What Is Plegridy?
Plegridy (peginterferon beta-1a) Autoinjector is an interferon beta-1a used to treat patients with relapsing forms of multiple sclerosis.
What Are Side Effects of Plegridy?
Common side effects of Plegridy Autoinjector include:
- injection site reactions (redness, itching, pain, swelling, warmth, rash, bruising),
- flu-like illness,
- muscle or joint pain,
- nausea, and
PLEGRIDY (peginterferon beta-1a) is an interferon beta-1a to which a single, linear 20,000 dalton (Da) methoxy poly(ethyleneglycol)-O-2-methylpropionaldehyde molecule is covalently attached to the alpha amino group of the N-terminal amino acid residue.
The interferon beta-1a portion of PLEGRIDY is produced as a glycosylated protein using genetically-engineered Chinese hamster ovary cells into which the human interferon beta gene has been introduced. The amino acid sequence of the recombinant interferon beta-1a is identical to that of the human interferon beta counterpart. The molecular mass of PLEGRIDY is approximately 44,000 Da, consistent with the mass of the protein (approximately 20,000 Da), the carbohydrate moieties (approximately 2,500 Da), and the attached poly(ethylene glycol). However, because of the extended and flexible nature of the attached poly(ethylene glycol) chain, the apparent mass of PLEGRIDY in solution is greater than 300,000 Da. The more than 10-fold increase in apparent mass of PLEGRIDY compared to interferon beta-1a has been shown to contribute to the reduced clearance in vivo.
PLEGRIDY 125 micrograms contains 125 micrograms of interferon beta-1a plus 125 micrograms of poly(ethylene glycol). Using the World Health Organization International Standard for interferon beta, PLEGRIDY has a specific antiviral activity of approximately 100 million International Units (MIU) per mg of protein as determined using an in vitro cytopathic effect assay. PLEGRIDY 125 micrograms contains approximately 12 MIU of antiviral activity. PLEGRIDY contains no preservative.
PLEGRIDY PEN Single-Dose Prefilled Pen
PLEGRIDY PEN is composed of an autoinjector that surrounds a prefilled glass syringe containing 0.5 mL of a sterile solution in water for injection of 63, 94, or 125 micrograms of peginterferon beta-1a, 15.8 mg of L-arginine HCl, 0.79 mg of sodium acetate trihydrate, 0.25 mg of glacial acetic acid, and 0.025 mg of polysorbate 20. The pH is approximately 4.8.
PLEGRIDY Single-Dose Prefilled Syringe
A prefilled syringe of PLEGRIDY for subcutaneous injection contains 0.5 mL of a sterile solution in water for injection of 63, 94, or 125 micrograms of peginterferon beta-1a, 15.8 mg of L-arginine HCl, 0.79 mg of sodium acetate trihydrate, 0.25 mg of glacial acetic acid, and 0.025 mg of polysorbate 20. The pH is approximately 4.8.
PLEGRIDY is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
DOSAGE AND ADMINISTRATION
PLEGRIDY is administered subcutaneously.
The recommended dosage of PLEGRIDY is 125 micrograms injected subcutaneously every 14 days.
Patients should start treatment with 63 micrograms on day 1. On day 15 (14 days later), the dose is increased to 94 micrograms, reaching the full dose of 125 micrograms on day 29 (after another 14 days). Patients continue with the full dose (125 micrograms) every 14 days thereafter (see Table 1). A PLEGRIDY Starter Pack is available containing two prefilled pens or syringes: 63 micrograms (dose 1) and 94 micrograms (dose 2).
Table 1: Schedule for Dose Titration
|Dose||Time*||Amount (micrograms)||Color of Pen or Syringe Label|
|Dose 1||On day 1||63||Orange|
|Dose 2||On day 15||94||Blue|
|Dose 3||On day 29 and every 14 days thereafter||125 (full dose)||Grey|
|*Dosed every 14 days|
Important Administration Instructions (All Dosage Forms)
Healthcare professionals should train patients in the proper technique for self-administering subcutaneous injections using the prefilled pen or syringe. Patients should be advised to rotate sites for subcutaneous injections. The usual sites for subcutaneous injections are abdomen, back of the upper arm, and thigh.
Each PLEGRIDY pen and syringe is provided with the needle pre-attached. Prefilled pens and syringes are for a single dose only and should be discarded after use.
Premedication For Flu-like Symptoms
Prophylactic and concurrent use of analgesics and/or antipyretics may prevent or ameliorate flulike symptoms sometimes experienced during treatment with PLEGRIDY.
Dosage Forms And Strengths
- Injection: 125 micrograms of PLEGRIDY per 0.5 mL of solution in a single-dose prefilled pen
- Injection: Starter Pack containing 63 micrograms per 0.5 mL of solution in a single-dose prefilled pen and 94 micrograms per 0.5 mL solution in a single-dose prefilled pen
- Injection: 125 micrograms of PLEGRIDY per 0.5 mL of solution in a single-dose prefilled syringe
- Injection: Starter Pack containing 63 micrograms per 0.5 mL of solution in a single-dose prefilled syringe and 94 micrograms per 0.5 mL of solution in a single-dose prefilled syringe
Storage And Handling
PLEGRIDY is supplied as a sterile, clear liquid for subcutaneous injection in two presentations, a prefilled pen and a prefilled syringe.
PLEGRIDY PEN Single-Dose Prefilled Pen
Each dose of PLEGRIDY is stored in a 1 mL capacity glass syringe with a rubber stopper and rigid needle shield. A 29 gauge, 0.5 inch staked needle is pre-affixed to the syringe. A single prefilled syringe contains 0.5 mL of solution of PLEGRIDY containing 63 micrograms, 94 micrograms, or 125 micrograms of peginterferon beta-1a. The glass syringe is contained within
- a single-dose, disposable, injection device (prefilled pen). The following packaging configurations are available:
- A carton containing two single-dose prefilled pens, each providing 125 micrograms of PLEGRIDY. The NDC is 64406-011-01.
A Starter Pack carton containing two single-dose prefilled pens; dose 1 provides 63 micrograms of PLEGRIDY, and dose 2 provides 94 micrograms of PLEGRIDY. The NDC is 64406-012-01.
PLEGRIDY Single-Dose Prefilled Syringe
Each dose of PLEGRIDY is stored in a 1 mL capacity glass syringe with a rubber stopper and rigid needle shield. A 29 gauge, 0.5 inch staked needle is pre-affixed to the syringe. A single prefilled syringe contains 0.5 mL of solution of PLEGRIDY containing 63 micrograms, 94 micrograms, or 125 micrograms of peginterferon beta-1a. The following packaging configurations are available:
- A carton containing two single-dose prefilled syringes, each providing 125 micrograms of PLEGRIDY. The NDC is 64406-015-01.
- A Starter Pack carton containing two single-dose prefilled syringes; dose 1 provides 63 micrograms of PLEGRIDY, and dose 2 provides 94 micrograms of PLEGRIDY. The NDC is 64406-016-01.
Storage And Handling
Store in the closed original carton to protect from light until ready for injection.
Store in a refrigerator between 2°C to 8°C (36°F to 46°F). Do not freeze. Discard if frozen. Once removed from the refrigerator, PLEGRIDY should be allowed to warm to room temperature (about 30 minutes) prior to injection. Do not use external heat sources such as hot water to warm PLEGRIDY.
If refrigeration is unavailable, PLEGRIDY may be stored between 2°C to 25°C (36°F to 77°F) for a period up to 30 days, protected from light. PLEGRIDY can be removed from, and returned to, a refrigerator if necessary. The total combined time out of refrigeration, within a temperature range of 2°C to 25°C (36°F to 77°F), should not exceed 30 days.
