Xolair split vial issue

[diana.papshev]

Anonymous comment and request from one of our members:

"We’ve been noticing that about a third of our Xolair patients are getting split vial dosing (225 mg q 2 weeks or 375 mg q 2 weeks), where there is a wasting of one 1 vial of drug per month. This occurs because Xolair is available only in 150 mg vials. Because the drug is weight based and depends on the patient IgE level, based on PPI dosing, some patients are recommended to receive 225 mg every 2 weeks or 375 mg every 2 weeks. Because of this label dosing, a ½ of vial of drug is wasted when the patient receives their dose which results in 1 full vial of drug going to waste per month at an annual cost of approximately $7,500. I like to point out that some patients are dosed only once a month (i.e.300 mg q4h or 150 mg q4week) based on their weight and IgE levels. This is possible because of the medications long half life. Theoretically it appears feasible that these patients that are ordered 225 mg q2weeks or 375 mg q2weeks could receive their medication dosed at 300 mg week 1 and 150 mg week 3, or 450 mg week 1 and 300 mg week 3 respectively. Because the drug is labeled such that a patient should not receive no more than 150 mg per injection, changing the dosing to the above alternate dosing (i.e. 300 mg week 1 and 150 mg week 3, or 450 mg week 1 and 300 mg week 3) would also result in one less injection per month for the patient. In summary if patients ordered Xolair 225 mg q2weeks or 375 mg q2 weeks, were to have their Xolair dosed at 300 mg week 1 and 150 mg week 3, or 450 mg week 1 and 300 mg week 3, would result in annual cost savings of approximately $7500.00 and result in 1 less injection per month for the patient.

Are other plans noticing this costly waste of Xolair? Are any plans considering any strategies to avoid the wasting of Xolair when it is prescribed at 225 mg q2weeks or 375 mg q2weeks? Has anyone considered requiring to consolidate dosing – from 225 mg q 2 weeks to 300 mg on wk 1 followed by 150 mg on wk 3 or from 375 mg q 2 weeks to 450 mg on wk 1 followed by 300 mg on wk 3?"

[jjjorden]

at the plan I work for we push providers to do the split dosing when patients require a dose of 225 mg q2weeks (changing the dosing to 300 mg on wk 1 followed by 150 mg on wk 3) or 375 mg q2 weeks (changing the dosing to 450 mg on wk 1 followed by 300 mg on wk 3). It does save us considerable amount of money and while some providers do give us push back (at which time we will allow the FDA approved dosing) a lot will take our position that due to the long half like of Xolair this type of dosing is safe and effective.

Hope this helps

[chantell.reagan]

Theoretically, the proposed consolidated dosing regimen can work based on omalizumab’s long half-life and pharmacokinetic profile. According to the prescribing information, omalizumab’s serum elimination half-life averages 26 days. In addition, phase I/II studies indicated that omalizumab can be dosed every 4 weeks. However, the proposed regimen raises two relevant questions:

1. Can the total monthly Xolair dose be split unevenly and given every 2 weeks?

Since alternative dosing regimens have not been evaluated in clinical studies, there is not enough information to suggest whether the monthly dose can be delivered in alternating uneven biweekly doses (i.e. total monthly dose of 450 mg = 300mg and 150mg alternated every 2 weeks) and/or if the dosing interval can be changed to deliver equal doses (i.e. total monthly dose of 450mg = 150 mg given every 9 days). But it should be noted, that the recommended Xolair dosing is usually an overestimation of the minimum required dose. Originally, the dosing formula was based on 3 variables: the patient’s body weight in kilograms, pretreatment free IgE level, and the constant 0.016 (minimum Xolair dose (mg/4 weeks) = weight x IgE x 0.016). Later, for simplicity and consistency, the dosing chart was implemented in phase III trials, leading to the current recommendations in the prescribing information. However, some practitioners have raised the point that wide patient weight and IgE level ranges in the dosing chart can lead to substantial overestimation of patient doses, sometimes as much as twice the dose that would have been produced by the dosing formula. For example, for a 71-kg patient with IgE level of 250 IU/mL (lower ends in the dosing chart), the recommended dose (per dosing chart) is 225 mg q 2 weeks but the calculated dose (per formula) is only 284 mg per 4 weeks. In this case, it could be argued that the patient may be dosed at 300 mg q 4 weeks (although off-label).

2. Can a patient receive a dose greater than 375 mg per administration cycle with multiple injection sites (which is greater than the recommended maximum single dose in prescribing information)?

The label states that no more than 150mg can be given per site; it also states that there was no evidence of dose-limiting toxicities when single intravenous doses of up to 4000 mg were administered. So, it could be surmised that a dose of 450 mg should not pose a greater risk of toxicity.

So, the bottom line is that there is no data that would oppose the proposed consolidated dosing. Theoretically it’s possible but it will depend on a health plan’s/PBM’s willingness to defend/promote off-label dosing…