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New Drug Rilis FDA 2010

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Berikut deskripsi singkat dari obat-obatan yang telah dirilis FDA selama tahun 2010. Obat berikut termasuk NME (New molecular entities), maksudnya adalah produk obat yang mengandung zat aktif baru yang dipasarkan di US.

Tabel 1. Obat baru terpilih yang telah disetujui FDA (2009–2010)

Generik Nama Dagang Perusahaan Indikasi Tanggal Persetujuan
Asenapine Saphris Merck & Co., Inc. Treatment akut untuk skizoprenia dan manic atau episode campuran yang dihibungkan pada penyakt bipolar pada dewasa Juli 2009
Bepotastine Bepreve ISTA Pharmaceuticals Treatment rasa gatal yang dihubungkan dengan alergi konjungtivitis Agustus 2009
Dronedarone Multaq Sanofi-Aventis U.S. LLC Untuk menurunkan risiko kardiovaskuler hospitalization pada pasien dengan paroksimal atau persistent atrial fibrillation atau atrial flutter Juli 2009
Liraglutide Victoza Novo Nordisk Inc. Treatment  diabetes mellitus tipe 2 Januari 2010
Tocilizumab Actemra Genentech, Inc. Treatment pasien dewasa dengan tingkat sedang sampai parah rheumatoid arthritis aktif Januari 2010
Ustekinumab Stelara Centocor Ortho Biotech Inc. Treatment pasien dewasa pada penyakit plak psoriasis dari tingkat sedang sampai parah Desember 2009

Untuk informasi lebih lanjut bisa di baca packaging insert, pada website masing-masing produk. Berikut summary-nya dan link website produk.

Asenapine (Saphris, Merck & Co., Inc.) [link]

Asenapine, a second-generation antipsychotic, has been approved in a sublingual tablet for acute treatment of schizophrenia and manic or mixed episodes associated with bipolar disorder.

senapine is a dibenzo-oxepino pyrrole, and like most second-generation antipsychotics, is an antagonist at dopamine (D2) and serotonin (5-HT2A) receptors (FIGURE 1). It has high affinity for other dopamine and serotonin receptors, as well as alpha-adrenergic and histaminergic (H1) receptors, but low affinity for muscarinic receptors. When administered sublingually, the drug is 35% bioavailable; oral bioavailability of oral asenapine is very low (<2%) due to extensive first-pass metabolism. Steady state is achieved within 3 days of twice-daily dosing. Asenapine is cleared by direct conjugation and CYP450 1A2 oxidation and is eliminated in both the urine and feces primarily as metabolites. It has a half-life of 24 hours.

Bepotastine (Bepreve, ISTA Pharmaceuticals) [link]

Bepotastine besilate 1.5% ophthalmic solution is a H1-receptor antagonist agent approved for the topical treatment of itching associated with allergic conjunctivitis in patients 2 years of age and older. Allergic conjunctivitis is the most common form of ocular allergy, with itching as the main symptom. Treatment of ocular itching involves antihistamines (both oral and ophthalmic), ophthalmic formulations of mast cell stabilizers, nonsteroidal anti-inflammatory drugs (NSAIDs), and, in severe cases, corticosteroids. Ocular antihistamines are effective and have a more rapid onset of action than oral antihistamines. Bepotastine was first developed in Japan as an oral systemic formulation for the treatment of allergic rhinitis.

Bepotastine is similar in structure to ethanolamine antihistamines and is a topically active, direct H1-receptor antagonist and an inhibitor of mast-cell histamine release. Its onset of action is approximately 3 minutes and duration of effect is 8 hours. Bepotastine is only minimally absorbed from its application site. Absorbed drug is eliminated renally, predominately in the unchanged form.

Dronedarone (Multaq, Sanofi-aventis) [link]

Dronedarone was approved to reduce the risk of cardiovascular (CV) hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL) who have experienced a recent episode of AF/AFL, have associated CV risk factors (age >70, hypertension, diabetes, previous cerebrovascular accident, left atrial diameter ≥50 mm, left ventricular ejection fraction <40%), and are in sinus rhythm or will be cardioverted. Amiodarone, the most effective drug for this indication, has a number of limitations, including toxicity.

Dronedarone is a benzofuran, noniodinated derivative of amiodarone (FIGURE 3) with antiarrhythmic properties belonging to all four Vaughan-Williams class mechanisms. It blocks sodium, potassium, and calcium channels and has alpha-and beta-blocking properties, but which of these produce dronedarone’s clinical effects remains unclear.

Dronedarone has higher oral bioavailability (35%-65%) than amiodarone and achieves steady state levels more readily (408 days). It is also significantly less lipophilic than amiodarone, resulting in a substantially smaller volume of distribution and a much shorter elimination half-life (13-19 hours). It is extensively metabolized by CYP3A4 isozymes, initially by N -debutylation to form the active N -debutyl metabolite. This metabolite undergoes oxidative deamination to form the inactive propanoic acid metabolite and direct oxidation. These metabolites undergo further metabolism to yield over 30 uncharacterized metabolites. The N -debutyl metabolite exhibits pharmacologic activity but is significantly less potent than the parent drug. Dronedarone and its metabolites are eliminated primarily in the feces (>80%).

Liraglutide (Victoza, Novo Nordisk) [link]

Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist given by subcutaneous (SC) injection, has been approved by the FDA for treatment of patients with type 2 diabetes. It can be used alone or in addition to oral antidiabetic drugs such as metformin or glimepiride. Liraglutide is not recommended for first-line therapy and is not approved for use with insulin. Liraglutide is the second GLP-1 agonist marketed in the U.S.; the first, exenatide (Byetta), has been available since 2005.

Liraglutide is an acylated human GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP- 1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein in pancreatic beta cells. This results in increased intracellular cyclic AMP (cAMP) and promotes insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner, delays gastric emptying, and promotes satiety and weight loss.

GLP-1(7-37) has a half-life of 1.5 to 2 minutes due to rapid degradation by the ubiquitous endogenous enzymes dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after SC administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once-daily administration, is a result of self-association that delays absorption, plasma protein binding, and stability against metabolic degradation by DPP-IV and NEP.

Tocilizumab (Actemra, Genentech) [link]

Tocilizumab has been approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) inhibitor therapies (i.e., infliximab). RA is a chronic, progressive inflammatory disease of the synovium of the joints and surrounding tissues and is associated with intense pain, irreversible joint destruction, and systemic complications. It is estimated to affect 1.3 million Americans. Several key cytokines are involved and are elevated in the inflammatory process, including interleukin-6 (IL-6). Tocilizumab is the first IL-6 receptor-inhibiting monoclonal antibody approved to treat RA and may be used alone or in combination with methotrexate or other disease modifying antirheumatic drugs (DMARDs). It has been approved for a number of inflammatory disease states, including RA in Japan (2005) and the European Union (2009).

Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R) and has been shown to inhibit IL-6–mediated signaling through these receptors. IL-6 is a pleiotropic proinflammatory cytokine produced by a variety of cell types including T and B cells, lymphocytes, monocytes, and fibroblasts. IL-6 is involved in diverse physiologic processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells, leading to local production of IL-6 in joints affected by inflammatory processes such as RA. In clinical trials, tocilizumab doses of 4 to 8 mg/kg decreased levels of C-reactive protein, rheumatoid factor, erythrocyte sedimentation rate, and serum amyloid, and increased hemoglobin levels.

Ustekinumab (Stelara, Centocor Ortho Biotech) [link]

Ustekinumab, an interleukin antagonist given by SC injection, has been approved for treatment of adults with moderate-to-severe plaque psoriasis. It is the first agent in its class for this indication; the other biologic agents for psoriasis are T-cell or TNF inhibitors. Plaque psoriasis affects 6 million people in the U.S. and is an immune system disorder characterized by rapid overproduction of skin cells resulting in thickened patches of inflamed, red skin, often covered with silvery scales. Mild-to-moderate psoriasis is generally treated with topical corticosteroids (main therapy), calcitriol, calcipotriene, or tazarotene. Phototherapy is used when the disease is widespread or unresponsive to topical agents. Systemic drugs such as methotrexate, cyclosporine, and TNF inhibitors are usually reserved for moderate-to-severe disease.

Ustekinumab is a human immunoglobulin G1 (IgG1) antibody directed against the p40 subunit of IL-12 and IL-23 cytokines, which are present in psoriasis skin lesions. These cytokines activate inflammatory and immune responses thought to be involved in the keratinocyte hyperplasia characteristic of psoriasis.

In clinical trials, the median tmax was 13.5 days and 7 days after a single SC administration of 45 mg and 90 mg doses, respectively. Following multiple SC doses, steady-state serum concentrations were achieved by week 28. There was no apparent accumulation in serum ustekinumab concentration over time when given SC every 12 weeks.

The metabolism of ustekinumab has not been characterized, but as a human IgG1-kappa monoclonal antibody, it is likely degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. The mean half-life ranged from 15 to 46 days across all psoriasis studies following IV and SC administration. When given the same dose, subjects weighing >100 kg had lower median serum ustekinumab concentrations compared with those subjects weighing ≤100 kg. No pharmacokinetic data are available in patients with hepatic or renal impairment.

Referensi: Medscape, 11/11/2010, New Drug Review 2010

Daftar obat [link]


Author: admin

menebar ilmu pengetahuan

One thought on “New Drug Rilis FDA 2010

  1. terima kasih informasinya pak. sy minta izin membaca

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