Side effects of vesicare

Why Myrbetriq?

What is MYRBETRIQ? MYRBETRIQ is a prescription medicine for adults that can be used alone or with solifenacin succinate to treat the following symptoms due to a condition called overactive bladder:

  • Urge urinary incontinence: a strong need to urinate with leaking or wetting accidents
  • Urgency: a strong need to urinate right away
  • Frequency: urinating often

It is not known if MYRBETRIQ, when used alone or with solifenacin succinate, is safe and effective in children.

How should I take MYRBETRIQ

  • If your doctor prescribes MYRBETRIQ and solifenacin succinate together, you should take 1 MYRBETRIQ tablet and 1 solifenacin tablet at the same time, 1 time a day.
  • You should take MYRBETRIQ with water and swallow the tablet whole.
  • Do not chew, break, or crush the tablet.
  • You can take MYRBETRIQ with or without food.
  • You can take MYRBETRIQ and solifenacin succinate together with or without food.

The most common side effects of MYRBETRIQ, when used with solifenacin succinate, include:

  • dry mouth
  • urinary tract infection
  • constipation
  • fast heartbeat

USE OF MYRBETRIQ Myrbetriq® (mirabegron) is a prescription medicine for adults that can be used alone or with solifenacin succinate to treat overactive bladder (OAB) with symptoms of urgency, frequency and leakage.

IMPORTANT SAFETY INFORMATION FOR MYRBETRIQ Myrbetriq is not for everyone. Do not take Myrbetriq if you have an allergy to mirabegron or any ingredients in Myrbetriq. Myrbetriq may cause your blood pressure to increase or make your blood pressure worse if you have a history of high blood pressure. It is recommended that your doctor check your blood pressure while you are taking Myrbetriq. Myrbetriq may increase your chances of not being able to empty your bladder. Tell your doctor right away if you have trouble emptying your bladder or you have a weak urine stream.

Myrbetriq may cause allergic reactions that may be serious. If you experience swelling of the face, lips, throat or tongue, with or without difficulty breathing, stop taking Myrbetriq and tell your doctor right away.

Tell your doctor about all the medicines you take including medications for overactive bladder or other medicines such as thioridazine (Mellaril™ and Mellaril-S™), flecainide (Tambocor®), propafenone (Rythmol®), digoxin (Lanoxin®), or solifenacin succinate (VESIcare®). Myrbetriq may affect the way other medicines work, and other medicines may affect how Myrbetriq works.

Before taking Myrbetriq, tell your doctor if you have liver or kidney problems. The most common side effects of Myrbetriq include increased blood pressure, common cold symptoms (nasopharyngitis), dry mouth, flu symptoms, urinary tract infection, back pain, dizziness, joint pain, headache, constipation, sinus irritation, and inflammation of the bladder (cystitis).

The most common side effects of MYRBETRIQ, when used with solifenacin succinate, include dry mouth, urinary tract infection, constipation, and fast heartbeat.

For further information, please talk to your healthcare professional and see accompanying Patient Product Information and complete Prescribing Information for Myrbetriq® (mirabegron).

USE OF VESICARE VESIcare® (solifenacin succinate) is for overactive bladder with symptoms of urgency, frequency, and leakage.

IMPORTANT SAFETY INFORMATION FOR VESICARE VESIcare is not for everyone. If you have certain stomach or glaucoma problems, or trouble emptying your bladder, do not take VESIcare. VESIcare may cause allergic reactions that may be serious. If you experience swelling of the face, lips, throat, or tongue, stop taking VESIcare and get emergency help. Tell your doctor right away if you have severe abdominal pain, or become constipated for three or more days. VESIcare may cause blurred vision, so use caution while driving or doing unsafe tasks. Common side effects are dry mouth, constipation, and indigestion.
For further information, please talk to your healthcare professional and see accompanying Patient Product Information and complete Prescribing Information for VESIcare® (solifenacin succinate).
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088.
Myrbetriq® and VESIcare® are registered trademarks of Astellas Pharma Inc. All other trademarks or registered trademarks are the property of their respective owners.

VESIcare

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

VESIcare has been evaluated for safety in 1811 patients in randomized, placebo-controlled trials. Expected adverse reactions of antimuscarinic agents are dry mouth, constipation, blurred vision (accommodation abnormalities), urinary retention, and dry eyes. The incidence of dry mouth and constipation in patients treated with VESIcare was higher in the 10 mg compared to the 5 mg dose group.

In the four 12-week double-blind clinical trials, severe fecal impaction, colonic obstruction, and intestinal obstruction were reported in one patient each, all in the VESIcare 10 mg group. Angioneurotic edema has been reported in one patient taking VESIcare 5 mg. Compared to 12 weeks of treatment with VESIcare, the incidence and severity of adverse reactions were similar in patients who remained on drug for up to 12 months.

The most frequent adverse reaction leading to study discontinuation was dry mouth (1.5%). Table 1 lists the rates of identified adverse reactions, derived from all reported adverse events, in randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with VESIcare 5 or 10 mg once daily for up to 12 weeks.

Table 1: Percentages of Patients with Identified Advers e Reactions , Derived from All Advers e Events Exceeding Placebo Rate and Reported by 1% or More Patients for Combined Pivotal Studies

Post-Marketing Experience

Because these spontaneously reported events are from the worldwide postmarketing experience, the frequency of events and the role of solifenacin in their causation cannot be reliably determined.

The following events have been reported in association with solifenacin use in worldwide postmarketing experience:

General: peripheral edema, hypersensitivity reactions, including angioedema with airway obstruction, rash, pruritus, urticaria, and anaphylactic reaction;

Central Nervous: headache, confusion, hallucinations, delirium and somnolence;

Cardiovascular: QT prolongation; Torsade de Pointes, atrial fibrillation, tachycardia, palpitations;

Hepatic: liver disorders mostly characterized by abnormal liver function tests, AST (aspartate aminotransferase), ALT (alanine aminotransferase), GGT (gamma-glutamyl transferase);

Renal: renal impairment;

Metabolism and nutrition disorders: decreased appetite, hyperkalemia;

Dermatologic: exfoliative dermatitis and erythema multiforme;

Eye disorders: glaucoma;

Gastrointestinal disorders: gastroesophageal reflux disease and ileus;

Respiratory, thoracic and mediastinal disorders: dysphonia;

Musculoskeletal and connective tissue disorders: muscular weakness.

Read the entire FDA prescribing information for VESIcare (Solifenacin Succinate)

Solifenacin

Before taking solifenacin,

  • tell your doctor and pharmacist if you are allergic to solifenacin, any other medications, or corn.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking. Be sure to mention any of the following: amiodarone (Cordarone, Pacerone); antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), and ketoconazole (Nizoral); carbamazepine (Tegretol); cimetidine (Tagamet); cisapride (Propulsid); clarithromycin (Biaxin); cyclosporine (Neoral, Sandimmune); danazol (Danocrine); delavirdine (Rescriptor); dexamethasone (Decadron); diltiazem (Cardizem, Dilacor, Tiazac); disopyramide (Norpace); dofetilide (Tikosyn); erythromycin (E.E.S., E-Mycin, Erythrocin); ethosuximide (Zarontin); fluoxetine (Prozac, Sarafem); fluvoxamine (Luvox); HIV protease inhibitors such as indinavir (Crixivan) and ritonavir (Norvir); isoniazid (INH, Nydrazid);metronidazole (Flagyl); moxifloxacin (Avelox); nefazodone; phenobarbital (Luminal, Solfoton); phenytoin (Dilantin);pimozide (Orap); procainamide (Procanbid, Pronestyl); quinidine (Quinaglute, Quinidex); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane); sotalol (Betapace); sparfloxacin (Zagam); thioridazine (Mellaril); troglitazone (Rezulin); troleandomycin (TAO); verapamil (Calan, Covera, Isoptin, Verelan); and zafirlukast (Accolate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor what herbal products you are taking, especially St. John’s wort.
  • tell your doctor if you or any of your family members have or have ever had prolonged QT interval (a problem with the way electricity is conducted in the heart that may cause fainting) or unexplained fainting; and if you have or have ever had glaucoma (an eye disease that can cause vision loss); any type of blockage in the bladder or digestive system; difficulty emptying your bladder or a weak urine stream; myasthenia gravis (a disorder of the nervous system that causes muscle weakness); ulcerative colitis (a condition which causes swelling and sores in the lining of the colon and rectum); benign prostatic hypertrophy (BPH, enlargement of the prostate, a male reproductive organ); constipation; or liver or kidney disease.
  • tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking solifenacin, call your doctor. Do not take solifenacin while you are breastfeeding.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking solifenacin.
  • you should know that solifenacin may cause blurred vision. Do not drive a car or operate machinery until you know how this medication affects you.
  • you should know that solifenacin may make it harder for your body to cool down when it gets very hot. Avoid exposure to extreme heat, and call your doctor or get emergency medical treatment if you have fever or other signs of heat stroke such as dizziness, upset stomach, headache, confusion, and fast pulse after you are exposed to heat.

Vesicare

How does this medication work? What will it do for me?

Solifenacin belongs to the family of medications known as antispasmodics. It is used to relieve symptoms associated with an overactive bladder, such as urinary urgency (a need to urinate right away), urinary frequency, and urge incontinence (leaking or wetting caused by an unstoppable urge to urinate).

This medication works by relaxing the bladder. It helps to reduce bladder spasms, the urge to pass urine, and the frequency of urination.

It is usually necessary to take this medication for at least 4 weeks before you can expect maximum benefit from the treatment.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

5 mg
Each light yellow, round, film-coated tablet debossed with logo “150” contains 5 mg of solifenacin succinate (equivalent to 3.8 mg of solifenacin). Nonmedicinal ingredients: corn starch, hypromellose 2910, lactose monohydrate, magnesium stearate, polyethylene glycol 8000, talc, titanium dioxide, and yellow ferric oxide.

10 mg
Each light pink, round, film-coated tablet debossed with logo “151” contains 10 mg of solifenacin succinate (equivalent to 7.5 mg of solifenacin). Nonmedicinal ingredients: cornstarch, hypromellose 2910, lactose monohydrate, magnesium stearate, polyethylene glycol 8000, red ferric oxide, talc, and titanium dioxide.

How should I use this medication?

The recommended dose of solifenacin is 5 mg once daily. If there are few side effects with a 5 mg dose, the dose can be increased to 10 mg once daily.

If you have severe kidney function impairment or moderate liver function impairment, or if you are taking certain medications (e.g., ketoconazole, clarithromycin, diclofenac, nefazodone, verapamil), doses above 5 mg daily are not recommended.

Solifenacin should be taken with liquids and swallowed whole. It may be taken with or without food.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is very important to take this medication exactly as prescribed. If you miss a dose of this medication, take your next dose at the usual time. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take solifenacin if you:

  • are allergic to solifenacin or to any of the ingredients of the medication
  • are dependent on dialysis
  • have gastroparesis (delayed emptying of the stomach)
  • have narrow-angle glaucoma
  • have urinary retention (an inability to empty the bladder)

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • blurred vision
  • constipation
  • dry eyes
  • dry mouth
  • headache
  • heartburn
  • nausea
  • tiredness
  • upper abdominal pain
  • vomiting

Although most of these side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • constipation for more than 3 days
  • fatigue
  • severe abdominal pain
  • signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
  • signs of a urinary tract infection (e.g., burning when passing urine, blood in the urine, or increased urgency to urinate)
  • swelling of the feet, ankles, or lower leg

Stop taking the medication and seek immediate medical attention if any of the following occur:

  • fast or irregular heartbeat
  • inability to urinate
  • signs of a severe allergic reaction (e.g., hives; difficulty breathing; or swelling of the mouth, lips, tongue, or throat)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Abnormal heart rhythm: Solifenacin may cause a heart rhythm disturbance called QT prolongation. If you have a history of QT prolongation or are taking certain medications (e.g., amiodarone, sotalol), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Bladder outflow obstruction: If you have a medical problem that obstructs the flow of urine from the bladder (e.g., enlarged prostate, prostate cancer), this medication may make you unable to urinate. If you have a problem with urinary flow, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Blurred vision: Solifenacin may cause blurred vision. Avoid activities such as driving, operating machinery, or performing hazardous work until you know how solifenacin affects your vision.