Instructions For Disposal
Dispose in a sharps-bin container or other hard plastic or metal sealable container. Always follow local regulations for disposal.
Manufactured by: Biogen Inc., Cambridge, MA 02142. Revised: N/A
The following serious adverse reactions are discussed in more detail in other sections of labeling:
- Hepatic Injury [see WARNINGS AND PRECAUTIONS]
- Depression and Suicide [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
- Anaphylaxis and Other Allergic Reactions [see WARNINGS AND PRECAUTIONS]
- Injection Site Reactions [see WARNINGS AND PRECAUTIONS]
- Congestive Heart Failure [see WARNINGS AND PRECAUTIONS]
- Decreased Peripheral Blood Counts [see WARNINGS AND PRECAUTIONS]
- Thrombotic Microangiopathy [see WARNINGS AND PRECAUTIONS]
- Autoimmune Disorders [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of PLEGRIDY cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice.
In clinical studies (Study 1 and Study 2), a total of 1468 patients with relapsing multiple sclerosis received PLEGRIDY for up to 177 weeks (41 months), with an overall exposure equivalent to 1932 person-years. A total of 1093 patients received at least 1 year, and 415 patients at least 2 years of treatment with PLEGRIDY. A total of 512 and 500 patients, respectively, received PLEGRIDY 125 micrograms every 14 days or every 28 days during the placebo-controlled phase of Study 1 (year 1). The experience in year 2 of Study 1 and in the 2-year safety extension study (Study 2) was consistent with the experience in the 1-year placebo-controlled phase of Study 1.
In the placebo-controlled phase of Study 1, the most common adverse drug reactions for PLEGRIDY 125 micrograms subcutaneously every 14 days were injection site erythema, influenza-like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia (all had incidence more than 10% and at least 2% more than placebo). The most commonly reported adverse event leading to discontinuation in patients treated with PLEGRIDY 125 micrograms subcutaneously every 14 days was influenza-like illness (in less than 1% of patients).
Table 2 summarizes adverse reactions reported over 48 weeks from patients treated in the placebo-controlled phase of Study 1 who received subcutaneous PLEGRIDY 125 micrograms (n=512), or placebo (n=500), every 14 days.
Table 2: Adverse reactions in the 48-week
placebo-controlled phase of Study 1 with an incidence 2% higher for PLEGRIDY
than for placebo
|Nervous System Disorders|
|Musculoskeletal and Connective Tissue Disorders|
|General Disorders and Administration Site Conditions|
|Injection site erythema||62||7|
|Influenza like illness||47||13|
|Injection site pain||15||3|
|Injection site pruritus||13||1|
|Injection site edema||3||0|
|Injection site warmth||3||0|
|Injection site hematoma||3||1|
|Injection site rash||2||0|
|Body temperature increased||6||3|
|Alanine aminotransferase increased||6||3|
|Aspartate aminotransferase increased||4||2|
|Skin and Subcutaneous Tissue Disorder|
For therapeutic proteins, there is a potential for immunogenicity. In Study 1, fewer than 1% of patients treated with PLEGRIDY every 14 days for 1 year developed neutralizing antibodies. Approximately 7% of PLEGRIDY-treated patients developed antibodies to PEG.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to PLEGRIDY with the incidence of antibodies to other products may be misleading.
Influenza-like illness was experienced by 47% of patients receiving PLEGRIDY 125 micrograms every 14 days and 13% of patients receiving placebo. Fewer than 1% of PLEGRIDY-treated patients in Study 1 discontinued treatment due to flu-like symptoms.
No Information provided
Included as part of the PRECAUTIONS section.
Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, have been reported with interferon beta. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with interferon beta.
Elevations in hepatic enzymes and hepatic injury have been observed with the use of PLEGRIDY in clinical studies. The incidence of increases in hepatic transaminases was greater in patients taking PLEGRIDY than in those taking placebo. The incidence of elevations of alanine aminotransferase above 5 times the upper limit of normal was 1% in placebo-treated patients and 2% in PLEGRIDY-treated patients. The incidence of elevations of aspartate aminotransferase above 5 times the upper limit of normal was less than 1% in placebo-treated patients and less than 1% in PLEGRIDY-treated patients. Elevations of serum hepatic transaminases combined with elevated bilirubin occurred in 2 patients. Both cases resolved following discontinuation of PLEGRIDY.
Monitor patients for signs and symptoms of hepatic injury.
Depression And Suicide
Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta than in patients receiving placebo.
In clinical studies, the overall incidence of adverse events related to depression and suicidal ideation in multiple sclerosis patients was 8% in both the PLEGRIDY and placebo groups. The incidence of serious events related to depression and suicidal ideation was similar and less than 1% in both groups.
Advise patients to report immediately any symptom of depression or suicidal ideation to their healthcare provider. If a patient develops depression or other severe psychiatric symptoms, consider stopping treatment with PLEGRIDY.
Seizures are associated with the use of interferon beta.
The incidence of seizures in multiple sclerosis clinical studies was less than 1% in patients receiving PLEGRIDY and placebo.
Exercise caution when administering PLEGRIDY to patients with a seizure disorder.
Anaphylaxis And Other Allergic Reactions
Anaphylaxis and other serious allergic reactions are rare complications of treatment with interferon beta.
Less than 1% of PLEGRIDY-treated patients experienced a serious allergic reaction such as angioedema or urticaria. Those who did have serious allergic reactions recovered promptly after treatment with antihistamines or corticosteroids.
Discontinue PLEGRIDY if a serious allergic reaction occurs.
Injection Site Reactions
Injection site reactions, including injection site necrosis, can occur with the use of subcutaneous interferon beta.
In clinical studies, the incidence of injection site reactions (e.g., injection site erythema, pain, pruritus, or edema) was 66% in the PLEGRIDY group and 11% in the placebo group; the incidence of severe injection site reactions was 3% in the PLEGRIDY group and 0% in the placebo group. One patient out of 1468 patients who received PLEGRIDY in clinical studies experienced injection site necrosis. The injury resolved with standard medical treatment.
Decisions to discontinue therapy following necrosis at a single injection site should be based on the extent of the necrosis. For patients who continue therapy with PLEGRIDY after injection site necrosis has occurred, avoid administration of PLEGRIDY near the affected area until it is fully healed. If multiple lesions occur, discontinue PLEGRIDY until healing occurs.
Congestive Heart Failure
In clinical studies, the incidence of cardiovascular events was 7% in both PLEGRIDY and placebo treatment groups. No serious cardiovascular events were reported in the PLEGRIDY group.
Monitor patients with significant cardiac disease for worsening of their cardiac condition during initiation and continuation of treatment with PLEGRIDY.
Decreased Peripheral Blood Counts
In clinical studies, decreases in white blood cell counts below 3.0 x 109/L occurred in 7% of patients receiving PLEGRIDY and in 1% receiving placebo. There is no apparent association between decreases in white blood cell counts and an increased risk of infections or serious infections. The incidence of clinically significant decreases in lymphocyte counts (below 0.5 x 109/L), neutrophil counts (below 1.0 x 109/L), and platelet counts (below 100 x 109/L) were all less than 1% and similar in both placebo and PLEGRIDY groups. Two serious cases were reported in patients treated with PLEGRIDY: one patient (less than 1%) experienced severe thrombocytopenia (defined as a platelet count less than or equal to 10 x 109/L), and another patient (less than 1%) experienced severe neutropenia (defined as a neutrophil count less than or equal to 0.5 x 109/L). In both patients, cell counts recovered after discontinuation of PLEGRIDY. Compared to placebo, there were no significant differences in red blood cell counts in patients treated with PLEGRIDY.
Monitor patients for infections, bleeding, and symptoms of anemia. Monitor complete blood cell counts, differential white blood cell counts, and platelet counts during treatment with PLEGRIDY. Patients with myelosuppression may require more intensive monitoring of blood cell counts.
Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported with interferon beta products. Cases have been reported several weeks to years after starting interferon beta products. Discontinue PLEGRIDY if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.
In clinical studies, the incidence of autoimmune disorders was less than 1% in both PLEGRIDY and placebo treatment groups.
If patients develop a new autoimmune disorder, consider stopping PLEGRIDY.
Patient Counseling Information
See FDA-approved patient labeling (Medication Guide and Instructions for Use).
Instruct patients to carefully read the supplied PLEGRIDY Medication Guide and Instructions for Use, and caution patients not to change the PLEGRIDY dose or schedule of administration without medical consultation.
Instructions For Self-Injection Technique And Procedures
Provide appropriate instruction for methods of self-injection, including careful review of the PLEGRIDY Medication Guide and Instructions for Use. Instruct patients in the use of aseptic technique when administering PLEGRIDY.
Inform patients that a healthcare provider should show them or their caregiver how to prepare to inject PLEGRIDY before administering the first dose. Tell patients not to re-use needles or syringes, and instruct patients on safe disposal procedures. Inform patients to dispose of used needles and syringes in a puncture-resistant container, and instruct patients regarding safe disposal of full containers.
- to rotate areas of injection with each dose to minimize the likelihood of injection site reactions
- NOT to inject into an area of the body where the skin is irritated, reddened, bruised, infected, or scarred in any way
- to check the injection site after 2 hours for redness, swelling, and tenderness
- to contact their healthcare professional if they have a skin reaction and it does not clear up in a few days
Pregnancy And Pregnancy Registry
Advise patients that PLEGRIDY should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Encourage patients to enroll in the PLEGRIDY Pregnancy Registry if they become pregnant while taking PLEGRIDY [see Use In Specific Populations].
Advise patients that severe hepatic injury, including rare cases of hepatic failure, has been reported during the use of interferon beta. Advise patients of symptoms of hepatic dysfunction, and instruct patients to report them immediately to their physician.
Depression And Suicide
Advise patients that depression, suicidal ideation, and suicide have been reported with the use of interferon beta. Instruct patients to report symptoms of depression or thoughts of suicide to their physician immediately.
Advise patients that seizures have been reported in patients using PLEGRIDY. Instruct patients to report seizures immediately to their physician.
Anaphylaxis And Other Allergic Reactions
Advise patients of the symptoms of allergic reactions and anaphylaxis, and instruct patients to seek immediate medical attention if these symptoms occur.
Injection Site Reactions
Advise patients that injection site reactions can occur and that the reactions can include injection site necrosis. Instruct patients to report promptly any break in the skin that is associated with blue-black discoloration, swelling, or drainage of fluid from the injection site.
Advise patients that worsening of significant cardiac disease has been reported in patients using interferon beta. Advise patients of symptoms of worsening cardiac condition, and instruct patients to report them immediately to their physician.
Inform patients that flu-like symptoms are common following initiation of therapy with PLEGRIDY. Prophylactic and concurrent use of analgesics and/or antipyretics may prevent or ameliorate flu-like symptoms sometimes experienced during interferon treatment.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
The carcinogenic potential of PLEGRIDY has not been tested in animals.
PLEGRIDY was not mutagenic when tested in an in vitro bacterial reverse mutation (Ames) test and was not clastogenic in an in vitro assay in human lymphocytes.
Impairment Of Fertility
In monkeys administered interferon beta by subcutaneous injection over the course of one menstrual cycle, menstrual irregularities, anovulation, and decreased serum progesterone levels were observed. These effects were reversible after discontinuation of drug.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. PLEGRIDY should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
PLEGRIDY has not been tested for developmental toxicity in pregnant animals. In monkeys given interferon beta by subcutaneous injection every other day during early pregnancy, no teratogenic or other adverse effects on fetal development were observed. Abortifacient activity was evident following 3 to 5 doses.
