Switching Between Intuniv (Extended-Release Guanfacine) and Immediate-Release Products

Natalie asked

My daughter is on extended-release guanfacine 1mg and has been for a few months. She is having swings in mood and irritability bad. She didn't have that with the regular tablets. We would like to stop the extended-release guanfacine. Would it be a good idea to just switch back to the 1mg non-extended release tabs?

Answer

There is no single recommended way to switch from Intuniv (extended release guanfacine) to immediate-release guanfacine. What is quite important, however, is that the medication is not stopped abruptly.

Stopping guanfacine without a gradual taper can sometimes cause dangerous spikes in blood pressure. The prescribing information for Intuniv discusses this:

"Infrequent, transient elevations in blood pressure above original baseline (i.e., rebound) have been reported to occur upon abrupt discontinuation of guanfacine. To minimize these effects, the dose should generally be tapered in decrements of no more than 1 mg every 3 to 7 days."

It is always important to monitor blood pressure and pulse when reducing the dose or discontinuing guanfacine.

While the prescribing information for Intuniv (extended release guanfacine) does discuss switching from the immediate-release form to the extended-release form, it doesn't discuss how to go back. I go over both situations below.

Switching From Immediate-Release To Extended-Release

Even though the immediate-release and extended-release guanfacine products are both indicated to be dosed only once-daily, switching from one formulation to the other isn't as easy as simply swapping doses. This is due to their differences in both the rate and extent of their absorption.

Going back to the prescribing information for Intuniv (extended release guanfacine), they discourage switching products on an mg-to-mg basis:

Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. INTUNIV® has a delayed Tmax [time to maximum concentration], reduced Cmax [maximum concentration] and lower bioavailability compared to those of the same dose of immediate-release guanfacine.

The recommended way to switch from immediate-release guanfacine to extended-release is to:

• Discontinue the immediate-release guanfacine.


• Initiate dosing at 1mg of Intuniv (extended release guanfacine) and increase as necessary in increments of no more than 1 mg/week.

Switching From Extended-Release To Immediate-Release

As stated above, there, unfortunately, isn't much guidance available regarding a switch from extended-release to the immediate-release product.

What is important to know, is that the different formulations, even though they are the same drug (guanfacine), have pretty significant differences in their pharmacokinetic profiles.

Key differences include:

• Intuniv (extended-release guanfacine) is less bioavailable than the immediate-release formulation. This means that the rate and extent of absorption for extended-release guanfacine are lower. According to the prescribing information for Intuniv, the relative bioavailability to the immediate-release guanfacine is 58%...so essentially only half as bioavailable.

• Immediate-release guanfacine reaches higher concentrations in the body than Intuniv (extended-release guanfacine). In fact, the difference is significant as data shows that the maximum concentration for Intuniv (extended-release guanfacine) is 60% lower than the immediate-release formulation.

• After taking a dose by mouth of immediate-release guanfacine, maximum concentrations in the body are reached in, on average, 2.6 hours. For Intuniv (extended-release guanfacine), it takes nearly 5 hours.

All of this is to say that you will probably notice a difference in effect if you switch formulations at the same dose. The immediate-release product will likely have stronger effects at the same dose when compared to extended-release formulations.

If you need to switch from to the immediate-release form, you should discuss with your doctor the best approach for your particular medical situation.

Stopping Guanfacine

This was discussed earlier, but to reiterate, if you plan on stopping guanfacine completely, remember not to do so 'cold-turkey'. It should ideally be tapered down (i.e. slowly decreased) by no more than 1 mg every 3 to 7 days to avoid rebound effects.

Be sure to discuss how to do so with your doctor.

Additional Information

You stated that your daughter is taking 1mg of Intuniv (extended-release guanfacine). This is the recommended starting dose, regardless of what she was taking before.

It makes sense though that this new 1mg dose isn't working as well. As discussed above, the immediate-release form has far better absorption and reaches higher concentrations in the blood than the extended-release form at the same dose.

If necessary (and it often is), she will need to slowly increase her dose by no more than 1mg per week (up to a maximum daily dose of 4mg) and stay at a dose that is effective.

If you and the doctor decide to stop Intuniv (extended-release guanfacine) and go back to the immediate-release version, how to do so is really on a case-by-case basis.

Since your daughter is on 1mg of Intuniv (extended-release guanfacine), her options are more limited since the tablet cannot be cut and 1mg is already the lowest dose. The doctor may recommend extended-dosing intervals or simply switch your daughter back to the immediate-release version with no taper.

If the doctor does simply go back to a 1mg dose of the immediate-release product, remember it is better absorbed and will likely have stronger initial effects and an increased risk of side effects, at least initially. Common side effects include:

• Dizziness
• Drowsiness
• Mood swings
• Headache
• Insomnia
• Dry mouth
• Constipation

The important thing to remember is to not completely stop taking the drug due to the risks I described earlier (e.g. increased blood pressure).