Alimta Special Precautions

Pemetrexed can suppress bone marrow function as manifested by neutropenia, thrombocytopenia and anaemia (or pancytopenia) (see Adverse Reactions). Myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy and pemetrexed should not be given to patients until absolute neutrophil count (ANC) returns to ≥1,500 cells/mm³ and platelet count returns to ≥100,000 cells/mm³. Dose reductions for subsequent cycles are based on nadir ANC, platelet count and maximum non-haematologic toxicity seen from the previous cycle (see Dosage & Administration).
Less toxicity and reduction in Grade 3/4 haematologic and non-haematologic toxicities eg, neutropenia, febrile neutropenia and infection with Grade 3/4 neutropenia were reported when pre-treatment with folic acid and vitamin B₁₂ was administered. Therefore all patients treated with pemetrexed must be instructed to take folic acid and vitamin B₁₂ as a prophylactic measure to reduce treatment-related toxicity (see Dosage & Administration).
Skin reactions have been reported in patients not pre-treated with a corticosteroid. Pre-treatment with dexamethasone (or equivalent) can reduce the incidence and severity of skin reactions (see Dosage & Administration).
An insufficient number of patients has been studied with CrCl of <45 mL/min. Therefore, the use of pemetrexed in patients with CrCl of <45 mL/min is not recommended (see Dosage & Administration).
Patients with mild to moderate renal insufficiency (CrCl 45-79 mL/min) should avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs) eg, ibuprofen, aspirin (>1.3 g daily) for 2 days before, on the day of and 2 days following pemetrexed administration (see Interactions).
In patients with mild to moderate renal insufficiency eligible for pemetrexed therapy NSAIDs with long elimination t_½ should be interrupted for at least 5 days prior to, on the day of, and at least 2 days following pemetrexed administration (see Interactions).
Serious renal events, including acute renal failure, have been reported with pemetrexed alone or in association with other chemotherapeutic agents. Many of the patients in whom these occurred had underlying risk factors for the development of renal events including dehydration or preexisting hypertension or diabetes.
The effect of third space fluid, eg pleural effusion or ascites, on pemetrexed is not fully defined. A phase 2 study of pemetrexed in 31 solid tumour patients with stable 3rd space fluid demonstrated no difference in pemetrexed dose normalized plasma concentrations or clearance compared to patients without 3rd space fluid collections. Thus, drainage of 3rd space fluid collection prior to pemetrexed treatment should be considered, but may not be necessary.
Due to the gastrointestinal toxicity of pemetrexed given in combination with cisplatin, severe dehydration has been observed. Therefore, patients should receive adequate antiemetic treatment and appropriate hydration prior to and/or after receiving treatment.
Serious cardiovascular events, including myocardial infarction and cerebrovascular events have been uncommonly reported during clinical studies with pemetrexed, usually when given in combination with another cytotoxic agent. Most of the patients in whom these events have been observed had preexisting cardiovascular risk factors (see Adverse Reactions).
Immunodepressed status is common in cancer patients. As a result, concomitant use of live attenuated vaccines is not recommended (see Contraindications and Interactions).
Cases of radiation pneumonitis have been reported in patients treated with radiation either prior, during or subsequent to their pemetrexed therapy. Particular attention should be paid to these patients and caution exercised with use of other radiosensitising agents.
Cases of radiation recall have been reported in patients who received radiotherapy weeks or years previously.
Effects on the Ability to Drive or Operate Machinery: No studies on the effects on the ability to drive and use machines have been performed. However, it has been reported that pemetrexed may cause fatigue. Therefore, patients should be cautioned against driving or operating machines if this event occurs.
Impairment of Fertility: Pemetrexed can have genetically damaging effects. Sexually mature males are advised not to father a child during the treatment and up to 6 months thereafter. Contraceptive measures or abstinence are recommended. Owing to the possibility of pemetrexed treatment causing irreversible infertility, men are advised to seek counseling on sperm storage before starting treatment.
Use in pregnancy: There are no data from the use of pemetrexed in pregnant women but pemetrexed, like other anti-metabolites, is suspected to cause serious birth defects when administered during pregnancy. Animal studies have shown reproductive toxicity (see Pharmacology: Toxicology under Actions). Pemetrexed should not be used during pregnancy unless clearly necessary, after a careful consideration of the needs of the mother and the risk for the foetus.
Contraception in Males and Females: Women of childbearing potential must use effective contraception during treatment with pemetrexed. Pemetrexed can have genetically damaging effects. Sexually mature males are advised not to father a child during the treatment and up to 6 months thereafter. Contraceptive measures or abstinence are recommended.
Use in children and adolescents: Alimta is not recommended for use in children <18 years due to insufficient data on safety and efficacy.