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PLEGRIDY during pregnancy. Encourage patients to enroll by calling 1-866-810-1462 or visiting https://www.plegridypregnancyregistry.com/.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PLEGRIDY is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Safety and effectiveness in geriatric patients have not been established.
Monitor for adverse reactions due to increased drug exposure in patients with severe renal impairment [see CLINICAL PHARMACOLOGY].
No Information provided
PLEGRIDY is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta or peginterferon, or any other component of the formulation [see WARNINGS AND PRECAUTIONS].
Mechanism Of Action
The mechanism by which PLEGRIDY exerts its effects in patients with multiple sclerosis is unknown.
After single-dose or multiple-dose subcutaneous administration of PLEGRIDY to healthy subjects, serum PLEGRIDY peak concentration (Cmax) and total exposure over time (area under the curve, or AUC) increased in proportion to doses from 63 to 188 micrograms. PLEGRIDY did not accumulate in the serum after multiple doses of 125 micrograms every 14 days. Pharmacokinetic parameters for PLEGRIDY, including Cmax and AUC, did not differ significantly between healthy volunteers and multiple sclerosis patients or between single-dose and multiple-dose administrations. However, the coefficient of variation between individual patients for AUC, Cmax, and half-life was high (41% to 68%, 74% to 89%, and 45% to 93%, respectively).
After 125 microgram subcutaneous doses of PLEGRIDY in multiple sclerosis patients, the maximum concentration occurred between 1 and 1.5 days, the mean Cmax was 280 pg/mL, and the AUC over the 14 day dosing interval was 34.8 ng.hr/mL.
In multiple sclerosis patients taking 125 microgram subcutaneous doses of PLEGRIDY every 14 days, the estimated volume of distribution was 481 liters.
Metabolism And Elimination
Clearance mechanisms for PLEGRIDY include catabolism and excretion. The major pathway of elimination is renal. The half-life is approximately 78 hours in multiple sclerosis patients. The mean steady state clearance of PLEGRIDY is approximately 4.1 L/hr. PLEGRIDY is not extensively metabolized in the liver.
Body weight, gender, and age do not require dosage adjustment.
Renal impairment can increase the Cmax and AUC for PLEGRIDY. Results of a pharmacokinetic study in patients with mild, moderate, and severe renal impairment (creatinine clearance 50 to 80, 30 to 50, and less than 30 mL/minute, respectively) showed increases above normal for Cmax of 27%, 26%, and 42%, and for AUC, increases of 30%, 40%, and 53%. The half-life was 53, 49, and 82 hours in patients with mild, moderate, and severe renal impairment, respectively, compared to 54 hours in normal subjects.
In the same study, subjects with end stage renal disease requiring hemodialysis two or three times weekly had AUC and Cmax of PLEGRIDY values that were similar to those of normal controls. Each hemodialysis session removed approximately 24% of circulating PLEGRIDY from the systemic circulation [see Use In Specific Populations].
The efficacy of PLEGRIDY was demonstrated in the randomized, double-blind, and placebocontrolled phase (year 1) of Study 1. The trial compared clinical and MRI outcomes at 48 weeks in patients who received PLEGRIDY 125 micrograms (n=512) or placebo (n=500) by the subcutaneous route, once every 14 days.
Study 1 enrolled patients who had a baseline Expanded Disability Status Scale (EDSS) score from 0 to 5, who had experienced at least 2 relapses within the previous three years, and had experienced at least 1 relapse in the previous year. The trial excluded patients with progressive forms of multiple sclerosis. The mean age of the study population was 37 years, the mean disease duration was 3.6 years, and the mean EDSS score at baseline was 2.46. The majority of the patients were women (71%).
The trial scheduled neurological evaluations at baseline, every 12 weeks, and at the time of a suspected relapse. Brain MRI evaluations were scheduled at baseline, week 24, and week 48.
