Romiplostim

Trade Names:Nplate- Injection, lyophilized 250 mcg- Injection, lyophilized 500 mcg

Pharmacology

Increases platelet production by binding and activation of the thrombopoietin (TPO) receptor.

Pharmacokinetics

Absorption

C _max is 7 to 50 h postdose (median, 14 h).

Distribution

Serum concentration does not correlate with the dose.

Elimination

Elimination half-life ranges from 1 to 34 days (median, 3.5 days). Elimination is dependent in part on TPO receptors on platelets.

Indications and Usage

Treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Contraindications

Standard considerations.

Dosage and Administration

Romiplostim may only be prescribed by health care providers enrolled in the Network of Experts Understanding and Supporting (NEXUS) program and must be administered by prescribers or health care providers under their direction. This program provides educational materials and a mechanism for proper use of romiplostim.

Subcutaneous Start with 1 mcg/kg based on actual body weight. Adjust the dose weekly by increments of 1 mcg/kg until the platelet count is at least 50 × 10 ⁹ /L as needed to reduce the risk of bleeding (max, 10 mcg/kg/week). If the platelet count is less 50 × 10 ⁹ /L, increase the dose by 1 mcg/kg. If the platelet count is more than 200 × 10 ⁹ /L for 2 consecutive weeks, reduce the dose by 1 mcg/kg. If the platelet count is more than 400 × 10 ⁹ /L, do not administer. Continue to assess the platelet count weekly. After the platelet count has fallen to less than 200 × 10 ⁹ /L, resume at a dose reduced by 1 mcg/kg. Discontinue romiplostim if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 wk of therapy at the max dose of 10 mcg/kg.

General Advice

• Use the lowest dose to achieve and maintain a platelet count of at least 50 × 10 ⁹ /L as needed to reduce the risk of bleeding.
• Use 0.72 mL of sterile water for injection to reconstitute 250 mcg vial; use 1.2 mL to reconstitute 500 mcg vial. Do not reconstitute with bacteriostatic water for injection.
• Do not shake. Gently swirl and invert the vial to reconstitute.
• Discard any unused portion. Do not pool unused portions. Do not administer more than 1 dose from a vial.

Storage/Stability

Store in the refrigerator between 36° and 46°F. Do not freeze. Protect from light. Reconstituted romiplostim can be stored at 77°F or refrigerated between 36° and 46°F for up to 24 h prior to administration. Protect from light.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Dizziness (17%); insomnia (16%); paresthesia (6%).

GI

Abdominal pain (11%); dyspepsia (7%).

Musculoskeletal

Arthralgia (26%); myalgia (14%); shoulder pain (8%).

Miscellaneous

Pain in extremity (13%); antibody development (10%); development of binding antibody to endogenous TPO (5%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

No clinical studies have been conducted in patients with renal function impairment; use with caution.

Hepatic Function

No clinical studies have been conducted in patients with hepatic function impairment; use with caution.

Bone marrow

Risk for development or progression of reticulum fiber disposition within the bone marrow may be increased by romiplostim.

Hyporesponsiveness

Failure or loss of a platelet response with romiplostim should prompt a search for causative factors, including neutralizing antibodies to romiplostim or bone marrow fibrosis.

Malignancies

Stimulation of the TPO receptor on the surface of hematopoietic cells by romiplostim may increase the risk for hematologic malignancies.

Thrombocytopenia

Discontinuation of romiplostim may result in thrombocytopenia that is of greater severity than was present prior to therapy, which may increase the risk of bleeding.

Thrombotic/thromboembolic complications

May result from excessive increases in platelet counts.

Overdosage

Symptoms

Platelet counts may increase excessively and result in thrombotic/thromboembolic complications.

Patient Information

• Inform patients that weekly blood studies are performed until a stable dose is established, and that thereafter monthly monitoring is necessary.
• Inform patients that blood studies must be performed for at least 2 wk after discontinuation of therapy.
• Instruct patients to avoid situations or medications that increase the risk for bleeding.

Copyright © 2009 Wolters Kluwer Health.