Oxymorphone dosing

Figure 34-39 Metabolism of oxycodone and oxymorphone. Values in parentheses are percent of oxycodone dose excreted in urine. For oxymorphone dose, 1.9% is excreted as the parent drug, 44% as conjugates, and 3% as oxymorphoi.

For patients on a regimen of mixed opioids, calculate the approximate oral oxymorphone dose for each opioid and sum the totals to estimate the total daily oxymorphone dose. 

Split calculated oxymorphone dose into two divided doses (i.e. 20 mg SR oxymorphone BID)... 

This may or may not be required. If the patient complains of moderate to severe breakthrough pain, provide immediate release oxymorphone 2.5-5 mg every 6 h as required. If frequent breakthrough doses are required, increase the SR oxymorphone dose to 20 mg BID, and assess the quality of analgesia and incidence of adverse events. If, on the other hand, the patient notices improved pain relief, does not require breakthrough doses, but still complains of sedation, nausea or vomiting, consider reducing the SR oxymorphone dose to 7.5 mg BID. 

OXYMORPHONE HYDROCHLORIDE Use smaller doses of oxymorphone than those recommended below for debilitated and elderly patients and those with severe liver disease. 

Nalbuphine hydrochloride is structurally related to oxymorphone and naloxone. It is approximately equipotent with morphine. Nalbuphine is metabolised in the liver to inactive metabolites. The plasma terminal half-life is approximately 5 h. The onset of analgesia is within 2-3 min of intravenous administration and 15 min after intramuscular injection, and lasts 3-6 h with an adult dose of 10 mg. With equi-analgesic doses, similar degrees of respiratory depression to that of morphine occur up to a dose of approximately 0.45 mg-kg-1. With higher doses a ceiling effect occurs. Sedation, possibly mediated by K-receptor activation, occasionally occurs. The incidence of psychotomimetic side effects is lower than with pentazocine. The abuse potential is low, but is can cause withdrawal symptoms in opioid-dependent subjects. It has occasionally been used to reverse opioid-induced respiratory depression. 

Dosages and routes of administration Oxymorphone is used parenterally by intramuscular or subcutaneous doses of 1-1.5 mg and as suppositories with a content of 5 mg. For patient controlled analgesia (PCA) i.v. bolus doses up to 300 pg are used (Sinatra and Harrison, 1989). 

Oxymorphone (Numorphan ), dihydromorphinone hydrochloride, is also about ten times as active as morphine and has a rapid onset of action that lasts for about 6 h. It is administered subcutaneously or intramuscularly in doses of 1 ml (1.5 mg) or as a rectal suppository (2 and 5 mg). 

Disposition in the Body. Absorbed after oral administration. Metabolised to some extent by D-demethylation to oxymorphone which is active, and by A-demethylation to noroxycodone. About 30 to 60% of a dose is excreted in the urine in 24 hours as free and conjugated oxycodone, conjugated oxymorphone, and noroxycodone. 

Toxicity. The estimated minimum lethal dose is 50 mg. Prolonged use of oxymorphone may lead to dependence of the morphine type. 

Dose. 0.5 to 1.5 mg of oxymorphone hydrochloride given parenterally doses of 5 to 10 mg have been given by mouth. 

Therapeutic doses of morphine cause dilation of cutaneous blood vessels. The skin of the face, neck, and upper thorax frequently becomes flushed. These changes may be due in part to the release of histamine and may be responsible for the sweating and pruritus that occasionally follow the systemic administration of morphine. Histamine release probably accounts for the urticaria commonly seen at the site of injection, which is not mediated by opioid receptors and is not blocked by naloxone. It is seen with morphine and meperidine but not with oxymorphone, methadone, fentanyl, or sufentanil. 

For morphine, hydromorphone, and oxymorphone, rectal administration is an alternate route for patients unable to take oral medications, but equianalgesic doses may differ from oral and parenteral doses because of pharmacokinetic differences. 

Cxymorphone is a potent p agonist (10 times greater than morphine) that is used to treat severe pain. It is used by intramuscular, subcutaneous, intravenous, and rectal routes of administration. The intramusoular dose of oxymorphone (1 mg) has a half-life of 3 to 4 hours. It is a Schedule II drug. Cxymorphone, because of its 14-hydroxy group, has low antitussive activity. 

Quinidine, given as 200 mg 3 hours before and 100 mg 6 hours after a single 20-mg dose of oxycodone almost completely inhibited the formation of the metabolite, oxymorphone in 10 healthy extensive metabolisers of the cytochrome P450 isoenzyme CYP2D6. Despite this, the psychomotor and subjective effects of oxycodone were not altered (note that analgesia was not assessed). The AUC of the metabolite noroxycodone was increased about 85%, and the oxycodone AUC was slightly increased by 13%. Similar results were found in the preliminary report of another study. ... 

Patients maybe advanced to step 3 of the ladder in situations where pain has progressed to severe or very severe intensity, and is inadequately controlled with weak opioids. At this step, potent opioids including morphine, hydromorphone, oxymorphone, and transdermal delivered (TDS) fentanyl are commonly prescribed. In general, sustained-release opioids are provided daily or twice daily for basehne pain control with immediate-release opioids taken as needed for breakthrough pain. Total daily opioid dose is increased as required, thereby allowing patients to gain freedom from pain. 

Robinson et al. [8] noted that oxymorphone injectable was less likely to release histamine in dogs than equivalent doses of morphine. Since cardiovascular effects associated with histamine release (vasodilatation, hypotension) are minimal with oxymorphone this opioid may offer safety advantages for patients presenting with cardio- and cerebrovascular disease. 

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