Consumer medicine information

Sandomigran

Pizotifen

BRAND INFORMATION

Brand name

Sandomigran Tablets

Active ingredient

Pizotifen

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Sandomigran.

What is in this leaflet

This leaflet answers some common questions about Sandomigran.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. Some more recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine.

You can also download the most up to date leaflet from www.novartis.com.au.

Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Sandomigran against the benefits they expect it will have for you.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Sandomigran is used for

Sandomigran is used to prevent "vascular" headaches, including migraine, cluster headaches and vasomotor headaches.

Vascular headaches are thought to be caused by temporary changes in the size of small blood vessels in the brain. These changes cause the pain and problems with vision that often happen during a severe headache. Sandomigran prevents an attack by stopping the blood vessels from changing in size.

Sandomigran is only used to prevent severe headaches from happening. It will not stop an attack once it has started.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

Sandomigran is only available with a doctor's prescription. It is not addictive.

There is not enough information to recommend this medicine for children.

Before you take Sandomigran

When you must not take it

Do not take Sandomigran if you have an allergy to pizotifen (the active ingredient) or to any of the other ingredients of Sandomigran listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath, wheezing or difficulty breathing;
  • swelling of the face, lips, tongue or other parts of the body;
  • rash, itching or hives on the skin.

Do not take Sandomigran after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

In that case, return it to your pharmacist.

Before you start to take it

Tell your doctor if you have any of the following medical conditions:

  • increased pressure in the eye due to glaucoma
  • difficulty in passing urine (water), due to prostate trouble or any other cause
  • convulsions, fits, or seizures

Your doctor may want to take special precautions if you have one of the above conditions.

Tell your doctor if you are pregnant or intend to become pregnant.

Experience with Sandomigran in pregnancy is very limited. If it is necessary for you to take this medicine during pregnancy, your doctor will discuss with you the benefits and risks involved.

Tell your doctor if you are breast-feeding or intend to breast-feed.

Small amounts of Sandomigran pass into breast milk. Although such small amounts are unlikely to harm your baby, breast-feeding while taking this medicine is not recommended. Your doctor will discuss with you the benefits and the risks involved.

Tell your doctor if you are lactose intolerant.

This medicine contains lactose.

Tell your doctor if you have allergies to any other medicines, foods, dyes or preservatives.

Your doctor will want to know if you are prone to allergies.

Taking other medicines

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

Some medicines and Sandomigran may interfere with each other. These may include:

  • medicines to calm you down, treat anxiety, or help you to sleep
  • medicines found in cough, cold and allergy preparations (antihistamines)
  • monoamine oxidase inhibitors (MAOI) which belong to a group of medicines called antidepressants
  • cisapride, a medicine used to treat heartburn

These medicines may worsen the drowsiness that sometimes happens when you take Sandomigran. You may need to take different amounts of your medicines or you may need to take different medicines. Your doctor and pharmacist have more information.

If you have not told your doctor about any of these things, tell him/her before you start taking this medicine.

How to take Sandomigran

Follow all directions given to you by your doctor and pharmacist carefully.

These instructions may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How much to take

The usual starting dose is one tablet of Sandomigran each day. To avoid making you drowsy, the dose is gradually increased, usually to three tablets each day.

If your headaches are still not controlled, your doctor may gradually increase the dose up to a maximum of nine tablets each day, divided into two or three doses.

When to take it

Your doctor may tell you to take all of the tablets at one time (usually at night) or he/she may tell you to divide the tablets over the day (for example, 1 tablet in the morning and 2 tablets at night).

How to take it

Take the tablets with a full glass of water.

They can be taken with or without food.

Try to take the tablets at about the same times each day.

Taking them at the same times each day will help you to remember to take them.

How long to take it

Continue taking Sandomigran every day for as long as your doctor prescribes.

To prevent severe headaches, you must take this medicine every day, even if you feel well.

If you forget to take it

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

Otherwise, take it as soon as you remember, and then go back to taking it as you would normally.

