pemetrexed

pemetrexed

Alimta

Pharmacologic class: Folic acid antagonist

Therapeutic class: Antineoplastic, antimetabolite

Pregnancy risk category D

Action

Disrupts folate-dependent metabolic processes essential for cell replication

Availability

Powder for injection: 500 mg sterile lyophilized powder in single-use vials

Indications and dosages

➣ Malignant pleural mesothelioma in patients whose disease is unresectable or who otherwise aren't eligible for curative surgery (given with cisplatin)

Adults: 500 mg/m² as an I.V. infusion over 10 minutes on day 1 of each 21-day cycle. The recommended dose of cisplatin is 75 mg/m² infused over 2 hours starting approximately 30 minutes after pemetrexed administration ends.

➣ Nonsquamous non-small-cell lung cancer

Adults: 500 mg/m² I.V. infusion over 10 minutes on day 1 of each 21-day cycle for single-agent use, or in combination with cisplatin infused over 2 hours starting approximately 30 minutes after pemetrexed administration ends

Dosage adjustment

• Hematologic toxicities, based on nadir absolute neutrophil and platelet counts

• Grade 2 to 4 neurotoxicity

• Grade 3 or higher nonhematologic toxicities (except neurotoxicity)

• Grade 3 or 4 diarrhea or any diarrhea requiring hospitalization

• Creatinine clearance below 45 ml/minute

Contraindications

• Severe hypersensitivity reaction to drug or its components

Precautions

Use cautiously in:

• hepatic or renal impairment, neurotoxicity

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Reconstitute 500-mg vial with 20 ml preservative-free normal saline solution injection, yielding 25 mg/ml. Gently swirl vial until powder dissolves completely.

• Further dilute appropriate volume of reconstituted solution to 100 ml with preservative-free normal saline solution injection; administer I.V. over 10 minutes.

• Know that drug is physically incompatible with diluents containing calcium, including Ringer's and lactated Ringer's solutions. Administration with other drugs and diluents isn't recommended.

• Administer I.V. only.

• As ordered, pretreat with dexamethasone (or equivalent) 4 mg P.O. twice daily on day before, day of, and day after pemetrexed administration to minimize cutaneous reactions.

• When administering with cisplatin, hydrate patient with 1 to 2 L fluid infused over 8 to 12 hours before and after cisplatin administration. Maintain adequate hydration and urine output for 24 hours.

• To reduce toxicity, ensure that patient receives at least five daily doses of low-dose folic acid or multivitamin with folic acid within 7 days before first pemetrexed dose. Folic acid therapy should continue throughout course of therapy and for 21 days after final dose. Patient also must receive one I.M. injection of vitamin B₁₂ during week before first pemetrexed dose and every three cycles thereafter.

• Discontinue drug if creatinine clearance is below 45 ml/minute or patient has hematologic or nonhematologic Grade 3 or 4 toxicity after two dosage reductions (except Grade 3 transaminase elevation).

• Withdraw drug immediately in patients with Grade 3 or 4 neurotoxicity.

Adverse reactions

CNS: fatigue, sensory neuropathy, altered mood, depression

CV: thrombosis, embolism

EENT: pharyngitis

GI: nausea, vomiting, constipation, diarrhea without colostomy, dysphagia, esophagitis, pain on swallowing, stomatitis, anorexia

GU: renal failure

Hematologic: neutropenia, leukopenia, anemia, thrombocytopenia, febrile neutropenia

Hepatic: abnormal liver function

Musculoskeletal: myalgia, arthralgia

Respiratory: dyspnea

Skin: rash, desquamation, alopecia

Other: fever, dehydration, noncardiac chest pain, infection without neutropenia or with Grade 3 or Grade 4 neutropenia, edema, other constitutional symptoms, allergic reaction, hypersensitivity reaction

Interactions

Drug-drug. Ibuprofen: decreased pemetrexed clearance and increased concentration

Nephrotoxic agents: possible decrease in pemetrexed clearance

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, serum creatinine: increased

Creatinine clearance, hematocrit, hemoglobin, platelets, WBCs: decreased

Patient monitoring

• Monitor CBC and platelet counts frequently.

• Monitor renal and liver function tests and blood chemistry results (especially serum creatinine) periodically.

• Know that patients with mild to moderate renal insufficiency should avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs) with short elimination half-lives (such as aspirin, diclofenac, and ibuprofen) for 5 days before, on day of, and for 2 days after pemetrexed administration. If concomitant NSAID use is necessary, monitor patient closely for toxicities (especially myelosuppression and renal and GI toxicity).

• Be aware that all patients should avoid NSAIDs with long half-lives (such as diflunisal, piroxicam, and sulindac) for at least 5 days before, on day of, and for 2 days after pemetrexed administration. If concomitant NSAID use is necessary, monitor patient closely for toxicities (especially myelosuppression and renal and GI toxicity).

Patient teaching

• Instruct patient to take folic acid and vitamin B₁₂ before and during therapy, as prescribed.

• Advise patient to drink ten 8-oz glasses of fluid and to urinate frequently during first 24 hours after therapy that includes cisplatin.

• Teach patient to recognize signs and symptoms of anemia and to contact prescriber if temperature above 100.4 °F (38 °C) develops.

• Tell patient to consult prescriber before taking products containing ibuprofen.

• Advise female with childbearing potential to avoid pregnancy during therapy.

• Instruct breastfeeding patient to stop breastfeeding during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved