pemetrexed

High Alert

Malignant pleural mesothelioma as initial therapy when tumor is unresectable or patient is not a candidate for surgery (in combination with cisplatin).
Metastatic non-squamous non–small-cell lung cancer (NSCLC) as initial therapy in patients without epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations (in combination with platinum-based therapy and pembrolizumab).
Locally advanced or metastatic non-squamous NSCLC as initial therapy (in combination with cisplatin).
Locally advanced or metastatic non-squamous NSCLC as maintenance treatment in patients whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy (as monotherapy).
Recurrent, metastatic non-squamous NSCLC after previous chemotherapy (as monotherapy).

Action ⬆ ⬇

Disrupts folate dependent metabolic processes involved in thymidine and purine synthesis. Converted intracellularly to polyglutamate form which increases duration of action.

Therapeutic effects:

Decreases growth and spread of mesothelioma.
Improved survival in patients with non-squamous NSCLC.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Minimal metabolism; 70–90% excreted unchanged in urine.

Half-Life: 3.5 hr (normal renal function).

Time/Action Profile ⬆ ⬇

(hematologic effects)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	8–15 days	21 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
CCr <45 mL/min;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Concurrent use of NSAIDs in patients with CCr 45–79 mL/min (avoid those with short half-lives);
Third space fluid accumulation (ascites, pleural effusions); consider drainage prior to therapy;
Hepatic impairment (dose alteration recommended);
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: chest pain

Derm: desquamation, rash, radiation recall, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

GI: constipation, nausea, stomatitis, vomiting, anorexia, diarrhea, esophagitis, mouth pain

GU: ↓fertility (men)

Hemat: anemia, hemolytic anemia, leukopenia, thrombocytopenia

Neuro: neuropathy

Resp: pharyngitis, INTERSTITIAL PNEUMONITIS

Misc: fever, infection

Interactions ⬆ ⬇

Drug-drug:

NSAIDs, especially those with short half-lives, ↑ levels and risk of toxicity; avoid for 2 days before, day of, and 2 days after treatment. Probenecid↑ levels.
Concurrent use of nephrotoxic agents↑ risk of nephrotoxicity.

Route/Dosage ⬆ ⬇

Non-Squamous Non–Small-Cell Lung Cancer

IV (Adults ): Initial therapy (with cisplatin): 500 mg/m² on Day 1 of each 21-day cycle for up to 6 cycles (administer before cisplatin); Initial therapy (with platinum-based therapy and pembrolizumab): 500 mg/m² on Day 1 of each 21-day cycle for 4 cycles (administer before carboplatin or cisplatin and after pembrolizumab). Following completion of platinum-based therapy, pemetrexed may be administered as monotherapy or with pembrolizumab as maintenance therapy until disease progression or unacceptable toxicity; Maintenance treatment (as monotherapy) or disease recurrence (as monotherapy): 500 mg/m² on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Mesothelioma

IV (Adults ): 500 mg/m² on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 100 mg/vial; 500 mg/vial; 1 g/vial
Solution for injection: 10 mg/mL; 25 mg/mL

Assessment ⬆ ⬇

Monitor for rash during therapy. Pretreatment with dexamethasone 4 mg orally twice daily the day before, the day of, and the day after administration reduces incidence and severity or reaction.
Monitor for hematologic and GI toxicities (mucositis, diarrhea). If any Grade 3 or 4 toxicities, except mucositis or diarrhea, requiring hospitalization occur, decrease doses of pemetrexed and cisplatin by 75%. If Grade 3 or 4 mucositis occurs, decrease pemetrexed dose by 50% and cisplatin by 100% of previous dose.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur; monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Assess for neurotoxicity during therapy. If Grade 0–1 neurotoxicity occurs, decrease pemetrexed and cisplatin doses by 100% of previous dose. If Grade 2 neurotoxicity occurs, decrease pemetrexed dose by 100% and cisplatin dose by 50% of previous dose. If Grade 3 or 4 neurotoxicity occurs, discontinue therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC and platelet counts for nadir and recovery and renal function, before each dose and on days 8 and 15 of each cycle and chemistry for renal and liver functions periodically. May cause neutropenia, thrombocytopenia, leukopenia, and anemia. A new cycle should not be started unless the ANC is ≥1500 cells/mm³, platelet count is ≥100,000 cells/mm³, and CCr is ≥45 mL/min. If nadir of ANC is <500/mm³ and nadir of platelets are ≥50,000/mm³,↓ doses of pemetrexed and cisplatin by 75%. If nadir of platelets is <50,000/mm³ regardless of ANC nadir,↓ pemetrexed and cisplatin doses by 50%.

Implementation ⬆ ⬇

Do not confuse pemetrexed with pralatrexate.
Pemetrexed should be administered under supervision of a physician experienced in the use of chemotherapeutic agents.
- To reduce toxicity, 0.4–1 mg of folic acid must be taken daily for 7 days preceding 1st dose of pemetrexed and should continue during and for 21 days after last dose. Patients must also receive an injection of vitamin B₁₂ 1 mg IM during the wk preceding 1st dose of pemetrexed and every 3 cycles thereafter. Subsequent doses of vitamin B₁₂ may be given on same day as pemetrexed. Also administer dexamethasone 4 mg twice daily the day before, the day of, and the day after pemetrexed administration.

IV Administration:

Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers.
Intermittent Infusion: Reconstitution: Calculate number of pemetrexed 500-mg vials needed; vials contain excess to facilitate delivery. Reconstitute 500 mg with 20 mL of preservative-free 0.9% NaCl.Concentration: 25 mg/mL. Swirl gently until powder is completely dissolved. Solution is clear and colorless to yellow or green-yellow. Do not administer if discolored or containing particulate matter. Diluent: Dilute further to 100 mL with preservative-free 0.9% NaCl. Solution is stable at room temperature or if refrigerated for up to 24 hr.
Rate: Infuse over 10 min.

Patient/Family Teaching ⬆ ⬇

Explain purpose of pemetrexed to patient.
Emphasize the importance of taking prophylactic folic acid and vitamin B₁₂ to reduce treatment-related hematologic and GI toxicity.
Advise patient to notify health care professional immediately if signs and symptoms of infection (fever, sore throat), anemia, or neurotoxicity occur.
Instruct patients to notify health care professional if persistent vomiting, diarrhea, or signs of dehydration appear.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially NSAIDs, and to avoid alcohol during therapy.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 6 mo after last dose of pemetrexed and to avoid breastfeeding during and for at least 1 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for at least 3 mo after last dose. If pregnancy is planned or suspected, notify health care professional promptly. May impair fertility in males.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