Drug Safety Alerts

After reports of brain swelling (encephalitis and meningoencephalitis), the makers of Zinbryta^®(daclizumab) have decided to withdraw it from the market.¹

If you are taking Zinbryta, please call your program nurse.

Zinbryta was approved by the FDA (US Food and Drug Administration) in 2016 as an option for adults with relapsing multiple sclerosis. The drug carried a boxed warning about the risks of liver damage.

Zinbryta can still be used while its makers, Biogen Inc. and AbbVie, are working with the FDA on a withdrawal date. If you are taking Zinbryta, work with your doctor to explore other treatment options. CVS Health is also reaching out to doctors who have patients taking Zinbryta.

Reference

¹ Biogen and AbbVie announce the voluntary worldwide withdrawal of marketing authorizations for Zinbryta^® (daclizumab) for relapsing multiple sclerosis. BusinessWire website www.businesswire.com. Accessed March 2, 2018.

The FDA (US Food and Drug Association) has sent out a warning for people who use Varubi (rolapitant) to treat CINV (chemotherapy-induced nausea and vomiting). Varubi may cause a severe allergic reaction. Look for signs of:

• Wheezing or a hard time breathing
• Swelling of the face or throat
• Hives or redness on skin
• Itching
• Abdomen cramping or pain
• Throwing up
• Back or chest pain
• Low blood pressure
• Shock (cold skin, rapid pulse, dizzy, etc.)

Background:

Varubi is used in adults who are on chemotherapy and using other drugs to control CINV. Doctors and patients should watch for signs of a reaction during and after giving Varubi. Check for allergies to Varubi's ingredients, like soybean oil or legumes. Do not give Varubi to patients who may have a reaction. Allergic reactions can be treated.

If the patient has an allergic reaction:

• Stop Varubi infusion
• Treat the reaction (epinephrine or other antihistamine)
• Do not use Varubi again

How to report side effects:

Use the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

• Submit a report online at: www.fda.gov/MedWatch/report
• Download the report form or call 1-800-332-1088 to request one by mail. Fill out and return to the address on the form. Or, fax it to 1-800-332-0178.

Reference

1. Varubi (rolapitant) Injectable Emulsion: Health Care Provider Letter - Anaphylaxis and Other Serious Hypersensitivity Reactions. www.fda.gov. January 16, 2018. Accessed January 16, 2018.

The FDA (US Food and Drug Administration) approved hydroxyurea (Siklos^®) for use in children with SCD (sickle cell disease) on December 21, 2017. Hydroxyurea can help lower the number of pain crises and blood transfusions in children ages 2 and older.¹

Taking Hydroxyurea (Siklos):

This drug comes in 100 mg and 1,000 mg tablets. The dose is based on the child's weight and blood counts.² The tablet is taken once a day with a glass of water or small amount of food. For children who can't swallow the tablets, mix the tablet in a small amount of water in a teaspoon.

Read more about how to handle hydroxyurea in the Instructions for Use.³

References

1. Sickle cell anemia drug gains FDA approval. Specialty Pharmacy Times website. December 21, 2017. www.specialtypharmacytimes.com. Accessed December 21, 2017.
2. Siklos [package insert]. Medunik USA; December 2017.
3. FDA approves hydroxyurea for treatment of pediatric patients with sickle cell anemia. Prescribing Guide. www.fda.gov. Accessed January 11, 2018.

The FDA (US Federal Drug Administration) has approved Soliris for adults who have generalized myasthenia gravis. Soliris is only used with patients who have not been able to control symptoms with standard therapy. This drug is used to slow or stop the immune system from making muscles weak.¹

Soliris is offered through a limited program. Only your doctor can enroll you in this program.

Risk for Infection

If you take Soliris, your doctor will watch you for a certain type of infection called meningococcal(muh-ning-go-ka-kul) disease. This is sometimes called meningitis (men-nin-ji-tis). Meningitis needs early treatment so it isn't fatal. If you have any signs of infection, call your doctor right away. Look for²:

• Fever
• Stiff neck
• Headache
• Nausea or vomiting
• Bothered by bright light
• Confusion

Your doctor may need to give you a meningococcal vaccine at least two weeks before you start treatment. But, your doctor may decide that you need to start taking Soliris sooner.³ Talk with your doctor about when you can start treatment.

