-SR, or M-ESLON are sustained release preparations of morphine and are available in strengths of 15, 30, 60, 100 mg and 200 mg.

MS Contin and MOS-SR:

• Should be swallowed whole, only the 200 mg tablet can be split
• Expensive
• Convenient because can be used q12h

When pain control is poor:

• Do not use MS Contin
• First control pain on shorter acting strong narcotic analgesic, then switch to slow-release preparation

In some cases sustained release preparation cannot be used because rapidly changing narcotic requirements due to progressive disease often require flexibility of a shorter acting narcotic (e.g. morphine solution or hydromorphone). M-ESLON capsules can be opened and drug can be sprinkled on food or into liquid, hence they are useful for patients who cannot swallow pills or have feeding tubes.

To convert to sustained release preparation, calculate total 24-hour dose of morphine solution or immediate release tablets, then divide by 2 to obtain q12h dose of MS Contin, MOS-SR, or M-ESLON (e.g. patient on 60 mg morphine solution po q4h round the clock; this equals 360 mg/24 hours; dose of MS Contin, M-ESLON, or MOS-SR = 180 mg q12h po).

Always prescribe morphine solution, morphine immediate release tablets, or other short acting strong narcotic analgesic along with sustained-release morphine preparation; use q3-4h for breakthrough pain; if more than two doses morphine solution required per 24 hours increase dose of sustained-release preparation by 15-30 mg per dose at lower dose ranges and by 30-60 mg per dose at higher ranges.

The amount of morphine solution prescribed for breakthrough pain is approximately 10-20% of the single dose of sustained-release preparation; (e.g., 5-10 mg q4h at lower dose ranges and 10-20 mg q4h at higher ranges). Hydromorphone (Dilaudid) 2-4 mg po q3-4h can be used instead of morphine solution for breakthrough pain.

In most cases it is unwise to use sustained-release morphine more frequently than q12h; q8h dose frequency usually causes excessive drowsiness and confusion, especially in elderly, or in those with renal and/or hepatic dysfunction; this is probably because of peak effect of drug at four to eight hours after ingestion. When intestinal "hurry" or malabsorption is present, q8h dosing is appropriate.

Dose increments of sustained release morphine should be made every 48 hours (unlike shorter acting drugs, e.g. morphine solution and hydromorphone).

Hydromorphone (Dilaudid)

A good alternate strong narcotic analgesic available in 1, 2, 4, and 8 mg tablets and 3 mg suppositories. A new preparation (sustained release hydromorphone capsules) is now available, in 3 mg and 6 mg strengths, for oral use.

2 mg hydromorphone po is equivalent to 10 mg morphine solution po.

Use q4h although in some cases rapid turnover of drug occurs and q3h dose may rarely be required; can be used q 3-4 h for breakthrough pain, along with sustained release morphine q 12 h.

Some notice less nausea and constipation than with morphine solution.

Methadone

An alternate strong narcotic analgesic indicated in uncommon situation of true allergy to morphine or hydromorphone as it is structurally different (NOTE: nausea and vomiting is not a manifestation of narcotic allergy). Experience in its use is important, because it is not equianalgesic with morphine, plus exact dose and frequency may be difficult to determine. It is available in Canada for oral use only.

Physician requires permit from Federal Government in order to prescribe; few pharmacists outside hospitals are willing to dispense.

Available in 2 mg/ml solution; by law is made up in Tang (orange juice) to prevent intravenous use by addicts on maintenance program; Tang base may be irritating to mouth or stomach of cancer patient with pain so it is preferable to request pharmacist to make up in water instead.

Usual starting dose is 5-10 mg po q6-8h (equivalent to 5-10 mg morphine solution.

Note: q6-8h dose frequency; Methadone has longer half-life than other strong narcotic analgesics and longer duration of analgesic effect; it may accumulate and cause respiratory depression, especially in elderly; careful follow-up of patient on Methadone for pain management is vital.

Diamorphine (heroin)

Available in Canada for parenteral use only, in 30 mg ampule, for reconstitution with 1 ml sterile water.

(See Section 7.1.2 Intermittent Subcutaneous or Intramuscular Injections.)

Advantage is more rapid onset of analgesic effect; may therefore be useful in controlling incident pain (e.g. pain on transfer to stretcher, turning in bed).

Duration of analgesic is short (about 3 hours), hence its limited usefulness in chronic pain control. Hydromorphone is almost as rapid in onset of analgesic effect, lasts longer, and is more economical.

Expensive.

No real advantage over parenteral hydromorphone.

Fentanyl (Duragesic)

• A synthetic opioid in four patch sizes: 25, 50, 75, and 100 µg/hr (microgram/hr)
• Maximum recommended daily dose is 300µg/hr
• Useful when swallowing pills is difficult; in situations where parenteral route is preferred
• Each patch supplies 72 hr of fentanyl, absorbed through the skin; plasma levels rise slowly over 12-18 hours; elimination half-life is 21 hours, so this method is unsuitable for rapid dose titration, when pain is poorly controlled
• Rapidly acting short duration analgesic should also be provided for breakthrough or incident pain (e.g. morphine, hydromorphone)
• Usual side effects are nausea, confusion, and skin irritation; in general, it is well tolerated, but very expensive