Consumer medicine information

Solifenacin Sandoz

Solifenacin succinate

BRAND INFORMATION

Brand name

Solifenacin Sandoz

Active ingredient

Solifenacin succinate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Solifenacin Sandoz.

SUMMARY CMI

SOLIFENACIN SANDOZ®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Solifenacin Sandoz?

Solifenacin Sandoz contains the active ingredient solifenacin succinate. Solifenacin Sandoz is used to treat the symptoms of overactive bladder.

For more information, see Section 1. Why am I using Solifenacin Sandoz? in the full CMI.

2. What should I know before I use Solifenacin Sandoz?

Do not use if you have ever had an allergic reaction to solifenacin succinate or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Solifenacin Sandoz? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Solifenacin Sandoz and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Solifenacin Sandoz?

  • The usual dose is 5 to 10 mg of Solifenacin Sandoz once a day. Your doctor will decide the most suitable dose for you.
  • Talk to your doctor or pharmacist if you feel that the effect of Solifenacin Sandoz is too strong or too weak

More instructions can be found in Section 4. How do I use Solifenacin Sandoz? in the full CMI.

5. What should I know while using Solifenacin Sandoz?

Things you should do
  • Before starting any new medicine, tell your doctor or pharmacist that you are taking Solifenacin Sandoz.
  • Tell all the doctors, dentists and pharmacists who are treating you that you are taking Solifenacin Sandoz.
  • If you become pregnant while taking Solifenacin Sandoz, tell your doctor.
  • Visit your doctor regularly so they can check on your progress.
Things you should not do
  • Do not stop taking Solifenacin Sandoz, or lower the dose, without checking with your doctor.
  • Do not use Solifenacin Sandoz to treat any other conditions unless your doctor tells you to.
  • Do not give Solifenacin Sandoz to anyone else, even if they have the same condition as you.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Solifenacin Sandoz affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep your tablets in a cool dry place where the temperature stays below 25°C.

For more information, see Section 5. What should I know while using Solifenacin Sandoz? in the full CMI.

6. Are there any side effects?

There are a number of side effects associated with this medicine. It is important to be aware of them so that you can identify any symptoms if they occur (see the full CMI for more details). The most common and serious side effects are allergic reactions including swelling of the face, lips, throat or tongue, difficulty breathing; chest pain or tightness; swelling of the feet or legs; changes in electrical activity of the heart (ECG), irregular heartbeat (Torsade de Points).

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

SOLIFENACIN SANDOZ®

Active ingredient(s): solifenacin succinate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Solifenacin Sandoz. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Solifenacin Sandoz.

Where to find information in this leaflet:

1. Why am I using Solifenacin Sandoz?
2. What should I know before I use Solifenacin Sandoz?
3. What if I am taking other medicines?
4. How do I use Solifenacin Sandoz?
5. What should I know while using Solifenacin Sandoz?
6. Are there any side effects?
7. Product details

1. Why am I using Solifenacin Sandoz?

Solifenacin Sandoz contains the active ingredient solifenacin succinate. Solifenacin Sandoz belongs to a group of medicines called anticholinergic medicines. It works by acting on specialised cells to reduce the activity of your bladder and help you control your bladder.

Solifenacin Sandoz is used to treat the symptoms of overactive bladder. These symptoms include needing to rush to the toilet to urinate without warning, needing to urinate frequently, or wetting yourself because you did not get to the toilet in time.

Your doctor may have prescribed Solifenacin Sandoz for another reason. Ask your doctor if you have any questions about why Solifenacin Sandoz has been prescribed for you.

Solifenacin Sandoz is available only with a doctor's prescription.

There is no evidence that Solifenacin Sandoz is addictive.

2. What should I know before I use Solifenacin Sandoz?

Warnings

Do not use Solifenacin Sandoz if:

  • you are allergic to solifenacin succinate, or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include skin rash, itching or hives, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, wheezing or shortness of breath. Always check the ingredients to make sure you can use this medicine.
  • you suffer from urinary retention (inability to urinate or empty your bladder completely)
  • you are undergoing haemodialysis
  • you have severe kidney disease or moderate liver disease and are also taking medicines that can decrease the removal of Solifenacin Sandoz from the body (see Section 3. What if I am taking other medicines?)
  • you have severe liver disease
  • you have uncontrolled glaucoma (high pressure in the eyes, with gradual loss of eye sight)
  • you have myasthenia gravis, a disease of the muscles causing drooping eyelids, double vision, difficulty in speaking or swallowing and sometimes muscle weakness in the arms or legs
  • you have a blocked gastro-intestinal tract or other gastro-intestinal disorders such as ulcerative colitis or toxic megacolon.
  • the expiry date (Exp.) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering.

