Nplate

Mechanism of Action

Fusion antibody-peptide that is a thrombopoietin receptor agonist; stimulates proliferation, differentiation, and activity of monocytes, neutrophils, eoxinophils, and macrophages

Pharmacokinetics

Peak plasma time: 1-3 hr (SC)

Onset: 7-14 days (increase in WBC)

Half-life elimination: 60 min (IV); 2.7 hr (SC)

Nplate is indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Limitations Of Use

• Nplate is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP [see WARNINGS AND PRECAUTIONS].
• Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding [see WARNINGS AND PRECAUTIONS].
• Nplate should not be used in an attempt to normalize platelet counts [see WARNINGS AND PRECAUTIONS].

Your doctor or pharmacist can provide more information about romiplostim.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Romiplostim is a man-made form of a protein that increases production of platelets (blood-clotting cells) in your body.

Romiplostim is used to prevent bleeding episodes in people with chronic immune thrombocytopenic purpura (ITP), a bleeding condition caused by a lack of platelets in the blood.

Romiplostim is usually given after other medications have been tried without successful treatment of symptoms.

Romiplostim is not a cure for ITP and it will not make your platelet counts normal if you have this condition.

Romiplostim may also be used for purposes not listed in this medication guide.

General

• Monitor CBC, including platelet count and peripheral blood smear, weekly until achieve a stable platelet count (≥50,000/mm3 for ≥4 weeks without dosage adjustment); monitor at least monthly thereafter.1

• After romiplostim discontinuance, monitor CBC, including platelet count, weekly for at least 2 weeks; potential for worsening thrombocytopenia following discontinuance.1

• May be used with other drugs to treat ITP such as corticosteroids, danazol, azathioprine, immune globulin IV (IGIV), and Rho(D) immune globulin.1 If the platelet count increases to ≥50,000/mm3, medical therapies for ITP may be reduced or discontinued.1

Administration

Reconstitution

Romiplostim lyophilized powder is supplied in single-use vials containing 375 mcg (to deliver 250 mcg) or 625 mcg (to deliver 500 mcg) of the drug.1 Reconstitute lyophilized romiplostim using only sterile water for injection without preservatives; do not use bacteriostatic water for injection.1 (See Storage under Stability.) Reconstitute the powder by adding 0.72 or 1.2 mL of preservative-free sterile water for injection to a vial labeled as containing 250 or 500 mcg, respectively, of romiplostim.1

Gently swirl and invert the vial to facilitate dissolution, which generally takes <2 minutes; do not shake or vigorously agitate the vial.1

Reconstitution of the lyophilized drug as directed provides a clear and colorless solution containing 250 or 500 mcg per 0.5 or 1 mL, respectively, for sub-Q administration.1

Sub-Q Administration

Administer by sub-Q injection.1

A clinician should administer romiplostim;1 5 the patient should not self-administer the drug.2

Injection volumes of the drug may be very small; administer romiplostim using a syringe calibrated in increments of 0.01 mL.1 Exercise extra care to ensure the accuracy of the administered dose because of the potential for serious adverse effects following administration of excessive doses.1 5

Dosage

Adults

Initially, 1 mcg/kg weekly based on actual body weight.1

Adjust dosage at weekly intervals in increments of 1 mcg/kg (up to a maximum dosage of 10 mcg/kg weekly) until a platelet count of ≥50,000/mm3 is achieved.1

Reduce dosage by 1 mcg/kg weekly if platelet count is >200,000/mm3 for 2 consecutive weeks.1 Do not administer if platelet count is >400,000/mm3; assess the platelet count weekly and resume romiplostim at a dosage reduced by 1 mcg/kg weekly once the platelet count is <200,000/mm3.1 Discontinue romiplostim if, after 4 weeks of therapy at the maximum recommended dosage of 10 mcg/kg weekly, the platelet count has not increased to a level sufficient to avoid clinically important bleeding.1

Monitor CBC, including platelet count and peripheral blood smear, weekly until a stable platelet count (≥50,000/mm3 for ≥4 weeks without dosage adjustment) has been achieved; monitor CBC, including platelet count and peripheral blood smear, at least monthly thereafter.1 Because of the potential for worsening thrombocytopenia following discontinuance of romiplostim, monitor CBC, including platelet count, weekly for at least 2 weeks after drug discontinuance.1

Prescribing Limits

Adults

Maximum 10 mcg/kg weekly.1

Special Populations

No special population dosage recommendations at this time.1

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• difficulty with breathing
• pain in the chest, groin, or legs, especially the calves
• pinpoint red spots on the skin
• severe, sudden headache
• slurred speech
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sudden, unexplained shortness of breath
• unusual bleeding or bruising
• vision changes

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• difficulty with moving
• dizziness
• headache
• heartburn
• indigestion
• muscle aching or cramping
• muscle pains or stiffness
• pain in the arms or legs
• pain in the joints
• pain in the shoulder
• stomach discomfort, upset, or pain
• swollen joints
• trouble sleeping

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If you have an allergy to romiplostim or any other part of Nplate (romiplostim).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Nplate with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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

• It is given as a shot into the fatty part of the skin.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• Shortness of breath.
• A burning, numbness, or tingling feeling that is not normal.
• Any unexplained bruising or bleeding.
• Coughing up blood.
• Chest pain or pressure.
• Very bad belly pain.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Change in eyesight.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Nplate, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Nplate. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Nplate (romiplostim).

Review Date: October 4, 2017

      Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

Progression from myelodysplastic syndromes (MDS) to acute myelogenous leukemia (AML) has been observed in clinical trials with Nplate.

A randomized, double-blind, placebo-controlled trial enrolling patients with severe thrombocytopenia and International Prognostic Scoring System (IPSS) low or intermediate-1 risk MDS was terminated due to more cases of AML observed in the Nplate arm. This trial consisted of a 58-week study period with a 5-year long-term follow-up phase. The subjects were randomized 2:1 to treatment with Nplate or placebo (167 Nplate, 83 placebo). During the 58-week study period, progression to AML occurred in 10 (6.0%) subjects in the Nplate arm and 4 (4.8%) subjects in the placebo arm (hazard ratio [95%CI] = 1.20 [0.38, 3.84]). Of the 250 subjects, 210 (84.0%) entered the long-term follow-up phase of this study. With 5-years of follow-up, 29 (11.6%) subjects showed progression to AML, including 20/168 (11.9%) subjects in the Nplate arm versus 9/82 (11.0%) subjects in the placebo arm (HR [95% CI] = 1.06 [0.48, 2.33]). The incidence of death (overall survival) was 55.7% (93/167) in the Nplate arm versus 54.2% (45/83) in the placebo arm (HR [95% CI] = 1.03 [0.72, 1.47]). In the baseline low IPSS group, there was a higher incidence of death in the Nplate arm [41.3% (19/46)] compared to the placebo arm [30.4% (7/23)] [HR (95% CI) = 1.59 (0.67, 3.80)].

In a single-arm trial of Nplate given to 72 subjects with thrombocytopenia-related MDS, 8 (11.1%) subjects were reported as having possible disease progression, of which 3 (4.2%) had confirmation of AML during follow-up. In addition, in 3 (4.2%) subjects, increased peripheral blood blast cell counts decreased to baseline after discontinuation of Nplate.

Nplate is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.

      Thrombotic/Thromboembolic Complications

Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate.

To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate in an attempt to normalize platelet counts. Follow the dose adjustment guidelines [see Dosage and Administration (2.1)].

      Loss of Response to Nplate

Hyporesponsiveness or failure to maintain a platelet response with Nplate should prompt a search for causative factors, including neutralizing antibodies to Nplate [see Adverse Reactions (6.3)]. To detect antibody formation, submit blood samples to Amgen (1-800-772-6436). Amgen will assay these samples for antibodies to Nplate and thrombopoietin (TPO). Discontinue Nplate if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.

      Laboratory Monitoring

Obtain CBCs, including platelet counts, weekly during the dose adjustment phase of Nplate therapy and then monthly following establishment of a stable Nplate dose. Obtain CBCs, including platelet counts, weekly for at least 2 weeks following discontinuation of Nplate [see Dosage and Administration (2.1)].

      Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of romiplostim has not been evaluated. The mutagenic potential of romiplostim has not been evaluated. Romiplostim had no effect on the fertility of rats at doses up to 37 times the MHD based on systemic exposure.

      Animal Toxicology and/or Pharmacology

In a 4-week repeat-dose toxicity study in which rats were dosed subcutaneously three times per week, romiplostim caused extramedullary hematopoiesis, bone hyperostosis, and marrow fibrosis at clinically equivalent and higher doses. In this study, these findings were not observed in animals after a 4-week post treatment recovery period. Studies of long-term treatment with romiplostim in rats have not been conducted; therefore, it is not known if the fibrosis of the bone marrow is reversible in rats after long-term treatment.

Call your doctor for instructions if you miss an appointment for your Nplate injection.

Other drugs may interact with romiplostim, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.