Soliris is a formulation of eculizumab which is a recombinant humanized monoclonal IgG_2/4;κ antibody produced by murine myeloma cell culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148 kDa.

Soliris is a sterile, clear, colorless, preservative-free 10 mg/mL solution for intravenous infusion and is supplied in 30-mL single-use vials. The product is formulated at pH 7 and each vial contains 300 mg of eculizumab, 13.8 mg sodium phosphate monobasic, 53.4 mg sodium phosphate dibasic, 263.1 mg sodium chloride, 6.6 mg polysorbate 80 (vegetable origin) and Water for Injection, USP.

Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

Patients must be administered a meningococcal vaccine at least two weeks prior to initiation of Soliris therapy and revaccinated according to current medical guidelines for vaccine use. [see WARNINGS and PRECAUTIONS].

Recommended Dosage Regimen

Soliris therapy consists of:

• 600 mg every 7 days for the first 4 weeks, followed by
• 900 mg for the fifth dose 7 days later, then
• 900 mg every 14 days thereafter.

Soliris should be administered at the recommended dosage regimen time points, or within two days of these time points. [see WARNINGS and PRECAUTIONS ]

Preparation for Administration

Soliris must be diluted to a final admixture concentration of 5 mg/mL using the following steps:

• Withdraw the required amount of Soliris from the vial into a sterile syringe.
• Transfer the recommended dose to an infusion bag.
• Dilute Soliris to a final concentration of 5 mg/mL by adding the appropriate amount (equal volume of diluent to drug volume) of 0.9% Sodium Chloride Injection, USP; 0.45% Sodium Chloride Injection, USP; 5% Dextrose in Water Injection, USP; or Ringer's Injection, USP to the infusion bag.

The final admixed Soliris 5 mg/mL infusion volume is 120 mL for 600 mg doses or 180 mL for 900 mg doses. Gently invert the infusion bag containing the diluted Soliris solution to ensure thorough mixing of the product and diluent. Discard any unused portion left in a vial, as the product contains no preservatives.

Prior to administration, the admixture should be allowed to adjust to room temperature [18°-25° C, 64-77° F]. The admixture must not be heated in a microwave or with any heat source other than ambient air temperature. The Soliris admixture should be inspected visually for particulate matter and discoloration prior to administration.

Administration

Do Not Administer As An Intravenous Push Or Bolus Injection

The Soliris admixture should be administered by intravenous infusion over 35 minutes via gravity feed, a syringe-type pump, or an infusion pump. Admixed solutions of Soliris are stable for 24 hours at 2-8° C (36-46° F) and at room temperature.

If an adverse reaction occurs during the administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time should not exceed two hours. Monitor the patient for at least one hour following completion of the infusion for signs or symptoms of an infusion reaction.

Dosage Forms and Strength

Soliris is supplied as 300 mg single-use vials each containing 30 mL of 10 mg/mL sterile, preservative-free eculizumab solution.

Storage and Handling

Soliris (eculizumab) is supplied as 300 mg single-use vials containing 30 mL of 10 mg/mL sterile, preservative-free Soliris solution per vial.

Soliris vials must be stored in the original carton until time of use under refrigerated conditions at 2-8º C (36-46º F) and protected from light. Do not use beyond the expiration date stamped on the carton. Refer to Dosage and Administration for information on the stability and storage of diluted solutions of Soliris.

DO NOT FREEZE. DO NOT SHAKE.

NDC 25682-001-01 Single unit 300 mg carton: Contains one (1) 30 mL vial of Soliris (10 mg/mL).

Manufactured by:
Alexion Pharmaceuticals, Inc.
352 Knotter Drive
Cheshire, CT 06410 USA
US License Number 1743
FDA rev date: 3/16/2007

Clinical Trial Experience

Meningococcal infections are the most important adverse reactions experienced by patients receiving Soliris therapy. In PNH clinical studies, two patients experienced meningococcal sepsis. Both patients had previously received a meningococcal vaccine. In clinical studies among patients without PNH, meningococcal meningitis occurred in an unvaccinated patient [see WARNINGS and PRECAUTIONS].