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

This may increase the chance of you getting an unwanted side effect.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone number 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Sandomigran. Do this even if there are no signs of discomfort or poisoning. Keep the telephone numbers for these places handy.

Some of the symptoms of an overdose may include drowsiness, nausea (feeling sick), dizziness or light headedness, slow breathing, coma, and convulsions (particularly in children). Children may also become overexcited.

While you are taking Sandomigran

Things you must do

If you become pregnant while taking Sandomigran, tell your doctor.

Your doctor can discuss with you the risks of taking it while you are pregnant.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Sandomigran.

Be sure to keep all of your doctor's appointments so that your progress can be checked.

This helps your doctor to give you the best treatment and to prevent unwanted side effects from happening.

Tell any other doctor, dentist or pharmacist who treats you that you are taking Sandomigran.

Things you must not do

Do not take Sandomigran to treat a severe headache once it has started.

This medicine is only used to prevent severe headaches. It will not stop an attack once it has started.

Do not give this medicine to anyone else, even if their condition seems similar to yours.

Do not take it to treat any other complaints unless your doctor tells you to.

This medicine is not appropriate for common 'tension' headaches.

Do no change or stop taking your tablets without checking with your doctor first.

Your doctor may want you to reduce the dosage gradually before stopping completely. This is to prevent any worsening of your condition and reduce the risk of withdrawal symptoms such as depression, trembling, nausea, anxiety, generally feeling unwell, dizziness, sleep disorder and weight loss.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how Sandomigran affects you.

This medicine may make you feel drowsy, dizzy, or have other central nervous system effects, especially when you first start to take it. If that happens, do not drive or do anything else that could be dangerous.

Be careful when drinking alcohol while you are taking Sandomigran.

The combination could make you feel drowsier than usual.

Side effects

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

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by these lists of possible side effects. You may not experience any of them. Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor as soon as possible if you notice any of the following:

  • signs of fluid build up such as swelling of the ankles, feet or lower legs
  • faintness, dizziness or lightheadedness
  • numbness or tingling feeling in arms or legs
  • skin rash
  • seeing, feeling or hearing things that are not there (hallucinations)
  • signs of an allergic reaction such as swelling of the face or itchy skin
  • yellowing of your skin or the whites of your eyes, abnormal darkening of the urine or unexplained nausea, vomiting and tiredness (signs of jaundice or hepatitis)
  • convulsions, fits, or seizures

Tell your doctor if you notice any of the following and they worry you:

  • drowsiness
  • fatigue
  • dry mouth
  • nausea (feeling sick)
  • constipation
  • aching muscles
  • increased appetite, weight gain
  • problems with sexual function
  • problems sleeping
  • a feeling of deep sadness, anxiety or sudden mood changes

Tell your doctor if you notice anything else that is making you feel unwell.

Some people may have other side effects not yet known or mentioned in this leaflet.

After taking Sandomigran

Storage

  • Keep your medicine in the original container until it is time to take it.
  • Store it in a cool dry place.
  • Do not store Sandomigran or any other medicine in the bathroom or near a sink.
  • Do not leave it in the car or on window sills.

Keep the medicine where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Sandomigran is an off-white, sugar-coated tablet supplied in packs of 100 tablets.

Ingredients

Sandomigran tablets contain 0.5 mg pizotifen (as the malate salt) as the active ingredient. They also contain:

  • colloidal anhydrous silica
  • lactose
  • magnesium stearate
  • maize starch
  • purified talc
  • povidone
  • acacia
  • sucrose
  • titanium dioxide
  • cetyl palmitate

Sponsor

Sandomigran is supplied in Australia by:
NOVARTIS Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
North Ryde NSW 2113
Telephone 1 800 671 203

® = Registered Trademark

This leaflet was prepared in May 2011.

Australian Registration Number:
Sandomigran 0.5 mg tablet
AUST R 69608

(smg050215c based on PI smg050215i)

BRAND INFORMATION

Brand name

Sandomigran Tablets

Active ingredient

Pizotifen

Schedule

S4

 

1 Name of Medicine

Pizotifen malate.

