Fentanyl dosing

Dose titration - Base appropriate dosage increments on the daily dose of supplementary opioids, using the ratio of 45 mg/24 h of oral morphine to a 12.5 mcg/h increase in transdermal fentanyl dose. 

Transdermal administration of fentanyl has been extensively reviewed (44). In systemic availability studies, 92% of the fentanyl dose delivered from the transdermal therapeutic system into the skin reached the systemic circulation as unchanged unmetabolized fentanyl (41). Morphine, codeine, and hydromorphone are not good candidates for transdermal administration. Pethidine has a high transdermal permeability but poor analgesic potency. Besides fentanyl, only sufentanil and buprenor-phine would be suitable opioids for transdermal administration (45). 

The terminal half-life of fentanyl 100 mierograms/kg was reported to be more than doubled, from 155 to 340 minutes, by pretreatment with cimetidine (10 mg/kg the night before and 5 mg/kg 90 minutes before the fentanyl dose). This increase in half-life probably oeeurs beeause cimetidine inhibits the metabolism of fentanyl by the liver, thereby delaying its elear-ance from the body. The clinical importance of this interaction has not been assessed, but if both drugs are used concurrently, be alert for increased and prolonged fentanyl etfects. 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

Colpaert, F. C., Niemegeers, C. J. E., and Janssen, P. A. J. (1980) Factors regulating drug cue sensitivity Limits of discriminability and the role of a progressively decreasing training dose in fentanyl-saline discrimination. J. Pharmacol. Exp. Ther., 212 474-480. 

Darwish M, Kirby M, Robertson P, Tracewell W, and Jiang JG (2006) Pharmacokinetic properties of fentanyl effervescent buccal tablets A phase I, open-label, crossover study of single dose 100, 200, 400, and 800 micrograms in healthy adult volunteers. Clin. Ther. 28 707-714. 

Russia remains secretive about this operation. Reporters learned that they drilled holes in the floor and used vents high on the wall to pump gas into the theater. Regrettably, however, they were unable to learn the precise nature of the gas, beyond the admission by a Russian scientist that it was a derivative of Fentanyl. Several highly potent drugs fit that definition, including carfentanil, sufentanil, alfentanil, remifentanil and etorphine. Any of these can produce anesthesia, lasting from minutes to hours. A Russian medical authority later added that they used 5x the effective dose in order to guarantee a rapid effect on the terrorists. It is not clear exactly what this means. 

The interior volume of the theater, estimated from illustrations, was probably less than three hundred thousand cubic feet, i.e., about 10,000 cubic meters. Based on doses used for anesthesia, a concentration of as little as 2-3 mg per cubic meter of a super-potent Fentanyl derivative might be sufficient for a building that size, if instantaneous incapacitation is not required. This assumes continuous inhalation for about 30 minutes. Thus, if evenly distributed, the total amount of drug required might be in the range of a few dozen grams - almost certainly less than a pound. If the Russian authority pumped in 5x the effective dose (as it claimed), its uneven distribution in the air would likely have caused many deaths. But only one in six died. 

Some articles, for example, include an identical table of effective and lethal doses of high potency Fentanyl derivatives. The estimated safety margins are as high as 30,000. I could find no source for these data. I sent out several inquiries but thus far have received no definitive answers. I also discussed the questions with Harry Salem, who continues to study the toxicology of opioids at Edgewood. He is hopeful that the concomitant use of drugs tailored to suppress the effect of potent opioids on respiration may produce much safer agents. 

Parenterals are administered to the body by injection. They must be sterile, nonpyro-genie, and particulate-free. Examples of compoimded parenterals include high-dose analgesics for patient controlled analgesia (morphine sulfate 50 mg/mL), antiemetic injections, fentanyl and bupivacaine injections for ambulatory pump reservoirs, oncology combinations, and others (Table 10). 

Fentanyl transdermal system should only be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 25 mcg/h. 

Fentanyl transdermal patches are intended for transdermal use (on intact skin) only. Using damaged or cut fentanyl transdermal patches can lead to the rapid release of the contents of the fentanyl transdermal patch and absorption of a potentially fatal dose of fentanyl. 

Only use in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 25 meg/h. Patients who are considered opioid tolerant are those who have been taking, for a week or longer, morphine 60 mg/day or more, oral oxycodone 30 mg/day or more, oral hydromorphone 8 mg/day or more, or an equianalgesic dose of another opioid. 

Refer to Fentanyl Transdermal monograph for dosing conversion. 

Concomitant narcotic administration - The respiratory depressant effect of fentanyl may persist longer than the analgesic effect. Consider the total dose of all opioid analgesics used before ordering narcotic analgesics during recovery from anesthesia. Use opioids in reduced doses initially, %to 1/3 those usually recommended. 

Initial Fentanyl Transdermal Dose Based on Daily Morphine Equivalence Dose ... 

Do not use this table to convert from fentanyl transdermal system to other therapies because this conversion to fentanyl is conservative. Use of this table for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible. 

The majority of patients are adequately maintained with transdermal fentanyl administered every 72 hours. A small number of patients may require systems to be applied every 48 hours.During the initial application, patients should use short-acting analgesics for the first 24 hours as needed until analgesic efficacy with the transdermal system is attained. Thereafter, some patients still may require periodic supplemental doses of other short-acting analgesics for breakthrough pain. 

Discontinuation - Upon system removal, it takes 17 hours or more for the fentanyl serum concentration to fall by 50% after system removal. Titrate the dose of the new analgesic based on the patient s report of pain until adequate analgesia has been attained. For patients requiring discontinuation of opioids, a gradual downward titration is recommended because it is not known at what dose level the opioid may be discontinued without producing the signs and symptoms of abrupt withdrawal. 

Conversion from transdermal fentanyl to CR tablets Eighteen hours following the removal of the transdermal fentanyl patch, treatment with CR tablets can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg every 12 hours of CR tablets, should be initially substituted for each fentanyl transdermal patch 25 mcg/h. Closely follow the patient for early titration as there is very limited clinical experience with this conversion. 

Skeletal muscle r/g /cf/fy Alfentanil, fentanyl, and sufentanil may cause skeletal muscle rigidity, particularly of the truncal muscles. The incidence and severity of muscle rigidity is usually dose-related. Alfentanil, fentanyl, and sufentanil may produce muscular rigidity that involves all skeletal muscles, including those of the neck and extremities. 

Uses HTN, stable or unstable angina Action CCB relaxes coronary vascular smooth muscle Dose 2.5-10 mg/d PO -1- w/ h atic impair Caution [C, ] Disp Tabs SE Peripheral edema, HA, palpitations, flushing Interactions t Effect of hypotension M7 antih5rpCTtensives, fentanyl, nitrates, quinidine, EtOH, grapefruit juice t risk of neurotox W/Li -1- effects W/ NSAIDs EMS Concurrent EtOH and... 

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