tepotinib

Absorption: 72% absorbed following oral administration; absorption ↑ with high-fat, high-calorie meals.

Distribution: Extensively distributed to tissues.

Protein Binding: 98%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 and CYP2C8 isoenzymes. Primarily excreted in feces (85%; 45% as unchanged drug), with 13.6% excreted in urine (7% as unchanged drug).

Half-Life: 32 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	8 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment;
Severe hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema

Derm: pruritus, rash

F and E: hyperkalemia, hyponatremia

GI: ↑amylase, ↑lipase, ↑liver enzymes, abdominal pain, constipation, diarrhea, hypoalbuminemia, nausea, vomiting, HEPATOTOXICITY

GU: ↑serum creatinine

Hemat: anemia, leukopenia, lymphopenia

Metab: ↓appetite

MS: pain

Neuro: fatigue, dizziness, headache

Resp: cough, dyspnea, pleural effusion, pneumonia, INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

May ↑ levels and risk of toxicity of P-glycoprotein substrates, including dabigatran; avoid concurrent use. If concurrent use unavoidable, ↓ dose of P-glycoprotein substrate.

Route/Dosage ⬆ ⬇

PO (Adults ): 450 mg once daily; continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Assess respiratory status and for signs and symptoms of ILD/pneumonitis (dyspnea, cough, fever). If symptoms of ILD/pneumonitis occur, immediately hold therapy. If ILD/pneumonitis diagnosis confirmed, permanently discontinue tepotinib.
Assess for signs and symptoms of pancreatitis (severe stomach pain, back pain, nausea/vomiting). If Grade 3 or 4 pancreatitis occurs, permanently discontinue tepotinib.
Assess for peripheral edema, pruritus, and musculoskeletal pain. If Grade 2 adverse reactions occur, maintain dose level; if adverse reaction is intolerable, hold tepotinib until reaction is resolved; then resume at ↓ dose. If Grade 3 adverse reactions occur, hold tepotinib until reaction is resolved; then resume at ↓ dose. If Grade 4 adverse reactions occur, permanently discontinue tepotinib.

Lab Test Considerations:

Verify a negative pregnancy test before starting therapy.
Monitor MET exon 14 skipping alterations status in tumor specimen or plasma.
Obtain hepatitis B virus screening and management.
Monitor liver function tests (ALT, AST, total bilirubin, alkaline phosphatase) before starting therapy, every 2 wk during 1st 3 mo, and then once monthly or as clinically indicated. If Grade 3 ↑ ALT and/or AST without ↑ total bilirubin, hold tepotinib until recovered to baseline. If recovered to baseline within 7 days, resume therapy at same dose; otherwise, resume at ↓ dose. If Grade 4 ↑ ALT and/or AST without ↑ total bilirubin, permanently discontinue tepotinib. If ↑ ALT and/or AST >3 times upper limit of normal (ULN) with total bilirubin >2 times ULN in the absence of cholestasis or hemolysis, permanently discontinue teptotinib. If Grade 3 ↑ total bilirubin without concurrent ↑ ALT and/or AST, hold tepotinib until recovered to baseline. If recovered within 7 days, resume at ↓ dose; otherwise, permanently discontinue tepotinib. If Grade 4 ↑ total bilirubin without concurrent ↑ ALT and/or AST, permanently discontinue tepotinib.
May ↑ amylase and lipase. If Grade 3 ↑ lipase or amylase, hold tepotinib until Grade ≤2. If recovered within 14 days, resume therapy at ↓ dose; otherwise, permanently discontinue tepotinib. If Grade 4 ↑ lipase or amylase, permanently discontinue tepotinib.
May ↓ lymphocytes, hemoglobin, leukocytes, and platelets.
May ↑ serum creatinine, potassium, and GGT and ↓ sodium.

Implementation ⬆ ⬇

First Dose Reduction: 225 mg once daily. If unable to tolerate 225 mg once daily, permanently discontinue tepotinib.
PO: Administer once daily with food at the same time every day. DNC: Swallow tablets whole. Do not chew, crush, or split tablets.
Tablets may be dispersed in 30 mL of noncarbonated water if patient has trouble swallowing solids. Do not use any other liquid. Stir, without crushing, until tablet is dispersed into small pieces (tablets will not completely dissolve); drink immediately or within 1 hr. Do not chew pieces of the tablet. Rinse the glass with additional 30 mL and drink immediately to ensure no residue remains in glass and full dose is administered.
Nasogastric tube:≥8 French gauge is required. Disperse tablets in 30 mL of noncarbonated water; do not use any other liquid. Stir, without crushing, until tablet is dispersed into small pieces (tablets will not completely dissolve). Administer 30 mL of liquid down the nasogastric tube immediately or within 1 hr. Immediately rinse twice with 30 mL each time to ensure full dose is administered.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to take as directed. Advise not to make up a missed dose within 8 hr of the next scheduled dose. If vomiting occurs, advise to take the next dose at the scheduled time. Emphasize the importance of routine laboratory testing.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications. Advise patient to avoid alcohol and hepatotoxic medications.
Advise patient to notify health care professional if new or worsening respiratory symptoms or signs or symptoms of pancreatitis or hepatotoxicity occur.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Advise patient to use effective contraception during treatment and for 1 wk after last dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