pemetrexed

pemetrexed,

an antineoplastic-antimetabolite.

indications This drug is used in combination with cisplatin in the treatment of malignant pleural mesothelioma and as a single agent in the treatment of non-small cell lung cancer.

contraindications Pregnancy, an absolute neutrophil count less than 1500 cells/mm³, a creatinine clearance count of less than 45 mL/min, thrombocytopenia (less than 100,000/mm³), anemia, and known hypersensitivity to this drug prohibit its use.

adverse effects Adverse effects of this drug include creatinine elevation. Life-threatening effects include thrombosis and embolism, renal failure, neutropenia, leukopenia, thrombocytopenia, myelosuppression, anemia, and infection with or without neutropenia. Common side effects include fatigue, fever, mood alteration, neuropathy, chest pain, nausea, vomiting, anorexia, diarrhea, ulcerative stomatitis, constipation, dysphagia, dehydration, rash, desquamation, and dyspnea.

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pemetrexed Warning - High-alert drug!

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 I.V. infusion over 10 minutes on day 1 of each 21-day cycle (given in combination with cisplatin infused over 2 hours starting approximately 30 minutes after pemetrexed administration ends)

➣ Non-small-cell lung cancer

Adults: 500 mg/m² I.V. infusion over 10 minutes on day 1 of each 21-day cycle

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.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

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 100.4ºF (38ºC) 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.