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PubMed · 9769621

Sublingual morphine: efficacy reviewed.

Abstract

Current guidelines on the treatment of moderate to severe cancer pain recommend the use of scheduled doses of opioids for persistent pain combined with "as needed" doses of similar agents for breakthrough pain. Oral drugs given on an "as needed" basis can be problematic for patients with difficulty in swallowing or for those who suffer from nausea and vomiting. Further, breakthrough pain can become excruciating in a relatively short time, a drawback for analgesics that require gastrointestinal (GI) absorption before pain relief can begin. Hence, there is considerable interest in the development of novel drug administration routes to provide rapid relief of breakthrough pain, particularly through a route that bypasses the GI system. Sublingually administered morphine has sometimes been used in the treatment of breakthrough pain because some believe it provides effective analgesia via an appropriate alternate route. Available pharmacological data, however, do not consistently support the rapid absorption of morphine through the sublingual mucosa, and clinical data concerning the efficacy of sublingual morphine for the treatment of cancer pain are limited, not well-controlled, and inconclusive. While there seems to be a need for provision of rapid, effective analgesia to cancer patients by an alternative route, sublingual morphine may not satisfy this requirement. Newer formulations of analgesics should be tested in the treatment of breakthrough pain due to cancer.

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BibTeXRIS

P H Coluzzi. 1998. Sublingual morphine: efficacy reviewed.. https://doi.org/10.1016/s0885-3924(98)00046-3

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Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.

BACKGROUND: Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. RESULTS: The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated. CONCLUSIONS: Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.

Administration, Sublingual↗

Pharmacokinetics of the combination tablet of buprenorphine and naloxone.

The sublingual combination tablet formulation of buprenorphine and naloxone at a fixed dose ratio of 4:1 has been shown to be as effective as the tablet formulation containing only buprenorphine in treating opiate addiction. The addition of naloxone does not affect the efficacy of buprenorphine for two reasons: (1) naloxone is poorly absorbed sublingually relative to buprenorphine and (2) the half-life for buprenorphine is much longer than for naloxone (32 vs. 1 h for naloxone). The sublingual absorption of buprenorphine is rapid and the peak plasma concentration occurs 1 h after dosing. The plasma levels for naloxone are much lower and decline much more rapidly than those for buprenorphine. Increasing dose results in increasing plasma levels of buprenorphine, although this increase is not directly dose-proportional. There is a large inter-subject variability in plasma buprenorphine levels. Due to the large individual variability in opiate dependence level and the large variability in the pharmacokinetics (PK) of buprenorphine, the effective dose or effective plasma concentration is also quite variable. Doses must be titrated to a clinically effective level for individual patients.

Administration, Sublingual↗