Canadian Direct-To-OTC Sale Of Nicotine Inhaler Proposed

The Canadian Therapeutic Products Programme is soliciting comments on nonprescription availability of nicotine inhalation devices.

The proposal to allow sale of nicotine administered by an inhalation device without a prescription is "based on a review of the clinical evidence and safety data provided in a New Drug Submission and on a general review of the known pharmacological and toxicological properties of nicotine, reported adverse drug reactions, abuse potential studies and available literature," TPP says in a Nov. 14 letter to stakeholders.

"The benefits of having nicotine inhaler available as a nonprescription drug clearly outweigh the risks," TPP concludes, adding that retaining an Rx classification "unnecessarily restricts the availability of a safe and effective smoking cessation product."

"The current proposal does not involve a prescription to nonprescription switch, but rather would allow the new inhalation dosage form for nicotine to be sold as a nonprescription drug immediately upon approval," TPP states.

J&J/Merck submitted the new drug submission requesting nonprescription status for the Nicotrol Inhaler, which has never been sold in Canada.

J&J's McNeil Consumer Healthcare division formerly marketed the Nicotrol line, which includes the inhaler, Rx nasal spray and transdermal patch, under a license from Pharmacia. McNeil divested the Nicotrol line to Pharmacia in June (¹ (Also see "J&J/Merck Pepcid Complete Combines H2 Antagonist/Antacid Ingredients" - Pink Sheet, 23 Oct, 2000.)).

J&J/Merck is overseeing the Canadian Nicotrol business on Pharmacia's behalf during the transition period, Pharmacia reported.

Pharmacia said a switch NDA for the inhaler has not been filed in the U.S. The inhaler received FDA clearance in May 1997, launching as a prescription drug in 1998 (² (Also see "McNeil Nicotrol Inhaler Rx test marketing." - Pink Sheet, 23 Feb, 1998.)).

The TPP letter notes the inhalation dosage form has been available internationally since 1996 and is sold as a nonprescription drug in 13 countries, including Denmark, Sweden and the U.K.

"There is no evidence from the postmarket data that this product is being abused by either children or non-smokers," TPP states. "There have been no reports of inappropriate use, overdose or product dependence."

In Canada, nicotine gum 2 mg and 4 mg and transdermal patches were initially approved as Rx drugs but were switched to nonprescription status in 1992, 1997 and 1998, respectively, according to TPP.

Following a 30-day initial comment period, the proposed change in the status of nicotine inhalation delivery will be published in the Canada Gazette I and subject to another 60 days of public comment before a final rule issues. After the change is formalized at the federal level, Pharmacia or J&J/Merck also must seek provincial approval for one of three categories of non-Rx sale.

Treatment with a nicotine inhaler plus nicotine patch results in significantly higher cessation rates than inhaler plus placebo patch, French and Swedish researchers report in the Nov. 13 Archives of Internal Medicine. Pharmacia provided funding for the study.

Abraham Bohadana, MD, French National Institute of Health, et al., studied two groups of 200 subjects each who had smoked 10 or more cigarettes per day for three or more years.

Group 1 received the inhaler plus nicotine patch for six weeks, the inhaler plus placebo patch for six weeks, then inhaler alone for 14 weeks. Group 2 received the inhaler plus placebo patch for 12 weeks, then the inhaler for 14 weeks. Complete self-reported abstinence and expired carbon dioxide concentration below 10 parts per million were the main outcomes measured.

The combination therapy group had greater abstinence rates than the monotherapy group at six weeks (60.5% vs. 47.5%), 12 weeks (42%, 31%), six months (25%, 22.5%) and one year (19.5%, 14%), the authors note. "The higher abstinence rates in Group 1 up to one year can probably be explained by higher levels of nicotine substitution during the first six weeks."

The researchers say this is believed to be the first double-blind, placebo-controlled trial to examine inhaler/patch combination therapy. In new clinical practice guidelines released in June, the Public Health Service cited evidence that "combining the nicotine patch with either nicotine gum or nasal spray increases long-term abstinence rates over those produced by a single form" of therapy (³ (Also see "Nicotine Replacement Combination Therapy Urged In PHS Clinical Guidelines" - Pink Sheet, 3 Jul, 2000.)).