Gastrointestinal disorders: Solifenacin can slow movement through the gastrointestinal tract. If you have decreased gastrointestinal movement caused by a medical problem (e.g., diabetes), surgery, or medications, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Heat stroke: Solifenacin causes a decrease in sweating, which is one of the body’s way of cooling off. When solifenacin is taken during very hot weather, it can cause fever and heat stroke due to the body being unable to cool down enough. Take care not to overheat when you are taking this medication. Stay in a cool environment if possible, limit the length of time you spend outdoors, and drink plenty of water to reduce the risk of heat stroke.

Kidney function: If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you have severe kidney function impairment, do not take daily doses greater than 5 mg of solifenacin.

Liver function: The liver is responsible for removing solifenacin from the body. If the liver is not working well, the medication can build up in the body, causing unwanted side effects. If you have reduced liver function or liver disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you have moderate liver function impairment, do not take daily doses greater than 5 mg of solifenacin, and have your doctor monitor your condition closely. Do not take solifenacin if you have severe liver function impairment.

Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. Women of childbearing age should talk to their doctor about whether birth control is appropriate. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: It is not known if solifenacin passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children.

What other drugs could interact with this medication?

There may be an interaction between solifenacin and any of the following:

  • aclidinium
  • amantadine
  • amiodarone
  • anagrelide
  • antihistamines (e.g., cetirizine, chlorpheniramine, dimenhydrinate, diphenhydramine)
  • aprepitant
  • atropine
  • antipsychotics (e.g., chlorpromazine, haloperidol, clozapine, quetiapine, risperidone)
  • azole antifungals (e.g., itraconazole, ketoconazole, voriconazole)
  • benztropine
  • bosentan
  • botulinum toxin
  • calcium channel blockers (e.g., amlodipine, nifedipine, verapamil)
  • cannabis
  • chloroquine
  • cobicistat
  • conivaptan
  • cyclobenzaprine
  • darifenacin
  • deferasirox
  • disopyramide
  • dofetilide
  • domperidone
  • donepezil
  • dronedarone
  • enzalutamide
  • flavoxate
  • flecainide
  • galantamine
  • glucagon
  • glycopyrrolate
  • grapefruit juice
  • HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., delavirdine, efavirenz, etravirine, nevirapine)
  • HIV protease inhibitors (e.g., darunavir, indinavir, lopinavir, saquinavir, tipranavir)
  • ipratropium
  • macrolide antibiotics (e.g., clarithromycin, erythromycin)
  • methadone
  • metoclopramide
  • mifepristone
  • mirabegron
  • mitotane
  • modafinil
  • monoamine oxidase inhibitors (e.g. moclobemide, selegiline)
  • nabilone
  • narcotic medications (e.g., morphine, codeine)
  • nefazodone
  • nitroglycerin
  • orphenadrine
  • oxybutynin
  • potassium chloride, potassium supplements
  • pramlitinide
  • primaquine
  • procainamide
  • propafenone
  • protein kinase inhibitors (e.g., crizotinib, dabrafenib, dasatinib, imatinib)
  • quinidine
  • quinine
  • quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
  • rifabutin
  • rifampin
  • rilpivirine
  • rivastigmine
  • St. John’s wort
  • scopolamine
  • selective serotonin reuptake inhibitors (SSRI; e.g., fluoxetine, paroxetine, sertraline)
  • seizure medications (e.g., carbamazepine, phenobarbital, phenytoin)
  • serotonin antagonists (e.g., granisetron, ondansetron)
  • siltuximab
  • simeprevir
  • sotalol
  • tetrabenazine
  • tiotropium
  • thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
  • tocilizumab
  • tolterodine
  • trazodone
  • tricyclic antidepressants (e.g., amitriptyline, desipramine, nortriptyline)
  • umeclidinium

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

  • stop taking one of the medications,
  • change one of the medications to another,
  • change how you are taking one or both of the medications, or
  • leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications that you are taking. Also tell them about any supplements you take. Since caffeine, decongestants, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2020. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Vesicare

Two types of drugs you may want to avoid for the sake of your brain

Recent reports have linked two common classes of drugs to dementia. Fortunately, there are alternatives to both.

Image: Thinkstock

Updated: June 14, 2018Published: October, 2015

If you’re worried about developing dementia, you’ve probably memorized the list of things you should do to minimize your risk—eating a healthy diet, exercising regularly, getting adequate sleep, and keeping your mind and soul engaged. In addition, some of the drugs you may be taking to help you accomplish those things could increase your risk of dementia. In two separate large population studies, both benzodiazepines (a category that includes medications for anxiety and sleeping pills) and anticholinergics (a group that encompasses medications for allergies and colds, depression, high blood pressure, and incontinence) were associated with an increased risk of dementia in people who used them for longer than a few months. In both cases, the effect increased with the dose of the drug and the duration of use.

These findings didn’t come entirely as a surprise to doctors who treat older people. “The Beer’s List published by the American Geriatrics Society has long recognized benzodiazepines, antihistamines, and tricyclic antidepressants as potentially inappropriate for older adults, given their side effects,” says Dr. Lauren J. Gleason, a physician in the Division of Aging at Harvard-affiliated Brigham and Women’s Hospital. Such drugs are on the list because they share troubling side effects—confusion, clouded thinking, and memory lapses—that can lead to falls, fractures, and auto accidents.

What the studies found

It’s important to note that neither of these studies was a randomized controlled clinical trial, so neither proved that either type of drug causes dementia.

The anticholinergic study. Researchers tracked nearly 3,500 men and women ages 65 or older who took part in Adult Changes in Thought (ACT), a long-term study conducted by the University of Washington and Group Health, a Seattle health care system. They used Group Health’s pharmacy records to determine all the drugs, both prescription and over-the-counter, that each participant took in the 10 years before starting the study. Participants’ health was tracked for an average of seven years. During that time, 800 of them developed dementia. When the researchers examined medication use, they found that people who used anticholinergic drugs were more likely to have developed dementia than those who didn’t use them. Moreover, dementia risk increased along with the cumulative dose. Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.

The University of Washington study is the first to include nonprescription drugs. It is also the first to eliminate the possibility that people were taking the drugs to alleviate early symptoms of undiagnosed dementia. For people who took anticholinergic bladder medications, the increased risk was just as high as for those taking tricyclic antidepressants, which are also anticholinergics.

The benzodiazepine study. A team of researchers from France and Canada linked benzodiazepine use to an increased risk of being diagnosed with Alzheimer’s disease. In the study, the greater people’s cumulative dose of benzodiazepines, the higher their risk.

The researchers relied on a database maintained by the Quebec health insurance program. From it, they identified nearly 2,000 men and women over age 66 who had been diagnosed with Alzheimer’s disease. They randomly selected more than 7,000 others without Alzheimer’s who were matched for age and sex to those with the disease. Once the groups were set, the researchers looked at the drug prescriptions during the five to six years preceding the Alzheimer’s diagnosis.

People who had taken a benzodiazepine for three consecutive months or less had about the same dementia risk as those who had never taken one. But those who had taken a benzodiazepine for three to six months had a 32% greater risk of developing Alzheimer’s, and those taking one for more than six months had an 84% greater risk than those who hadn’t taken one.

The type of drug taken also mattered. People who were on a long-acting benzodiazepine like diazepam (Valium) or flurazepam (Dalmane) were at greater risk than those on a short-acting one like triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), or temazepam (Restoril).

Why these drugs have a stronger effect in older people

As we age, our ability to process medication changes. The kidneys and liver clear drugs more slowly, so drug levels in the blood remain higher for a longer time. People also gain fat and lose muscle mass over time. Both these changes affect the way drugs are distributed to and broken down in body tissues. And because these drugs are stored in body fat, they can continue to produce effects days after people stop taking them, especially in people with a higher proportion of body fat. In addition, older people tend to take more prescription and over-the-counter medications, each of which has the potential to suppress or enhance the effects of the others.

Why the drugs affect your mind

Both anticholinergics and benzodiazepines affect the activity of neurotransmitters—chemical messengers that work in the central nervous system—but the drugs work in slightly different ways.

Anticholinergic drugs block the action of acetylcholine. In the brain, acetylcholine is involved in learning and memory. In the rest of the body, it stimulates the autonomic nerves—those that regulate contractions of blood vessels, airways, and our cardiovascular and digestive systems. The strongest anticholinergic drugs include some antihistamines, tricyclic antidepressants, medications to control overactive bladder, and sleeping pills.

Benzodiazepines boost another neurotransmitter’s effectiveness. They make gamma-aminobutyric acid (GABA)—which slows the activity of neurons in the brain-—more potent. For that reason, they are used to calm anxiety and help people sleep.

If you take one of these drugs

Dr. Gleason suggests having a thorough discussion with your doctor to review the potential benefits and harms of these medications—and all the others you take. If a drug appears problematic, the two of you can explore alternatives by considering the reason it was prescribed and seeing if there is a different type of drug that can be used as a replacement.

Don’t stop taking the drugs on your own. It isn’t safe to quit most benzodiazepines and anticholinergic drugs “cold turkey.” Work with your clinician to develop a plan for tapering off them.

Medications to avoid or use briefly

Common drugs that might increase dementia risk

Possible alternatives

Allergies, colds

Anticholinergics

brompheniramine (Dimetapp)

carbinoxamine (Palgic)

chlorpheniramine (Chlor-Trimeton)

diphenhydramine (Benadryl)

hydroxyzine (Atarax, Vistaril)

cetirizine (Zyrtec)

desloratadine (Clarinex)

fexofenadine (Allegra)

loratadine (Claritin)

Anxiety

Benzodiazepines

alprazolam (Xanax)

chlordiazepoxide (Librium)

clonazepam (Klonopin)

clorazepate (Tranxene)

diazepam (Valium)

flurazepam (Dalmane)

lorazepam (Ativan)

oxazepam (Serax)

paroxetine (Paxil)

bupropion (Wellbutrin)

buspirone (BuSpar)

citalopram (Celexa)

fluoxetine (Prozac)

sertraline (Zoloft)

venlafaxine (Effexor)

Depression

Anticholinergics

amitriptyline (Elavil)

clomipramine (Anafranil)

doxepin (Sinequan)

imipramine (Tofranil)

paroxetine (Paxil)

trimipramine (Surmontil)

bupropion (Wellbutrin)

buspirone (Buspar)

citalopram (Celexa)

fluoxetine (Prozac)

sertraline (Zoloft)

venlafaxine (Effexor)

Insomnia

Anticholinergics

mirtazapine (Remeron)

nefazodone (Serzone)

trazodone (Desyrel)

Benzodiazepines

estazolam (ProSom)

quazepam (Doral)

temazepam (Restoril)

triazolam (Halcion)

Melatonin

Nondrug approaches

practicing relaxation techniques

avoiding alcohol and heavy meals before bedtime

exercising vigorously early in the day

Urge incontinence

Anticholinergics

darifenacin (Enablex)

fesoterodine (Toviaz)

flavoxate (Urispas)

oxybutynin (Ditropan)

solifenacin (Vesicare)

tolterodine (Detrol)

trimipramine (Surmontil)

trospium (Sanctura)

Nondrug approaches

bladder training

physical exercise

weight loss for overweight or obese women

Minimally invasive procedures

Botox injections

implantable bladder stimulators

Sources: DeGage SB, et al. “Benzodiazepine use and risk of Alzheimer’s disease: Case-control study,” BMJ (Sept. 9, 2014), Vol. 351, published online; Salahudeen MS et al. “Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: A systematic review,” BMC Geriatrics (March 15, 2015), Vol.15, No.31, published online.

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solifenacin (VESIcare)

Brand Names: VESIcare

Generic Name: solifenacin

  • What is solifenacin (VESIcare)?
  • What are the possible side effects of solifenacin (VESIcare)?
  • What is the most important information I should know about solifenacin (VESIcare)?
  • What should I discuss with my healthcare provider before taking solifenacin (VESIcare)?
  • How should I take solifenacin (VESIcare)?
  • What happens if I miss a dose (VESIcare)?
  • What happens if I overdose (VESIcare)?
  • What should I avoid while taking solifenacin (VESIcare)?
  • What other drugs will affect solifenacin (VESIcare)?
  • Where can I get more information (VESIcare)?

What is solifenacin (VESIcare)?

Solifenacin is used to treat symptoms of overactive bladder, such as frequent or urgent urination, and incontinence (urine leakage).

Solifenacin may also be used for purposes not listed in this medication guide.

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What are the possible side effects of solifenacin (VESIcare)?

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Stop using solifenacin and call your doctor at once if you have:

  • severe stomach pain, or constipation for 3 days or longer;
  • pain or burning when you urinate;
  • confusion, hallucinations;
  • vision changes, eye pain, or seeing halos around lights;
  • little or no urination;
  • dehydration symptoms–feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin; or
  • high potassium level–nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement.

Common side effects may include:

  • blurred vision;
  • dry mouth;
  • pain or burning when you urinate;
  • constipation; or
  • heat stroke–decreased sweating, dizziness, tiredness, nausea, feeling hot.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the most important information I should know about solifenacin (VESIcare)?

You should not use this medicine if you have untreated or uncontrolled narrow-angle glaucoma, a blockage in your digestive tract (stomach or intestines), or if you are unable to urinate.

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USE AND DOSE

VESIcare is for overactive bladder with symptoms of urgency, frequency, and leakage. The recommended dose of VESIcare is 5 mg once daily. If the 5 mg dose is well tolerated, your doctor may increase the dose to 10 mg once daily.

IMPORTANT SAFETY INFORMATION

VESIcare is not for everyone. If you have certain stomach or glaucoma problems, or trouble emptying your bladder, do not take VESIcare. VESIcare may cause allergic reactions that may be serious. If you experience swelling of the face, lips, throat, or tongue, stop taking VESIcare and get emergency help. Tell your doctor right away if you have severe abdominal pain, or become constipated for three or more days. VESIcare may cause blurred vision, so use caution while driving or doing unsafe tasks. Common side effects are dry mouth, constipation, and indigestion.

Please see accompanying complete Prescribing Information.

You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Easy-to-read medicine information about solifenacin – what it is, how to take solifenacin safely and possible side effects.

Type of medicine

Also called

  • Medicine to treat urinary symptoms such as incontinence
  • Belongs to a group of medicines known as anti-cholinergics.
  • Vesicare®

What is solifenacin?

  • Solifenacin is used to treat some bladder control problems and urinary conditions such as overactive bladder, incontinence, urinary frequency (the need to pass urine more often than usual) and urinary urgency (the need to pass urine more urgently than usual).
  • It works by relaxing the muscles in the bladder and in this way controls the release of urine eases the symptoms.
  • Read more about bladder control problems.

Dose

  • The usual starting dose of solifenacin is 5 milligrams once daily.
  • Depending on your response, your doctor may increase your dose gradually to 10 milligrams once a daily.
  • Always take your solifenacin exactly as your doctor has told you. The pharmacy label on your medicine will tell you how much solifenacin to take, how often to take it, and any special instructions.

How to take solifenacin

  • Take solifenacin tablets with a glass of water at the same time each day.
  • You can take solifenacin with or without food.
  • To reduce your urinary symptoms, you must keep taking solifenacin every day.
  • Limit drinking alcohol while your are taking solifenacin. Alcohol can increase the risk of side effects.
  • If you forget your dose, take it as soon as you remember that day. But, if it is nearly time for your next dose, just take the next dose at the right time. Do not take double the dose.

Possible side effects

Like all medicines, solifenacin can cause unwanted side effects, although not everyone gets them. Often unwanted side effects improve as your body gets used to the new medicine.

Side effects What should I do?
  • Constipation
  • This is quite common when you first start taking solifenacin.
  • Read more for advice on managing constipation
  • Tell your doctor if troublesome.
  • Dry mouth
  • To prevent dry mouth, avoid using mouthwashes with alcohol.
  • Chewing on sugar-free gum, and drinking small sips of water as needed, may also be helpful.
  • Tell your doctor if troublesome.
  • Read more about dry mouth.
  • Drowsiness, sleepiness or feeling tired
  • This is common when starting solifenacin or after increasing the dose.
  • Be careful when driving or using tools until you know how this medicine affects you.
  • Feeling dizzy
  • This usually happens when you start your medication. It should wear off in a few weeks.
  • Try not to stand up too quickly. You are at risk of falls.
  • If you feel dizzy, don’t drive.
  • Reduced sweating
  • Fever
  • Heat stroke
  • Avoid hot environmental conditions.
  • Increase your fluid intake in hot weather or when exercising.
  • Tell your doctor if troublesome.

  • Signs of an allergic reaction such as skin rash, hives or itches, swelling of the face, lips, mouth
  • Tell your doctor immediately or ring HealthLine.

Interactions

  • Solifenacin may interact with a few medications and herbal supplements, so check with your doctor or pharmacist.
  • Solifenacin may also interact with some medicines available over-the-counter, without a prescription such as some antihistamines (also in anti-allergy, anti-nausea and cough/cold preparations), meclozine (e.g. Sea-legs®), prochlorperazine (e.g. Buccastem®) and anti-diarrhoeals (e.g. Diastop®). Ask your pharmacist.

Learn more

Medsafe Consumer Information Sheet Vesicare

PMC

Clinical trials

There have been several large, randomized clinical trials evaluating the efficacy, safety, tolerability, and persistence with solifenacin (Table 1). Each of these trials will be discussed.

Table 1

Clinical trials evaluating the efficacy of solifenacin in the treatment of overactive bladder

Clinical trial phase Trial design Duration (months) Primary outcome measure Secondary outcome measures Quality of life assessment
2 Dose finding study. Randomized, single-blind placebo- and tolterodine-controlled trial. 2 Change from baseline to the last study visit in the number of voids/24 hours
  • Change in volume voided per void

  • Incontinence, urgency per 24 hours

  • Total sum score of Contilife questionnaire

  • Contilife questionnaire

3 2 studies 013, 014. Placebo-controlled trials assessing solifenacin 10 mg 3 Mean number micturition episodes/24 hours
  • Change from baseline in mean number of urgency, all incontinence, urge incontinence episodes

  • Nil

Randomized, double-blind placebo- and tolterodine- controlled trial of solifenacin
  • Change from baseline in mean voided volume/void

  • Contilife questionnaire

  • KHQ

Randomized, double-blind, placebo-controlled trial solifenacin 5/10 mg
  • KHQ

Extension study Open-label 1-year study of solifenacin 5 mg/10 mg in patients with OAB 12 Mean number of micturition episodes/24 hours
  • Urgency, incontinence, nocturia episodes/24 hours

  • Volume voided per void

  • Satisfaction with treatment

  • Tolerability of treatment

  • KHQ

Head to head Prospective, double-blind, study to compare the efficacy and safety of solifenacin 5/10 mg and tolterodine extended release; STAR trial 3 Mean number micturition episodes/24 hours
  • Urgency, urge incontinence, all incontinence, nocturia episodes.

  • Pad test

  • Number of patients requesting dose escalation

  • PBC

Post marketing Prospective, double-blind, 2-arm study comparing the efficacy of placebo and solifenacin; SUNRISE – (preliminary data available) 4 PIUS questionnaire – score changes
  • Total urgency episodes/24 hours

  • Urgency bother visual analogue scale

  • Number of micturition episodes, incontinence episodes/24 hours

  • Treatment satisfaction visual analogue scale

  • PBC

  • Treatment satisfaction visual analogue scale

  • Urgency bother visual analogue scale

  • PIUS

Post marketing Randomized, double-blind, placebo-controlled, parallel-group, flexible dosing study of solifenacin; VENUS – (preliminary data available) 3 Warning time, Change in number of urgency episodes/ 24 hours
  • Indevus urgency severity scale

  • Urgency perception scale

  • Indevus urgency severity scale (IUSS)

  • Urgency perception scale

Abbreviations: KHQ, Kings health questionnaire; PBC, perception of bladder condition.

Chapple et al (2004a) conducted a phase 2 study to evaluate the effective dose of solifenacin for the treatment of OAB. This was a multicenter, double blind, placebo and tolterodine controlled trial. Following a single blind 2-week placebo run in, patients were randomized to 4 weeks of either placebo, solifenacin (2.5 mg, 5 mg, 10 mg, or 20 mg doses) or twice-daily immediate-release tolterodine (2 mg). 265 patients were enrolled and 192 patients completed the study.

The primary outcome measure of the study was the change from baseline, in the mean number of voids per 24 hours. Secondary outcome measures included the change in volume of urine voided per void, and the mean number of urgency and incontinence episodes per 24 hours. Quality of life changes were assessed using the 27 item Contilife questionnaire.

Results of the study showed a significant reduction in the mean number of voids per 24 hours, and an increase in the mean volume voided per void in the study group taking 5 mg, 10 mg, and 20 g of solifenacin, when compared with the placebo group. There was no statistically significant reduction in voiding frequency, and volume voided per void in the tolterodine and 2.5 mg solifenacin treated patients compared with placebo (Figure 1).

Changes in bladder diary variables in a phase 2, solifenacin dose finding study.

The efficacy and tolerability of solifenacin was found to be dose dependant, with the greatest reduction in frequency occurring with the 20 mg dose. Neither solifenacin nor tolterodine treated patients experienced a significant reduction in the number of urgency or incontinence episodes. Quality of life assessment using the Contilife questionnaire showed an improvement in 4 domains (daily life activities, emotional consequences, sexuality, and self-image) in the solifenacin treated patients, compared with improvement in the daily life activities domain in the tolterodine treated group, when compared with placebo.

Dry mouth and constipation were the most commonly reported adverse events. The incidence of dry mouth was greatest in the solifenacin 20 mg treated group (n = 14, 38%), followed by the tolterodine treated group (n = 9, 24%), and then the 5 and 10 mg dose treated groups (n = 5, 14% for both groups).

Patients taking 20 mg of solifenacin reported the highest incidence of adverse events, followed by those patients taking tolterodine. The lowest incidence of adverse events was reported by patients taking 2.5 and 5 mg solifenacin.

Fourteen patients (7%) discontinued from the study due to adverse events; 7 of these patients were in the 20 mg solifenacin-treated group (one subject dropped out during the placebo run-in period), 6 patients were in the 10 mg solifenacin group, and 1 patient was taking 5 mg of solifenacin.

There have been 4 phase 3 trials, a 1-year open label extension study and a solifenacin and tolterodine head-to-head study assessing the safety and tolerability of solifenacin in patients with OAB.

Two initial phase 3 clinical trials were designed to evaluate the efficacy and safety of 10 mg solifenacin in double blind, placebo-controlled trials (studies 013 and 014). The primary endpoint for both studies was the change from baseline to 12 weeks in the number of micturitions in 24 hours. The mean change in the number of incontinence episodes per 24 hours and mean volume voided per micturition, were used as secondary endpoints. Both studies showed solifenacin 10 mg to be superior to placebo in reducing micturition frequency, incontinence and urgency episodes, and the volume voided per micturition episode. There was no statistically significant reduction in nocturia episodes in both studies. 1208 patients were recruited into the studies. Pharmacokinetic studies were performed before drug dosing, at steady state and post-dosing. Both studies reported mild to moderate adverse events, the most commonly reported being dry mouth and constipation. In study 013 there was one discontinuation due to dry mouth.

Cardozo et al (2004) conducted a 12-week, multicenter, randomized, double blind placebo controlled trial assessing the efficacy of 5 and 10 mg doses of solifenacin. Safety and tolerability of solifenacin were secondary study objectives. Patients were randomized to once daily doses of placebo, 5 mg or 10 mg of solifenacin.