The primary outcome was the annualized relapse rate over 1 year. Secondary outcomes included the proportion of patients relapsing, number of new or newly enlarging T2 hyperintense lesions, and time to confirmed disability progression. Confirmed disability progression was defined as follows: if the baseline EDSS score was 0, a sustained 12-week increase in EDSS score of 1.5 points was required; if the baseline EDSS score was greater than 0, a sustained 12-week increase in EDSS score of 1 point was required. Table 3 and Figure 1 show the results of Study 1.
Table 3: Clinical and MRI Results of Study 1
|Endpoint||PLEGRIDY 125 micrograms every 14 days||Placebo||p-value|
|Clinical outcomes at 48 weeks||N=512||N=500|
|Annualized relapse rate||0.26||0.40||0.0007|
|Proportion of patients with relapses||0.19||0.29||0.0003|
|Relative risk reduction||39%|
|Proportion of patients with disability progression||0.07||0.11||0.0383|
|Relative risk reduction||38%|
|MRI outcomes at 48 weeks||N=457||N=476|
|Mean number of new or newly enlarging T2 hyperintense lesions||3.6||10.9||<0.0001|
|Mean number of Gd enhancing lesions||0.2||1.4||<0.0001|
Figure 1: Time to first relapse
(peginterferon beta-1a) injection for subcutaneous use
Read this Medication Guide before you start using PLEGRIDY, and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.
What is the most important information I should know about PLEGRIDY?
PLEGRIDY can cause serious side effects, including:
- Liver problems or worsening of liver problems, including liver failure and death. Symptoms may include: yellowing of your skin or the white part of your eye, nausea, loss of appetite, tiredness, bleeding more easily than normal, confusion, sleepiness, dark colored urine, and pale stools.
- During your treatment with PLEGRIDY you will need to see your healthcare provider and have regular blood tests to check for these possible side effects.
- Depression or suicidal thoughts. Symptoms may include: new or worsening depression (feeling hopeless or bad about yourself), thoughts of hurting yourself or suicide, irritability (getting upset easily), nervousness, or new or worsening anxiety.
Call your healthcare provider right away if you have any of the symptoms listed above.
What is PLEGRIDY?
- PLEGRIDY is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
- It is not known if PLEGRIDY is safe and effective in people under 18 or over 65 years of age.
Who should not use PLEGRIDY?
Do not take PLEGRIDY if you:
- are allergic to interferon beta or peginterferon beta-1a, or any of the other ingredients in PLEGRIDY. See the end of this Medication Guide for a complete list of ingredients in PLEGRIDY.
Before using PLEGRIDY, tell your healthcare provider if you:
- are being treated for a mental illness or had treatment in the past for any mental illness, including depression and suicidal behavior
- have or had liver problems, low blood cell counts, bleeding problems, heart problems, seizures (epilepsy), thyroid problems, or any kind of autoimmune disease
- take prescription and over-the-counter medicines, vitamins, and herbal supplements
- are pregnant or plan to become pregnant. It is not known
if PLEGRIDY will harm your unborn baby. Tell your healthcare provider if you
become pregnant during your treatment with PLEGRIDY.
- If you become pregnant while taking PLEGRIDY, talk to your doctor about enrolling in the PLEGRIDY Pregnancy Registry. You can enroll in this registry by calling 1-866-810-1462 or visiting https://www.plegridypregnancyregistry.com/. The purpose of this registry is to collect information about the safety of Plegridy during pregnancy.
- are breastfeeding or plan to breastfeed. It is not known if PLEGRIDY passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use PLEGRIDY.
How should I use PLEGRIDY?
- See the Instructions for Use for detailed instructions to prepare for and to inject your dose of PLEGRIDY.
- Use PLEGRIDY exactly as your healthcare provider tells you. A healthcare provider should show you how to inject your PLEGRIDY before you use it for the first time.
