Routes of Administration 1. Oral route is the preferred route of analgesic administration because it is the most convenient and cost-effective. EXACTLY THE SAME RESULTS CAN BE OBTAINED WITH ORAL ADMINISTRATION AS WITH PARENTERAL IF BIOTRANSFORMATION IS TAKEN INTO ACCOUNT. If the oral route is impractical or unavailable, rectal and transdermal administration are minimally invasive alternatives . {See Table III- Method for Converting Other Opioids to Eqianalgesic Dose of Morphine [Pages___ ] and TABLE IV-Oral and Parenteral Opioid Analgesic Dose Equivalencies and Relative Potency of Drugs as compared with 10MG Morphine IM for Treatment of Pain. [__ ]}. 2. Rectal is an alternative route for patients experiencing nausea and vomiting or fasting. Neutropenia and thrombocytopenia are relative contraindications. This route is not useful in the presence of diarrhea or among those who are physically unable to insert the suppository. Colostomy or similar stoma can be used provided the flow of effluent is slow enough to allow absorption. {e.g., Dilaudid© 2 mgs po is equipotent to 2 mgs per rectum}. 3. Transdermal administration bypasses gastrointestinal absorption. Fentanyl (Duragesic©) is the only opioid available by this route. The maximum recommended dose is 300 ug/hr. Patients requiring larger doses should be considered for equipotent dose of an oral or parenteral/SQ dose. Plasma levels rise slowly over 12-18 hours after transdermal patch placement and slowly fall off 20-24 hours after removal. Therefore, a transdermal system is inappropriate for rapid dose titration and only considered in non-opioid naive patients who have relatively stable pain. As with controlled release opioids, immediate release opioids should be provided for the treatment of breakthrough pain. Dosage can be determined based on the daily morphine equivalent dose {See Table II Equianalgesic doses for Converting Morphine to Transdermal Fentanyl, Page--}. 4. Transnasal is an alternative route when the oral route is unavailable. The transnasal route provides for rapid absorption and action. The only commercially available transnasal formation is the mixed opioid agonist-antagonist, butorphanol {Stadol©}. It is primarily used in the treatment of acute headaches. Butorphanol, regardless of the route, is not recommended for use in cancer pain treatment. 5. Subcutaneous or intravenous continuous infusions may benefit patients with persistent nausea or vomiting, dysphagia or difficulty swallowing, intestinal obstruction, malabsorption, analgesic requirements which make oral dosing impractical, as well as patients who require rapid titration of opioids. Medications may be given as repeated intermittent bolus doses or by continuous infusion. Intravenous provides almost immediate analgesia; subcutaneous may require up to 15 minutes for effect. Bolus IV dosing provides a shorter duration of action than other routes. Continuous infusions provide steady blood levels. The use of an infusion pump may be the best strategy for delivery of a continuous infusion. Patient-controlled analgesia (PCA) devices can be used to combine continuous infusion with intermittent bolus doses, allowing more flexible pain control. It is recommended that the hourly SQ volume limit not exceed 5 cc. Medications can be concentrated to maintain SQ volume limits; maximal concentrations: fentanyl 50 ug/ml, morphine 50 mgs/ml, hydromorphone 50 mgs/ml. Intravenous and subcutaneous infusions can be administered at home provided that the caregiver received appropriate instruction. The subcutaneous site should be inspected and possibly be rotated every 48-72 hrs in neutropenic patients to minimize risk of site infection. {See Table III-Method for Converting Other Opioids to Equianalgesic Dose of Morphine [Pages__] and TABLE IV-Oral and Parenteral Opioid Analgesic Dose Equivalencies and Relative Potency of Drugs as Compared with 10 MG Morphine IM for Treatment of Pain [___]}. 6. Intramuscular injections should be avoided because injections are painful and inconvenient, and absorption is erratic. Thrombocytopenic patients are a risk for hematomas at the injection site and neutropenic patients or individuals on chronic steroid therapy are at increased risk for site infection and systemic infection. If this route is used, a concentrated opioid should be given to keep the volume of injection as small as possible. Hydromorphone (Dilaudid HP©) is available in a 10 mg/ml form. This is the most concentrated commercially available injectable opioid. This preparation may also be administered subcutaneously. 7. Intraspinal and intraventricular administration are options if maximal doses of opioids and adjuvants administered through other routes are ineffective or produce intolerable side effects {e.g., nausea/vomiting, excessive sedation, confusion}. Opioids can be administered via indwelling percutaneous or tunneled catheters into the epidural or intrathecal space. Intraventricular opioids are given via an Ommaya© reservoir surgically placed in the lateral ventricle. Administration can be by intermittent bolus injections or continuous infusion with bolus dosing. One advantage of these routes is that the equipotent dosing is far less in comparison to systemic delivery; less total dose may reduce side effects. Secondly, the duration of action is longer than with any other route of administration. Proper patient selection and consideration of long term maintenance are critical.