Using Soliris

Soliris is a weekly IV infusion. Your dose will increase slowly over a few weeks. Tell your doctor right away if you have any bone or muscle pain.

References

1. FDA approves Soliris® (eculizumab) for the treatment of patients with generalized myasthenia gravis (gMG). Press release. Alexion website. October 23, 2017. http://www.alexion.com/. Accessed October 30, 2017.
2. Meningococcal Disease: Signs and Symptoms. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/symptoms.html. Accessed November 3, 2017.
3. Soliris [package insert]. New Haven, CT: Alexion Pharmaceuticals, Inc.; October 2017.

The FDA (US Federal Drug Administration) has approved Gocovri™ the first drug to treat dyskinesia (dis-ken-ee-shuh) in patients with Parkinson's disease. Dyskinesias are stiff, jerky, movements often from the treatment used for Parkinson's disease.

Patients may be using levodopa (lev-oh-dow-puh) with or without other drugs that raise dopamine (dow-puh-meen) levels in the brain.¹ It may not help with symptoms that are being managed with amantadine (uh-man-tuh-deen).¹

Take Gocovri once a day, at bedtime, with or without food.² It can be taken by mouth or sprinkled on soft food.

Talk with your doctor if you have:

• Hallucinations
• Dizziness
• Dry mouth
• Swelling in your feet or legs
• Constipation (hard stools)
• Falls
• Feeling dizzy or faint when you stand up from sitting or lying down

References

1. FDA approves extended-release amantadine (Gocovri) for treatment of dyskinesia. 2017/08/25. Parkinson's Disease Foundation website. www.pdf.org. Accessed 2017/09/27.
2. Gocovri [package insert]. Emeryville, CA: Adamas Pharma, LLC; August 2017.

The FDA (US Food and Drug Administration) has approved the first generic version of Copaxone^® (glatiramer acetate) 40 mg/mL. This version is used three times a week.¹ Copaxone 20 mg/mL is used once a day and was already approved by the FDA.

Copaxone is used to treat relapsing forms of MS (multiple sclerosis).² It is a single, pre-filled shot. Patients should watch for reactions at the injection site.

The generic version of Copaxone may cost less. Check with your doctor to see if this drug is right for you.

References

1. Mylan announces U.S. FDA approval of first generic for Copaxone^® 40 mg/mL 3-times-a-week and may be eligible for 180-day exclusivity. PR Newswire website. www.prnewswire.com. Accessed 2017/10/4.
2. Copaxone [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; August 2016.

The FDA (US Food and Drug Administration) has approved new uses for two drugs in children with partial-onset (focal) seizures¹.

• Children who are 16 and older can now take brivaracetam (Briviact^®, UCB Inc) by itself.
• Children who are 4 and older can now take eslicarbazepine acetate (Aptiom^®, Sunovion).

About these drugs:

Brivaracetam¹

Brivaracetam was used as an add-on drug. Now, it can now be used by itself and works just as well. This gives patients and their doctors another treatment option. Brivaracetam can be taken by mouth (tablet or liquid) or as a shot.

Eslicarbazepine¹

Eslicarbazepine was used in adults with partial-onset seizures. Now it can be used in children who are ages 4-17. Eslicarbazepine is taken once a day, whole or crushed, with or without food.

The FDA studied data on this drug to support the use of it in children.

Reference

1. Brooks M. FDA grants new indication for two antiepileptic drugs. 2017/09/15. Medscape website. www.medscape.com. Accessed 2017/09/15.

A small number of cyclobenzaprine HCl tablets may be mislabeled as amantadine HCl 100 mg. This recall is for Lot # 16710:

• Cyclobenzaprine HCl 5mg, 50-count unit dose
• Amantadine HCl 100mg, 50-count unit dose

Check the label on your medicine bottles. You may also ask your pharmacy about this recall and they can check your medicine.

About these drugs:

Do not stop taking amantadine suddenly. This may cause Parkinson's crisis (increase in the signs or symptoms of Parkinson's disease).

Taking cyclobenzaprine by accident can cause problems if you also use:

• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin norepinephrine reuptake inhibitors (SNRIs)
• Tricyclic antidepressants (TCAs)
• Tramadol
• Bupropion
• Meperidine
• Verapamil
• MAO inhibitors

Cyclobenzaprine can also cause problems if you drink alcohol or take drugs that affect your nervous system (like barbiturates or sleep aids). It can be unsafe to drive or use machinery.

