Actemra is the brand name of the drug called Tocilizumab. It is available worldwide including in Pakistan by the only brand name - ACTEMRA. It is a human monoclonal antibody that antagonizes the effects of Interleukin-6.

Interleukin 6 (IL-6) plays an important role in the activation of the inflammatory cascade. Although interest in its use has recently increased owing to the cytokine release storm associated with COVID-19 infection, it has been used previously for other conditions as well.

Complete Drug Information is available here - Actemra (Tocilizumab)

Approved uses of Actemra (Tocilizumab) include:

• Giant cell arteritis
• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Systemic onset juvenile idiopathic arthritis
• Cytokine release syndrome
• Cytokine storm in COVID-19 infections

Important Side effects of Actemra (Tocilizumab):

It is contraindicated in patients who are allergic to tocilizumab or any component of the formulation and in patients with active infections.

Blood Toxicity:

It can cause blood toxicity manifesting as low platelet counts and neutrophil counts. Treatment should not be uninitiated if the platelet counts are less than 100,000/ul and the ANC (Absolute neutrophil count) is less than 2000/ul.

Liver Toxicity:

Actemra is hepatotoxic and severe drug-induced liver injury can occur that may be life-threatening and require liver transplantation.

Actemra treatment must not be initiated if the baseline liver functions (AST and ALT) are elevated by more than 1.5 times the upper limits of normal.

When the treatment is initiated, the liver functions should be monitored frequently. Asymptomatic patients who have elevated liver enzymes by more than five times the upper limits of normal during the treatment should discontinue the treatment.

Symptomatic patients with liver enzymes elevated by greater than three times the upper limits of normal should discontinue the treatment.

Infections:

Since Actemra (Tocilizumab) is an immune modulator, its use can result in serious infections including serious bacterial, viral, and fungal infections.

Notably, patients may develop pneumonia, urinary tract infections, and septicemia.

It can cause the reactivation of shingles (herpes zoster). The reactivation of latent tuberculosis is another serious side effect.

All patients must be screened for latent tuberculosis and treated accordingly. The risks and benefits of therapy should be specially assessed in patients who have been having recurrent infections, are immune-compromised, and are predisposed to infections.

Hyperlipidemia:

It can also cause abnormalities in lipid levels. Patients may notice a rise in the total cholesterol, LDL, triglyceride levels, and/or HDL levels.

Frequent monitoring is recommended in those with underlying dyslipidemia.

Demyelinating diseases:

The use of Actemra has been associated with demyelinating diseases such as multiple sclerosis, chronic inflammatory demyelinating disease, and Guillain Barre syndromes.

GI perforation:

Bowel perforation has been observed in patients on Actemra (Tocilizumab) injections. Any patient on Actemra therapy who develops abdominal pain should be evaluated for bowel perforation.

How to administer Actemra (Tocilizumab):

It may be administered as an intravenous slow infusion or a subQ injection depending on the indications.

Intravenous administration of Actemra:

It is administered as a slow intravenous infusion over one hour via a separate intravenous line after dilution in a 100 ml Normal Saline.

A rapid intravenous bolus administration should be avoided

The second dose (if required as in patients with cytokine storm) should be administered at an interval of a minimum of eight hours.

It should not be administered with other drugs. Opaque solutions should be discarded and not administered intravenously.

SubQ administration of Actemra:

The subQ injection can be administered after allowing the injection at room temperature for 30 - 45 minutes. It should not be administered if the solution is opaque.

Administration into scars, moles and inflamed areas should be avoided.

How to switch from Intravenous Actemra to SubQ injections?

The first SubQ dose should be administered at the next scheduled intravenous dose.

What is the recommended dose of Actemra in cytokine release storm in patients with COVID-19 infection (Coronavirus infection):

A single dose of Actemra intravenously is recommended. In patients with persistent hypotension and cytopenias, two additional doses may be administered at an interval of eight hours between doses. In younger and lean patients, the following weight-based protocol may be followed:

• • Patients weighing less than 30 kgs:

    • 12 mg/kg

  • Patients weighing more than 30 kgs:

    • 8 mg/kg

  • The maximum dose is 800 mg per dose

Actemra in Pakistan:

Actemra is available in Pakistan in 80 mg, 200 mg, and 400 mg injections. It can be purchased directly from the company.

It is marketed by Roche Pharmaceuticals and the drug is provided only after a valid prescription to seriously ill patients especially those who are in the ICU and on ventilatory support.

Patients can directly call on this number 03041111085 for any inquiry regarding drug availability and cost.

Actemra injection cost in Pakistan:

Because of the drug hoarding practices, the cost and availability of the drug is a major issues in Pakistan. As per the DRAP (Drug Regulatory Authority of Pakistan), the following maximum Retail prices have been approved:

• Actemra 80 mg/4 ml injection costs Rs. 11,952 per vial
• Actemra 200 mg/10 ml injection costs Rs. 29,882 per vial
• Actemra 400 mg/20 ml injection costs Rs. 59,764 per vial.

Actemra in Pakistan - Common Myths:

People get really scared when the doctors ask them to arrange the injection of Actemra. It is believed to be poisonous and that it kills people.

In the local language, people call it "Zehr wala Injection". To some extent, this belief is due to the deaths that occurred in patients who received the injection.

However, it should be understood that Injection Actemra is only advised to those patients who have failed to respond to other treatments and are extremely sick. These patients are already on their deathbeds and Actemra may be the only hope.

Having said that, I am not a strong advocate of Actemra (Tocilizumab) injection in our setup for the following reasons:

• It is associated with serious bacterial, viral, and fungal infections and since our patients die of secondary infections, it could be devastating in such cases.
• Since Tocilizumab (Actemra) causes immune modulation, it may result in the proliferation of the COVID-19 virus as well. No recommendations are available regarding its use in COVID-19 PCR-positive patients.
• Another serious issue is the reactivation of latent Tuberculosis. Since Tuberculosis is endemic in our setup, we have to be very cautious when using the drug.
• Furthermore, all the COVID-19 patients are also receiving glucocorticoids and that could further make the host susceptible to serious infections.
• Lastly, it is too costly. The total treatment may vary from Rs.60,000 to Rs. 180,000.

Complete Drug Information is available here - Actemra (Tocilizumab)