The data described below reflect exposure to Soliris in 196 adult patients with PNH, age 18-85, of whom 55% were female. All had signs or symptoms of intravascular hemolysis. Soliris was studied in a placebo-controlled clinical study (in which 43 patients received Soliris and 44, placebo); a single arm clinical study and a long term extension study. 182 patients were exposed for greater than one year. All patients received the recommended Soliris dose regimen.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 1 summarizes the adverse reactions that occurred at a numerically higher rate in the Soliris group than the placebo group and at a rate of 5% or more among patients treated with Soliris.

TABLE 1

ADVERSE REACTIONS REPORTED IN 5% OR MORE OF SOLIRIS TREATED PATIENTS AND GREATER THAN PLACEBO IN THE CONTROLLED CLINICAL STUDY

In the placebo-controlled clinical study, serious adverse reactions occurred among 4 (9%) patients receiving Soliris and 9 (21%) patients receiving placebo. The serious reactions included infections and progression of PNH. No deaths occurred in the study and no patients receiving Soliris experienced a thrombotic event; one thrombotic event occurred in a patient receiving placebo.

Among 193 patients with PNH treated with Soliris in the single arm, clinical study or the follow-up study, the adverse reactions were similar to those reported in the placebo-controlled clinical study. Serious adverse reactions occurred among 16% of the patients in these studies. The most common serious adverse reactions were: viral infection (2%), headache (2%), anemia (2%), and pyrexia (2%).

Immunogenicity

As with all proteins there is a potential for immunogenicity. Low titers of antibodies to Soliris were detected in 3/196 (2%) of all PNH patients treated with Soliris. No apparent correlation of antibody development to clinical response was observed. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to Soliris in an enzyme linked immunosorbent assay (ELISA) and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in the assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Soliris with the incidence of antibodies to other products may be misleading.

Drug interaction studies have not been performed with Soliris.

No information provided.

Serious Meningococcal Infections

The use of Soliris increases a patient's susceptibility to serious meningococcal infections (septicemia and/or meningitis). All patients without a history of prior meningococcal vaccination must receive the meningococcal vaccine at least 2 weeks prior to receiving the first dose of Soliris and revaccinated according to current medical guidelines for vaccine use. Quadravalent, conjugated meningococcal vaccines are strongly recommended. Vaccination may not prevent meningococcal infections.

All patients must be monitored for early signs and symptoms of meningococcal infections and evaluated immediately if an infection is suspected. Physicians should strongly consider discontinuation of Soliris during the treatment of serious meningococcal infections.

In clinical studies, 2 out of 196 PNH patients developed serious meningococcal infections while receiving treatment with Soliris; both had been vaccinated. [see ADVERSE REACTIONS].

Other Infections

Soliris blocks terminal complement; therefore patients may have increased susceptibility to infections, especially with encapsulated bacteria. Use caution when administering Soliris to patients with any systemic infection.

Monitoring After Soliris Discontinuation

Since Soliris therapy increases the number of PNH cells [in study 1, the proportion of PNH RBCs increased among Soliris-treated patients by a median of 28% from baseline (range from -25% to 69%)], patients who discontinue treatment with Soliris may be at increased risk for serious hemolysis. Serious hemolysis is identified by serum LDH levels greater than the pre-treatment level, along with any of the following: greater than 25% absolute decrease in PNH clone size (in the absence of dilution due to transfusion) in one week or less; a hemoglobin level of <5 gm/dL or a decrease of >4 gm/dL in one week or less; angina; change in mental status; a 50% increase in serum creatinine level; or thrombosis. Monitor any patient who discontinues Soliris for at least 8 weeks to detect serious hemolysis and other reactions.

If serious hemolysis occurs after Soliris discontinuation, consider the following procedures/treatments: blood transfusion (packed RBCs), or exchange transfusion if the PNH RBCs are >50% of the total RBCs by flow cytometry; anticoagulation; corticosteroids; or reinstitution of Soliris.

In clinical studies, 16 of 196 PNH patients discontinued treatment with Soliris. Patients were followed for evidence of worsening hemolysis and no serious hemolysis was observed.

Thrombosis Prevention and Management

The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.

