Serious side effects
It happens rarely, but some people have serious side effects after taking Disys.
Call a doctor straight away if you have:
The antihypertensive effects of Diovan (Disys) were demonstrated principally in 7 placebocontrolled, 4- to 12-week trials (1 in patients over 65 years) of dosages from 10 to 320 mg/day in patients with baseline diastolic blood pressures of 95-115 mmHg. The studies allowed comparison of once-daily and twice-daily regimens of 160 mg/day; comparison of peak and trough effects; comparison (in pooled data) of response by gender, age, and race; and evaluation of incremental effects of hydrochlorothiazide.
Administration of Disys to patients with essential hypertension results in a significant reduction of sitting, supine, and standing systolic and diastolic blood pressure, usually with little or no orthostatic change.
In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs at approximately 2 hours, and maximum reduction of blood pressure is achieved within 6 hours. The antihypertensive effect persists for 24 hours after dosing, but there is a decrease from peak effect at lower doses (40 mg) presumably reflecting loss of inhibition of angiotensin II. At higher doses, however (160 mg), there is little difference in peak and trough effect. During repeated dosing, the reduction in blood pressure with any dose is substantially present within 2 weeks, and maximal reduction is generally attained after 4 weeks. In long-term follow-up studies (without placebo control), the effect of Disys appeared to be maintained for up to 2 years. The antihypertensive effect is independent of age, gender or race. The latter finding regarding race is based on pooled data and should be viewed with caution, because antihypertensive drugs that affect the renin-angiotensin system (that is, ACE inhibitors and angiotensin-II blockers) have generally been found to be less effective in low-renin hypertensives (frequently blacks) than in high-renin hypertensives (frequently whites). In pooled, randomized, controlled trials of Diovan that included a total of 140 blacks and 830 whites, Disys and an ACE-inhibitor control were generally at least as effective in blacks as whites. The explanation for this difference from previous findings is unclear.
Abrupt withdrawal of Disys has not been associated with a rapid increase in blood pressure.
The blood pressure-lowering effect of Disys and thiazide-type diuretics are approximately additive.
The 7 studies of Disys monotherapy included over 2,000 patients randomized to various doses of Disys and about 800 patients randomized to placebo. Doses below 80 mg were not consistently distinguished from those of placebo at trough, but doses of 80, 160 and 320 mg produced dose-related decreases in systolic and diastolic blood pressure, with the difference from placebo of approximately 6-9/3-5 mmHg at 80 to 160 mg and 9/6 mmHg at 320 mg. In a controlled trial the addition of HCTZ to Disys 80 mg resulted in additional lowering of systolic and diastolic blood pressure by approximately 6/3 and 12/5 mmHg for 12.5 and 25 mg of HCTZ, respectively, compared to Disys 80 mg alone.
Patients with an inadequate response to 80 mg once daily were titrated to either 160 mg once daily or 80 mg twice daily, which resulted in a comparable response in both groups.
In controlled trials, the antihypertensive effect of once-daily Disys 80 mg was similar to that of once-daily enalapril 20 mg or once-daily lisinopril 10 mg.
There are no trials of Diovan demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits.
There was essentially no change in heart rate in Disys-treated patients in controlled trials.
Do not use if you are pregnant. Stop using Disys and tell your doctor right away if you become pregnant.
If you have diabetes, do not use Disys together with any medication that contains aliskiren (a blood pressure medicine).
Q: Is there a chance that the cost of Diovan will reduce in the near future?
A: Diovan (Disys) is classified as an angiotensin II receptor blocker (ARB). Diovan is approved for the treatment of hypertension (high blood pressure), reduction of cardiovascular mortality in patients that have left ventricular dysfunction following a heart attack and for the treatment of heart failure. Currently, Diovan is available only as a brand-name product. Novartis, the drug company that makes Diovan has a patent on the product. Teva, a generic company is in the process of being approved to make a generic equivalent of Diovan. The patent on Diovan expires in September of 2012. The generic will likely become available shortly after, according to a press release from the drug company. Generic medications are less expensive alternatives to brand-name medications. Generic medications can look differently and can have a few other minor differences from their brand-name counterpart. However, their labeling and directions must be virtually the same as that of the brand-name product. Generic products must contain the same active ingredient as the brand-name products. Both brand-name and generic drug manufacturing facilities must meet the U.S. Food and Drug Administration's (FDA) specifications. Generics, as well as brand-name medications, must follow the same standards of good manufacturing practices. The FDA requires that generic drugs be bioequivalent to the brand-name medication. This means that both generic drugs and brand-name drugs will work the same way in your body. Generics are considered, by the FDA, to be identical to brand-name drugs in dose, strength, quality, route of administration, safety, efficacy, and intended use. For more specific information, consult with your doctor or pharmacist for guidance based on your health status and current medications, particularly before taking any action. Jen Marsico, RPh
How should this medicine be used?
Disys comes as a tablet and a solution (liquid) to take by mouth. For the treatment of high blood pressure, the tablet is usually taken once a day, and the solution is usually taken twice a day with or without food. For the treatment of heart failure or heart attack, it is usually taken twice a day with or without food. To help you remember to take Disys, take it at around the same time(s) 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 Disys exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Each Disys product releases the medication differently in your body and cannot be used interchangeably. Only take the Disys product prescribed by your doctor and do not switch to a different Disys product unless your doctor says that you should. Your doctor will probably only tell you to take Disys solution if you are unable to swallow tablets.
Your doctor may start you on a low dose of Disys and gradually increase your dose.
Disys controls high blood pressure and heart failure but does not cure them. Your blood pressure may decrease during the first 2 weeks of your treatment, but it may take 4 weeks for you to notice the full benefit of Disys. Continue to take Disys even if you feel well. Do not stop taking Disys without talking to your doctor.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
Serious allergic reaction
In rare cases, Disys may cause a serious allergic reaction (anaphylaxis).
Blood pressure drugs
When taken with Disys, these drugs can increase your risk of low blood pressure, high blood potassium, and kidney problems. Examples of these drugs include:
- angiotensin receptor blockers (ARBs), such as:
Q: I'm having terrible nightmares lately. Could this be a side effect of the Diovan I've been taking?
A: There are no reports of nightmares among patients taking Diovan (Disys). However, you are encouraged to report any negative side effects of prescription drugs to your health care practitioner and to the Food and Drug Administration (FDA) by visiting www.fda.gov/medwatch or by calling (800) FDA-1088. For more specific information about your nightmares, consult with your doctor or pharmacist. Michelle McDermott, PharmD
What is Disys, and how does it work (mechanism of action)?
WARNING : Today, the U.S. Food and Drug Administration posted a warning letter to Torrent Pharmaceuticals in Ahmedabad, Gujarat, India. Torrent manufactures losartan potassium tablets and has been one subject of an ongoing global investigation into nitrosamine impurities in angiotensin II receptor blockers (ARBs) such as Disys, losartan and irbesartan.
The warning letter outlines several manufacturing violations at Torrent’s Taluka-Kadi, Indrad, Gujarat facility, including failure to follow written procedures for production and process control and failure to adequately investigate batch discrepancies. Failure to correct these violations may result in further action by the agency. The warning letter is another result of the agency’s ongoing investigation.
FDA reminds patients taking recalled ARBs to continue taking their current medicine until their pharmacist provides a replacement or their doctor prescribes a different medication that treats the same condition.
The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) was a randomized, controlled, multinational, double-blind study in 14,703 patients with acute myocardial infarction and either heart failure (signs, symptoms or radiological evidence) or left ventricular systolic dysfunction (ejection fraction ≤40% by radionuclide ventriculography or ≤35% by echocardiography or ventricular contrast angiography). Patients were randomized within 12 hours to 10 days after the onset of myocardial infarction symptoms to one of three treatment groups: Disys (titrated from 20 or 40 mg twice daily to the highest tolerated dose up to a maximum of 160 mg twice daily), the ACE inhibitor, captopril (titrated from 6.25 mg three times daily to the highest tolerated dose up to a maximum of 50 mg three times daily), or the combination of Disys plus captopril. In the combination group, the dose of Disys was titrated from 20 mg twice daily to the highest tolerated dose up to a maximum of 80 mg twice daily; the dose of captopril was the same as for monotherapy. The population studied was 69% male, 94% Caucasian, and 53% were 65 years of age or older. Baseline therapy included aspirin (91%), betablockers (70%), ACE inhibitors (40%), thrombolytics (35%) and statins (34%). The mean treatment duration was 2 years. The mean daily dose of Diovan in the monotherapy group was 217 mg.
The primary endpoint was time to all-cause mortality. Secondary endpoints included (1) time to cardiovascular (CV) mortality, and (2) time to the first event of cardiovascular mortality, reinfarction, or hospitalization for heart failure. The results are summarized in the following table.
There was no difference in overall mortality among the three treatment groups. There was thus no evidence that combining the ACE inhibitor captopril and the angiotensin II blocker Disys was of value.
The data were assessed to see whether the effectiveness of Disys could be demonstrated by showing in a non-inferiority analysis that it preserved a fraction of the effect of captopril, a drug with a demonstrated survival effect in this setting. A conservative estimate of the effect of captopril (based on a pooled analysis of 3 post-infarction studies of captopril and 2 other ACE inhibitors) was a 14% to 16% reduction in mortality compared to placebo. Disys would be considered effective if it preserved a meaningful fraction of that effect and unequivocally preserved some of that effect. As shown in the table, the upper bound of the CI for the hazard ratio (Disys/captopril) for overall or CV mortality is 1.09 to 1.11, a difference of about 9% to 11%, thus making it unlikely that Disys has less than about half of the estimated effect of captopril and clearly demonstrating an effect of Disys. The other secondary endpoints were consistent with this conclusion.
Effects on Mortality Amongst Subgroups in VALIANT
There were no clear differences in all-cause mortality based on age, gender, race, or baseline therapies, as shown in the figure above.
How should I take Disys?
Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.
Take Disys at the same time(s) each day, with or without food.
If a child taking Disys cannot swallow a capsule whole, your pharmacist can mix the medicine into a liquid. Shake this liquid well just before you measure a dose. Measure the medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).
Your blood pressure will need to be checked often. Your kidney function may also need to be checked.
You may have very low blood pressure while taking Disys. Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual.
It may take 2 to 4 weeks of using this medicine before your blood pressure is under control. Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.
Talk with your doctor if your symptoms do not improve after 4 weeks of treatment.
Store at room temperature away from moisture and heat.
Q: Does Diovan really cause hair loss and weight gain? I suffer from both.
A: Diovan (Disys) is an angiotensin II receptor antagonist used to treat hypertension (high blood pressure), and it can cause weight gain, but does not list hair loss as a side effect. If the hair loss started around the time the medication was started, and there are no other new circumstances, you may want to report the side effect. Other common side effects from Diovan (Disys) may include dry mouth, loss of appetite, diarrhea, constipation, stomach pain, insomnia, headache, dizziness, anxiety, tiredness, back pain, weakness, or impotence, loss of interest in sex, or trouble having an orgasm. This is not a complete list of the side effects associated with Diovan (Disys). Patti Brown, PharmD
Taking potassium-sparing diuretics with Disys can increase the amount of potassium in your body. Examples of these drugs include:
Take Disys even if you feel well, as you will still be getting the benefits of the medicine.
What Are Side Effects Associated with Using Disys?
Side effects associated with use of Disys, include the following:
Other side effects of Disys include:
Postmarketing side effects of Disys reported include:
This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.
6. How to cope with s >
What to do about:
- feeling dizzy - if Disys makes you feel dizzy when you stand up, try getting up very slowly or stay sitting down until you feel better. If you begin to feel dizzy, lie down so that you don't faint, then sit until you feel better. Do not drive or use tools or machines if you feel dizzy, have muscle cramps or muscle pain, or if you just feel a bit shaky.
- headaches - make sure you rest and drink plenty of fluids. Do not drink too much alcohol. Ask your pharmacist to recommend a painkiller. Headaches should usually go away after the first week of taking Disys. Talk to your doctor if they last longer than a week or are severe.
- feeling sick (nausea) - try taking your tablets with or after a meal or snack. It may also help if you don't eat rich or spicy food.
- being sick (vomiting) or diarrhoea - drink plenty of fluids, such as water or squash, to prevent dehydration. If you're being sick, take small, frequent sips. Speak to a pharmacist if you have signs of dehydration, such as peeing less than usual or having dark, strong-smelling pee. If you get severe diarrhoea or vomiting from a stomach bug or illness, tell your doctor. You may need to stop taking Disys for a while until you feel better.
- pain in your joints or muscles - if you get unusual muscle pain, weakness or tiredness that isn't from exercise or hard work, talk to your doctor. You may need a blood test to check what might be causing it.
Warnings for people with certain health conditions
For people with severe heart failure or kidney disease: This drug may increase your risk of kidney problems and reduce how much urine you make. If you have kidney disease, you should not take Disys and aliskiren together.
For people with diabetes: You should not take Disys if you’re taking the drug aliskiren.
Disys inhibits the pressor effect of angiotensin II infusions. An oral dose of 80 mg inhibits the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. No information on the effect of larger doses is available.
Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of Disys; very little effect on serum potassium was observed.
In multiple-dose studies in hypertensive patients with stable renal insufficiency and patients with renovascular hypertension, Disys had no clinically significant effects on glomerular filtration rate, filtration fraction, creatinine clearance, or renal plasma flow.
In multiple-dose studies in hypertensive patients, Disys had no notable effects on total cholesterol, fasting triglycerides, fasting serum glucose, or uric acid.