Nplate (romiplostim)

Nplate is a prescription medicine used to treat low blood platelet counts (thrombocytopenia) in:

• adults with immune thrombocytopenia (ITP) when certain medicines or surgery to remove your spleen have not worked well enough.
• children 1 year of age and older with ITP for at least 6 months when certain medicines or surgery to remove your spleen have not worked well enough.

Nplate is not for use in people with a precancerous condition called myelodysplastic syndrome (MDS), or low platelet count caused by any condition other than ITP.

Nplate is only used if your low platelet count and medical condition increase your risk of bleeding.

Nplate is used to try to keep your platelet count about 50,000 per microliter in order to lower the risk for bleeding. Nplate is not used to make your platelet count normal.

It is not known if Nplate is safe and effective in children under the age of 1.

Nplate can cause serious side effects, including:

• Worsening of a precancerous blood condition to a blood cancer (leukemia). Nplate is not for use in people with a precancerous condition called myelodysplastic syndromes (MDS), or for any condition other than immune thrombocytopenia (ITP). If you have MDS and receive Nplate, your MDS condition may worsen and become an acute leukemia. If MDS worsens to become acute leukemia you may die sooner from the acute leukemia.
• Higher risk for blood clots.
  • You may have a higher risk of getting a blood clot if your platelet count becomes high during treatment with Nplate. You may have severe complications or die from some forms of blood clots, such as clots that spread to the lungs or that cause heart attacks or strokes.
  • If you have a chronic liver disease, you may get blood clots in the veins of your liver. This may affect your liver function.
• Injection of too much Nplate may cause a dangerous increase in your blood platelet count and serious side effects. Your healthcare provider may change your dose or stop Nplate depending upon the change in your blood platelet count. You must have blood platelet counts done before you start, during, and after Nplate therapy is stopped.

Nplate may cause serious side effects.

The most common side effects of Nplate in adults include:

• headache
• tingling or numbness in hands and feet
• joint pain
• bronchitis
• dizziness
• inflammation of the sinuses (sinusitis)
• trouble sleeping
• vomiting
• muscle tenderness or weakness
• diarrhea
• pain in the arms and legs
• upper respiratory tract infection
• stomach (abdomen) pain
• cough
• shoulder pain
• nausea
• indigestion
• pain in mouth and throat (oropharyngeal pain)

The most common side effects of Nplate in children 1 year of age and older include:

• bruising
• upper respiratory tract infection
• pain in mouth and throat (oropharyngeal pain)

People who take Nplate may have an increased risk of developing new or worsening changes in the bone marrow called “increased reticulin”. These changes may improve if you stop taking Nplate. Your healthcare provider may need to check your bone marrow for this problem during treatment with Nplate.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Amgen at 1-800-77-AMGEN (1-800-772-6436).

Recommended Dosage Regimen

For All Patients

• Use the lowest dose of Nplate to achieve and maintain a platelet count ≥ 50 x 10⁹/L as necessary to reduce the risk for bleeding. Administer Nplate as a weekly subcutaneous injection with dose adjustments based upon the platelet count response.
• The prescribed Nplate dose may consist of a very small volume (e.g., 0.15 mL). Administer Nplate only with a syringe that contains 0.01 mL graduations.
• See Section below for monitoring recommendations during Nplate therapy.
• Discontinue Nplate if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of Nplate therapy at the maximum weekly dose of 10 mcg/kg.

For Adult Patients With ITP

• The initial dose of Nplate is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating the initial dose. In adults, future dose adjustments are based on changes in platelet counts only.
• Adjust the weekly dose of Nplate by increments of 1 mcg/kg until the patient achieves a platelet count ≥ 50 x 10⁹/L as necessary to reduce the risk for bleeding; do not exceed a maximum weekly dose of 10 mcg/kg. In clinical studies, most adult patients who responded to Nplate achieved and maintained platelet counts ≥ 50 x 10⁹/L with a median dose of 2 mcg/kg.
• Adjust the dose as follows for adult patients:
  • If the platelet count is < 50 x 10⁹/L, increase the dose by 1 mcg/kg.
  • If platelet count is > 200 x 10⁹/L and ≤ 400 x 10⁹/L for 2 consecutive weeks, reduce the dose by 1 mcg/kg.
  • If platelet count is > 400 x 10⁹/L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 x 10⁹/L, resume Nplate at a dose reduced by 1 mcg/kg.

For Pediatric Patients With ITP

• The initial dose of Nplate is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating initial dose. In pediatric patients, future dose adjustments are based on changes in platelet counts and changes in body weight. Reassessment of body weight is recommended every 12 weeks.
• Adjust the weekly dose of Nplate by increments of 1 mcg/kg until the patient achieves a platelet count ≥ 50 x 10⁹/L as necessary to reduce the risk for bleeding; do not exceed a maximum weekly dose of 10 mcg/kg. In a pediatric placebo-controlled clinical study, the median of the most frequent dose of Nplate received by patients during weeks 17 through 24 was 5.5 mcg/kg.
• Adjust the dose as follows for pediatric patients:
  • If the platelet count is < 50 x 10⁹/L, increase the dose by 1 mcg/kg.
  • If platelet count is > 200 x 10⁹/L and ≤ 400 x 10⁹/L for 2 consecutive weeks, reduce the dose by 1 mcg/kg.
  • If platelet count is > 400 x 10⁹/L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 x 10⁹/L, resume Nplate at a dose reduced by 1 mcg/kg.

• Nplate may be used with other medical ITP therapies, such as
  • corticosteroids,
  • danazol,
  • azathioprine,
  • intravenous immunoglobulin (IVIG), and
  • anti-D immunoglobulin

• Based on findings from animal reproduction studies, Nplate may cause fetal harm when administered to a pregnant woman.
• Available data with Nplate use in pregnant women are insufficient to draw conclusions about any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• There is no information regarding the presence of romiplostim in human milk, the effects on the breastfed child, or the effects on milk production.
• Maternal IgG is known to be present in human milk.
• The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to romiplostim are unknown.
• Due to the potential for serious adverse reactions in a breastfed child from Nplate, advise women not to breastfeed during treatment with Nplate.