Gavreto (pralsetinib)

Gavreto (pralsetinib) [the_ad id=”28610″]

What is Gavreto and how does it work?

Gavreto is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC) that:

has spread to other parts of the body (metastatic), and
is caused by abnormal rearranged during transfection (RET) genes. Your healthcare provider will perform a test to make sure that
Gavreto is right for you.

It is not known if Gavreto is safe and effective in children.

What are the side effects of
Gavreto?

Gavreto may cause serious side effects, including:

Lung problems.
Gavreto may cause severe or life-threatening inflammation of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you have any new or worsening symptoms, including:
High blood pressure (hypertension). High blood pressure is common with
Gavreto and may sometimes be severe. You should check your blood pressure regularly during treatment with
Gavreto. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including:
Liver problems. Liver problems (increased liver function blood test results) can happen during treatment with
Gavreto and may sometimes be serious. Your healthcare provider will do blood tests before and duringtreatment with
Gavreto to check you for liver problems. Tell your healthcare provider right away if you get any signs or symptoms of liver problem during treatment, including:
Bleeding problems.
Gavreto can cause bleeding which can be serious and cause death. Tell your healthcare provider if you have any signs or symptoms of bleeding during treatment, including:
Risk of wound healing problems. Wounds may not heal properly during treatment with
Gavreto. Tell your healthcare provider if you plan to have any surgery before or during treatment with
Gavreto. You should not take Gavreto for at least 5 days before surgery. Your healthcare provider should tell you when you may start taking
Gavreto again after surgery.

The most common side effects of
Gavreto include:

tiredness
constipation
muscle and joint painhigh blood pressure
decreased white blood cell and red blood cell counts
decreased levels of phosphate in the blood
decreased levels of body salt (sodium) in the blood
decreased levels of calcium in the blood
abnormal liver function blood tests

Gavreto may affect fertility in males and females, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.

These are not all of the possible side effects of
Gavreto.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the dosage for Gavreto?

Patient Selection

Select patients for treatment with Gavreto based on the presence of a RET gene fusion. Information on FDA-approved tests is available at http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

The recommended dosage of Gavreto is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking Gavreto). Continue treatment until disease progression or until unacceptable toxicity.

If a dose of Gavreto is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for Gavreto the next day.

Do not take an additional dose if vomiting occurs after Gavreto but continue with the next dose as scheduled.

Dosage Modifications For Adverse Reactions

The recommended dose reductions and dosage modifications for adverse reactions are provided in Table 1 and Table 2.

Table 1: Recommended Dose Reductions for Gavreto for Adverse Reactions

Dose Reduction	Recommended Dosage
First	300 mg once daily
Second	200 mg once daily
Third	100 mg once daily

Permanently discontinue Gavreto in patients who are unable to tolerate 100 mg taken orally once daily.

The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2: Recommended Dosage Modifications for Gavreto for Adverse Reactions

Adverse Reaction	Severity*	Dosage Modification
ILD/Pneumonitis	Grade 1 or 2	Withhold Gavreto until resolution. Resume by reducing the dose as shown in Table 1. Permanently discontinue Gavreto for recurrent ILD/pneumonitis.
ILD/Pneumonitis	Grade 3 or 4	Permanently discontinue for confirmed ILD/pneumonitis.
Hypertension	Grade 3	Withhold Gavreto for Grade 3 hypertension that persists despite optimal antihypertensive therapy. Resume at a reduced dose when hypertension is controlled.
Hypertension	Grade 4	Discontinue Gavreto.
Hepatotoxicity	Grade 3 or Grade 4	Withhold Gavreto and monitor AST/ALT once weekly until resolution to Grade 1 or baseline. Resume at reduced dose (Table 1). If hepatotoxicity recurs at Grade 3 or higher, discontinue Gavreto.
Hemorrhagic Events	Grade 3 or Grade 4	Withhold Gavreto until recovery to baseline or Grade 0 or 1. Discontinue Gavreto for severe or life-threatening hemorrhagic events.
Other Adverse Reactions	Grade 3 or 4	Withhold Gavreto until improvement to ≤ Grade 2. Resume at reduced dose (Table 1). Permanently discontinue for recurrent Grade 4 adverse reactions.
* Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03

Dose Modification For Use With Combined P-Glycoprotein (P-gp) And Strong CYP3A Inhibitors

Avoid coadministration of Gavreto with known combined P-gp and strong CYP3A inhibitors. If coadministration with a combined P-gp and strong CYP3A inhibitor cannot be avoided, reduce the current dose of Gavreto as recommended in Table 3. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume Gavreto at the dose taken prior to initiating the combined P-gp and strong CYP3A inhibitor.

Table 3: Recommended Dosage Modifications for Gavreto for Coadministration with Combined P-gp and Strong CYP3A Inhibitors

Current Gavreto Dosage	Recommended Gavreto Dosage
400 mg orally once daily	200 mg orally once daily
300 mg orally once daily	200 mg orally once daily
200 mg orally once daily	100 mg orally once daily

Dose Modification For Use With Strong CYP3A Inducers

Avoid coadministration of Gavreto with strong CYP3A inducers. If coadministration with a strong CYP3A inducer cannot be avoided, increase the starting dose of Gavreto to double the current Gavreto dosage starting on Day 7 of coadministration of Gavreto with the strong CYP3A inducer. After the inducer has been discontinued for at least 14 days, resume Gavreto at the dose taken prior to initiating the strong CYP3A inducer.

SLIDESHOW

Lung Cancer Symptoms, Stages, Treatment
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What drugs interact with Gavreto?

Effects Of Other Drugs On Gavreto

Strong CYP3A Inhibitors

Avoid coadministration with strong CYP3A inhibitors. Coadministration of
Gavreto with a strong CYP3A inhibitor increases pralsetinib exposure, which may increase the incidence and severity of adverse reactions of
Gavreto.

Avoid coadministration of Gavreto with combined P-gp and strong CYP3A
inhibitors. If coadministration with a combined P-gp and strong CYP3A inhibitor
cannot be avoided, reduce the Gavreto dose.

Strong CYP3A Inducers

Coadministration of Gavreto with a strong CYP3A inducer decreases pralsetinib
exposure, which may decrease efficacy of Gavreto. Avoid coadministration of
Gavreto with strong CYP3A inducers. If coadministration cannot be avoided,
increase the Gavreto dose.

Is safe to take Gavreto when pregnant or breastfeeding?

Based on findings from animal studies and its mechanism of action, Gavreto can cause fetal harm when administered to a pregnant woman. There are no available data on Gavreto use in pregnant women to inform drug-associated risk.

There are no data on the presence of pralsetinib or its metabolites in human milk or their effects on either the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, women should be advised not to breastfeed during treatment with Gavreto and for 1 week after the final dose.

Medically Reviewed on 10/2/2020

References

FDA Prescribing Information

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