To learn more about this recall, call 1-931-292-6222 or visit www.fda.gov.

1. Apace Packaging LLC Issues Voluntary Nationwide Recall of Cyclobenzaprine HCL and Amantadine HCL (Lot 16710) Due to Potential Mislabeling. US Food and Drug Administration. https://www.fda.gov. Accessed 2017/08/02.

The FDA (US Food and Drug Administration) has approved a new form of belimumab (Benlysta^®). Benlysta is injected through a short needle under the skin. The drug treats adults with lupus (systemic lupus erythematosus) who are on standard therapy. The FDA approved belimumab for IV therapy in 2011.

Patients can now choose to self-treat at home instead of going to the hospital or treatment center. If Benlysta is right for you, your doctor can show you how to inject the drug. This is a single dose, and it is taken once a week. You can use a prefilled syringe or an autoinjector. This form of belimumab is just as safe as the IV form.

Only 6.1% of patients had injection site reactions during clinical trials.¹ As with any injection site reactions, know when to talk to your doctor. Watch for:

• Pain, redness, or swelling that lasts more than 3 days
• Swelling, bruising, or bleeding that does not go away
• Burning or itching

GlaxoSmithKline, the maker of belimumab, says the drug will be ready in late August. To learn more, visit www.gsksource.com.

References

1. FDA Clears Self-injectable Belimumab (Benlysta) for SLE. Medscape.com Website. http://www.medscape.com/. Accessed 2017/7/21.

The FDA (U.S. Food and Drug Administration) has approved L-glutamine oral powder (Endari^®) for patients age five years and older with sickle cell disease. Endari can help reduce pain episodes in sickle cell disease. It will be ready for patients toward the end of 2017.

Dosage:

The Endari oral dose is 5 grams to 15 grams, and taken twice a day based on body weight.

While taking Endari, watch for:

• Constipation (hard stools)
• Stomach pain
• Nausea
• Headache
• Cough
• Pain in the hands and feet
• Back and chest pain

If you notice any of these symptoms, talk to your doctor right away.

Background

Endari was studied in patients ages 5 to 58 years old with sickle cell disease. Patients had two or more pain crises within the 12 months before they joined in the study.

Two groups of patients were studied: one group took Endari and the other group took a placebo (a pill without any drug in it). Through the Phase 3 study, about 66% of the patients also took hydroxyurea. Both groups of patients, those on hydroxyurea and those who weren't, were helped by L-glutamine.¹

Endari was studied over 48 weeks. Patients taking Endari had fewer hospital visits for sickle cell crisis (severe pain) and overnight stays. Patients taking Endari also had fewer events of acute chest syndrome (when sickle cell disease keeps the lungs from getting enough oxygen).²

References

1. Niihara Y, Viswanathan K, Miller S. 1318 Phase 3 Study of L-Glutamine Therapy in Sickle Cell Anemia and Sickle ß0-Thalassemia Subgroup Analyses Show Consistent Clinical Improvement. American Society of Hematology 58th Annual Meeting and Exposition; 2016/12/3; San Diego, CA.
2. FDA approves new treatment for sickle cell disease. FDA Website. https://www.fda.gov/. Accessed 2017/7/10.

There is a GlaxoSmithKline recall alert for 3 lots of Ventolin^® HFA 200D inhalers. This recall is only for U.S. hospitals, drug stores, and distributers.

The recall is due to complaints of the package leaking. The inhaler may give fewer doses than shown on the dose counter. For some people, this may cause breathing problems.

You should not return or throw away your inhaler at this time. Check the lot number on your inhaler package. This recall is only for a small lot of inhalers. You can still get your refills at your local drug store.

For questions, call GlaxoSmithKline toll-free at 1-888-825-5249.

The lot numbers are:

• 6ZP0003
• 6ZP9944
• 6ZP9848

References

1. GlaxoSmithKline Recalling Ventolin Inhalers for Possible Package Leakage. Asthma and Allergy Foundation of America Website. https://community.aafa.org. Accessed 2017/4/9.

The FDA (US Food and Drug Administration) has approved a new version of raltegravir (Isentress^® HD). This is a 1200-mg once -daily dose of raltegravir. The previous raltegravir required twice a day dosing.

