Alimta® (pemetrexed): Use in Patients With COVID-19 (Coronavirus disease 2019)

Use of Pemetrexed in a Patient With COVID-19

COVID-19 is an infectious respiratory disease caused by SARS-CoV-2, previously referred to as "2019 novel coronavirus."¹

Lilly has not studied the use of pemetrexed in patients with COVID-19.

Clinicians should use their clinical judgment in determining the most appropriate approach in treating a patient with pemetrexed who has confirmed or suspected COVID-19.

Potential Risk and Benefit Considerations

Clinical Use

Treating physicians should assess the patient’s individual benefit/risk ratio considering the patient's signs and symptoms, prior medical history, concomitant medications, and other individual factors when making pemetrexed treatment decisions in the context of COVID-19. Adverse reactions of pemetrexed to be considered in particular, in the context of COVID-19, include

• myelosuppression

• interstitial pneumonitis, and

• increased risk of toxicity with ibuprofen in patients with renal impairment (see below for further information).²

Pemetrexed dose adjustments, made at the physician’s discretion, should follow the label. Supportive treatment should be provided as clinically indicated and patients monitored appropriately.³

Myelosuppression-Related Warnings and Precautions

Pemetrexed can cause severe myelosuppression (as manifested by neutropenia, thrombocytopenia, and anemia or pancytopenia) resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. Patients treated with pemetrexed must be instructed to take folic acid and vitamin B₁₂ with pemetrexed as a prophylactic measure to reduce treatment-related toxicity.²

Interstitial Pneumonitis-Related Warnings and Precautions

Serious interstitial pneumonitis, including fatal cases, can occur with pemetrexed treatment². Treatment should be withheld for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnoea, cough, or fever pending diagnostic evaluation. If pneumonitis is confirmed, pemetrexed should be permanently discontinued.³

Potential Drug-Drug Interaction With Ibuprofen

Ibuprofen decreases the clearance of pemetrexed and increases its exposure (AUC). Patients with mild to moderate renal impairment (CrCl 45-79 mL/min)

• have increased risk of pemetrexed toxicity, and

• should avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of pemetrexed.²

Monitor patients more frequently for myelosuppression, renal, and GI toxicity if concomitant administration of ibuprofen cannot be avoided.²

Aspirin, administered in low to moderate doses (325 mg every 6 hours), does not affect the pharmacokinetics of pemetrexed.³

Additional Consideration From Clinical Trial Experience

Dyspnoea and cough are common adverse reactions (incidence ≥20%) of pemetrexed when administered in combination with pembrolizumab and platinum chemotherapy.³

Infectious Disease Resources for COVID-19

For the most current information regarding COVID-19, please refer to the following resources: 

• Coronavirus disease (COVID-19) outbreak on the regional office of the EU WHO

• COVID-19 on the ECDC web page.

• European Society for Medical Oncology (ESMO)

• Coronavirus (COVID-19) National Institute for Health and Care Excellence (NICE).^4-7

References

1. Naming the coronavirus disease (COVID-19) and the virus that causes it. World Health Organization. Accessed March 17, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it

2. Alimta [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands

3. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

4. Coronavirus disease (COVID-19) outbreak. World Health Organization Europe. Accessed March 20, 2020. http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov

5. COVID-19. European Centre for Disease Prevention and Control. Accessed March 20, 2020. https://www.ecdc.europa.eu/en/novel-coronavirus-china

6. European Society for Medical Oncology. Accessed March 23th. https://www.esmo.org/newsroom/covid-19-and-cancer/covid-19-useful-resources

7. [NICE] National Institute for Health and Care Excellence. Coronavirus (COVID-19). Available from: https://www.nice.org.uk/covid-19. Accessed 25 March 2020.

Glossary

AUC = area under the curve

COVID-19 = coronavirus disease 2019

CrCl = creatinine clearance

ECDC = European Centre for Disease Prevention and Control

ESMO = European Society for Medical Oncology

EU WHO = World Health Organization (European regional office)

GI = gastrointestinal

Lilly = Eli Lilly and Company

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2