Mircera

• Auryxia

• Velphoro

© Mircera Patient Information is supplied by Cerner Multum, Inc. and Mircera Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Appropriate studies have not been performed on the relationship of age to the effects of methoxy polyethylene glycol-epoetin beta injection in the pediatric population. Safety and efficacy have not been established.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Call your doctor for instructions if you miss more than one dose.

Other drugs may interact with epoetin beta and methoxy polyethylene glycol, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Methoxy polyethylene glycol-epoetin beta injection is used to treat anemia in patients with chronic kidney disease (CKD).

Methoxy polyethylene glycol-epoetin beta injection causes the bone marrow to produce red blood cells. If the body does not produce enough red blood cells, severe anemia can occur. This often occurs in people with chronic kidney failure whose kidneys are not working properly.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of methoxy polyethylene glycol-epoetin beta injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of methoxy polyethylene glycol-epoetin beta injection in the elderly. However, elderly patients are more likely to have kidney, liver, or heart problems, which may require more monitoring or an adjustment in the dose of this medicine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding problems or
• Inflammatory or metabolic conditions, chronic or
• Vitamin deficiency—Should be corrected first before using this medicine.

• Blood clots, history of or
• Cancer or
• Congestive heart failure or
• Heart attack, history of or
• Heart bypass surgery or
• Heart or blood vessel disease or
• Stroke, history of—The chance of side effects may be increased.

• Hypertension (high blood pressure), controlled or
• Seizures, history of—Use with caution. May make these conditions worse.

• Hypertension (high blood pressure), uncontrolled or
• Pure red cell aplasia (PRCA, bone marrow disease)—Should not be used in patients with these conditions.

• It is used to treat anemia.
• It may be given to you for other reasons. Talk with the doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep using Mircera as you have been told by your doctor or other health care provider, even if you feel well.
• It is given as a shot into a vein or into the fatty part of the skin.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Follow how to use as you have been told by the doctor or read the package insert.
• Do not shake.
• Do not mix with other liquids.
• Throw syringe away after use. Do not use the same syringe more than one time.
• Do not use if the solution is cloudy, leaking, or has particles.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

No formal drug/drug interaction studies have been performed.

Pregnancy: Category C

Risk Summary

There are no adequate and well-controlled studies in pregnant women. Mircera should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal Data

When methoxy polyethylene glycol-epoetin beta was administered subcutaneously to rats and rabbits during gestation, bone malformation was observed in both species at 50 mcg/kg once every three days. This effect was observed as missing caudal vertebrae resulting in a thread-like tail in one rat fetus, absent first digit metacarpal and phalanx on each forelimb resulting in absent pollex in one rabbit fetus, and fused fourth and fifth cervical vertebrae centra in another rabbit fetus. Dose-related reduction in fetal weights was observed in both rats and rabbits. At doses 5 mcg/kg once every three days and higher, methoxy polyethylene glycol-epoetin beta caused exaggerated pharmacodynamic effects in dams. Once-weekly doses of methoxy polyethylene glycol-epoetin beta up to 50 mcg/kg/dose given to pregnant rats did not adversely affect pregnancy parameters, natural delivery or litter observations. Increased deaths and significant reduction in the growth rate of the F1 generation were observed during lactation and early post weaning period. However, no remarkable effect on reflex, physical and cognitive development or reproductive performance was observed in F1 generation of any dose groups.

Nursing Mothers

It is not known whether Mircera is excreted into human breast milk. In one study in rats, methoxy polyethylene glycol-epoetin beta was excreted into maternal milk. Because many drugs are excreted in human milk, caution should be exercised when Mircera is administered to a nursing woman.

Pediatric Use

The safety and efficacy of Mircera in pediatric patients have not been established.

Geriatric Use

Clinical studies of Mircera did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Hepatic Impairment

In a study comparing 12 patients with severe (Child-Pugh Classification Grade C) hepatic impairment to 12 healthy volunteers, the single-dose pharmacokinetic disposition of Mircera was not altered in patients with hepatic impairment. No adjustment of the starting dose is necessary in patients with hepatic impairment.

Mircera, methoxy polyethylene glycol-epoetin beta, is an ESA which differs from erythropoietin through formation of a chemical bond between either the N-terminal amino group or the ε-amino group of any lysine present in erythropoietin, predominantly Lys52 and Lys45, and methoxy polyethylene glycol (PEG) butanoic acid (approximately 30,000 daltons). This results in a total molecular weight of approximately 60,000 daltons. Mircera is formulated as a sterile, preservative-free protein solution for intravenous or subcutaneous administration.

Injectable solutions of Mircera in prefilled syringes (30 mcg, 50 mcg, 75 mcg, 100 mcg, 120 mcg, 150 mcg, 200 mcg, or 250 mcg in 0.3 mL) are formulated in an aqueous solution containing mannitol (9 mg), methionine (0.447 mg), poloxamer 188 (0.03 mg), sodium phosphate monobasic monohydrate (0.414 mg), and sodium sulphate (1.704 mg). Mircera 360 mcg in 0.6 mL is formulated in an aqueous solution containing mannitol (18 mg), methionine (0.894 mg), poloxamer 188 (0.06 mg), sodium phosphate monobasic monohydrate (0.828 mg), and sodium sulphate (3.408 mg). The solution is clear, colorless to slightly yellowish and the pH is 6.2 ± 0.2.

See Medication Guide and Instructions for Use

Prior to treatment, inform patients of the risks and benefits of Mircera.

Inform patients:

Administer Mircera under the direct supervision of a healthcare provider or, in situations where a patient has been trained to administer Mircera at home, provide instruction on the proper use of Mircera, including instructions to:

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Common side effects of Mircera include: death. Other side effects include: upper respiratory tract infection. See below for a comprehensive list of adverse effects.