Check with your doctor if you:

  • have any other medical conditions, especially the following:
    - low potassium levels or a family history of heart rhythm problems. Solifenacin Sandoz may have an effect on the electro-cardiogram (ECG - a heart tracing) and may add to the effect of other medicines on the ECG. You should advise your doctor of any other medicines you are currently taking, particularly those affecting the heart rhythm. Your doctor may wish to perform an ECG if you have any risks of having an abnormal heart rhythm.
    - blockage to your bladder that causes difficulty urinating
    - obstruction of the digestive system (constipation)
    - glaucoma (high pressure in the eyes, with gradual loss of eye sight)
    - hiatus hernia or gastric reflux or are currently being treated with some medicines (such as bisphosphonates) which may make your reflux worse
    - autonomic neuropathy, a nerve problem which sometimes occurs with diabetes and can lead to diarrhoea, impotence or low blood pressure
    - severe kidney disease
    - moderate liver disease
  • are allergic to any other medicines, foods, dyes or preservatives.

Do not give Solifenacin Sandoz to children.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Tell your doctor if you are pregnant. Solifenacin Sandoz may affect your developing baby if you take it during pregnancy. Your doctor will decide if you should take it. Do not take Solifenacin Sandoz if you are breastfeeding.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may be affected by Solifenacin Sandoz, or may affect how well it works.

Some medicines can slow down the removal of Solifenacin Sandoz from the body. If you are taking any of the following, 5 mg a day is the maximum recommended dosage:

  • some antifungal medicines such as ketoconazole, itraconazole
  • ritonavir and nelfinavir, medicines to treat HIV infection.

If you are taking any of the above medicines and you also have severe kidney disease or moderate liver disease, you should not take Solifenacin Sandoz.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Solifenacin Sandoz.

4. How do I use Solifenacin Sandoz?

How much to take

  • The usual dose is 5 to 10 mg of Solifenacin Sandoz once a day. Your doctor will decide the most suitable dose for you.
  • Talk to your doctor or pharmacist if you feel that the effect of Solifenacin Sandoz is too strong or too weak.
  • Follow all directions given to you by your doctor and pharmacist carefully.

When to take Solifenacin Sandoz

  • Try to take Solifenacin Sandoz at the same time each day.

How to take Solifenacin Sandoz

  • Solifenacin Sandoz is taken by mouth. It can be taken with or without food.
  • Swallow the tablets whole with a glass of water.
  • Do not crush or chew the tablets.
  • If you crush or chew Solifenacin Sandoz tablets, they may not work as well.

If you forget to use Solifenacin Sandoz

Solifenacin Sandoz should be used regularly at the same time each day. If you miss your dose at the usual time, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

How long to take Solifenacin Sandoz for

To properly control your condition, Solifenacin must be taken every day.

Keep taking Solifenacin Sandoz for as long as your doctor recommends.

If you use too much Solifenacin Sandoz

If you think that you have used too much Solifenacin Sandoz, you may need urgent medical attention.

You should immediately:

  • phone the Australian Poisons Information Centre
    (by calling 13 11 26), or the New Zealand National Poisons Information Centre (by calling 0800 POISONS or 0800 764766), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Solifenacin Sandoz?

Things you should do

Before starting any new medicine, tell your doctor or pharmacist that you are taking Solifenacin Sandoz.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Solifenacin Sandoz.

If you become pregnant while taking Solifenacin Sandoz, tell your doctor.

Visit your doctor regularly so they can check on your progress.

Things you should not do

  • Do not stop taking Solifenacin Sandoz, or lower the dose, without checking with your doctor.
  • Do not use Solifenacin Sandoz to treat any other conditions unless your doctor tells you to.
  • Do not give Solifenacin Sandoz to anyone else, even if they have the same condition as you

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Solifenacin Sandoz affects you.