Laboratory Monitoring

Serum LDH levels increase during hemolysis and may assist in monitoring Soliris effects, including the response to discontinuation of therapy. In clinical studies, six patients achieved a reduction in serum LDH levels only after a decrease in the Soliris dosing interval from 14 to 12 days. All other patients achieved a reduction in serum LDH levels with the 14 day dosing interval [see CLINICAL PHARMACOLOGY and CLINICAL STUDIES].

Infusion Reactions

As with all protein products, administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no PNH patients experienced an infusion reaction which required discontinuation of Soliris. Soliris administration should be interrupted in all patients experiencing severe infusion reactions and appropriate medical therapy administered.

Patient Counseling Information

See MEDICATION GUIDE.

Prior to treatment, patients should fully understand the risks and benefits of Soliris, in particular the risk of meningococcal infection. Ensure that patients receive the Medication Guide.

Patients should be informed that they are required to receive a meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris, if they have not previously been vaccinated. They are required to be revaccinated according to current medical guidelines for meningococcal vaccine use while on Soliris therapy. Patients should also be informed that vaccination may not prevent meningococcal infection. Patients should be educated about any of the signs and symptoms of meningococcal infection, and strongly advised to seek immediate medical attention if these signs or symptoms occur. These signs and symptoms are as follows:

• moderate to severe headache with nausea or vomiting
• moderate to severe headache and a fever
• moderate to severe headache with a stiff neck or stiff back
• fever of 103° F (39.4° C) or higher
• fever and a rash
• confusion
• severe muscle aches with flu-like symptoms, and eyes sensitive to light

Patients should be informed that they would be provided with the Patient Safety Card that they should carry with them at all times. This card describes symptoms which, if experienced, should prompt the patient to immediately seek medical evaluation.

Patients should be informed that there is a potential for serious hemolysis when Soliris is discontinued and that they will be monitored by their healthcare professional for at least 8 weeks following Soliris discontinuation.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been conducted to evaluate the carcinogenic and genotoxic potential of Soliris. Effects of Soliris upon fertility have not been studied in animals. Intravenous injections of male and female mice with a murine anti-C5 antibody at up to 4-8 times the equivalent of the clinical dose of Soliris had no adverse effects on mating or fertility.

Use in specific Populations

Pregnancy

Pregnancy Category C:

PNH is a serious illness. Pregnant women with PNH and their fetuses have high rates of morbidity and mortality during pregnancy and the postpartum period. There are no adequate and well-controlled studies of Soliris in pregnant women. Soliris, a recombinant IgG molecule (humanized anti-C5 antibody), is expected to cross the placenta. Animal studies using a mouse analogue of the Soliris molecule (murine anti-C5 antibody) showed increased rates of developmental abnormalities and an increased rate of dead and moribund offspring at doses 2-8 times the human dose. Soliris should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal reproduction studies were conducted in mice using doses of a murine anti-C5 antibody that approximated 2-4 times (low dose) and 4-8 times (high dose) the recommended human Soliris dose, based on a body weight comparison. When animal exposure to the antibody occurred in the time period from before mating until early gestation, no decrease in fertility or reproductive performance was observed. When maternal exposure to the antibody occurred during organogenesis, two cases of retinal dysplasia and one case of umbilical hernia were observed among 230 offspring born to mothers exposed to the higher antibody dose; however, the exposure did not increase fetal loss or neonatal death. When maternal exposure to the antibody occurred in the time period from implantation through weaning, a higher number of male offspring became moribund or died (1/25 controls, 2/25 low dose group, 5/25 high dose group). Surviving offspring had normal development and reproductive performance.

Labor and Delivery

No information is available on the effects of Soliris during labor and delivery.

Nursing Mothers

It is not known whether Soliris is secreted into human milk. IgG is excreted in human milk, so it is expected that Soliris will be present in human milk. However, published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Caution should be exercised when Soliris is administered to a nursing woman. The unknown risks to the infant from gastrointestinal or limited systemic exposure to Soliris should be weighed against the known benefits of breastfeeding.

Pediatric Use

The safety and effectiveness of Soliris therapy in pediatric patients below the age of 18 have not been established.

