trifluridine/tipiracil (Rx)

Brand and Other Names:Lonsurf
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

trifluridine/tipiracil

tablet

  • 15mg/6.14mg
  • 20mg/8.19mg

Metastatic Colorectal Cancer

Indicated for patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy (if RAS wild-type)

Dose is based on trifluridine component rounded to the nearest 5-mg increment

35 mg/m² PO BID on Days 1-5 and Days 8-12 of each 28-day cycle; not to exceed 80 mg/dose

Continue until disease progression or unacceptable toxicity

Metastatic Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Indicated for patients previously treated with ≥2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy

Dose is based on trifluridine component rounded to the nearest 5-mg increment

35 mg/m² PO BID on Days 1-5 and Days 8-12 of each 28-day cycle; not to exceed 80 mg/dose

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Obtain CBC counts prior to and on Day 15 of each cycle

Do not initiate the cycle until

  • ANC ≥1500/mm³ or febrile neutropenia is resolved
  • Platelets ≥75,000/mm³
  • Grade 3 or 4 nonhematological adverse reactions are resolved to Grade ≤1

Within a treatment cycle, withhold for any of the following

  • ANC <500/mm³ or febrile neutropenia
  • Platelets <50,000/mm³
  • Grade 3 or 4 nonhematological adverse reactions

Resume drug after reducing dose by 5 mg/m²/dose from the previous dose level

  • Febrile neutropenia
  • Uncomplicated grade 4 neutropenia (which has recovered to ≥1500/mm³) or thrombocytopenia (which has recovered to ≥75,000/mm³) that results >1 week delay in start of next cycle
  • Nonhematologic grade 3 or 4 adverse reaction, except for grade 3 nausea and/or vomiting controlled by antiemetic therapy or grade 3 diarrhea responsive to antidiarrheal medication
  • A maximum of 3 dose reductions are permitted to a minimum dose 20mg/m² BID
  • Do not escalate dose after it has been reduced

Hepatic impairment

  • Mild (total bilirubin [TB] ≤ULN and AST >ULN, or TB <1-1.5x ULN and any AST): No dosage adjustment required
  • Moderate-to-severe: Not studied

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment required; however, patients with moderate impairment (30-59 mL/min) may require dose modification for increased toxicity
  • Severe (CrCl <30 mL/min): Not studied

Safety and efficacy not established

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Adverse Effects

>10% (Metastatic Colorectal Cancer)

Anemia (77%)

Neutropenia (67%)

Asthenia/fatigue (52%)

Nausea (48%)

Thrombocytopenia (42%)

Decreased appetite (39%)

Neutropenia, Grade 3 or 4 (38%)

Diarrhea (32%)

Vomiting (28%)

Infections (27%)

Pyrexia (19%)

Anemia, Grade 3 or 4 (18%)

>10% (Metastatic Gastric Cancer)

Neutropenia (66%)

Anemia (63%)

Neutropenia, Grade 3 or 4 (38%)

Nausea (37%)

Decreased appetite (34%)

Thrombocytopenia (34%)

Vomiting (25%)

Diarrhea (23%)

Infections (23%)

Anemia, Grade 3 or 4 (19%)

1-10% (Metastatic Colorectal Cancer)

Stomatitis (8%)

Asthenia/fatigue, Grade 3 or 4 (7%)

Dysgeusia (7%)

Alopecia (7%)

Infections, Grade 3 or 4 (6%)

Thrombocytopenia, Grade 3 or 4 (5%)

Decreased appetite, Grade 3 or 4 (4%)

Diarrhea, Grade 3 or 4 (3%)

Nausea, Grade 3 or 4 (2%)

Vomiting, Grade 3 or 4 (2%)

Pyrexia, Grade 3 or 4 (1%)

1-10% (Metastatic Gastric Cancer)

Decreased appetite, Grade 3 or 4 (9%)

Thrombocytopenia, Grade 3 or 4 (6%)

Infections, Grade 3 or 4 (5%)

Vomiting, Grade 3 or 4 (4%)

Nausea, Grade 3 or 4 (3%)

Diarrhea, Grade 3 or 4 (3%)

<1%

Interstitial lung disease

Metastatic colorectal cancer

  • Stomatitis, Grade 3 or 4
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Warnings

Contraindications

None

Cautions

Severe and life-threatening myelosuppression reported, including anemia, neutropenia, thrombocytopenia, and febrile neutropenia; obtain CBC count prior to and on Day 15 of each cycle, or more frequently as indicated

Stomatitis may occur

Associated with a moderate emetic potential; antiemetics to prevent nausea and vomiting recommended; patient should report severe gastrointestinal toxicity to healthcare professional

Grade 3 or 4 bilirubin elevations reported in patients with hepatic impairment

Based on animal studies and its mechanism of action, trifluridine/tipiracil can cause fetal harm when administered to pregnant women (see Pregnancy)

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Pregnancy

Pregnancy

Based on animal data and its mechanism of action, drug can cause fetal harm

Embryo-fetal lethality and embryo-fetal toxicity occurred in pregnant rats when given during gestation at doses resulting in exposures lower than or similar to human exposures at the recommended clinical dose

There are no available data use in pregnant women

Verify pregnancy status in females of reproductive potential before initiating treatment

Contraception

  • Females of reproductive potential: Use effective contraception during treatment and for ≥6 months after final dose
  • Males with female partners of reproductive potential: Use condoms during treatment and for ≥ 3 months after final dose

Lactation

There are no data on the presence of trifluridine, tipiracil or its metabolites in human milk or its effects on the breastfed child or on milk production

In nursing rats, trifluridine and tipiracil or their metabolites were present in breast milk

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 day following the final dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Trifluridine: Thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation

Tipiracil: Thymidine phosphorylase inhibitor; inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase

Absorption

Peak plasma time (trifluridine): 2 hr

Food effect

  • A standardized high-fat, high-calorie meal decreased trifluridine peak plasma concentration, tipiracil peak plasma concentration and AUC by ~40%, but did not change trifluridine AUC compared to those in a fasting state in patients with cancer following single-dose administration

Distribution

Protein bound: >96% trifluridine (independent of drug concentration and presence of tipiracil); <8% tipiracil

Metabolism

Trifluridine and tipiracil are not metabolized by cytochrome P450 (CYP) enzymes

Trifluridine is mainly eliminated by metabolism via thymidine phosphorylase to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY)

Elimination

Half-life (steady-state): 2.1 hr trifluridine; 2.4 hr tipiracil

Urinary excretion: 1.5% unchanged trifluridine; 19.2% FTY; 29.3% unchanged tipiracil

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Administration

Oral Administration

Dose is based on trifluridine component rounded to nearest 5-mg increment

Administer with food; swallow whole

Do not take additional doses to make up for missed or held doses

Cytotoxic drug; follow applicable special handling and disposal procedures

Storage

Store at controlled room temperature 20-25°C (68-77°F); excursions are permitted from 15-30°C (59-86°F)

If stored outside of original bottle, discard after 30 days

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.