CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. TNF- :Tumor necrosis factor - is an inflammatory cytokine produced during acute inflammation and can lead to cell damage and death. See additional information. Titrate as follows to the target dose to reduce risk of GI symptoms. pregnancy (except anthrax infection and malaria tx use) pts ; 8 yo avoid: breastfeeding during tx and x5 days after D/C (Lyme dz use) avoid: breastfeeding (>3wk tx duration in non-Lyme dz use) There was a dose-related increase in spontaneous abortions, with most abortions occurring during Weeks 3 to 4 of dosing in the first trimester, at doses approximately 2.1-times the MRHD and greater (on an area under the curve [AUC] basis at doses 50 mg/kg/day). A similar reduction in systemic exposure may be seen with coadministration of apremilast and barbiturates which may result in a loss of efficacy of apremilast. Apremilast is contraindicated in patients with a known hypersensitivity to apremilast or any excipients in the formulation. Table 1: Recommended Dosing for the Prevention of Nausea and Vomiting Associated with HEC. Plaque Psoriasis: The LIBERATE trial evaluated the efficacy and safety of Apremilast in patients with moderate to severe plaque psoriasis. Massage Therapy: It is also possible to obtain some relief from massage therapy. Send the page "" Apremilast is known chemically as N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide. [25], O=S(=O)(C)C[C@H](c1ccc(OC)c(OCC)c1)N3C(=O)c2cccc(c2C3=O)NC(=O)C, InChI=1S/C22H24N2O7S/c1-5-31-19-11-14(9-10-18(19)30-3)17(12-32(4,28)29)24-21(26)15-7-6-8-16(23-13(2)25)20(15)22(24)27/h6-11,17H,5,12H2,1-4H3,(H,23,25)/t17-/m1/s1, Discovery and development of thalidomide and its analogs, "Otezla 30 mg Film-Coated Tablets Summary of Product Characteristics (SmPC)", "Otezla (aprelimast) dosing, indications, interactions, adverse effects, and more", "Apremilast (Otezla) Use During Pregnancy", "Otezla- apremilast tablet, film coated Otezla- apremilast kit", "Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis", "Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis", "Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis", "A novel stable and non-solvate crystal form II on Apremilast and processes for the preparation thereof", "Oral Otezla (apremilast) Approved by the U.S. Food and Drug Administration for the Treatment of Patients with Moderate to Severe Plaque Psoriasis", Apremilast for the Treatment of Psoriatic Arthritis, "Celgene launches new psoriasis drug Otezla in UK", "FDA approves Otezla to treat psoriatic arthritis", "FDA Approves OTEZLA (apremilast) for the Treatment of Oral Ulcers Associated with Behet's Disease", "Amgen To Acquire Otezla For $13.4 Billion in Cash or Approximately $11.2 Billion Net of Anticipated Future Cash Tax Benefits", "Amgen Reports Fourth Quarter And Full Year 2020 Financial Results", https://en.wikipedia.org/w/index.php?title=Apremilast&oldid=1098342428, Pages with non-numeric formatnum arguments, Articles containing unverified chemical infoboxes, Creative Commons Attribution-ShareAlike License 3.0, This page was last edited on 15 July 2022, at 10:39. Apremilast is FDA approved for treating psoriatic arthritis in adult patients with moderately to severely active disease, plaque psoriasis in adult patients who are candidates for phototherapy If you are not based in New Zealand, we suggest you refer to your national drug approval agency for further information about medicines (eg, the Australian Therapeutic Goods Administration and the US Food and Drug Administration) or a national or state-approved formulary (eg, the New Zealand Formulary and New Zealand Formulary for Children and the British National Formulary and British National Formulary for Children). Apremilast has moderate interactions with at least 11 other drugs. Worsening of previous symptoms of depression - to be noted and brought to the doctor's attention. PASI-75 Response: The percentage of participants who achieved at least 75 % improvement from baseline in PASI score at Week 16. Apremilast pharmacokinetics were characterized in subjects with mild, moderate, and severe renal impairment as defined by a creatinine clearance of 60 to 89, 30 to 59, and less than 30 mL per minute, respectively, by the CockcroftGault equation. A conventional synthetic immunomodulator (methotrexate,1 leflunomide or sulfasalazine) is medically Patients treated with Apremilast tablets should have their weight monitored regularly. 