6.7 Physicochemical Properties

Pizotifen is a cycloheptathiophene derivative structurally related to cyproheptadine and the tricyclic antidepressants. The malate salt is a white to yellow-tinged crystalline powder. MW= 429.54, pKa 6.95 in water.
Molecular formula: C19H21NS.C4H6O5. Molecular weight: 429.54. Chemical name (IUPAC): 4-(1-methyl-4-piperidylidene)- 9,10-dihydro-4H-benzo-[4,5] cyclohepta[1,2-b] thiophene hydrogen malate.

Chemical structure.


CAS number.

15574-96-6.

2 Qualitative and Quantitative Composition

Tablets containing 500 micrograms of pizotifen present as 725 micrograms of pizotifen malate.

Excipients with known effects.

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

3 Pharmaceutical Form

Off-white, circular biconvex sugar coated tablet, approx 6 mm in diameter.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antimigraine drug, ATC code: N02CX01.

Mechanism of action.

Sandomigran (pizotifen) is a competitive serotonin antagonist. It also possesses antihistamine, antibradykinin and weak anticholinergic properties. It is suitable for the prophylactic treatment of migraine, reducing the frequency of attacks, but is without effect in the migraine attack.
The migraine attack is thought to consist of a prodromal phase of constriction followed by dilatation of the extracranial vessels. The mode of action of pizotifen in preventing migraine is not fully understood, but it is known to inhibit the reuptake of serotonin by blood platelets, preventing loss of tone of extracranial vessels. It also possesses appetite-stimulating and antidepressant properties.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The absorption of pizotifen is rapid (absorption half-life 0.5-0.8 hours) and nearly complete (estimated 80%). Peak plasma levels are achieved 4-6 hours following a single oral dose.

Distribution.

Volume of distribution is at least 7 litres/kg. Protein binding amounts to 91%.

Metabolism.

Metabolism is extensive and the drug is widely distributed. The main metabolite is N-glucuronide.

Excretion.

The main metabolite (N-glucuronide) is eliminated with a half-life of about 23 hours. Less than 1% of the drug is excreted in the urine unchanged although as much as 55% of a dose has been detected in the urine as metabolites. In patients with kidney insufficiency dosage adjustment may therefore be necessary.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Prophylactic (interval) treatment of vascular headaches: typical and atypical migraine; vasomotor headache; cluster headache (Horton's syndrome).
Sandomigran is without effect in the migraine attack. For this purpose preparations containing ergotamine are recommended.

4.3 Contraindications

Hypersensitivity to pizotifen or any of the excipients in the formulation.

4.4 Special Warnings and Precautions for Use

Use in renal impairment.

Caution is required in patients with renal impairment. Dosage adjustment may be necessary.

Hepatic impairment.

Hepatic injury has been reported, ranging from transaminase elevations to severe hepatitis. Pizotifen treatment should be discontinued if there is any clinical evidence of hepatic dysfunction during treatment and until the cause of the liver abnormality is determined.
Caution is required in patients with hepatic impairment. Dosage adjustment may be necessary.

Anticholinergic effects.

In view of the very slight anticholinergic effect of pizotifen, caution is required in patients with narrow angle glaucoma (except those successfully treated by surgery) or urinary retention (e.g. prostatic enlargement). Up to now, no untoward reactions have been reported in such patients given the recommended dosage.

Epilepsy.

Seizures as undesirable effects have been observed more frequently in patients with epilepsy. Pizotifen should be used with caution in patients with epilepsy.

Withdrawal symptoms.

Withdrawal symptoms like depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder and weight decreased have been reported following abrupt cessation of pizotifen (see Section 4.8 Adverse Effects (Undesirable Effects)), therefore gradual withdrawal is recommended.

Glucose-galactose malabsorption.

Sandomigran coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption should not take Sandomigran.