The primary endpoint for this 12-week trial was the mean change in micturition episodes in 24 hours. Changes from baseline in the mean umber of urgency, nocturia and incontinence episodes, and the mean volume voided per void, were used as secondary endpoints. 907 patients took part in the trial, and data from 857 patients was analyzed. 281 patients received placebo, 286 received 5 mg solifenacin and placebo, and 290 received 10 mg of solifenacin.

The mean reductions in the number of micturition, urgency, and nocturia episodes in 24 hours are shown in Figure 2. The reductions in urinary frequency and urgency episodes with solifenacin treatment were statistically significant for both doses of solifenacin. One of the major findings of this study was the significant reduction in nocturia episodes in patients taking a 10 mg dose of solifenacin.

Reduction from baseline in the number of micturition and urgency episodes in 24 hours, and episodes of nocturia in patients receiving placebo, 5 mg, or 10 mg of solifenacin in a phase 3 trial (drawn from data of Cardozo et al 2004).

Half of the patients who were incontinent at baseline and received treatment with solifenacin (5 mg and 10 mg) were dry at the end of the study period. Rates of dry mouth were 7.7%, 23%, and 2.3% for solifenacin 5 mg, 10 mg and placebo respectively. 29 patients (3.2%) withdrew from the study due to adverse events; this was greatest in the solifenacin 10 mg treated group (n = 12, 3.9%), then the placebo group (n = 10, 3.3%). Seven patients (2.3%) in the 5 mg solifenacin-treated group withdrew from the study due to adverse events.

A 12-week phase 3a study assessing the efficacy of 5 mg and 10 mg solifenacin was conducted in a multicenter, double-blind, placebo-controlled trial, using 2 mg of immediate release tolterodine as an active comparator (Chapple et al 2004b). The primary aim was to assess the efficacy of solifenacin 5 and 10 mg whilst the secondary aims were to compare the safety and efficacy with that of 2 mg immediate release (IR) tolterodine. After a 2-week placebo run-in period, subjects were randomized to either 2 mg IR tolterodine twice daily, placebo, solifenacin 5 mg or 10 mg. Baseline to end of study changes in the mean number of urgency, mixed incontinence and urgency incontinence episodes were used as study outcome measures. In addition, the mean number of voids per 24 hours and mean volume voided per void were also assessed.

1077 men and women received one of the study drugs. Results of the study showed a statistically significant reduction in the number of urgency and urgency incontinence episodes in the patients receiving solifenacin, when compared with placebo. These changes were not statistically significant in the tolterodine-treated group when compared with placebo. There was a significant reduction in urinary frequency with all active treatments, this effect being greatest in the solifenacin 10 mg, and then the 5 mg group. There was a statistically significant improvement in volume of urine per void in the solifenacin- and tolterodine-treated groups, when compared with placebo. The changes in study outcome measures are shown in Figure 3.

The percentage change from baseline in the mean number of urgency, incontinence, and urge incontinence episodes and mean voids in a 24-hour period (Drawn from data of Chapple et al 2004b).

The incidence of dry mouth was 14%, 21.3%, and 18.6% in the 5 mg and 10 mg solifenacin- and tolterodine-treated patients respectively. Constipation was reported in a greater number of patients receiving solifenacin than tolterodine.

The study found the 5 and 10 mg doses of solifenacin to be more effective than placebo, in the treatment of OAB.

These preliminary studies lead to the STAR study; a head to head clinical trial comparing the efficacy of the existing market leader tolterodine extended release with dose flexible solifenacin. This was a prospective, double blind, 2 arm, parallel group, 12-week study (Chapple et al 2005). 1200 subjects were randomized, 593 were commenced on 5 mg solifenacin and 607 on 4 mg extended release tolterodine. The study design is described in Figure 4.

Design of the STAR study.

In this type of study the initial analysis is one of non-inferiority of the test drug, and once established assessment of superiority may follow. The results of the study showed that solifenacin was not inferior to tolterodine in reducing the number of voids per 24 hours; 2.45 and 2.24 episodes, respectively. Solifenacin treatment resulted in a significant improvement in urgency, nocturia, urge incontinence, and overall incontinence when compared with tolterodine. Reduction in pad usage was significantly greater in the solifenacin-treated group than the tolterodine-treated group (1.72 and 1.19 respectively). Four weeks after treatment initiation, 48% of patients on solifenacin and 51% on tolterodine requested a dose increase.

The perception of bladder condition questionnaire (PBC) is a validated single-item questionnaire, which asks people to choose 1 of 6 responses describing the severity of their bladder condition. Assessment of the PBC questionnaire scores showed a greater improvement in the solifenacin-treated group than the tolterodine-treated group (1.51 and 1.33 respectively).

Adverse events were those associated with antimuscarinic therapy and were mild to moderate in severity.

The study concluded that the flexible dosing of solifenacin is more effective in treating OAB compared with the highest licensed dose of extended release tolterodine.

The duration of most clinical trials is 12 weeks, owing, among other factors, to cost constraints, intensity of surveillance, and the ethical considerations of long-term placebo treatment. Patients receive detailed follow up and incentives such as free study medication in order to complete the trial. Long term real world efficacy and persistence with treatment cannot be easily extrapolated from short-clinical trials.

Participants in a 12-week study were offered a 40-week open label extension of solifenacin at both 5 and 10 mg doses. The aim of the study was to assess the long-term efficacy and tolerability of solifenacin (Haab et al 2005). Participants were followed up at 3 intervals. Traditional outcome measures such as frequency, urgency, urgency incontinence, and nocturia episodes per 24-hour period and volume voided per void were used.

1633 patients took part in the study. 42% (685) of patients commenced and continued with a 5 mg dose of medication. 6.6% (108) chose to increase the dose of study medication but subsequently went back to the lower dose. 51% of patients’ dose escalated and continued with the 10 mg dose of solifenacin. 81% of study participants completed the study.

Figure 5 shows the changes in bladder diary variables over the 1-year extension period. At the end of the study period, the mean number of incontinence and micturition episodes per 24 hours had decreased by 66% and 23%, respectively. 58% of patients who experienced more than one incontinence episode per day at the beginning of the study were continent at the conclusion of the trial.