3 5 WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported during post marketing surveillance. AUC for the total number of oral ulcers (least-squares mean difference, 92.6; 95 % confidence interval [CI], 130.6 to 54.6; P<0.001): Behet's Disease Quality of Life score (change from baseline)(least-squares mean difference, 3.1 points; 95 % CI, 4.9 to 1.3): Take Apremilast as per prescription only. apremilast While no dose adjustment is needed in patients with mild or moderate renal impairment, the dose of Apremilast should be reduced to 30 mg once daily in patients with severe renal impairment [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. Apremilast is a prescription medication used to treat Psoriatic Arthritis, Plaque Psoriasis, and Oral Ulcers associated with Behet Disease, Oral Ulcers associated with Behet Disease. Placebo: 18 % of patients achieved 20 % improvement in ACR20 response criteria. DailyMed There was no effect of Apremilast approximately 1.0-times the MRHD (10 mg/kg/day). No teratogenic findings attributed to Apremilast were observed in either study; however, there was an increase in postimplantation loss at doses corresponding to a systemic exposure of 2.3-times the MRHD and greater ( 20 mg/kg/day). Visit other versions in US, UK, Australia, India, Philippines and Home Most events occurred within the first few weeks of treatment. Treatment with apremilast is associated with an increase in depression. [2][3], Its half-life is 69 hours. Thiopental: (Major) The coadministration of apremilast and barbiturates is not recommended. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Last reviewed at:13 Jul 2022-20 min read, Comprehensive Medical Second Opinion.Submit your Case, High Creatinine Levels | Symptoms | Diagnosis | Treatment, Poison Ivy - Causes | Symptoms | Diagnosis | Treatment | Prevention, I-Pill Versus Unwanted 72 - Side Effects | Precautions | Usage, Vaginal Folliculitis - How To Rid Vaginal Folliculitis | Diagnosis | Prevention. - Diarrhea. IL: Interleukins are a group of proteins that regulate immune responses. Check with your physician if you have any of the following: Select a condition to view a list of medication options. to drug/class/compon. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The resulting increase in cAMP levels down-regulates expression of a number of pro-inflammatory factors such as tumor necrosis factor alpha (TNF), interleukin 17, interleukin 23, and many others, and up-regulates the anti-inflammatory interleukin 10. Remember that Apremilast will only provide some control over your symptoms. Pharmacokinetic trials have compared Asian (Chinese and Japanese subjects) males to Caucasian male subjects; trials have also been performed among Hispanic and non-Hispanic Caucasians and African-Americans. Apremilast tablets dosage should be reduced to 30 mg once daily in patients with severe renal impairment (creatinine clearance (CLcr) of less than 30 mL per minute estimated by the CockcroftGault equation) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. Day 3: 10 mg PO in the morning and 20 mg PO in the evening. Lumacaftor; ivacaftor is a strong CYP3A4 inducer. Find medical information for amoxicillin on epocrates online, including its dosing, contraindications, drug interactions, and pill pictures. Day 2: 10 mg PO twice daily. A similar reduction in systemic exposure may be seen with coadministration of apremilast and barbiturates which may result in a loss of efficacy of apremilast. Before using Apremilast in patients with a history of depression and/or suicidal thoughts or behavior prescribers should carefully weigh the risks and benefits of treatment with Apremilast in such patients. Study PSOR-1 enrolled 844 subjects and Study PSOR-2 enrolled 413 subjects. WebMD does not provide medical advice, diagnosis or treatment. Topics AZ Apremilast was approved for the treatment of plaque psoriasis in patients: The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for apremilast for: It has been reported to be particularly effective in palmoplantar psoriasis. apremilast - Nausea. Apremilast is contraindicated in children until concrete results are obtained from other large-scale studies. Psoriatic arthritis usually occurs in those patients who have previously been diagnosed with psoriasis. Co-administration of the CYP450 inducer rifampin (600 mg once daily for 15 days) with a single oral dose of 30-mg Apremilast resulted in reduction of Apremilast AUC and Cmax by 72% and 43%, respectively [see Warnings and Precautions (5.3) and Drug Interactions (7.1)]. Coadministration of another strong CYP450 inducer decreased the apremilast AUC and Cmax by 72% and 43%, respectively. Dosage forms: CAP: 150 mg, 300 mg, 600 mg; TAB: 300 mg; ER TAB: 300 mg, 450 mg; SOL: 8 mEq per 5 mL Special Note [strength clarification] Info: 8 mEq lithium ion = 300 mg lithium carbonate; doses expressed as carbonate salt, except immediate-release SOL This reduction in systemic exposure may result in a loss of efficacy of apremilast. At doses of 20 mg/kg/day skeletal variations included incomplete ossification sites of tarsals, skull, sternebra, and vertebrae. Your doctor must be made aware of your medical history and relevant personal details that can impact how Apremilast affects your body. This should also include non-prescription medications, herbal and non-allopathic medications, vitamins, and nutritional