Covid 19 Remdesivir & Tocilizumab Injection

REMDESIVIR

Remdesivir is an intravenous nucleotide prodrug of an adenosine analog. Remdesivir binds to the viral RNA-dependent RNA polymerase and inhibits viral replication through premature termination of RNA transcription. It has demonstrated in vitro activity against SARS-CoV-2. In a rhesus macaque model of SARS-CoV-2 infection, remdesivir treatment was initiated soon after inoculation; the remdesivir-treated animals had lower virus levels in the lungs and less lung damage than the control animals.

Remdesivir is approved by the Food and Drug Administration (FDA) for the treatment of COVID-19 in hospitalized adult and pediatric patients (aged ≥12 years and weighing ≥40 kg). It is also available through an FDA Emergency Use Authorization (EUA) for the treatment of COVID-19 in hospitalized pediatric patients weighing 3.5 kg to <40 kg or aged <12 years and weighing ≥3.5 kg. Remdesivir should be administered in a hospital or a health care setting that can provide a similar level of care to an inpatient hospital.

Remdesivir has been studied in several clinical trials for the treatment of COVID-19. The recommendations from the COVID-19 Treatment Guidelines Panel (the Panel) are based on the results of these studies.

The safety and efficacy of combination therapy of remdesivir with corticosteroids have not been rigorously studied in clinical trials; however, there are theoretical reasons that combination therapy may be beneficial in some patients with severe COVID-19. For the Panel’s recommendations on using remdesivir with or without dexamethasone in certain hospitalized patients, see Therapeutic Management of Patients with COVID-19.

Monitoring and Adverse Effects

Remdesivir can cause gastrointestinal symptoms (e.g., nausea), elevated transaminase levels, an increase in prothrombin time (without a change in the international normalized ratio), and hypersensitivity reactions.

Liver function tests and prothrombin time should be obtained in all patients before remdesivir is administered and during treatment as clinically indicated. Remdesivir may need to be discontinued if alanine transaminase (ALT) levels increase to >10 times the upper limit of normal and should be discontinued if an increase in ALT level and signs or symptoms of liver inflammation are observed.3

Considerations in Patients With Renal Insufficiency

Each 100 mg vial of remdesivir lyophilized powder contains 3 g of sulfobutylether beta-cyclodextrin sodium (SBECD), whereas each 100 mg/20 mL vial of remdesivir solution contains 6 g of SBECD. SBECD is a vehicle that is primarily eliminated through the kidneys. A patient with COVID-19 who receives a loading dose of remdesivir 200 mg would receive 6 g to 12 g of SBECD, depending on the formulation. This amount of SBECD is within the safety threshold for patients with normal renal function.4 Accumulation of SBECD in patients with renal impairment may result in liver and renal toxicities. Clinicians may consider preferentially using the lyophilized powder formulation (which contains less SBECD) in patients with renal impairment.

Because both remdesivir formulations contain SBECD, patients with an estimated glomerular filtration rate (eGFR) of <50 mL/min were excluded from some clinical trials of remdesivir; other trials had an eGFR cutoff of <30 mL/min. Remdesivir is not recommended for patients with an eGFR <30 mL/min due to lack of data. Renal function should be monitored before and during remdesivir treatment as clinically indicated.3

In two observational studies that evaluated the use of remdesivir in hospitalized patients with COVID-19, no significant differences were reported in the incidences of adverse effects or acute kidney injury between patients with an estimated creatinine clearance (CrCl) <30 mL/min and those with an estimated CrCl ≥30 mL/min. One of these studies evaluated patients who primarily received the solution formulation of remdesivir (20 patients had an estimated CrCl <30 mL/min and 115 had an estimated CrCl ≥30 mL/min); the other study evaluated patients who received the lyophilized powder formulation (40 patients had an estimated CrCl <30 mL/min and 307 had an estimated CrCl ≥30 mL/min).

Drug-Drug Interactions

Clinical drug-drug interaction studies of remdesivir have not been conducted. In vitro, remdesivir is a substrate of cytochrome P450 (CYP) 3A4 and of the drug transporters organic anion-transporting polypeptide (OATP) 1B1 and P-glycoprotein. It is also an inhibitor of CYP3A4, OATP1B1, OATP1B3, and multidrug and toxin extrusion protein 1 (MATE1).3

Minimal to no reduction in remdesivir exposure is expected when remdesivir is coadministered with dexamethasone, according to information provided by Gilead Sciences (written communication, July 2020). Chloroquine or hydroxychloroquine may decrease the antiviral activity of remdesivir; coadministration of these drugs is not recommended. Remdesivir is not expected to have any significant interactions with oseltamivir or baloxavir, according to information provided by Gilead Sciences (written communications, August and September 2020).

Considerations in Pregnancy

  • Pregnant patients were excluded from the clinical trials that evaluated the safety and efficacy of remdesivir for the treatment of COVID-19, but preliminary reports of remdesivir use in pregnant patients from the remdesivir compassionate use program are reassuring.
  • Among 86 pregnant and postpartum hospitalized patients with severe COVID-19 who received compassionate use remdesivir, the therapy was well tolerated, with a low rate of serious adverse events.
  • Remdesivir should not be withheld from pregnant patients if it is otherwise indicated.

Considerations in Children

  • The safety and effectiveness of using remdesivir to treat COVID-19 have not been evaluated in pediatric patients aged <12 years or weighing <40 kg.
  • Remdesivir is available through an FDA EUA for the treatment of COVID-19 in hospitalized pediatric patients weighing 3.5 kg to <40 kg or aged <12 years and weighing ≥3.5 kg.
  • A clinical trial is currently evaluating the pharmacokinetics of remdesivir in children

Clinical Trials

Several clinical trials that are evaluating the use of remdesivir for the treatment of COVID-19 are currently underway or in development. Please see ClinicalTrials.gov for the latest information.

The above information has been taken from the www.covid19treatmentguidelines.nih.gov An official website of the National Institutes of Health

TOCILIZUMAB INJECTION

Using tocilizumab injection may decrease your ability to fight infection from bacteria, viruses, and fungi and increase the risk that you will get a serious or life-threatening infection that may spread through the body. Tell your doctor if you often get any type of infection or if you have or think you may have any type of infection now. This includes minor infections (such as open cuts or sores), infections that come and go (such as cold sores), and ongoing infections that do not go away. Also tell your doctor if you have or have ever had diabetes, human immunodeficiency virus (HIV), or any condition that affects your immune system, and if you live, have ever lived, or traveled to areas such as the Ohio and Mississippi River valleys and the Southwest where severe fungal infections are more common. Ask your doctor if you do not know if these infections are common in your area. Also tell your doctor if you are taking: abatacept (Orencia); adalimumab (Humira); anakinra (Kineret); certolizumab (Cimzia); etanercept (Enbrel); golimumab (Simponi); infliximab (Remicade); medications that suppress the immune system such as azathioprine (Azasan, Imuran), cyclosporine (Gengraf, Neoral, Sandimmune), methotrexate (Otrexup, Trexall, others), sirolimus (Rapamune), and tacrolimus (Prograf); oral steroids such as dexamethasone, methylprednisolone, and prednisone (Rayos); or rituximab (Rituxan). If you experience any of the following symptoms, call your doctor immediately: fever; chills; sweating; difficulty breathing; sore throat; cough; weight loss; diarrhea; stomach pain; blood in phlegm; extreme tiredness; muscle aches; warm, red, or painful skin; sores on the skin or in the mouth; burning when you urinate; frequent urination; or other signs of infection.

You may be infected with tuberculosis (TB; a type of lung infection) or hepatitis B (a type of liver disease) but not have any symptoms of the disease. In this case, tocilizumab injection may increase the risk that your infection will become more serious and you will develop symptoms. Your doctor will perform a skin test to see if you have an inactive TB infection and may order blood tests to see if you have an inactive hepatitis B infection. If necessary, your doctor will give you medication to treat this infection before you start using tocilizumab injection. Tell your doctor if you have or have ever had TB or hepatitis B, if you have visited any country where TB is common, or if you have been around someone who has TB. If you have any of the following symptoms of TB, or if you develop any of these symptoms during your treatment, call your doctor immediately: cough, chest pain, coughing up blood or mucus, weakness or tiredness, weight loss, loss of appetite, chills, fever, or night sweats. Also call your doctor immediately if you have any of these symptoms of hepatitis B or if you develop any of these symptoms during or after your treatment: excessive tiredness, yellowing of the skin or eyes, loss of appetite, nausea, vomiting, muscle aches, dark urine, clay-colored bowel movements, fever, chills, stomach pain, or rash.

Keep all appointments with your doctor and the laboratory. Your doctor will monitor your health carefully to be sure you do not develop a serious infection. Your doctor will order certain lab tests before and during your treatment to check your body’s response to tocilizumab injection.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with tocilizumab injection and each time you receive the medication. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer’s website to obtain the Medication Guide.

Talk to your doctor about the risks of using tocilizumab injection.

Why is this medication prescribed?

Tocilizumab injection is used alone or in combination with other medications to relieve the symptoms of certain types of arthritis and other conditions including:

  • rheumatoid arthritis (a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) in people who have not been helped by other disease-modifying antirheumatic drugs (DMARDs),
  • giant cell arteritis (a condition that causes swelling of blood vessels, especially in the scalp and head),
  • polyarticular juvenile idiopathic arthritis (PJIA; a type of childhood arthritis that affects five or more joints during the first six months of the condition, causing pain, swelling, and loss of function) in children 2 years of age or older.
  • systemic juvenile idiopathic arthritis (SJIA; a condition in children that causes inflammation in different areas of the body, causing fever, joint pain and swelling, loss of function, and delays in growth and development) in children 2 years of age or older,
  • cytokine release syndrome (a severe and possibly life-threatening reaction) that occurs in adults and children 2 years of age or older after receiving certain immunotherapy infusions.

Tocilizumab injection is in a class of medications called interleukin-6 (IL-6) receptor inhibitors. It works by blocking the activity of interleukin-6, a substance in the body that causes inflammation.

How should this medicine be used?

Tocilizumab injection comes as a solution (liquid) to be injected intravenously (into a vein) in your arm by a doctor or nurse in a medical office or hospital outpatient clinic or as a prefilled syringe to inject subcutaneously (under the skin) by yourself at home. When tocilizumab is given intravenously to treat rheumatoid arthritis or polyarticular juvenile idiopathic arthritis, it is usually given once every 4 weeks. When tocilizumab is given intravenously to treat systemic juvenile idiopathic arthritis, it is usually given once every 1 or 2 weeks. When tocilizumab is given intravenously to treat cytokine release syndrome, it is usually given once, but up to 3 additional doses may be given at least 8 hours apart. It will take about 1 hour for you to receive your dose of tocilizumab injection intravenously. When tocilizumab is given subcutaneously to treat rheumatoid arthritis or giant cell arteritis, it is usually given once weekly or once every other week.

You will receive your first subcutaneous dose of tocilizumab injection in your doctor’s office. If you will be injecting tocilizumab injection subcutaneously by yourself at home or having a friend or relative inject the medication for you, your doctor will show you or the person who will be injecting the medication how to inject it. You and the person who will be injecting the medication should also read the written instructions for use that come with the medication.

Thirty minutes before you are ready to inject tocilizumab injection, you will need to remove the medication from the refrigerator, take it out of its carton, and allow it to reach room temperature. When removing a prefilled syringe from the box, be careful not to touch the trigger fingers on the syringe. Do not try to warm the medication by heating it in a microwave, placing it in warm water, or through any other method.

Do not remove the cap from the prefilled syringe while the medication is warming. You should remove the cap no more than 5 minutes before you inject the medication. Do not replace the cap after you remove it. Do not use the syringe if you drop it on the floor.