Geriatric Use

In PNH studies, 15 patients 65 years of age or older were treated with Soliris. Although there were no apparent age-related differences observed in these studies, the number of patients aged 65 and over is not sufficient to determine whether they respond differently from younger patients.

No cases of Soliris overdose have been reported during clinical studies.

Do not initiate Soliris therapy in patients:

• with unresolved serious Neisseria meningitidis infection.
• who are not currently vaccinated against Neisseria meningitidis.

Mechanism of Action

Eculizumab, the active ingredient in Soliris, is a monoclonal antibody that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. Soliris inhibits terminal complement mediated intravascular hemolysis in PNH patients.

A genetic mutation in PNH patients leads to the generation of populations of abnormal RBCs (known as PNH cells) that are deficient in terminal complement inhibitors, rendering PNH RBCs sensitive to persistent terminal complement-mediated destruction. The destruction and loss of these PNH cells (intravascular hemolysis) results in low RBC counts (anemia), and also fatigue, difficulty in functioning, pain, dark urine, shortness of breath, and blood clots.

Pharmacodynamics

In the placebo-controlled clinical study, Soliris when administered as recommended reduced hemolysis as shown by the reduction of serum LDH levels from 2200 ± 1034 U/L (mean ± SD) at baseline to 700 ± 388 U/L by week one and maintained the effect through the end of the study at week 26 (327 ± 433 U/L). In the single arm clinical study, Soliris maintained this effect through 52 weeks [see CLINICAL STUDIES].

Pharmacokinetics

A population PK analysis with a standard 1-compartmental model was conducted on the multiple dose PK data from 40 PNH patients receiving the recommended Soliris regimen [see DOSAGE AND ADMINISTRATION]. In this model, the clearance of Soliris for a typical PNH patient weighing 70 kg was 22 mL/hr and the volume of distribution was 7.7 L. The half-life was 272 ± 82 hrs (mean ± SD). The mean observed peak and trough serum concentrations of Soliris by week 26 were 194 ± 76 mcg/mL and 97 ± 60 mcg/mL, respectively.

Studies have not been conducted to evaluate the PK of Soliris in special patient populations identified by gender, race, age (pediatric or geriatric), or the presence of renal or hepatic impairment.

Clinical Studies

The safety and efficacy of Soliris in PNH patients with hemolysis were assessed in a randomized, double-blind, placebo-controlled 26 week study (Study 1); PNH patients were also treated with Soliris in a single arm 52 week study (Study 2); and in a long term extension study. Patients received meningococcal vaccination prior to receipt of Soliris. In all studies, the dose of Soliris was 600 mg study drug every 7 ± 2 days for 4 weeks, followed by 900 mg 7 ± 2 days later, then 900 mg every 14 ± 2 days for the study duration. Soliris was administered as an intravenous infusion over 25 - 45 minutes.

Study 1:

PNH patients with at least four transfusions in the prior 12 months, flow cytometric confirmation of at least 10% PNH cells and platelet counts of at least 100,000/microliter were randomized to either Soliris (n = 43) or placebo (n = 44). Prior to randomization, all patients underwent an initial observation period to confirm the need for RBC transfusion and to identify the hemoglobin concentration (the "set-point") which would define each patient's hemoglobin stabilization and transfusion outcomes. The hemoglobin set-point was less than or equal to 9 g/dL in patients with symptoms and was less than or equal to 7 g/dL in patients without symptoms. Endpoints related to hemolysis included the numbers of patients achieving hemoglobin stabilization, the number of RBC units transfused, fatigue, and health-related quality of life. To achieve a designation of hemoglobin stabilization, a patient had to maintain a hemoglobin concentration above the hemoglobin set-point and avoid any RBC transfusion for the entire 26 week period. Hemolysis was monitored mainly by the measurement of serum LDH levels, and the proportion of PNH RBCs was monitored by flow cytometry. Patients receiving anticoagulants and systemic corticosteroids at baseline continued these medications.

Major baseline characteristics were balanced (see table 2).