supplements. If you see positive results with Apremilast, do not stop the medication. These changes result in redness, itching, PDE4 degrades cAMP into its inactive form AMP, thus allowing these, Apremilast is an inhibitor of PDE4 and prevents the degradation of cAMP to AMP, suppressing the production of proinflammatory cytokines including tumour necrosis factor TNF-, IL-17, and interferon (IFN)- and promoting the production of anti-. Drug Interactions . [3], Apremilast is absorbed well from the gut (73%), independently of food intake, and reaches peak blood plasma concentrations after 2.5 hours. Patients, their caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and if such changes occur to contact their healthcare provider. [18][22][23] Apremilast is taken by mouth. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Tablets must be swallowed whole and not crushed, chewed, or split. Apremilast Apremilast is administered orally. +91-99-432-70000+1 (844) 432-0202 (Toll free for US & Canada), Published on Apr 23, 2022 and last reviewed on Jul 13, 2022 Medically reviewed by Drugs.com. Apremilast has serious interactions with at least 30 other drugs. However, the condition worsens with time. [18] The estimated wholesale price is $22,500 for a year of treatment. Note that this may not provide an exact translation in all languages, Home You should confirm the information on the PDR.net site through independent sources and seek other professional guidance in all treatment and diagnosis decisions. 20 % improvement in at least 3 of 5 parameters: Assessment of pain as per patient [100 mm visual analog scale (VAS)]. Apremilast is metabolized primarily by CYP3A4, with minor metabolism by CYP1A2; barbiturates are strong CYP3A4 inducers and also induce CYP1A2. Consider Apremilast tablets dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting [see Warnings and Precautions (5.1)]. Barbiturates: (Major) The coadministration of apremilast and barbiturates is not recommended. Day 2: 10 mg PO twice daily. Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, January 2015. Following oral administration of radio-labeled Apremilast, about 58% and 39% of the radioactivity is recovered in urine and feces, respectively, with about 3% and 7% of the radioactive dose recovered as Apremilast in urine and feces, respectively. suicidal ideation / Delayed / 0.1-0.2angioedema / Rapid / Incidence not knownanaphylactoid reactions / Rapid / Incidence not known, migraine / Early / 2.0-2.0depression / Delayed / 1.0-1.3, diarrhea / Early / 7.7-41.3nausea / Early / 7.4-22.0headache / Early / 4.8-14.4weight loss / Delayed / 4.9-12.0infection / Delayed / 0.6-11.5vomiting / Early / 0.8-8.7abdominal pain / Early / 0.6-8.7back pain / Delayed / 2.0-7.7arthralgia / Delayed / 5.8-5.8dyspepsia / Early / 3.0-3.0fatigue / Early / 3.0-3.0pharyngitis / Delayed / 0.2-2.6insomnia / Early / 2.0-2.0folliculitis / Delayed / 1.0-1.0gastroesophageal reflux / Delayed / Incidence not knowncough / Delayed / Incidence not knownrash / Early / Incidence not knownanorexia / Delayed / Incidence not known. Dosage Considerations Should be Given as Follows: Common side effects of Apremilast include: Serious side effects of Apremilast include: This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Peds Dosing . What are the possible side effects and complication risks of these medications? Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature]. Severe diarrhea, nausea, and vomiting have been associated with apremilast therapy. DermNet does not provide an online consultation service.If you have any concerns with your skin or its treatment, see a dermatologist for advice. Coadministration with another strong CYP3A4 inducer decreased the single-dose apremilast AUC and Cmax by 72% and 43%, respectively. Coadministration of rifampin, another strong CYP3A4 inducer, with a single dose of apremilast resulted in a decrease in apremilast AUC and Cmax by 72% and 43%, respectively. In an embryo-fetal development study in mice, Apremilast was administered at doses of 250, 500, or 750 mg/kg/day to dams during organogenesis (gestation Day 6 through 15). Tablets should not be crushed, split, or chewed. - No dose adjustments of Apremilast are required in patients with liver disease. While no dose adjustment is needed in patients with mild or moderate renal impairment, the dose of Apremilast should be reduced to 30 mg once daily in patients with severe renal impairment [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. [56883] The specific mechanism by which apremilast exerts its therapeutic effect is not fully elucidated.[56870]. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. This information does not contain all possible interactions or adverse effects. Arch Dermatol 2012; 148: 95102. Regular, low-stress exercise forms can make a difference and improve your flexibility and mobility. Register Now. [21], Apremilast was approved by the US Food and Drug Administration (FDA) in 2014, for treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis, and approved in 2019, for oral ulcers associated with Behet's disease. The recommended initial dosage titration of Apremilast tablets from Day 1 to Day 5 is shown in Table 1. The condition causes your skin cells to grow at least ten times faster than is usual - and build up as a result. We comply with the HONcode standard for trustworthy health information. A similar reduction in systemic exposure may be seen with coadministration of apremilast and barbiturates which may result in a loss of efficacy of apremilast. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Drug History: Your doctor will need a complete and accurate list of all the medication you may be taking in order to determine if drug interactions may occur and cause reactions or reduce the effectiveness of Apremilast. Day 6 and thereafter: 30 mg PO twice daily. Apremilast Apremilast 20 mg Group: 28 % of patients achieved 20 % improvement in ACR20 response criteria. Plasma Clearance: 10 liters/hour (healthy subjects). In both studies, subjects were randomized 2:1 to Apremilast 30 mg BID or placebo for 16 weeks. Mean apparent volume of distribution (Vd) is 87 L. Following oral administration in humans, Apremilast is a major circulating component (45%) followed by inactive metabolite M12 (39%), a glucuronide conjugate of O-demethylated Apremilast. Clinical trials have shown that Apremilast may commonly cause the following side effects: Nausea. Vomiting. Diarrhea. Headache. Symptoms of cold (sneezing, runny nose, sore throat). Infections of the respiratory tract. Stomach pain. Weight loss. Depression. Suicidal ideation. [17], Otezla is available in the U.S., but is dispensed only through a network of specialty pharmacies. Psoriatic arthritis is a lifelong disease, occasionally punctuated with periods of remission. Do not crush, split, or chew the tablets. If unexplained or clinically significant weight loss occurs, weight loss should be evaluated, and discontinuation of Apremilast should be considered [see Adverse Reactions (6.1)]. If no chemotherapy is given on Days 2 and 3, administer Aprepitant capsules in the morning. Co-administration of Ketoconazole: No significant interactions. A similar reduction in systemic exposure may be seen with coadministration of apremilast and barbiturates which may result in a loss of efficacy of apremilast. Vardenafil CONFLICT OF INTEREST. The most common adverse reactions leading to discontinuation for subjects taking Apremilast were nausea (1.6%), diarrhea (1.0%), and headache (0.8%). For initial dosage titration in this group, it is recommended that Apremilast tablets be titrated using only the AM schedule listed in Table 1 and the PM doses be skipped. Table 3: Adverse Reactions Reported in 1% of Subjects on, Apremilast and With Greater Frequency Than in Subjects on Placebo; up to Day 112 (Week 16). In vitro, CYP metabolism of apremilast is primarily mediated by CYP3A4, with minor contributions from CYP1A2 and CYP2A6. Week 16 Crossover: For placebo patients not showing at least 20 % improvement in swelling and tenderness of joints. Apremilast may cause significant weight loss in some patients. It may be prescribed when other drugs for psoriasis fail to provide relief from the symptoms. 5 WARNINGS AND PRECAUTIONS Pill Identifier Tool Quick, Easy, Pill Identification, Drug Interaction Tool Check Potential Drug Interactions, Pharmacy Locator Tool Including 24 Hour, Pharmacies. Aflibercept, sold under the brand names Eylea and Zaltrap, is a medication used to treat wet macular degeneration and metastatic colorectal cancer.It was developed by Regeneron Pharmaceuticals and is approved in the United States and the European Union.. Advise patients of the possibility of side effects such as nausea, diarrhea, vomiting. The authors declare no conflict of interest. Find medical information for Keflex on epocrates online, including its dosing, contraindications, drug interactions, and pill pictures. Apremilast is metabolized primarily by CYP3A4; phenytoin is a strong CYP3A4 inducer. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. Warnings and Precautions: The effects of Apremilast that need to be considered include: Nausea, Vomiting, and Diarrhea: These side effects usually occur during the initial weeks of treatment, particularly in patients over 65 years of age or in those taking medications that can cause volume depletion or hypotension. Peds Dosing . [6], Apremilast is indicated in the United States for the treatment of adults with active psoriatic arthritis, adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy, and adults with oral ulcers associated with Behet's disease. Advise patients Apremilast tablets can be taken with or without food. Jun-Jul 2019;146(6-7):470-473. doi: 10.1016/j.annder.2019.04.016. Metformin: Uses, Interactions, Mechanism of Action - DrugBank Apremilast Apremilast, a phosphodiesterase 4 inhibitor, is another oral agent for the treatment of plaque psoriasis . - Stomach pain. The active ingredient in Apremilast tablets is Apremilast. 