Check the prefilled syringe to be sure that the expiration date printed on the package has not passed, Holding the syringe with the covered needle pointing down, look closely at the liquid in the syringe. The liquid should be clear or pale yellow and should not be cloudy or discolored or contain lumps or particles. Call your pharmacist if there are any problems with the package or the syringe and do not inject the medication.

You may inject tocilizumab injection on the front of the thighs or anywhere on your stomach except your navel (belly button) and the area 2 inches around it. If another person is injecting your medication, the outer area of the upper arms also may be used. Do not inject the medication into skin that is tender, bruised, red, hard, or not intact, or that has scars, moles, or bruises. Choose a different spot each time you inject the medication, at least 1 inch away from a spot that you have used before. If the full dose is not injected, call your doctor or pharmacist.

Do not reuse tocilizumab prefilled syringes and do not recap the syringes after use. Discard any used syringes in a puncture-resistant container and ask your pharmacist how to throw away the container.

Tocilizumab injection may help control your symptoms, but it will not cure your condition. Your doctor will watch you carefully to see how well tocilizumab injection works for you. Your doctor may adjust your dose or delay your treatment if you have certain changes in your laboratory results. It is important to tell your doctor how you are feeling during your treatment.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before receiving tocilizumab injection,

  • tell your doctor and pharmacist if you are allergic to tocilizumab, any other medications, or any of the ingredients in tocilizumab injection. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin, Jantoven); aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin, others) and naproxen (Aleve, Naprosyn, others); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor, in Caduet), lovastatin (Altoprev, in Advicor), and simvastatin (Zocor, in Vytorin); oral contraceptives (birth control pills); or theophylline (Elixophyllin, Theo-24, others). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with tocilizumab injection, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
  • tell your doctor if you have or have ever had cancer; diverticulitis (small pouches in the lining of the large intestine that can become inflamed); ulcers in your stomach or intestines; high cholesterol and triglycerides; any condition that affects the nervous system such as multiple sclerosis (MS; a disease in which the nerves do not function properly and people may experience weakness, numbness, loss of muscle coordination and problems with vision, speech, and bladder control) or chronic inflammatory demyelinating polyneuropathy (CIDP; a disorder of the immune and nervous systems); or liver disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while receiving tocilizumab injection, call your doctor.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are receiving tocilizumab injection.
  • ask your doctor whether you should receive any vaccinations before you begin your treatment with tocilizumab injection. If possible, all vaccinations for children should be brought up to date before beginning treatment. Do not have any vaccinations during your treatment without talking to your doctor.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do if I forget a dose?

If you miss an appointment to receive a tocilizumab infusion, call your doctor.

If you forget to inject a subcutaneous dose of tocilizumab, inject the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not inject a double dose to make up for a missed one. Call your doctor or pharmacist if you do not know when to inject tocilizumab injection.

What side effects can this medication cause?

Tocilizumab injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • headache
  • runny nose or sneezing
  • redness, itching, pain, or swelling in the place where tocilizumab was injected

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

  • rash
  • flushing
  • hives
  • itching
  • swelling of the eyes, face, lips, tongue, throat, arms, hands, feet, ankles, or lower legs
  • difficulty breathing or swallowing
  • chest pain
  • dizziness or fainting
  • fever, ongoing stomach-area pain, or change in bowel habits
  • yellow eyes or skin; right upper abdominal pain; unexplained bruising or bleeding; loss of appetite; confusion; yellow or brown-colored urine; or pale stools

Tocilizumab may increase the risk of developing certain types of cancer. Talk to your doctor about the risks of receiving this medication.

Tocilizumab injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What should I know about storage and disposal of this medication?

Keep this medication in the package it came in, away from light, tightly closed, and out of reach of children. Store tocilizumab injection in the refrigerator, but do not freeze it. Keep the prefilled syringes dry. Discard any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of emergency/overdose

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

What other information should I know?

Ask your pharmacist any questions you have about tocilizumab injection.

Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

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