Adverse effects of 4 drugs approved in 2021

By Naveed Saleh, MD, MS
Published January 11, 2022

Key Takeaways

In the US, AEs cause between 3% and 7% of all hospitalizations, according to the Merck Manual. Moreover, between 10% and 20% of hospitalizations are marked by adverse drug reactions, 10% to 20% of which are severe. These statistics don’t reflect adverse drug reactions that occur in outpatient settings and nursing homes.

Unfortunately, with new drugs comes the potential for new AEs.

Efgartigimod (Vyvgart)

The FDA approved efgartigimod on Dec. 17, 2021. The drug is indicated for the treatment of myasthenia gravis in patients who are positive for the anti-acetylcholine receptor (AChR) antibody.

Efgartigimod belongs to a new class of drugs and is an antibody fragment that binds neonatal Fc receptor (FcRn). In this way, it stops FcRn from recycling immunoglobulin G into circulation. It decreases levels of the abnormal AChR and other IgG antibodies. Of note, abnormal AChR antibodies are present in myasthenia gravis.

In a 26-week randomized controlled trial, 167 patients received efgartigimod or placebo. During initial treatment, patients with myasthenia gravis who harbored AChR antibodies were more likely to respond compared with controls (68% compared with 30%, respectively). These patients also exhibited improvements in muscle weakness compared with controls.

The most common AEs included respiratory/urinary tract infections and headache. These effects stem from how the agent affects antibody levels, with a decrease in antibodies increasing susceptibility to infection. Other adverse effects included eyelid swelling, rash, and shortness of breath. 

In cases of hypersensitivity or infection, the infusion should be ceased, and appropriate therapy instituted. 

Pafolacianine (Cytalux)

Pafolacianine, approved on Nov. 29, 2021, is an imaging agent that helps surgeons isolate ovarian cancer lesions. Typically, these tumors are difficult to identify during surgery. Pafolacianine is given in intravenous form before surgery. 

Prior to FDA approval, this agent had previously received orphan-drug, priority, and fast track designations.

This drug works by binding to folate receptors, which are excessively transcribed in ovarian cancer. After binding, the conjugate glows under fluorescent light, helping the surgeon isolate the cancerous tissue. Status quo intervention involves preoperative imaging or identification under normal light or by palpation.

In a randomized trial involving 134 women, pafolacianine picked up at least one lesion not observed by standard visual/touch inspection in 26.9% of patients. 

The most prevalent AEs were infusion-related, and included nausea, vomiting, abdominal pain, and itching. This drug may also be a teratogen, and the use of folate or folic acid should be avoided within 48 hours of the administration. Of note, there’s a possibility of false-positive and false-negative results when using the agent during surgery.

Maribavir (Livtencity)

Maribavir, approved on Nov. 23, 2021, is the first drug to treat adults and children with post-transplant cytomegalovirus (CMV) infection that is unresponsive to current antiviral treatments. It blocks replication of CMV via human cytomegalovirus enzyme pUL97.

CMV is a type of herpes virus that commonly infects patients after a stem cell or organ transplant. CMV infection can lead to CMV disease, which can cause loss of the transplanted organ and death. 

A phase 3 trial supported the efficacy of maribavir. The primary endpoint was plasma CMV DNA levels at the end of 8 weeks of treatment. Of 235 patients receiving the experimental agent, 56% had concentrations of CMV DNA at unmeasurable values compared with 24% of the 117 participants treated with other antivirals.

AEs included taste disturbances, nausea, vomiting, diarrhea, and more. Drug-drug interactions with the antivirals ganciclovir and valganciclovir are possible, negating coadministration. Resistance to the agent should be monitored in those not responding to treatment or those who relapse.

Before FDA approval, this drug received breakthrough therapy and priority review designations.

Ropeginterferon alfa-2b (Besremi)

The biologic ropeginterferon alfa-2b is an injectable indicated for adults with polycythemia vera. Approved on Nov. 12, 2021, ropeginterferon alfa-2b is the first drug that patients take despite a previous history of treatments, as the first interferon developed to treat polycythemia vera.

Because polycythemia vera involves the overproduction of red blood cells, which can then form clots, treatment often involves phlebotomies and agents that decrease blood cell counts. Ropeginterferon alfa-2b is initially taken subcutaneously every 2 weeks for 1 year, and then taken once every 4 weeks. It is hypothesized to decrease red blood cell counts by binding to specific receptors in the body and triggering chain reactions that decrease blood cell production in bone marrow. 

In a single-arm trial involving 51 adults, participants received this agent for an average duration of 5 years. Therapy resulted in complete hematologic response, which was a red blood cell volume of fewer than 45% without phlebotomy, in 61% of participants. Additionally, normal hematologic response was defined as white cell counts and platelet counts within normal limits, a normal spleen size, and no blood clots. 

AEs include elevated liver enzymes, decreased white blood cell counts/platelets, joint pain, and upper airway infection, as well as depression, transient-ischemic attacks (TIAs), urinary tract infections, and depression.

Of note, interferon alfa products can lead to potentially lethal complications, including ischemia, autoimmune disorders, neuropsychiatric conditions, and infections. Patients with a history of severe psychiatric disorders should not take the drug. Those who are pregnant or allergic should also avoid the drug.

Share with emailShare to FacebookShare to LinkedInShare to Twitter