Raltegravir is used with other antiretroviral drugs for the treatment of HIV-1 in adults and children. To use once-daily Isentress HD, patients must:

• Weigh at least 40 kg (88 pounds)
• Have never been treated for HIV before
• Have had their virus suppressed while on raltegravir 400 mg twice-daily

Isentress HD is given in two 600-mg film-coated tablets — with or without food. The once-daily dosing works as well and is as safe the twice-daily version.

Patients taking raltegravir should watch for:

• Stomach pain
• Loose stools (diarrhea)
• Throwing up (vomiting)
• Loss of appetite

The once-daily version of Isentress HD will cost about the same as the twice-daily version. It will be ready for US drug stores in about four weeks.¹

References

1. Brooks M. FDA Clears Once-Daily Raltegravir (Isentress HD) for HIV. Medscape Website. 2017. http://www.medscape.com/. Accessed 2017/5/31.

The FDA (US Food and Drug Administration) has given a Warning box label to the type 2 diabetes drug canagliflozin (Invokana^®, Invokamet^®, Invokamet^® XR). This Warning label is based on new data from two large clinic studies. The FDA warns that canagliflozin can raise the risk of foot and leg amputation (remove a body limb).

Don't stop taking canagliflozin without first talking with your doctor. Call your doctor right away if you notice any of these signs in your feet or legs.

• New pain or feels tender,
• Sores or ulcers, or
• Infections.

Before starting canagliflozin, your doctor will look at your health record. Your doctor will also watch to see if you have any problems while taking this drug.¹

References

1. FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR). FDA Website. https://www.fda.gov/. Accessed 2017/5/16.

KOĀTE^® supply in the 1000 IU vial size can now be bought and shipped. The 250 IU and 500 IU vial sizes will be ready by June.

KOĀTE is a type of factor for patients with hemophilia A (hereditary factor VIII deficiency). It is used to help control and prevent bleeds. It can also be used in surgery.

Background:

KOĀTE supply was not high enough to meet public demand. Kedrion Biopharma has made changes to its operations. These include:

• Extending a contract with a US manufacturing partner for 10 years
• Creating a back-up plan to use another supplier, if needed
• Offering the Mix2Vial needle-free transfer device into the KOĀTE package
• Removing the latex-rubber stoppers in KOĀTE vials. ¹

Reference

1. Announcement from Kedrion Biopharma on May 8, 2017, CVSHealth. Natalie Watkins, Clinical Therapy Manager: Natalie.Watkins@CVSHealth.com, and Barb Baird, Account Manager: Barbara.baird@CVSHealth.com.

There is a new FDA (Federal Drug Administration) warning for two drugs codeine and tramadol. This warning is for children and nursing mothers.

Children who are younger than 12 should not be given these drugs at all. Infants can be exposed through breast milk. These drugs should be used with care in children who are 12 years or older.

Things to Know:

• ONLY adults should use codeine or tramadol.
• ALWAYS check medicine labels for these drugs.
• ASK your doctor to check the label with you if you're not sure.
• DO NOT use codeine or tramadol if you or your child has the CYP2D6 gene. This is known as a "ultra-rapid metabolizer." This means the body breaks down these drugs faster, before they have had a chance to work.
• WATCH children of any age who might be taking these drugs for signs of breathing problems.

Signs of Breathing Problems in Children or Nursing Infants:

• Slow or shallow breathing
• Trouble or noisy breathing
• Confused
• More tired than normal
• Trouble nursing

If you notice any of these signs, get urgent care or call 9-1-1.

Drug Label Changes

The FDA gives these drugs their strongest label warning. You will see this label on medicine that has one of these drugs in them.

Codeine should not be used to treat pain or cough in children who are younger than 12.

Tramadol should not be used to treat pain in children who are younger than 12.

Children who are between 12 and 18 years old should not get tramadol after surgery to remove their tonsils or adenoids. They also should not use tramadol if they are at risk for breathing problems, like being overweight or if they have a lung disease.

Again, mothers should not breastfeed when using codeine or tramadol. Infants can be exposed to these drugs through breast milk.

References

1. Codeine and Tramadol Medicines: Drug Safety Communication - Restricting Use in Children, Recommending Against Use in Breastfeeding Women. U.S. FDA Website. https://www.fda.gov/. Accessed 2017/4/20.