Solifenacin Sandoz may cause dizziness in some people.

Do not drive or operate machinery if you suffer from any of these side effects

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep your tablets in a cool dry place where the temperature stays below 25°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Solifenacin Sandoz.

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • nausea, vomiting
  • constipation
  • indigestion
  • heartburn (dyspepsia)
  • stomach discomfort
  • urinary tract infection, bladder pain
  • difficulty passing urine, inability to empty the bladder
  • urgent need to urinate
  • blurred vision
  • inability to empty the bladder
  • dry eyes
  • tiredness
  • muscle weakness
  • accumulation of fluid (swelling) in the lower limbs (oedema)
  • dizziness
  • sore / dry throat
  • cough
  • headache
  • sleepiness
  • hallucination
  • confusion
  • depression
  • fast heartbeat
  • palpitations
  • skin reactions such as rash, itching or hives.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • allergic reactions including swelling of the face, lips, throat or tongue, difficulty breathing
  • chest pain or tightness
  • swelling of the feet or legs changes in electrical activity of the heart (ECG), irregular heartbeat (Torsade de Points)
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Some of these side effects (for example, changes in electrical activity of the heart or liver function) can only be found when your doctor does tests from time to time to check your progress.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems or to Medsafe at pophealth.my.site.com/carmreportnz/s/. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Solifenacin Sandoz contains

Active ingredient
(main ingredient)		solifenacin succinate
Other ingredients
(inactive ingredients)		maize starch
lactose monohydrate
hypromellose
magnesium stearate
macrogol 6000
talc
titanium dioxide
iron oxide yellow (5 mg tablets only)
iron oxide red (10 mg tablets only)
Potential allergenslactose

Do not take this medicine if you are allergic to any of these ingredients.

What Solifenacin Sandoz looks like

Solifenacin Sandoz comes in two strengths of tablets.:

Solifenacin Sandoz 5 mg – round light yellow tablets with debossment “05” on one side.

Available in PVC/Al blisters or polyethylene bottles (with a polypropylene screw cap and desiccant insert) packed in a carton box.

Each blister pack contains 30 tablets (Aust R 311730).

Each bottle contains 30 tablets (Aust R 311728).

Solifenacin Sandoz 10 mg – round light pink tablets with debossment “10” on one side and score line on the other side. The 10 mg scored tablet can be divided into equal doses.

Available in PVC/Al blisters or polyethylene bottles (with a polypropylene screw cap and desiccant insert) packed in a carton box.

Each blister pack contains 30 tablets (Aust R 311729).

Each bottle contains 30 tablets (Aust R 311727).

Not all presentations may be marketed.

Who distributes Solifenacin Sandoz

Solifenacin Sandoz is supplied in Australia by:

Sandoz Pty Ltd
100 Pacific Highway
North Sydney, NSW 2060
Australia
Tel 1800 726 369

Solifenacin Sandoz is supplied in New Zealand by:

Sandoz New Zealand Limited
12 Madden Street
Auckland 1010
New Zealand
Tel: 0800 726 369

This leaflet was prepared in August 2024.

® Registered Trade Mark. The trade marks mentioned in this material are the property of their respective owners.

Published by MIMS November 2024

BRAND INFORMATION

Brand name

Solifenacin Sandoz

Active ingredient

Solifenacin succinate

Schedule

S4

 

1 Name of Medicine

Solifenacin succinate.

2 Qualitative and Quantitative Composition

Solifenacin Sandoz 5 mg film-coated tablet.

Each tablet contains 5 mg solifenacin succinate, corresponding to 3.8 mg solifenacin.

Solifenacin Sandoz 10 mg film-coated tablet.

Each tablet contains 10 mg solifenacin succinate, corresponding to 7.5 mg solifenacin.

Excipient with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solifenacin Sandoz 5 mg film-coated tablet.

Each 5 mg tablet is a round, light-yellow tablet with debossment "05" on one side.

Solifenacin Sandoz 10 mg film-coated tablet.

Each 10 mg tablet is a round, light-pink tablet with debossment "10" on one side and score line on the other side.
The 10 mg scored tablet can be divided into equal doses.

4 Clinical Particulars

4.1 Therapeutic Indications

Solifenacin Sandoz is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency or increased urinary frequency.

4.2 Dose and Method of Administration

Dosage.