TABLE 2
STUDY 1 PATIENT BASELINE CHARACTERISTICS

Patients treated with Soliris had significantly reduced (p< 0.001) hemolysis resulting in improvements in anemia as indicated by increased hemoglobin stabilization and reduced need for RBC transfusions compared to placebo treated patients (see table 3). These effects were seen among patients within each of the three pre-study RBC transfusion strata (4 - 14 units; 15 - 25 units; > 25 units). After 3 weeks of Soliris treatment, patients reported less fatigue and improved health-related quality of life. Because of the study sample size and duration, the effects of Soliris on thrombotic events could not be determined.

TABLE 3
STUDY 1 RESULTS

Study 2 and Extension Study:

PNH patients with at least one transfusion in the prior 24 months and at least 30,000 platelets/microliter received Soliris over a 52-week period. Concomitant medications included anti-thrombotic agents in 63% of the patients and systemic corticosteroids in 40% of the patients. Overall, 96 of the 97 enrolled patients completed the study (one patient died following a thrombotic event). A reduction in intravascular hemolysis as measured by serum LDH levels was sustained for the treatment period and resulted in a reduced need for RBC transfusion and less fatigue. 187 Soliris-treated PNH patients were enrolled in a long term extension study. All patients sustained a reduction in intravascular hemolysis over a total Soliris exposure time ranging from 10 to 54 months. There were fewer thrombotic events with Soliris treatment than during the same period of time prior to treatment. However, the majority of patients received concomitant anticoagulants; the effects of anticoagulant withdrawal during Soliris therapy was not studied [see WARNINGS and PRECAUTIONS].

MEDICATION GUIDE

Soliris
(eculizumab) (so-leer-is)

Read the Medication Guide before you start Soliris and before each dose (infusion). This Medication Guide does not take the place of talking with your doctor about your condition or your treatment. Talk to your doctor if you have any questions about your treatment with Soliris.

What Is The Most Important Information I Should Know About Soliris?

Soliris is a medicine that affects your immune system. Soliris can lower the ability of your immune system to fight infections.

• Soliris increases your chance of getting serious and life-threatening meningococcal infections.
  1. You must receive a meningococcal vaccine at least 2 weeks before your first dose of Soliris unless you have already had this vaccine.
  2. If you had a meningococcal vaccine in the past, you might need a booster dose before starting Soliris. Your doctor will decide if you need another dose of a meningococcal vaccine.
  3. A meningococcal vaccine does not prevent all meningococcal infections. You must be aware of the following signs and symptoms of a meningococcal infection:
     • moderate to severe headache with nausea or vomiting
     • moderate to severe headache and a fever
     • moderate to severe headache with a stiff neck or stiff back
     • fever of 103° F (39.4° C) or higher
     • fever and a rash
     • confusion
     • severe muscle aches with flu-like symptoms, and eyes sensitive to light

Call your doctor or get emergency medical care right away if you have any of these symptoms.

You will receive a Patient Safety Card that lists these symptoms and what to do if you have them. Carry it with you at all times. You will need to show the card to any healthcare provider that treats you.

What Is Soliris?

Soliris is a medicine called a monoclonal antibody. Soliris is used for the treatment of patients with a disease that affects red blood cells called Paroxysmal Nocturnal Hemoglobinuria (PNH).

Soliris works by blocking part of your immune system. This can help your PNH symptoms but it can also increase your chance for infection. It is important that you:

• have all recommended immunizations and vaccines before you start Soliris
• stay up-to-date with all recommended immunizations and vaccines during treatment with Soliris

Who Should Not Receive Soliris?

Do not receive Soliris if you:

• have a meningococcal infection
• have not been vaccinated with, or you are not up-to-date with a meningococcal vaccine. See "What is the most important information about Soliris?"

Tell your doctor if you:

• have an infection or fever
• are pregnant, become pregnant, or are breastfeeding. Soliris has not been studied in pregnant or nursing women.

How Do I Receive Soliris?

• Soliris is given through a vein (I.V. infusion) over 35 minutes.
• You will usually receive a Soliris infusion:
  • every 7 days for five weeks,
  • then every 14 days
• Following each infusion, you may be monitored for one hour for allergic reactions.

What If I Miss a Dose or Stop Soliris Treatment?

