Aliskiren From Wikipedia, the free encyclopedia Jump to: navigation, search Aliskiren

Systematic (IUPAC) name (2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide

Chemical data Formula Mol. mass SMILES InChI[show] Pharmacokinetic data Bioavailability Metabolism Half-life Excretion Low (approximately 2.5%) Hepatic, CYP3A4-mediated 24 hours Renal C30H53N3O6 551.758 g/mol eMolecules & PubChem

Therapeutic considerations Licence data EMA:Link, US FDA:link

Pregnancy cat. C in first trimester D in second and third trimesters Legal status POM (UK) -only (US)

Routes

PO (oral)

(what is this?) (verify) Aliskiren (INN) (trade names Tekturna, U.S.; Rasilez, U.K. and elsewhere) is the first in a class of drugs called direct renin inhibitor. Its current licensed indication is primary (previously essential) hypertension. Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[1][2] It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of primary hypertension.[3] Contents [hide] 1 Mechanism of action 2 Rationale for design 3 Adverse effects 4 Contraindications 5 Drug interactions 6 See also 7 References 8 External links [edit] Mechanism of action Renin is the first enzyme in the renin-angiotensin-aldosterone system which plays a role in blood pressure control. Renin cleaves angiotensinogen to angiotensin I, which is in turn converted by (ACE) to angiotensin II. Angiotensin II has both direct and indirect effects on blood pressure. It directly causes arterial smooth muscle to contract, leading to vasoconstriction and increased blood pressure. Angiotensin II also stimulates the production of aldosterone from the adrenal cortex, which causes the tubules of the kidneys to increase reabsorption of sodium, with water following thereby increasing plasma volume and blood pressure. Aliskiren binds to the S3bp binding pocket of renin, essential for its activity.[4] Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I. Aliskiren is also available as combination therapy with hydrochlorothiazide.[5] [edit] Rationale for design Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, doctors have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so.[6][7] Aliskiren may have renoprotective effects that are independent of its blood pressurelowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. According to the AVOID study, researchers found that treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-to-creatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). Furthermore, the AVOID trial shows that treatment with 300 mg of aliskiren daily reduces albuminuria in patients with hypertension, type 2 diabetes, and proteinuria who are receiving the recommended maximal renoprotective treatment with losartan and optimal antihypertensive therapy. Therefore, direct renin inhibition will have a critical role in strategic renoprotective pharmacotherapy, in conjunction with dual blockade of the

reninangiotensinaldosterone system with the use of ACE inhibitors and angiotensin IIreceptor blockers, very high doses of angiotensin IIreceptor blockers, and aldosterone blockade.[8] [edit] Adverse effects Angioedema Hyperkalemia (particularly when used with ACE inhibitors in diabetic patients) Hypotension (particularly in volume-depleted patients) Diarrhea and other GI symptoms Headache Dizziness Cough Rash Elevated uric acid, gout, and renal stones Rarely: allergic swelling of the face, lips or tongue and difficulty breathing [edit] Contraindications Pregnancy: other drugs such as ACE inhibitors, also acting on the renin-angiotensin system have been associated with fetal malformations and neonatal death[9] [10] Breast feeding: during animal studies, the drug has been found present in milk. Aliskiren has not yet been evaluated in patients with significantly impaired renal function. [edit] Drug interactions Aliskiren is a minor substrate of CYP3A4 and, more important, P-glycoprotein: Reduces furosemide blood concentration. Atorvastatin may increase blood concentration, however no dose adjustment needed. Possible interaction with ciclosporin ( the concomitant use of ciclosporin and aliskiren is contraindicated). Caution should be exercised when aliskiren is administered with ketoconazole or other moderate P-gp inhibitors (itraconazole, clarithromycin, telithromycin, erythromycin, amiodarone).

Why is this medication prescribed? Aliskiren is used alone or in combination with other medications to treat high blood pressure. Aliskiren is in a class of medications called direct renin inhibitors. It works by decreasing certain natural chemicals that tighten the blood vessels, so blood vessels relax and the heart can pump blood more efficiently. How should this medicine be used? Aliskiren comes as a tablet to take by mouth. It is usually taken once a day. Aliskiren should be taken the same way each time, either always with food or always without food. Take aliskiren at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take aliskiren exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Your doctor will probably start you on an low dose of aliskiren and may increase your dose after you have been taking this medication for at least two weeks. Aliskiren controls high blood pressure but does not cure it. Continue to take aliskiren even if you feel well. Do not stop taking aliskiren without talking to your doctor. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Other uses for this medicine Return to top This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. What special precautions should I follow? Return to top Before taking aliskiren, tell your doctor and pharmacist if you are allergic to aliskiren or any other medications. tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); antifungals such as ketoconazole (Nizoral); atorvastatin (Lipitor); diuretics ('water pills') such as hydrochlorothiazide (HCTZ) and furosemide (Lasix); irbesartan (Avapro); and other medications for heart disease or high blood pressure. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had diabetes, seizures, or kidney disease. tell your doctor if you plan to become pregnant or are breast-feeding. Do not breast-feed while taking aliskiren. you should know that aliskiren may cause dizziness, lightheadedness, and fainting. Lie down if you feel faint or dizzy, and call your doctor right away. What special dietary instructions should I follow? Return to top Unless your doctor tells you otherwise, continue your normal diet. What should I do if I forget a dose? Return to top Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. What side effects can this medication cause? Return to top Aliskiren may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: diarrhea stomach pain heartburn cough rash Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately: swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs hoarseness difficulty swallowing or breathing

lightheadedness fainting Aliskiren may cause other side effects. Call your doctor if you have any unusual problems while taking this medication. What storage conditions are needed for this medicine? Return to top Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not remove the desiccant (drying agent) from the bottle, if one has been provided. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication. In case of emergency/overdose Return to top In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911. Symptoms of overdose may include: fainting dizziness blurred vision nausea What other information should I know? Return to top Keep all appointments with your doctor. Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription. It is important for you to keep a written list of all of the prescription and nonprescription (over-thecounter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies. Brand names Return to top Tekturna Brand names of combination products Return to top Tekturna HCT (containing Aliskiren Hemifumarate and Hydrochlorothiazide) Valturna (containing Aliskiren Hemifumarate and Valsartan)