Adults, including the elderly.

The recommended dose is 5 mg solifenacin succinate once daily. If needed, the dose may be increased to a maximum of 10 mg solifenacin succinate once daily.

Children and adolescents.

Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Sandoz should not be used in children.

Method of administration.

Solifenacin Sandoz should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

Dosage adjustment.

Renal impairment.

No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance > 30 mL/min). Patients with severe renal impairment (creatinine clearance ≤ 30 mL/min) should be treated with caution and receive no more than 5 mg once daily.

Hepatic impairment.

No dose adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child-Pugh B) should be treated with caution and receive no more than 5 mg once daily. Solifenacin Sandoz is contraindicated in patients with severe hepatic impairment (Child-Pugh C).

Co-medication.

The maximum dose of Solifenacin Sandoz should be limited to 5 mg when treated simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4-inhibitors e.g. ritonavir, nelfinavir, itraconazole, ciclosporin, macrolide antibiotics. (Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.3 Contraindications

Solifenacin is contraindicated in:
patients with urinary retention;
patients with uncontrolled narrow-angle glaucoma;
patients who have demonstrated hypersensitivity to the drug substance or other components of the product;
severe gastro-intestinal condition (including toxic megacolon and gastric retention);
myasthenia gravis;
patients undergoing haemodialysis;
patients with severe hepatic impairment;
patients with severe renal impairment or moderate hepatic impairment and who are on treatment with a potent CYP3A4 inhibitor, e.g. ketoconazole.

4.4 Special Warnings and Precautions for Use

Solifenacin should be used with caution in patients with:
clinically significant bladder outflow obstruction at risk of urinary retention;
gastrointestinal obstructive disorders;
risk of decreased gastrointestinal motility;
in patients being treated for narrow-angle glaucoma;
hiatus hernia/gastro-oesophagal reflux and/or who are concurrently taking medicinal products that can cause or exacerbate oesophagitis;
autonomic neuropathy;
known risk factors for QT prolongation, such as pre-existing long QT syndrome and hypokalaemia.

Angioedema.

Angioedema with airway obstruction has been reported in some patients on solifenacin succinate. If angioedema occurs, solifenacin succinate should be discontinued and appropriate therapy and/or measures should be taken.

Anaphylactic reaction.

Anaphylactic reaction has been reported in some patients treated with solifenacin succinate. In patients who develop anaphylactic reactions, solifenacin succinate should be discontinued and appropriate therapy and/or measures taken.

QT prolongation and torsade de pointes.

QT Prolongation and Torsade de Pointes have been observed in patients with known risk factors for these conditions.
As with other drugs in this class, caution is advised in patients with known risk factors for QT prolongation (i.e. history of QT prolongation, long QT syndrome, hypokalaemia, bradycardia, coadministration of drugs known to prolong the QT interval) and relevant pre-existing cardiac diseases (i.e. myocardial ischaemia, arrhythmia, congestive heart failure) (see Section 5.1 Pharmacodynamic Properties, Clinical trials; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).
Appropriate investigations (e.g. ECG) should be considered in patients with risk factors for QTc prolongation.

Use in hepatic impairment.

Doses of solifenacin greater than 5 mg are not recommended in patients with moderate hepatic impairment (Child-Pugh B). Solifenacin is contraindicated for patients with severe hepatic impairment (Child-Pugh C) (see Section 4.3 Contraindications).
In patients with moderate hepatic impairment (Child-Pugh score of 7 to 9) the Cmax is not affected, AUC increased with 60% and t1/2 doubled. Pharmacokinetics of solifenacin in patients with severe hepatic impairment have not been studied.

Use in renal impairment.

Solifenacin should be used with caution in patients with reduced renal function. Solifenacin should be used with caution in patients with severe renal impairment (creatinine clearance < 30 mL/min), and doses should not exceed 5 mg for these patients.
The AUC and Cmax of solifenacin in mild and moderate renally impaired patients was not significantly different from that found in healthy volunteers. In patients with severe renal impairment (creatinine clearance ≤ 30 mL/min) exposure to solifenacin was significantly greater than in the controls with increases in Cmax of about 30%, AUC of more than 100% and t1/2 of more than 60%. A statistically significant relationship was observed between creatinine clearance and solifenacin clearance.
Pharmacokinetics in patients undergoing haemodialysis have not been studied.

