Morphine intranasal

Generic Name intranasal morphine (morphine mesylate/chitosan)... 

Intranasal morphine provides rapid analgesic onset (comparable to IV) together with a simple and non-invasive way to control moderate to severe pain. It consists of a combination of active ingredient morphine mesylate and ChiSys delivery system. ChiSys is based on the use of chitosan to evenly disperse and improve morphine absorption through the nasal mucosa. 

Fisher A, Green G, et al. A Phase I Absorption Study of Intranasal Morphine in Normal Volunteers. Javelin Pharmaceuticals, Inc... 

Christensen BCS, et al. The analgesic efficacy and safety of novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine and placebo in a postsurgical dental pain model. Pain Med 2008 107(6) 2018-2024. 

Intranasal morphine 7.5 mg ( = 45) or 15 mg ( = 45) has been compared with intravenous morphine 7.5 mg ( = 45) and oral morphine 60 mg ( = 45) in a placebo-controlled study in 225 patients with moderate to severe pain after third molar extraction [114 ]. Intranasal morphine 15 mg had similar efficacy to intravenous morphine and caused typical systemic opioid effects. The highest incidence of adverse events was experienced by those who received oral morphine. Nasal irritation was most common in those who received intranasal morphine 15 mg (11%). 

FinnJ, Wright J, FongJ, et al. A randomised crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adult patients with burns. Bums. 2004 30 262-268. 

The nepenthe (Gk "free from sorrow") mentioned in the Odyssey probably contained opium. Opium smoking was widely practiced in China and the Near East until recently. Isolation of active opium alkaloids and the introduction of the hypodermic needle, allowing parenteral use of morphine, increased opioid use in the West. The first of several "epidemics" of opioid use in the USA followed the Civil War. About 4% of adults in the USA used opiates regularly during the postbellum period. By the 1900s, the number had dropped to about 1 in 400 people in the USA, but the problem was still considered serious enough to justify passage of the Harrison Narcotic Act just before World War I. A new epidemic of opioid use started around 1964 and has continued unabated ever since. While fear of AIDS has reduced intravenous use of heroin, recent increases in its purity have led to markedly increased intranasal use. Present estimates are that the number of opioid-dependent people in the USA has stabilized at around 750,000. 

FIGURE 18 Morphine plasma concentration in human volunteers after intravenous administration of morphine and after nasal administration of morphine as chitosan solution and powder formulations Mor Chi Sol, morphine solution containing chitosan Mor Chi PWD, morphine-chitosan powder IN, intranasal. (Reproduced from ref. 105 with permission of the American Society for Pharmacology and Experimental Therapeutics.)... 

Intranasal diamorphine has been evaluated in a multicenter, randomized, controlled trial as an alternative to intramuscular morphine in 404 patients aged 3-16 years with suspected limb fractures (i.e. in acute pain of moderate to severe intensity) (60). They were randomized to either intramuscular morphine sulfate 0.2 mg/kg (n = 200) or intranasal diamorphine hydrochloride 0.1 mg/kg (n = 204). Intranasal diamorphine was significantly better tolerated 80% had no obvious discomfort compared with only 9% of those given morphine. There were no serious adverse effects of diamorphine, but the lack of blinding may have introduced bias. 

Intranasal diamorphine is as effective as intramuscular morphine and is much better tolerated by children, with no apparent increased risk of adverse effects (61,62). In a multicenter, randomized, controlled study, 404 children aged 3-16 years with a fracture of an arm or leg were given either nasal diamorphine 0.1 mg/kg or intramuscular morphine 0.2 mg/kg. The onset of pain relief was faster with nasal diamorphine, and there were no serious adverse effects. The frequencies of opioid-related mild adverse effects were similar in the two groups. 

Kendall JM, Latter VS. Intranasal diamorphine as an alternative to intramuscular morphine. Clin Pharmacokinet 2003 42 501-3. 

Ilium L, Watts P, Fisher AN, Hinchcliffe M, Norbury H, Jabbal-Gill I, Nankervis R, Davis SS. Intranasal delivery of morphine. J Pharmacol Exp Ther 2002 301(l) 391-400. 

No clinically significant interaction appears to occur between ci-metidine and butorphanol (intranasal), hydromorphone, morphine, pethidine or tramadol between famotidine and hydromorphone or between ranitidine and hydromorphone, morphine, or pethidine. However, isolated reports describe adverse reactions in patients taking methadone, morphine or mixed opium alkaloids with cimetidine, or morphine with ranitidine. 

Intranasal (IN) morphine (Rylomine ) is a patient-controlled nasal spray that delivers a single, metered dose of Morphine. Rylomine is currently in phase 3 clinical development and may have use as a rapid-acting analgesic in both acute and chronic pain settings. 

Median time to peak concentration (t ) after intranasal administration of morphine/chitosan combination is 13-27 min and dose-dependent absolute bioavailability is 60% to 83% (oral immediate-release morphine 1 hour and absolute bioavailability 25%... 

A single-spray unit dose device delivers 7.5 mg of morphine mesylate intranasally in a 0.1 mL metered dose. Based upon the results of the trial of IN morphine for post-operative pain control in orthopedic patients [3] the following doses can be recommended ... 

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