Use in the elderly.

No data available.

Paediatric use.

Experience in children is still limited.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The following drugs may exhibit drug interactions with pizotifen upon concomitant administration.

Anticipated drug interactions to be considered.

Pizotifen is extensively metabolized in the liver, primarily by N-glucuronidation. Increased plasma concentration of pizotifen upon concomitant administration of drugs which exclusively undergo glucuronidation cannot be excluded.

Central nervous system agents.

Central effects of sedatives, hypnotics, antihistamines, including certain common cold preparations, and alcohol may be enhanced.

Monoamine oxidase inhibitors.

MAOIs can prolong and intensify the anticholinergic effects of antihistaminic substances. Concomitant use with MAOIs should therefore be avoided.

Cisapride.

Concomitant administration of pizotifen with cisapride may lead to reduced efficacy of cisapride.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility was unimpaired in animal studies.
(Category B1)
No embryotoxic or teratogenic effects were observed in animal studies.
Clinical data with pizotifen in pregnancy are very limited; it should be administered in pregnancy only if the expected benefits outweigh the potential risks.
Animal studies show that pizotifen enters the milk.
Although the concentrations of pizotifen measured in the milk of treated mothers are not likely to affect the infant, its use in nursing mothers is not recommended.

4.8 Adverse Effects (Undesirable Effects)

The most common reactions are appetite-stimulating effect, increase in body weight and sedation (including somnolence and fatigue). It can usually be avoided by increasing the dosage gradually or reversed by a progressive reduction in dosage.
The appetite-stimulating effect of pizotifen may lead to an increase in body weight.
The following adverse reactions (see Table 1) are ranked under headings of frequency: the most frequent first, using the following convention. Very common: (1/10); common: (1/100, < 1/10); uncommon: (1/1,000, < 1/100); rare: (1/10,000, < 1/1,000); very rare: (1/10,000), including isolated reports.
Headache, hypotension and impotence have also been reported during treatment with Sandomigran, but a causal relationship was not established.

Adverse drug reactions from post-marketing spontaneous reports.

The following additional adverse drug reactions have been identified with pizotifen based on post-marketing spontaneous reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Hepatobiliary disorders.

Unknown: hepatic enzyme increased, jaundice, hepatitis.

Musculoskeletal and connective tissue disorders.

Unknown: muscle cramps.

Withdrawal symptoms.

Withdrawal reactions have been reported following abrupt cessation of pizotifen, therefore gradual withdrawal is recommended (see Section 4.4 Special Warnings and Precautions for Use). Withdrawal symptoms may include: depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder and weight decreased.

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.

4.2 Dose and Method of Administration

The dosage should be progressively increased, starting with 0.5 mg daily. The average maintenance dosage is 1.5 mg daily in single or divided doses. Recent studies have shown a single daily dose of 3 tablets (1.5 mg) taken at night to be effective. In refractory cases the dosage may be gradually raised to 3-4.5 mg daily in two or three divided doses.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned that Sandomigran may cause sedation, somnolence and dizziness. Therefore, caution should be exercised when driving or using machines.
Patients being treated with Sandomigran and presenting with sedation and/or somnolence episodes must be instructed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk.

4.9 Overdose

Symptoms.

Symptoms which may be expected are: drowsiness, nausea, dry mouth, tachycardia, pyrexia, hypotension, dizziness, excitatory states (in children), respiratory depression, convulsions (particularly in children), and coma.

Treatment.

Treatment is gastric lavage followed by administration of activated charcoal. If necessary, symptomatic treatment should be given including monitoring of the cardiovascular and respiratory symptoms; for excitatory states or convulsions: benzodiazepines.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Silica colloidal anhydrous, lactose, magnesium stearate, starch-maize, talc-purified, povidone, acacia, sucrose, titanium dioxide, cetyl palmitate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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

Store below 30°C. Protect from light.

6.5 Nature and Contents of Container

Sandomigran coated tablets are available in HDPE bottle containing 100 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes