Lucius Version of Axitinib: Dosage and Administration, Indications, Precautions

Lucius Version of Axitinib: Dosage and Administration, Indications, Precautions

Indications

Axitinib is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

Dosage and Administration

The recommended starting dose is 5 mg orally twice daily. Dosage adjustments may be made based on individual safety and tolerability.

May be taken with or without food, with doses administered approximately 12 hours apart.

Axitinib tablets should be swallowed whole; do not split, chew, or crush.

If coadministration with a strong CYP3A4/5 inhibitor is necessary, reduce the Axitinib dose by approximately half.

For patients with moderate hepatic impairment, reduce the starting dose by approximately half.

Use in Specific Populations

1. Pregnancy

Based on animal studies and its mechanism of action, Axitinib (Inlyta) can cause fetal harm when administered to pregnant women. No human data are available to inform the drug-related risk.

In developmental toxicity studies, Axitinib (Inlyta) exhibited teratogenicity, embryotoxicity, and fetotoxicity in animals at exposures below human exposures at the recommended starting dose.

Inform females of reproductive potential of the potential reproductive risks and potential risk to the fetus.

2. Lactation

There are no data on the presence of axitinib in human milk or its effects on breastfed infants or milk production.

Due to the potential for serious adverse reactions in breastfed children, advise lactating women not to breastfeed during treatment with Axitinib (Inlyta) and for 2 weeks after the last dose.

3. Males and Females of Reproductive Potential

Based on animal studies, Axitinib (Inlyta) can cause fetal harm when administered to pregnant women.

When Axitinib (Inlyta) is used in combination with avelumab or pembrolizumab, refer to the full prescribing information for avelumab or pembrolizumab for contraception recommendations.

Verify the pregnancy status of females of reproductive potential prior to initiating Axitinib (Inlyta) treatment.

Advise females of reproductive potential to use effective contraception during treatment with Axitinib (Inlyta) and for 1 week after the last dose.

Based on animal studies, advise male partners of females of reproductive potential to use effective contraception during treatment and for 1 week after the last dose.

Animal studies indicate that Axitinib may impair fertility in females and males of reproductive potential.

4. Pediatric Use

The safety and effectiveness of Axitinib (Inlyta) in pediatric patients have not been established.

5. Geriatric Use

In a controlled clinical study of Axitinib in patients with RCC, 123 out of 359 patients (34%) treated with Axitinib were ≥65 years of age.

No overall differences in safety or effectiveness of Axitinib were observed between patients ≥65 years of age and younger patients, although greater sensitivity in some older individuals cannot be ruled out. No dosage adjustment is required for geriatric patients.

6. Hepatic Impairment

In a dedicated hepatic impairment study, systemic exposure following a single dose of Axitinib was similar in subjects with baseline mild hepatic impairment (Child-Pugh Class A) compared to subjects with normal hepatic function, while systemic exposure was higher in subjects with baseline moderate hepatic impairment (Child-Pugh Class B).

No dosage adjustment is required for patients with mild hepatic impairment (Child-Pugh Class A). For patients with moderate hepatic impairment (Child-Pugh Class B), a reduced starting dose is recommended.

Axitinib has not been studied in subjects with severe hepatic impairment (Child-Pugh Class C).

7. Renal Impairment

No dedicated renal impairment study has been conducted with Axitinib.

Population pharmacokinetic analysis showed no significant difference in Axitinib clearance in patients with pre-existing mild to severe renal impairment (creatinine clearance [CLcr] 15 mL/min ≤ CLcr < 89 mL/min). No dosage adjustment is required for patients with pre-existing mild to severe renal impairment.

Use with caution in patients with end-stage renal disease (CLcr < 15 mL/min).

Warnings and Precautions

Hypertension: Hypertension, including hypertensive crisis, has been observed. Control blood pressure prior to initiating Axitinib. Monitor blood pressure and treat as needed. Reduce Axitinib dose in patients with persistent hypertension despite use of antihypertensive medications.

Thromboembolic Events: Arterial and venous thromboembolic events, which can be fatal, have been observed. Use with caution in patients at increased risk for these events.

Bleeding Events: Bleeding events, including fatal events, have been reported. Axitinib has not been studied in patients with brain metastases or recent active gastrointestinal bleeding, and there is insufficient evidence to support its use in these patients; therefore, do not use in these patients.

Gastrointestinal Perforation and Fistulae: Gastrointestinal perforation and fistulae, including fatal events, have occurred. Use with caution in patients at risk for gastrointestinal perforation or fistulae.

Hypothyroidism: Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function prior to initiating treatment and periodically throughout treatment.

Surgery: Discontinue Axitinib at least 24 hours prior to scheduled surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS has been observed. Permanently discontinue Axitinib if signs or symptoms of RPLS occur.

Proteinuria: Monitor for proteinuria prior to initiating treatment and periodically throughout treatment. Reduce dose or temporarily interrupt Axitinib for moderate to severe proteinuria.

Elevated Liver Enzymes: Elevations in liver enzymes have been observed during treatment with Axitinib. Monitor ALT, AST, and bilirubin prior to initiating treatment and periodically throughout treatment.

Hepatic Impairment: A reduced starting dose is recommended for patients with moderate hepatic impairment. Axitinib has not been studied in patients with severe hepatic impairment.

Fetal Risk: Based on its mechanism of action, Axitinib may cause fetal harm when administered to pregnant women. Inform females of reproductive potential of the potential risk to the fetus and advise against pregnancy.

Drug Interactions

1. CYP3A4/5 Inhibitors

Coadministration with ketoconazole (a strong CYP3A4/5 inhibitor) increased Axitinib plasma exposure in healthy volunteers.

Avoid coadministration of Axitinib with strong CYP3A4/5 inhibitors. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided.

Select concomitant medications with no or minimal CYP3A4/5 inhibitory potential. If coadministration with a strong CYP3A4/5 inhibitor is unavoidable, reduce the dose of Axitinib (Inlyta).

2. CYP3A4/5 Inducers

Coadministration with rifampin (a strong CYP3A4/5 inducer) decreased Axitinib plasma exposure in healthy volunteers.

Avoid coadministration of Axitinib with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, St. John's Wort). Select concomitant medications with no or minimal CYP3A4/5 inductive potential.

Moderate CYP3A4/5 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) may also decrease Axitinib plasma exposure and should be avoided if possible.

Overdosage

There is no specific treatment for Axitinib overdosage.

In a controlled clinical study of Axitinib in patients with RCC, one patient inadvertently received 20 mg twice daily for 4 days and experienced dizziness (Grade 1).

In clinical dose-finding studies of Axitinib, adverse reactions including hypertension, hypertension-related seizures, and fatal hemoptysis occurred in subjects who received starting doses of 10 mg twice daily or 20 mg twice daily.

In case of suspected overdosage, discontinue Axitinib and initiate supportive care.

Adverse Reactions

The most common adverse reactions (≥20%) are: diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight loss, vomiting, asthenia, and constipation.

Contraindications

None specified.

Composition

Active Ingredient

axitinib.

Inactive Ingredients

Microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, Opadry II Red 32K15441.

Opadry II Red 32K15441 film coating contains: lactose monohydrate, HPMC 2910/hypromellose 15cP, titanium dioxide, triacetin (glyceryl triacetate), and red iron oxide.

Dosage Form

Tablets.

Storage Conditions

Store Axitinib at room temperature between 20°C and 25°C (68°F and 77°F).

Excursions are permitted between 15°C and 30°C (59°F and 86°F) for short-term transport.

Keep Axitinib and all medications out of the reach of children.