Drugs Licensed in 2008 with Mechanisms Similar to Previously Approved Drugs

Generic Name	Brand Name	Pharmacology	2008 FDA Approved Indication	Pharmacologically Similar Agents
Bendamustine	Treanda	alkylating agent	Treatment of chronic lymphocytic leukemia	busulfan, carmustine, chlorambucil, cyclophosphamide, ifosfamide, melphalan
Certolizumab	Cimzia	tumor necrosis factor inhibitor	Management of Chron's disease

Table: New Pharmacological Drug Classes Introduced in 2008

Pharmacologic Class	First to be Marketed in the U.S.	FDA Approved Indication
C1 inhibitor	C1 inhibitor(CinryzeR)	Routine prophylaxis against angioedema attacks in patients with hereditary angioedema
CXCR4 chemokine receptor inhibitor	plerixa (MozobilR)	Mobilization of granulocyte-colony stimulating factor induced hematopoietic stem cells to the peripheral blood prior to collection

New Drug of the day : Romiplostim

New Pharmacological Drug Classes Introduced in 2008 

Romiplostim is an fusion protein (peptibody) that contains two identical single-chain subunits, each consisting of a human immunoglobulin IgG1 Fc domain covalently linked to a peptide containing two TPO receptor-binding domains. 

The drug is licensed for the treatment of thrombocytopenia in patients with refractory chronic immune thrombocytopenic purpura and acts as a thrombopoietin (TPO) receptor agonist to activate intracellular transcriptional pathways leading to increased platelet production.

As a class, TPO receptor agonists are thought to increase the risk for development of bone marrow fibrosis and may increase the risk for hematologic malignancies. 

Romiplostim is administered as a subcutaneous injection with the dose adjusted to the lowest dose necessary to reduce the risk of bleeding and achieve a platelet count ≥50 x 109/L. A maximum weekly dose of 10 mcg/kg is recommended with therapy discontinued if the platelet count does not increase sufficiently within 4 weeks of therapy. Hyporesponsiveness or failure to maintain a platelet response may signal the development of neutralizing antibodies. 

Discontinuation of therapy poses a risk for worsening of thrombocytopenia below baseline, with subsequent hemorrhage. Patients receiving romiplostim must be monitored prior to initiation of therapy, frequently during treatment, and for 2 weeks following cessation of therapy.

New Drug of the day : PLERIXA

New Pharmacological Drug Classes Introduced in 2008 

Plerixa started out as an investigational anti-retroviral drug for the treatment of AIDS. An unexpected finding of increased CD34+ hematopoietic stem cell counts in the peripheral blood of subjects exposed to the drug eventually lead to its licensing for use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection prior to autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma.

Plerixa is an inhibitor of the CXCR4 chemokine receptor. 

CXCR4, is normally responsible for ‘‘homing’’ (anchoring) stem cells in the bone marrow.¹⁶ Plerixa antagonizes the interaction between CXCR4 and its cognate ligand, stromal cell-derived factor-1α. Plerixa works synergistically with G-CSF and is given after "priming" with 4 daily doses of G-CSF. Plerixa is administered subcutaneously, in a dose of 0.24 mg/kg (up to 40 mg), approximately 11 hours prior to an apheresis session, in conjuction with additional daily G-CSF, for up to 4 consecutive days. 

Approximately 1/2 of non-Hodgkins lymphoma patients receiving plerixa will achieve a yield >5 x 10⁶ CD34+ cell harvests after 2 apheresis sessions. 

Data for patients with multiple myeloma suggests that approximately 75% will achieve a yield >6 x 10⁶ CD34+ cell harvests after 2 apheresis sessions. Plerixa is primarily eliminated by the kidneys. Drug-drug interactions may result from coadministration with drugs that reduce renal function or compete for active tubular secretion. (See Figure 4.) (CID: 16727404) 

The most common adverse reactions reported in patients who received plerixa in conjunction with G-CSF and aphresis were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, vomiting, abdominal pain, hyperhidrosis, abdominal distention, dry mouth, erythema, stomach discomfort, malaise, hypoesthesia, constipation, dyspepsia, and musculoskeletal pain. 

New Drug of the day : Methylnaltrexone

New Pharmacological Drug Classes Introduced in 2008 

Methylnaltrexone is a peripherally acting μ-opioid receptor antagonist FDA approved for the treatment of refractory opioid-induced constipation in patients with advanced illness (e.g., cancer, AIDS) who are receiving palliative care.

Administered subcutaneously no more frequently than once per day, methylnaltrexone stimulates laxation within 4 hours in approximately 60% of patients. 

Clinical experience confirms a much more rapid onset of action in patients who are opioid tolerant. Methylnaltrexone is a quaternary amine derivative of naltrexone with a limited ability to penetrate into the central nervous system. Side effects are largely extensions of normal gastrointestinal functions: abdominal pain, flatulence, nausea, and diarrhea. The drug is a weak CYP2D6 inhibitor with no known drug-drug interactions. Methylnaltrexone undergoes hepatic metabolism; however, N-demethylation to naltrexone is not thought to be a significant pathway.

Renal excretion of unchanged drug is the dominant route of elimination. The usual dose of methylnaltrexone is 8-12 mg, depending on body weight. Therapy for longer than 4 weeks in the target population of patients with terminal illness is unstudied. Methylnaltrexone was investigated as a treatment for postoperative ileus, but with disappointing results.