• If you forget or miss a Soliris infusion, call your doctor right away.
• Stopping treatment with Soliris may cause a sudden and serious breakdown of your red blood cells. Symptoms or problems from red blood cell breakdown include:
  • a large drop in your red blood cell count causing anemia
  • confusion
  • chest pain
  • kidney problems
  • blood clots
• Your doctor will need to monitor you closely for at least 8 weeks after stopping Soliris.

What Are The Possible Side Effects With Soliris?

Serious side effects with Soliris include:

• serious and life-threatening infections. See "What is the most imortant information I should know about Soliris?"

Common side effects with Soliris include:

• headaches
• runny nose and colds
• sore throat
• back pain
• nausea

Call your doctor if you have any of these side effects. These are not all the side effects with Soliris. Ask your doctor for more information.

General Information About Soliris

Medicines are sometimes prescribed for conditions other than those listed in a Medication Guide. If you have any concerns about Soliris, ask your doctor. Your doctor or pharmacist can give you information about Soliris that was written for health care professionals.

Soliris contains eculizumab in a solution of water, polysorbate, sodium phosphate and sodium chloride.

This Medication Guide has been approved by the U.S. Food and Drug Administration

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ECULIZUMAB - INJECTION

(e-kue-LIZ-oo-mab)

COMMON BRAND NAME(S): Soliris

WARNING: Eculizumab can lower your body's ability to fight an infection. It can increase your chance of getting a very serious (possibly fatal) brain/spinal cord infection (meningitis). Seek immediate medical attention if you develop any signs of a severe infection (including meningitis), such as high fever, chills, severe headache, persistent nausea/vomiting, stiff neck, mental/mood changes (e.g., confusion), eye sensitivity to light, fast heartbeat, change in the amount of urine.

You should receive the vaccine for meningitis (meningococcal vaccine) at least 2 weeks before receiving this medication. If you have been previously vaccinated for meningitis, ask your doctor if you need to be vaccinated again before receiving this medication. The vaccine will protect most people, but meningitis may occur even in people who have been vaccinated. Therefore, you should still watch for signs of meningitis even if you receive the vaccine. Consult your doctor for more details.

USES: This medication is used to treat a certain blood disorder (paroxysmal nocturnal hemoglobinuria). This disorder can cause a decrease in red blood cells (anemia). This medication helps to block the decrease in red blood cells and can improve the symptoms of anemia (e.g., tiredness, shortness of breath) and decrease the need for blood transfusions.

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start receiving eculizumab and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

This medication is given by injection into a vein by a health care professional. It is usually given every 7 days for 5 weeks, then every 14 days, or as directed by your doctor. Health care professionals must follow all the manufacturer's instructions for properly mixing and giving this drug. If you have any questions about using this medication properly, consult your doctor or pharmacist.

Do not stop receiving this medication without consulting your doctor. Your condition may become worse when the drug is stopped. If you do stop receiving the medication, you will need to be monitored by your doctor for at least 8 weeks to make sure that your condition does not worsen. Consult your doctor for more details.

Tell your doctor if your condition does not improve or worsens.

SIDE EFFECTS: See also Warning section.

Headache, tiredness, nausea, or muscle pain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: signs of infection (e.g., fever, persistent sore throat).

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before receiving eculizumab, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: current meningitis or other infection caused by the bacteria Neisseria meningitidis, no vaccination for meningitis.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: current/recent infection.

Before having surgery, tell your doctor or dentist that you are using this medication.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.

Wash your hands well to prevent the spread of infections.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Laboratory and/or medical tests (e.g., LDH levels) should be performed periodically during treatment and for 8 weeks after stopping treatment to monitor your progress or check for side effects. Consult your doctor for more details.

You will be provided with a Patient Safety Card with a list of symptoms you must watch for. Carry the Patient Safety Card with you at all times. If you develop any of the listed symptoms, you should seek immediate medical attention.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor to establish a new dosing schedule.

STORAGE: Refrigerate the medication between 36-46 degrees F (2-8 degrees C) away from light. Do not freeze or shake the medication. Use each vial only once. Discard any unused portion. After diluting, the medication may be stored at room temperature or in the refrigerator and used within 24 hours. Do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.