Wyeth-Ayerst's intravenous proton pump inhibitor Protonix will be launched in mid-April as a second-line alternative to Protonix (pantoprazole) tablets.

FDA approved Protonix I.V. March 22 for the "short-term treatment (seven to 10 days) of gastroesophageal reflux disease, as an alternative to oral therapy in patients who are unable to continue taking" oral Protonix.

"Safety and efficacy of Protonix I.V....as an initial treatment for GERD have not been demonstrated," the Indications section of labeling notes.

The limitation of Protonix I.V.' s indication to second-line treatment for patients unable to continue taking oral Protonix is highlighted in labeling with bolded text. A separate bolded statement in the Dosage and Administration section reiterates that Protonix I.V. is to be used "as an alternative to continued oral therapy."

"Treatment with Protonix I.V. for injection should be discontinued as soon as the patient is able to resume treatment with" oral Protonix, labeling emphasizes. "Safety and efficacy of Protonix I.V. for injection as a treatment for GERD for more than 10 days have not been demonstrated."

Labeling describes one clinical trial, in which 65 GERD patients with a history of erosive esophagitis were randomized to receive either 20 mg or 40 mg of oral pantoprazole once-daily for 10 days, and then were switched to either daily pantoprazole I.V. or placebo for seven days at the same dosage level.

The study showed that oral and I.V. pantoprazole 40 mg are "similar in their ability to suppress [maximum acid output] and [basal acid output] in patients with GERD," labeling states. Pantoprazole I.V. suppression of acid output was statistically superior to I.V. placebo.

The mean maximal acid output for oral pantoprazole at day 10 and I.V. pantoprazole at day seven was 6.49 mEq/h and 6.62 mEq/h, compared to 29.19 mEq/h for placebo I.V. The average basal acid output for oral and I.V. pantoprazole was .8 mEq/h and .53 mEq/h, respectively, compared to 4.14 mEq/h for I.V. placebo.

"Patients on oral Protonix who were switched to intravenous placebo experienced a significant increase in acid output within 48 hours of their last dose," labeling states. "At 48 hours after their last oral dose, patients treated with Protonix I.V....had a significantly lower mean basal acid output than those treated with placebo."

Wyeth originally expected to launch the I.V. and oral Protonix formulations together, and planned to highlight the multiple dosage forms in seeking to differentiate the product from Eisai/Janssen's proton pump inhibitor Aciphex (¹ Also see "Wyeth Prevenar Approval Expected By End of February" - Pink Sheet, 31 January, 2000.).

At the time of the tablet approval, Wyeth said it did not intend to launch the oral version until the I.V. was approved. However, the company launched the tablets in May 2000, predicting the I.V. would be approved in the third quarter.

Wyeth promoted the two dosage forms together in "Coming Soon" promotions in late 2000. The ads pictured a stomach with an I.V. bag in the background and a banner stating "approval expected soon."

FDA objected to the promotions in a Nov. 28, 2000 ad division letter, saying that Wyeth failed to disclose material facts related to the status of Protonix I.V. The letter went on to cite the reason why the I.V. had not yet been approved, which was redacted from the public version (² Also see "Wyeth Protonix I.V. "Coming Soon" Promotions Challenged By FDA" - Pink Sheet, 11 December, 2000.).

The Protonix I.V. approval letter indicates that one of the final review issues was reaching agreement on a filtration process for a zinc/pantoprazole precipitate.

Wyeth's Phase IV commitments include providing assurance the filter is being used; revising packaging to co-package one vial and one filter per box; and offering "a proposal to eliminate the filtration requirement for the product, i.e. reformulation."

Wyeth said it has no plans to promote Protonix I.V. with direct-to-consumer ads; the tablet version also was not backed by DTC advertising. The 2,300-rep sales force currently detailing oral Protonix will co-promote the tablets with the I.V. dose.

Adverse reactions reported with Protonix I.V. in at least 4% of patients were abdominal pain (12%), chest pain (6%), rash (6%) and pruritus (4%). Adverse events reported in Protonix tablet labeling are headache (6%) and diarrhea (4%).

Wyeth Protonix I.V. Indicated As Second-Line Therapy After Oral Pantoprazole

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