Use in the elderly.

No dosage adjustment based on patient age is required. Studies in the elderly have shown that Cmax, AUC and t1/2 values were 20-25% higher as compared to the younger volunteers (18-55 years). No overall differences were observed in the safety of solifenacin between older and younger patients treated for 4 to 12 weeks with 5 to 10 mg solifenacin succinate.

Paediatric use.

Safety and effectiveness in children have not yet been established. Therefore, solifenacin should not be used in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

In vitro studies have demonstrated that at therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, solifenacin succinate is not likely to interact with the CYP mediated metabolism of coadministered drugs.

Effect of other medicinal products on the pharmacokinetics of solifenacin.

In vitro drug metabolism studies have shown that solifenacin is a substrate of CYP3A4. Inducers or inhibitors of CYP3A4 may alter solifenacin pharmacokinetics. Simultaneous administration of ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, resulted in a twofold increase of the AUC of solifenacin, while ketoconazole at a dose of 400 mg/day resulted in a three-fold increase of the AUC of solifenacin. Therefore, the maximum dose of solifenacin should be restricted to 5 mg, when used simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. ritonavir, nelfinavir, itraconazole, ciclosporin, macrolide antibiotics).
The effects of enzyme induction on the pharmacokinetics of solifenacin and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on solifenacin exposure. Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. verapamil, diltiazem) and CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine).

Effect of solifenacin on the pharmacokinetics of other medicinal products.

Oral contraceptives.

Intake of solifenacin showed no pharmacokinetic interaction of solifenacin on combined oral contraceptives (ethinyl oestradiol/levonorgestrel).

Warfarin.

Intake of solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.

Digoxin.

Intake of solifenacin showed no effect on the pharmacokinetics of digoxin.

Drugs, which prolong the QT/QTc interval.

There is no satisfactory information on the concurrent use of solifenacin succinate with drugs known to prolong the QT/QTc interval. In the absence of such information on these combinations, the potential risk of pathological QT/QTc prolongation resulting in arrhythmias cannot be ruled out. Drugs known to prolong the QT/QTc interval include erythromycin, quinidine, procainamide, disopyramide, sotalol, amiodarone, cisapride, fluconazole, amitriptyline, haloperidol, chlorpromazine, thioridazine, pimozide and droperidol.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Solifenacin had no effect on reproductive function, fertility or early embryonic development after oral treatment of male and female mice, which resulted in 13 times exposure at the maximum recommended human dose (MRHD).
(Category B3)
Solifenacin (and/or its metabolites) has been shown to cross the placenta in pregnant mice. No embryotoxicity or teratogenicity was observed in mice treated with 1.2 times exposure at the maximum recommended human dose (MRHD). In one of two studies, higher doses (3.6 times exposure at the MRHD) resulted in maternal toxicity and reduced fetal body weight. No embryotoxic effects were observed in rabbits at up to 1.8 times exposure at the MRHD.
In utero and lactational exposures to maternal doses of solifenacin 3.6 times exposures at the MRHD resulted in reduced peripartum and postnatal survival, reductions in body weight gain, and delayed physical development (e.g. eye opening).
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, solifenacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
 Solifenacin is excreted into the breast milk of mice. There were no significant adverse effects at 1.2 times exposure at the maximum recommended human dose (MRHD) in a pre- and postnatal study in mice. Pups of female mice treated at 3.6 times exposure at the MRHD showed reduced body weights, postpartum pup mortality or delays in the onset of reflex and physical development during the lactation period. It is expected that solifenacin is excreted in human milk and solifenacin should not be administered during breast-feeding.

4.7 Effects on Ability to Drive and Use Machines

Since solifenacin, like other anticholinergics may cause blurred vision, and uncommonly somnolence and fatigue, the ability to drive and use machines may be negatively affected (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

In the four 12-week double-blind clinical trials 3027 patients were involved (1811 on solifenacin and 1216 on placebo), and approximately 90% of these patients completed the 12-week studies. The most frequent reason for discontinuation due to an adverse event was dry mouth, 1.5%. There were three intestinal serious adverse events in patients all treated with solifenacin 10 mg (one faecal impaction, one colonic obstruction, and one intestinal obstruction).
Table 1 lists the adverse events reported in ≥ 1.0% of the patients in the 12 week studies. The relationship to study medication for most of these events is uncertain; many are thought to represent spontaneous events reported by patients with bladder dysfunction (and other concomitant diseases) and are not necessarily causally related to solifenacin.
Adverse reactions reported in the clinical trials with a frequency of occurrence less than 1% are:

Gastrointestinal disorders.