- When you first use PLEGRIDY, your healthcare provider may tell you to slowly increase your dose so that you can adjust to the effects of PLEGRIDY before using the full dose. You should use a PLEGRIDY starter pack to slowly adjust your dose when you begin treatment.
- PLEGRIDY is given by injection under the skin (subcutaneous injection) of your stomach (abdomen), back of upper arm, or thigh 1 time every 14 days.
- Change (rotate) the site you choose with each injection to help decrease the chance that you will have an injection site reaction. Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected, or scarred in any way.
- Always use a new, PLEGRIDY prefilled pen or new, unopened single-use prefilled syringe for each injection.
What are the possible side effects of PLEGRIDY?
See “What is the most important information I should know about PLEGRIDY?”
PLEGRIDY may cause additional serious side effects, including:
- serious allergic reactions. Serious allergic reactions can happen quickly. Symptoms may include: itching, swelling of the face, eyes, lips, tongue, or throat, trouble breathing, feeling faint, anxiousness, skin rash, hives, skin bumps.
- injection site reactions. PLEGRIDY may commonly cause redness, pain, or swelling at the place where your injection was given. Call your healthcare provider right away if an injection site becomes swollen and painful or the area looks infected and it does not heal within a few days. You may have a skin infection or an area of severe skin damage (necrosis) requiring treatment by a healthcare provider.
- heart problems, including congestive heart failure. While
PLEGRIDY is not known to have any direct effects on the heart, some people who
did not have a history of heart problems developed heart muscle problems or
congestive heart failure after taking interferon beta. If you already have
heart failure, PLEGRIDY may cause your heart failure to get worse. Call your
healthcare provider right away if you have worsening symptoms of heart failure
such as shortness of breath or swelling of your lower legs or feet while using
- Some people using PLEGRIDY may have other heart problems, including low blood pressure, fast or abnormal heart beat, chest pain, heart attack, or a heart muscle problem (cardiomyopathy).
- autoimmune diseases. Problems with easy bleeding or bruising (idiopathic thrombocytopenia), thyroid gland problems (hyperthyroidism and hypothyroidism), and autoimmune hepatitis have happened in some people who use interferon beta.
- blood problems and changes in your blood tests. PLEGRIDY can decrease your white blood cells or platelets, which can cause an increased risk of infection, bleeding, or anemia and can cause changes in your liver function tests. Your healthcare provider should do blood tests while you use PLEGRIDY to check for side effects.
- seizures. Some people have had seizures while taking PLEGRIDY, including people who have never had seizures before.
The most common side effects of PLEGRIDY include:
- flu-like symptoms. Many people who use PLEGRIDY
have flu-like symptoms early in the course of therapy. These symptoms are not
really the flu. You cannot pass it on to anyone else. Symptoms may include: headache, muscle and joint aches, fever, chills, or tiredness.
- You may be able to manage these flu-like symptoms by taking over-the-counter pain and fever reducers and drinking plenty of water. For many people, these symptoms lessen or go away over time.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General Information about the safe and effective use of PLEGRIDY.
Medicines are sometimes prescribed for purposes other than those listed in this Medication Guide. If you would like more information, talk to your healthcare provider or pharmacist. You can ask your healthcare provider or pharmacist for information about PLEGRIDY that is written for health professionals. Do not use PLEGRIDY for a condition for which it was not prescribed. Do not give PLEGRIDY to other people, even if they have the same symptoms that you have. It may harm them. For more information, go to www.plegridy.com or call 1-800-456- 2255
What are the ingredients in PLEGRIDY?
Active ingredient: peginterferon beta-1a
- Single-Use Prefilled Pen: sodium acetate trihydrate, glacial acetic acid, arginine hydrochloride, polysorbate 20 in water for injection
- Single-Use Prefilled Syringe: sodium acetate trihydrate, glacial acetic acid, arginine hydrochloride, polysorbate 20 in water for injection
This Medication Guide has been approved by the U.S. Food and Drug Administration
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.