VITRAKVI Oral solution Ref.[10645] Active ingredients: Larotrectinib

Treatment with VITRAKVI should be initiated by physicians experienced in the administration of anticancer therapies.

The presence of an NTRK gene fusion in a tumour specimen should be confirmed by a validated test prior to initiation of treatment with VITRAKVI.

Posology

Adults

The recommended dose in adults is 100 mg larotrectinib twice daily, until disease progression or until unacceptable toxicity occurs.

Paediatric population

Dosing in paediatric patients is based on body surface area (BSA). The recommended dose in paediatric patients is 100 mg/m² larotrectinib twice daily with a maximum of 100 mg per dose until disease progression or until unacceptable toxicity occurs.

Missed dose

If a dose is missed, the patient should not take two doses at the same time to make up for a missed dose. Patients should take the next dose at the next scheduled time. If the patient vomits after taking a dose, the patient should not take an additional dose to make up for vomiting.

Dose modification

For all Grade 2 adverse reactions, continued dosing may be appropriate, though close monitoring to ensure no worsening of the toxicity is advised. Patients with Grade 2 ALT and/or AST increases, should be followed with serial laboratory evaluations every one to two weeks after the observation of Grade 2 toxicity until resolved to establish whether a dose interruption or reduction is required.

For Grade 3 or 4 adverse reactions:

• VITRAKVI should be withheld until the adverse reaction resolves or improves to baseline or Grade 1. Resume at the next dose modification if resolution occurs within 4 weeks.
• VITRAKVI should be permanently discontinued if an adverse reaction does not resolve within 4 weeks.

The recommended dose modifications for VITRAKVI for adverse reactions are provided in Table 1.

Table 1. Recommended dose modifications for VITRAKVI for adverse reactions:

^a Paediatric patients on 25 mg/m² twice daily should remain on this dose even if body surface area becomes greater 1.0 m² during the treatment. Maximum dose should be 25 mg twice daily at the third dose modification.

VITRAKVI should be permanently discontinued in patients who are unable to tolerate VITRAKVI after three dose modifications.

Special populations

Elderly

No dose adjustment is recommended in elderly patients (see section 5.2).

Hepatic impairment

The starting dose of VITRAKVI should be reduced by 50% in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A) (see section 5.2).

Renal impairment

No dose adjustment is required for patients with renal impairment (see section 5.2).

Co-administration with strong CYP3A4 inhibitors

If co-administration with a strong CYP3A4 inhibitor is necessary, the VITRAKVI dose should be reduced by 50%. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, VITRAKVI should be resumed at the dose taken prior to initiating the CYP3A4 inhibitor (see section 4.5).

Method of administration

VITRAKVI is for oral use.

VITRAKVI is available as a capsule or oral solution with equivalent oral bioavailability and may be used interchangeably.

The oral solution should be administered by mouth using an oral syringe of 1 mL or 5 mL volume or enterally by using a nasogastric feeding tube.

• For doses below 1 mL a 1 mL oral syringe should be used. The calculated dose volume should be rounded to the nearest 0.1 mL.
• For doses of 1 mL and higher a 5 mL oral syringe should be used. The dose volume should be calculated to the nearest 0.2 mL.
• VITRAKVI should not be mixed with feeding formulas, if administered via nasogastric feeding tube. Mixing with the feeding formulas could lead to tube blockages.
• For instructions for use of oral syringes and feeding tubes see section 6.6.

The oral solution can be taken with or without food but should not be taken with grapefruit or grapefruit juice.

There is limited experience of overdose with VITRAKVI. Symptoms of overdose are not established. In the event of overdose, physicians should follow general supportive measures and treat symptomatically.

2 years.

After first opening: 30 days.

Store in a refrigerator (2°C-8°C).

Store in a refrigerator (2°C-8°C).

Do not freeze.

For storage conditions after first opening of the medicinal product, see section 6.3.

Amber glass (type III) bottle with a child-resistant polypropylene (PP) cap with a polyethylene (PE) seal liner.

Each carton contains one bottle of 100 mL oral solution.

Instructions for use

Oral syringe:

• Use a suitable oral syringe with CE marking and bottle adapter (28 mm diameter) if applicable.
  • For volumes less than 1 mL use a 1 mL oral syringe with 0.1 mL graduation.
  • For volumes of 1 mL and higher use a 5 mL oral syringe with 0.2 mL graduation.
• Open the bottle: press the bottle cap and turn it counter clockwise.
• Insert the bottle adapter into the bottle neck and ensure it is well fixed.
• Take the oral syringe and ensure that the plunger is fully depressed. Put the oral syringe in the adapter opening. Turn the bottle upside down.
• Fill the oral syringe with small amount of solution by pulling the plunger down, then push the plunger upwards to remove any bubbles.
• Pull the plunger down to the graduation mark equal to the quantity in mL as prescribed.
• Turn the bottle the right way up and remove the oral syringe from the bottle adapter.
• Slowly depress the plunger, directing the liquid towards the inside cheek to allow for natural swallowing.
• Close the bottle with the original bottle cap (leaving the adapter in place).

Nasogastric feeding tube:

• Use a suitable nasogastric feeding tube. The outer diameter of the nasogastric feeding tube should be selected based on the patient characteristics. Typical tube diameter, tube lengths and derived prime volumes are presented in Table 7.
• The feeding should be stopped and the tube flushed with at least 10 mL water. NOTE: See exceptions regarding neonates and patients with fluid restrictions in the sub-point directly below.
• A suitable syringe should be used to administer VITRAKVI to the nasogastric feeding tube. The tube should be flushed again with at least 10 mL water to ensure VITRAKVI is delivered and to clear the tube. Neonates and children with fluid restrictions may require minimal flushing volume of 0.5 to 1 mL or flushing with air to deliver VITRAKVI.
• Restart the feeding

Table 7. Recommended tube dimensions per age group:

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.