Flatulence, gastro-oesophageal reflux diseases, throat irritation, eructation, dry throat.

Infections and infestations.

Cystitis.

Nervous system disorders.

Somnolence, dysgeusia, syncope.

General disorders and administration site disorders.

Thirst, suprapubic pain, chest tightness.

Renal and urinary disorders.

Difficulty in micturition, bladder pain, micturition urgency.

Respiratory, thoracic and mediastinal disorders.

Nasal dryness.

Investigations.

Abnormal liver function tests (AST, ALT, GGT), electrocardiogram QT prolonged.

Musculoskeletal and connective tissue disorders.

Peripheral swelling.

Skin and subcutaneous tissue disorders.

Dry skin.

Vascular disorders.

Hot flushes.

Post marketing experience.

The following adverse reactions have been spontaneously reported during worldwide post-approval use of solifenacin. The adverse reactions reported are presented below according to System Organ Class and frequency.
Adverse event frequencies are defined as follows: Very common (≥ 10%), common (≥ 1%, < 10%), uncommon (≥ 0.1%, < 1%), rare (> 0.01%, < 0.1%) and very rare (< 0.01%), not known (cannot be estimated from the available data).

Cardiac disorders.

Very Rare: Torsade de Pointes, atrial fibrillation, palpitations, tachycardia.

Eye disorders.

Very rare: glaucoma.

Gastrointestinal disorders.

Very rare: Gastro-oesophageal reflux disease, vomiting, ileus.

General disorders and administration site conditions.

Very rare: Peripheral oedema.

Hepatobiliary disorders.

Very rare: Liver disorders mostly characterised by abnormal liver function tests (AST, ALT, GGT).

Immune system disorders.

Very rare: Anaphylactic reaction.

Investigations.

Very rare: Electrocardiogram QT prolonged.

Metabolism and nutrition disorders.

Very rare: Decreased appetite, hyperkalaemia.

Musculoskeletal and connective tissue disorders.

Very rare: Muscular weakness.

Nervous system disorders.

Very rare: Dizziness, headache, somnolence.

Psychiatric disorders.

Very rare: Hallucinations, delirium, confusion state.

Renal and urinary disorders.

Very rare: Renal impairment, urinary retention.

Respiratory, thoracic and mediastinal disorders.

Very rare: dysphonia, nasal dryness.

Skin and subcutaneous tissue disorders.

Very rare: Pruritus, rash, urticaria, angioedema, erythema multiforme, exfoliative dermatitis.
Postmarketing pharmacovigilance data confirmed QT prolongation associated with therapeutic doses of solifenacin succinate in cases with known risk factors (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.9 Overdose

Overdosage with solifenacin succinate can potentially result in severe anticholinergic effects (headache, dry mouth, dizziness, drowsiness and blurred vision) and should be treated accordingly. The highest dose of solifenacin succinate accidentally given to a single patient was 280 mg in a 5 hour period, resulting in mental status changes not requiring hospitalization.
Overdosage with solifenacin succinate may prolong the QTc interval, therefore, in the event of overdosage, ECG monitoring is recommended and standard supportive measures for managing QT prolongation should be adopted.

Treatment of overdosage.

No cases of acute overdosage have been reported. In the event of an overdose with solifenacin succinate, treat with activated charcoal.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia) and 0800 POISON or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Urinary antispasmodics, ATC code: G04B D08.

Mechanism of action.

Solifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergic mediated functions, including contractions of urinary bladder smooth muscle and stimulation of the salivary secretion.

Clinical trials.

