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 nonsquamous 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 nonsquamous NSCLC as initial therapy (in combination with cisplatin).
Locally advanced or metastatic nonsquamous NSCLC as maintenance treatment in patients whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy (as monotherapy).
Recurrent metastatic nonsquamous 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:

Decreased growth and spread of mesothelioma.
Improved survival in patients with nonsquamous 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.

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);
3rd 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.
Nephrotoxic agents↑ risk of nephrotoxicity.

Route/Dosage ⬆ ⬇

Nonsquamous 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; 750 mg/vial; 1 g/vial
Solution for injection: 10 mg/mL; 25 mg/mL

Assessment ⬆ ⬇

Monitor for blistering and exfoliative skin toxicity during therapy. If severe skin toxicity occurs, permanently discontinue pemetrexed.
Monitor for signs/symptoms of interstitial pneumonitis (new onset dyspnea, cough, fever). If signs/symptoms of interstitial pneumonitis occur and diagnosis confirmed, permanently discontinue pemetrexed.
Assess for radiation recall (rash, redness, swelling, pain, peeling skin) in patients who received radiation weeks to years before starting pemetrexed therapy. If signs/symptoms of radiation recall occur, permanently discontinue pemetrexed.
Monitor for GI toxicities (mucositis, diarrhea). If Grade 3 or 4 GI toxicities, except mucositis, or diarrhea requiring hospitalization occurs,↓ pemetrexed dose by 75%; delay initiation of next cycle until recovery to Grade ≤2. If Grade 3 or 4 mucositis occurs,↓ pemetrexed dose by 50%; delay initiation of next cycle until recovery to Grade ≤2. If recurrent Grade 3 or 4 GI toxicity occurs after two dose reductions, permanently discontinue pemetrexed.
Monitor for neurologic toxicities. If Grade 3 or 4 neurologic toxicity occurs or after two dose reductions for any non-Grade 3 or 4 toxicity, permanently discontinue pemetrexed.
Monitor for bone marrow suppression. 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 dyspnea and orthostatic hypotension. Granulocyte-colony stimulating factor (G-CSF) may be used if necessary.

Lab Test Considerations:

Verify negative pregnancy test before initiation.
- Assess CCr before each dose and periodically as indicated. If CCr <45 mL/min, hold therapy until CCr recovers to ≥45 mL/min.
- Monitor CBC with differential before each dose and on Days 8 and 15 of each cycle and then as clinically indicated. May cause neutropenia, thrombocytopenia, leukopenia, and anemia. Delay initiation of next cycle until ANC ≥1500 cells/mm³ and platelets ≥100,000 cells/mm³. If ANC <500/mm³ and platelets ≥50,000/mm or platelets <50,000/mm³ without bleeding,↓ pemetrexed dose by 75%. If platelets <50,000/mm³ with bleeding,↓ pemetrexed dose by 50%. If Grade 3 or 4 myelosuppression occurs after two dose reductions, discontinue premetrexed.
- Monitor liver function tests periodically during therapy.

Implementation ⬆ ⬇

Do not confuse pemetrexed with pralatrexate.
Administer 0.4–1 mg of folic acid once daily for 7 days preceding 1st dose of pemetrexed, and continue during therapy and for 21 days after last dose.
Administer vitamin B₁₂ 1 mg IM as a single dose during the week preceding 1st dose and every 3 cycles thereafter. Subsequent doses of vitamin B₁₂ may be given on same day as pemetrexed. Do not substitute with oral vitamin B₁₂.
Administer dexamethasone 4 mg twice daily on the day before, the day of, and the day after administration to ↓ risk of skin toxicity.

IV Administration:

Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication.
Intermittent Infusion: Lyophilized powder for injection: Reconstitution: Calculate number of vials needed for dose; vials contain excess to facilitate delivery. Reconstitute with preservative-free D5W injection; use 4.2 mL for each 100-mg vial or 20 mL for each 500-mg vial. 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 contains particulates. Diluent: Further dilute with D5W for a total volume of 100 mL. May refrigerate reconstituted or diluted solution for up to 24 hr.
- Solution for injection: Determine volume needed for dose; withdraw calculated amount and transfer to empty IV bag. Do not dilute. Discard if solution is discolored or contains particulates. Immediately administer or store in bag at room temperature for up to 24 hr.
Rate: Infuse over 10 min.
Y-Site Compatibility:
- acyclovir
- allopurinol
- amikacin
- aminocaproic acid
- aminophylline
- amiodarone
- amphotericin B liposomal
- ampicillin
- ampicillin/sulbactam
- atracurium
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- carboplatin
- carmustine
- ceftriaxone
- cefuroxime
- cisatracurium
- cisplatin
- clindamycin
- cyclophosphamide
- cyclosporine
- cytarabine
- dactinomycin
- daptomycin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- docetaxel
- dopamine
- doxorubicin liposomal
- enalaprilat
- ephedrine
- epinephrine
- eptifibatide
- ertapenem
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- fluconazole
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hydrocortisone
- hydromorphone
- ifosfamide
- imipenem/cilastatin
- insulin regular
- isoproterenol
- ketorolac
- labetalol
- leucovorin
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- meropenem
- mesna
- methadone
- methylprednisolone
- metoclopramide
- metoprolol
- midazolam
- milrinone
- mitomycin
- morphine
- moxifloxacin
- nafcillin
- naloxone
- nitroglycerin
- norepinephrine
- octreotide
- oxaliplatin
- paclitaxel
- pamidronate
- pentobarbital
- phenobarbital
- phentolamine
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- promethazine
- propranolol
- remifentanil
- rocuronium
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiotepa
- tigecycline
- tirofiban
- trimethoprim/sulfamethoxazole
- vancomycin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- anidulafungin
- calcium chloride
- calcium gluconate
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- chloramphenicol
- chlorpromazine
- ciprofloxacin
- dacarbazine
- dantrolene
- daunorubicin
- diazepam
- dobutamine
- doxorubicin hydrochloride
- doxycycline
- droperidol
- epirubicin
- erythromycin
- gemcitabine
- gentamicin
- hydralazine
- idarubicin
- irinotecan
- metronidazole
- minocycline
- mitoxantrone
- nalbuphine
- nicardipine
- nitroprusside
- ondansetron
- pantoprazole
- pentamidine
- phenytoin
- prochlorperazine
- tobramycin
- topotecan
- vasopressin

Patient/Family Teaching ⬆ ⬇

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

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