20 % improvement in 76 swollen joint counts. The main metabolite is O-desmethylapremilast glucuronide. This includes your psychological history - particularly depression. Rifampin is a strong CYP3A4 inducer and also induces CYP1A2 and CYP2D6. Apremilast is an immunosuppressant drug indicated for inflammatory disorders like psoriasis. Inflammation of the blood vessels, joints, brain, and nervous system. - Vomiting. *Two subjects treated with Apremilast experienced serious adverse reaction of abdominal pain. 2 Tocilizumab was granted Learn more. Amneal Pharmaceuticals LLC Apremilast is recommended as a treatment option for mouth sores in Behet's disease. Based on findings from animal reproduction studies, Apremilast may increase the risk for fetal loss. Apremilast is metabolized primarily by CYP3A4, with minor metabolism by CYP1A2; barbiturates are strong CYP3A4 inducers and also induce CYP1A2. Carbamazepine is a strong CYP3A4 inducer and also induces CYP1A2. CrCl less than 30 mL/minute: Do not exceed 30 mg PO once daily. Apremilast may be taken with or without food. The exact mechanism of action of Apremilast is unclear and incompletely established. Drug interaction studies were performed with Apremilast and CYP3A4 substrates (oral contraceptive containing ethinyl estradiol and norgestimate), CYP3A and P-gp inhibitor (ketoconazole), CYP450 inducer (rifampin) and frequently co-administered drug in this patient population (methotrexate). Decrease dose 50% in severe renal impairment. The symptom-controlling benefits of Apremilast are usually achieved within twelve to sixteen weeks (about four months) of beginning treatment. Patients already suffering from depression need to be cautious when taking the drug. Tablet Core: Cellulose, microcrystalline Lactose, monohydrate Croscarmellose, Sodium, Magnesium stearate. No evidence of Apremilast-induced tumors was observed in mice at oral doses up to 8.8-times the Maximum Recommended Human Dose (MRHD) on an AUC basis (1,000 mg/kg/day) or in rats at oral doses up to approximately 0.08- and 1.1-times the MRHD, (20 mg/kg/day in males and 3 mg/kg/day in females, respectively). The inhibition of PDE4 causes intracellular cAMP molecules to rise. Papp K, Cather JC, Rosoph L, et al. Bridgewater, NJ 08807, Apremilast Tablets, Two week starter pack, Otezla, Cosentyx, Enbrel, Humira, Ilumya, Stelara, Taltz, Duobrii, prednisone, Remicade. Rifampin is a strong CYP3A4 inducer and also induces CYP1A2 and CYP2D6. Apremilast is metabolized primarily by CYP3A4, with minor metabolism by CYP1A2; barbiturates are strong CYP3A4 inducers and also induce CYP1A2. Advise patients that the tablets should not be crushed, split, or chewed. Apremilast Nail Changes: The nails may display pitting or may be separated from the nail beds. Lancet 2012; 380: 73846. Apremilast Patients who reduced dosage or discontinued Apremilast generally improved quickly. Patients who have stopped taking Apremilast have experienced a reversal of its therapeutic effects within five weeks of quitting. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment. Apremilast tablets are contraindicated in patients with a known hypersensitivity to Apremilast or to any of the excipients in the formulation [see Adverse Reactions (6.1) ]. Behet's disease or Behet's syndrome is an inflammatory disorder of the blood vessels in your body that can cause a variety of apparently unrelated signs and symptoms. Otezla 30 mg Film-Coated Tablets Biologic agents such as Adalimumab and Etanercept can modify the body's biological response by targeting your immune system through a different pathway. A similar reduction in systemic exposure may be seen with coadministration of apremilast and barbiturates which may result in a loss of efficacy of apremilast. This reduction in systemic exposure may result in a loss of efficacy of apremilast. Pharmacokinetic trials have been conducted in healthy patients (volunteers). Apremilast tablets are available as oval shaped, film coated tablets in the following dosage strengths: Apremilast tablets are contraindicated in patients with a known hypersensitivity to Apremilast or to any of the excipients in the formulation [see Adverse Reactions (6.1)]. Apremilast is metabolized primarily by CYP3A4; phenytoin is a strong CYP3A4 inducer. Apremilast, an oral phosphodiesterase-4 inhibitor, is approved for use in the management of psoriasis and psoriatic arthritis. Tadalafil, a PDE-5 inhibitor, has FDA approval to treat both. What are the new drugs for the treatment of plaque psoriasis? Consult the relevant authorities for information on the local medicine disposal system if you are unaware of how it works. Apremilast is a substrate of CYP3A4; St. John's Wort is a strong CYP3A4 inducer.
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