Four randomised, double blind, placebo controlled pivotal studies were performed of 12 weeks duration to assess solifenacin for the treatment of overactive bladder in patients having symptoms of urinary frequency, urgency and/or urge or mixed incontinence (with the predominance of urge). Entry criteria required that patients have symptoms of overactive bladder for ≥ 3 months duration. These studies involved 3027 patients (1811 on solifenacin and 1216 on placebo), and approximately 90% of these patients completed the 12-week studies. Two of the four studies evaluated the 5 and 10 mg solifenacin doses and the other two evaluated only the 10 mg dose. The studies assessed the standard primary efficacy endpoint of number of micturitions per 24 hours, along with a number of usual secondary endpoints, including incontinence episodes, urgency episodes, urge incontinence episodes, nocturia episodes, all per 24 hours, and volume voided per micturition, using patient diaries.
As shown in Table 2, both the 5 mg and 10 mg doses of solifenacin produced statistically significant improvements in the primary and secondary endpoints compared with placebo. Efficacy was observed within one week of starting treatment and stabilises over a period of 12 weeks. After 12 weeks of treatment, approximately 50% of patients suffering from incontinence before treatment were free of incontinence episodes, and in addition, 35% of patients achieved a micturition frequency of less than 8 micturitions per day. All patients completing the 12-week studies were eligible to enter an open label, long term extension study and 81% of patients enrolling completed the additional 40-week treatment period demonstrating maintenance of effect. Treatment of the symptoms of overactive bladder also results in a benefit on a number of Quality of Life measures, such as general health perception, incontinence impact, role limitations, physical limitations, social limitations, emotions, symptom severity, severity measures and sleep/energy.

Clinical QT interval data.

Two dedicated QT studies have been performed with solifenacin.
The first study was an open label, multiple dose escalating study in 60 healthy subjects. In this study, solifenacin was administered starting at a dose of 10 mg once daily for 2 weeks and proceeded in 10 mg increments for 2 weeks at each dose level. The highest tolerated dose was 40 mg. The results are presented in Table 3. There was no significant change in QTc interval using the Bazett as well as the Friderica method for the 10 mg solifenacin compared to baseline. Depending on the method applied, some prolongation was seen for the 20 mg and 30 mg doses, which are higher than the recommended therapeutic dose. However, both methods suggest no prolongation for the 40 mg dose, which is four times the highest recommended therapeutic dose.
There were no QTc intervals > 500 msec; increases of > 60 msec occurred in 1 subject (on 30 mg), while change < 60 msec but > 30 msec occurred in 34 subjects (11 changes on 10 mg, 20 changes on 20 mg, 27 changes on 30 mg, 9 changes on 40 mg).
The second study was a double blind, multiple dose, placebo and positive controlled (moxifloxacin 400 mg) study in 76 female volunteers aged 19 to 79 years. This second QT study was a dedicated thorough QT study with the subjects randomized to one of two treatment groups after receiving placebo and moxifloxacin sequentially. One group (n = 51) went on to complete 3 additional sequential periods of dosing with solifenacin 10, 20, and 30 mg, while the second group (n = 25) in parallel completed a sequence of placebo and moxifloxacin. The 30 mg dose of solifenacin succinate (three times the highest recommended dose) was chosen for use in this study because this dose results in a solifenacin exposure that covers the exposure observed upon co-administration of 10 mg solifenacin with potent CYP3A4 inhibitors (e.g. ketoconazole, 400 mg). Due to the sequential dose escalating nature of the study, baseline ECG measurements were separated from the final QT assessment (of the 30 mg dose level) by 33 days.
The median difference from baseline in heart rate associated with the 10 and 30 mg doses of solifenacin succinate compared to placebo was -2 and 0 beats/minute, respectively. Because a significant period effect on QTc was observed, the QTc effects were analyzed utilizing the parallel placebo control arm rather than the pre-specified intra-patient analysis (Fridericia method). Representative results for solifenacin are shown in Table 4.
Moxifloxacin was included as a positive control in this study and, given the length of the study, its effect on the QT interval was evaluated in 3 different sessions. The placebo subtracted mean changes (90% Confidence Interval) in QTcF for moxifloxacin in the three sessions were 11 msec (7, 14), 12 msec (8,17) and 16 msec (12, 21), respectively.
There were no subjects with a mean QTc > 500 msec. Four subjects experienced increases in mean QTcF that were greater than 60 msec from the time-matched baseline. Three subjects received 30 mg solifenacin and the fourth received 400 mg moxifloxacin.
A change in QTc of < 60 msec but > 30 msec occurred in 29 subjects on 10 mg and in 31 subjects during 30 mg solifenacin treatment.
The QT interval prolonging effect appeared to be greater for the 30 mg compared to the 10 mg dose of solifenacin. Although the effect of the highest solifenacin dose (three times the maximum therapeutic dose) studied did not appear as large as that of the positive control moxifloxacin at its therapeutic dose, the confidence intervals overlapped. This study was not designed to draw direct statistical conclusions between the drugs or the dose levels.
Across the four controlled phase 3 studies, QTc interval prolongation was seen of approximately up to 5 msec, along with PR interval prolongation. There were 12 patients with a change in QTc from baseline of > 60 msec and 6 patients with QTc > 500 msec at any time point on solifenacin. There were no reports of VT or VF or association between these QT changes and death, syncope, dizziness or ventricular arrhythmias.