Median percentage reductions in frequency, urgency, and nocturia in long-term solifenacin treated patients. Reprinted with permission from Haab F, Cardozo L, Chapple C, et al. 2005. Long term open-label solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome. Eur Urol, 47:376–84. Copyright © 2005 Elsevier.

4.7% of patients withdrew from treatment due to adverse events (0.4% withdrawals were due to dry mouth). Dry mouth was reported by 10% of patients on the 5 mg dose and 17% on the 10 mg dose of solifenacin. The overall reported rate of dry mouth was 21%. More than half of episodes of dry mouth, constipation and blurred vision were mild in severity.

At the end of the study, patients were asked about satisfaction with treatment and tolerability, 85% were satisfied, and 99% found tolerability of solifenacin to be satisfactory or acceptable.

The Kings health questionnaire (KHQ) (Kelleher et al 1997b), a 10-domain quality of life instrument designed for the assessment of quality of life among patients with lower urinary tract dysfunction, was used in 2 of the phase 3 studies (Chapple et al 2004b; Cardozo et al 2004) and the open label extension study. The domains of the KHQ assess general health perceptions, incontinence impact, role, social and physical limitations, personal relationships, sleep/energy, emotions, severity measures, and symptom severity. There are 34 linguistic validations of the KHQ and it has been used in many studies of drug therapy for OAB (Kelleher et al 2005).

Quality of life data analysis of a 12-week trial conducted by Chapple et al (2004b) showed a significant improvement in 5 of the domains of the KHQ in patients taking 5 and 10 mg doses of solifenacin compared with placebo (role limitations, physical limitations, emotions, severity measures, and symptom severity). Patients taking 10 mg of solifenacin also reported a significantly greater score in the incontinence impact domain. Results from the phase 3 trial study by Cardozo et al (2004) also showed statistically significant improvements in 5 domains of the KHQ for both doses of solifenacin compared to placebo (incontinence impact, role limitations, emotions, sleep/energy, and symptom severity). Patients taking the 10 mg dose of solifenacin also reported an improvement in the physical limitations and severity measures domains (Figure 6).

Pooled changes from baseline in the KHQ domains for 2 of the phase 3 trials for solifenacin.

Quality of life data from the long term extension study showed a significant improvement in 9 of the 10 domains of the KHQ (with the exception of the personal relationships domain). Almost two thirds of this improvement occurred in the first 3 months of treatment and was sustained for the duration of the study. Analysis of these data showed a significant improvement in all quality of life domains for patients treated with 5 and 10 mg of solifenacin, which were 17% for the general health perceptions domain, and 35%–48% improvement in all other domains. Quality of life improvements continued throughout the 40-week extension period (Figure 7).

Changes from baseline in the KHQ domains for the open label solifenacin extension study.

Previous studies of solifenacin have used changes in micturition frequency as the primary outcome measure of treatment effectiveness. Two recent trials have used urgency as the primary outcome variable. The Venus trial (Vesicare efficacy and safety in patients with urgency study) investigated the efficacy and safety of 5 and 10 mg doses of solifenacin using a novel outcome measure of urgency called warning time. Warning time is defined as “the time from the first sensation of urgency to voluntary micturition or incontinence” (Chalifoux 1980). Warning time was measured using a stopwatch for a 1-day period prior to study-related visits.

739 patients participated in the study, 372 received either 5 or 10 mg solifenacin, and 367 received placebo. The results of the study showed a significant increase in warning time in patients receiving solifenacin, 186.4 seconds versus 54.7 seconds in the placebo group. Qualitative measures of urgency were evaluated using the urgency perception scale (UPS); a validated three point scale and the Indevus urgency severity scale (IUSS); a single item patient reported measure of urgency severity (Toglia et al 2006a). Full data from this trial had not been published at the time of preparing of this manuscript. Previous clinical trials evaluating tolterodine and darifenacin have used warning time as an endpoint measure; however have failed to show a significant increase in warning time (Toglia 2006b; Zinner et al 2006).

Cardozo et al (2003) have previously shown a significant improvement in warning time for darifenacin compared to placebo in a randomized, double blind, placebo controlled study. The dose of darifenacin used was 30 mg, namely twice the maximal licensed dose for the treatment of OAB.

The 16-week Sunrise study (solifenacin in the treatment of urgency symptoms of OAB in a rising dose, randomized, placebo controlled, double blind, efficacy trial) assessed the effects of 5 and 10 mg solifenacin on urgency severity and bother. The majority of clinical trials of OAB treatments use frequency and incontinence episodes as primary outcome variables as they are easy to objectively measure. Urgency is difficult to measure but remains the defining and most bothersome symptom of OAB and as such of greatest importance to patients and prescribers (Cardozo et al 2006a). All patients were offered dose escalation half way through the study, the dose of solifenacin dispensed was based on a second randomization, whereby patients taking 5 mg solifenacin had a 50% chance of receiving a 10 mg dose. Urgency severity and bother were chosen as the primary end points for the study. A validated 5-point urgency scale; the PIUS, and a visual analogue scale (VAS) assessing urgency bother were used. The perception of bladder condition (PBC) which is a validated, single item questionnaire, and a treatment satisfaction visual analogue scale were also used. Traditional bladder diary measurements namely, frequency, urgency and incontinence episodes per 24 hours were used as secondary outcome variables.

503 patients received solifenacin, starting at 5 mg, which could be increased to 10 mg if required. 206 patients received placebo. Patients receiving solifenacin achieved a significantly greater reduction in urgency, frequency, and urge incontinence episodes when compared with placebo. These trends were also reflected in the qualitative measures. There was a 42.4% and 31.7% reduction in the urgency bother VAS and PBC scores respectively. Treatment satisfaction was significantly increased.

The incidences of dry mouth and constipation were higher in patients receiving solifenacin (15.8% and 6.9% respectively) than placebo (2.7% and 2.2% respectively). The rate of blurred vision was equivocal. Discontinuation rates for solifenacin and placebo were similar (12.1% and 11.6%) (Cardozo et al 2006b). Full data from this trial had not been published at the time of preparing this manuscript.

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