5.2 Pharmacokinetic Properties

Absorption.

After intake of solifenacin tablets, maximum solifenacin plasma concentrations (Cmax) are reached after 3 to 8 hours and at steady state ranged from 32.3 to 69.9 nanogram/mL for the 5 and 10 mg solifenacin tablets, respectively. The tmax is independent of the dose. The Cmax and area under the curve (AUC) increase in proportion to the dose between 5 to 40 mg. Absolute bioavailability is approximately 90%. Food intake does not affect the Cmax and AUC of solifenacin.

Distribution.

The apparent volume of distribution of solifenacin following intravenous administration is about 600 L. Solifenacin is to a great extent (approximately 98%) bound to plasma proteins, primarily α1-acid glycoprotein.

Metabolism.

Solifenacin is extensively metabolised in the liver. The primary pathway for elimination is by way of CYP3A4; however, alternate metabolic pathways exist. The primary metabolic routes of solifenacin are through N-oxidation of the quinuclidin ring and 4R-hydroxylation of tetrahydroisoquinoline ring. One pharmacologically active metabolite (4R-hydroxy solifenacin), occurring at low concentrations and unlikely to contribute significantly to clinical activity, and three pharmacologically inactive metabolites (N-glucuronide and the N-oxide and 4R-hydroxy-N-oxide of solifenacin) have been found in human plasma after oral dosing.

Excretion.

After a single administration of 10 mg [14C-labelled]-solifenacin, about 70% of the radioactivity was detected in urine and 23% in faeces over 26 days. In urine, approximately 11% of the radioactivity is recovered as unchanged active substance; about 18% as the N-oxide metabolite, 9% as the 4R-hydroxy-N-oxide metabolite and 8% as the 4R-hydroxy metabolite (active metabolite). The systemic clearance of solifenacin is about 9.5 L/h. The elimination half-life of solifenacin following chronic dosing is approximately 45 - 68 hours.

5.3 Preclinical Safety Data

Genotoxicity.

Solifenacin was not mutagenic in the in vitro Salmonella typhimurium or Escherichia coli microbial mutagenicity test or chromosomal aberration test in human peripheral blood lymphocytes, with or without metabolic activation, or in the in vivo micronucleus test in rats.

Carcinogenicity.

No significant increase in tumors was found following the administration of solifenacin to male and female mice for 104 weeks up to 5 and 9 times exposure at the maximum recommended human dose (MRHD), respectively, and male and female rats for 104 weeks at doses that resulted in < 1 times exposure at the MRHD.

6 Pharmaceutical Particulars

6.1 List of Excipients

Core tablet.

Pregelatinised maize starch, lactose monohydrate, hypromellose, magnesium stearate.

Film coating.

Macrogol 6000, purified talc, hypromellose, titanium dioxide, iron oxide yellow, (Solifenacin Sandoz 5 mg), iron oxide red, (Solifenacin Sandoz 10 mg).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Do not store above 25°C.

6.5 Nature and Contents of Container

Solifenacin Sandoz 5 mg film-coated tablets.

Blister packs (PVC/Alu) and bottles (HPDE) of 30 tablets.

Solifenacin Sandoz 10 mg film-coated tablets.

Blister packs (PVC/Alu) and bottles (HPDE) of 30 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Solifenacin (3R)-1-azabicyclo[2.2.2]oct-3-yl(1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate monosuccinate. The empirical formula is C23H26N2O2.C4H6O4. The molecular weight is 480.55.
Molecular structure:

CAS number.

242478-38-2.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes