SATIVEX

Package leaflet: Information for the patient

Sativex Oromucosal Spray

delta-9-tetrahydrocannabinol and cannabidiol
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Sativex is and what it is used for
2. What you need to know before using Sativex
3. How to use Sativex
4. Possible side effects
5. How to store Sativex
6. Contents of the pack and other information

1. What Sativex is and what it is used for

What Sativex is
Sativex is an oral spray containing cannabis extracts known as cannabinoids.
What Sativex is used for
Sativex is used in multiple sclerosis (MS) to relieve symptoms of muscle stiffness, also known as "spasticity". Spasticity means there is an increase in normal muscle tone, causing the muscle to feel harder or stiffer. This makes moving the muscles more difficult than normal.
Sativex is used when other medicines have not improved muscle stiffness.
Your 4-week trial with Sativex
Only a specialist doctor can prescribe treatment with Sativex.

• Before starting Sativex therapy, the specialist will assess the severity of your muscle stiffness and evaluate how effectively other treatments have worked.
• You will then begin a 4-week trial treatment with Sativex. Afterwards, the specialist will perform another assessment to determine whether Sativex has improved your muscle stiffness.
• You may continue treatment with Sativex only if, after these four weeks, you have shown significant improvement in symptoms related to spasticity.

2. What you should know before using Sativex

Do not use Sativex:

• If you are allergic to cannabis extracts or to any of the other ingredients of this medicine (listed in section 6).
• If you or a close relative has mental health problems such as schizophrenia, psychosis, or other significant psychiatric disorders; this does not include depression associated with multiple sclerosis.
• If you are breastfeeding.

If any of the situations listed above apply to you, do not take this medicine. In case of doubt, consult your doctor or pharmacist before using Sativex.

Warnings and precautions

Talk to your doctor or pharmacist before using Sativex:

• If you are pregnant or planning to become pregnant.
• If you are under 18 years of age.
• If you have epilepsy or regularly suffer from epileptic seizures (fits).
• If you have kidney problems.
• If you have moderate or severe liver problems.
• If you have severe heart problems such as angina pectoris, if you have previously had a myocardial infarction, if you have uncontrolled hypertension, or if you have heart rate problems.
• If you are elderly, particularly if you find it difficult to carry out daily activities such as preparing hot food and drinks.
• If you have previously abused drugs or narcotics.

Whether you are male or female, you must use an effective method of contraception while taking this medicine (see also the following section “Pregnancy, breastfeeding and contraception (men and women)”.

If any of the situations listed above apply to you (or you are unsure), consult your doctor or pharmacist before using Sativex.

For those engaged in sports: using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.

Other medicines and Sativex

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, because Sativex may affect the action of other medicines and other medicines may affect the action of Sativex.

In particular, inform your doctor or pharmacist if you are taking medicines for:

• Anxiety or sleep problems (sedatives/hypnotics) such as benzodiazepines, for example diazepam or triazolam; other sedatives, for example zopiclone, zolpidem, buspirone, St. John’s wort (a herbal preparation).
• Muscle spasms (such as baclofen).
• Bacterial infections (antibiotics such as rifampicin, clarithromycin).
• Epilepsy or neuralgia (such as phenytoin, phenobarbital, carbamazepine).
• High cholesterol (called statins; for example atorvastatin or simvastatin).
• Fungal infections (such as itraconazole, fluconazole and ketoconazole).
• HIV infection (for example ritonavir).
• Thinning the blood (called coumarins; for example warfarin).
• Heart problems (called beta-blockers; for example bisoprolol, propranolol).
• Inflammation (corticosteroids such as hydrocortisone, beclometasone, prednisolone).
• Contraception or certain types of cancer (hormonal medicines such as ethinylestradiol, levonorgestrel or dydrogesterone).
• Anaesthesia before surgery, to relax muscles before the procedure (such as propofol).

If you think any of the above situations apply to you, consult your doctor or pharmacist before using Sativex.

If you consult other doctors or are admitted to hospital, inform them of all the medicines you are taking.

Sativex with food, drinks and alcohol

• In general, alcoholic drinks should be avoided when taking Sativex, especially at the beginning of treatment or when changing the dose. If you drink alcohol while taking Sativex, be aware that using Sativex together with alcohol may increase its side effects (e.g. loss of balance or reduced ability to react quickly), which may increase the risk of falls and other accidents.
• You may take Sativex with or without food (but first read section 3 “How to use Sativex”).

Pregnancy, breastfeeding and contraception (men and women)

• If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.
• Sativex must not be used during pregnancy unless specifically recommended by your doctor.
• Sativex may affect the effectiveness of hormonal contraceptive methods, such as the “pill” or contraceptive implants. This means you must use a second type of contraception. Both women and men taking this medicine should use a reliable barrier method of contraception, such as a condom, diaphragm, or cervical cap. Continue using this method for at least three months after stopping treatment.
• Sativex must not be taken during breastfeeding.

Driving and using machines

• When starting Sativex, do not drive or operate machinery until you have reached a stable daily dose and know how the medicine affects you.
• Sativex may cause drowsiness or dizziness, which may impair your judgment and ability to perform skilled tasks. Rare cases of transient loss of consciousness have also been reported.
• Once you are accustomed to taking Sativex at a stable dose, you should still not drive or operate machinery if Sativex causes effects such as drowsiness or dizziness that could impair your ability to perform these activities. If in doubt, do not drive or use machinery.

Consult your doctor or pharmacist if you are unsure whether it is safe for you to drive while taking this medicine.

Travelling abroad with Sativex

• Before travelling abroad, check whether it is legal to carry this medicine with you. This applies also to transit countries.
• Sativex is a controlled medication, and its legal status varies from country to country.
• In some countries, it may be illegal to drive while taking Sativex.

Sativex contains ethanol and propylene glycol

• Sativex contains up to 40 mg of ethanol (alcohol) per dose. The amount of alcohol in the maximum daily dose for most patients (12 sprays) is approximately equivalent to that in two teaspoons (10 ml) of beer and about one teaspoon (5 ml) of wine. The small amount of alcohol in this medicine will not have noticeable effects.
• This medicine contains propylene glycol, which may cause irritation. Each single spray delivers 100 microliters containing 52 mg of propylene glycol.

3. How to use Sativex

Use this medicine exactly as described in this leaflet or as your doctor has instructed you. If you have any doubts, consult your doctor or pharmacist.
Use Sativex only in the mouth, on the inner cheek walls or under the tongue.

• You may take Sativex with or without food. However, taking Sativex with food may affect the amount absorbed into your body. Whenever possible, try to take Sativex in the same way with regard to food each time, so that you achieve a consistent effect.

Opening the spray bottle and preparing for use

1. Remove the spray bottle from the refrigerator (see important storage information for Sativex in section 5).
2. Write the date of opening on one of the labels provided on the back of the package leaflet. Apply the label to the bottle so you can check the date. Do not use the spray after it has been open for more than 6 weeks (42 days).
3. Gently shake the spray bottle before use.
4. Remove the protective cap.
5. Hold the spray bottle between your thumb and middle finger, with your index finger on the nozzle.
6. Hold the bottle in an upright position and spray two or three times onto a tissue until a very fine mist is produced. These test sprays prime the pump and ensure proper functioning.
7. The spray is now ready for use. The pump will not need to be re-primed unless you open a new spray bottle.

How to use the spray

1. Hold the spray bottle between your thumb and middle finger, with your index finger on the nozzle.
2. Keep the bottle upright to direct the spray into your mouth. Aim the nozzle under the tongue or against the inner cheek walls. Each time you use the spray, direct it to a different spot in the mouth to avoid localized discomfort.
3. Press the nozzle firmly. Do not administer more than one spray at a time, even if you think you received only a small amount.
4. Replace the protective cap on the bottle.

If the spray accidentally gets into your eyes, rinse them with water as soon as possible.

• Do not inhale the spray.
• Do not spray in the presence of children or pets.
• Do not use the spray near open flames or sources of heat.

Deciding how much spray to use
The number of sprays needed each day depends on you. Each person requires a different number of sprays to achieve the best relief from muscle stiffness with the fewest side effects.

• When you start using Sativex, follow the days and times indicated in the table below until you find the number of sprays that works best for you.
• Once you feel you have reached the optimal number of sprays for you, do not increase the dose further. This may take a few days or up to two weeks. Try to use this number of sprays every day, distributing them evenly throughout the day.
• Do not use more than one spray at a time. Always wait at least 15 minutes between sprays.
• During the first two days of using Sativex, avoid overexertion until you know how the medicine affects you.
• If you start to experience side effects (usually dizziness), reduce your daily number of sprays by one until you find the best relief from muscle stiffness with the fewest side effects.
• Once you have found the most effective number of sprays, try to use this amount every day, distributing the sprays evenly throughout the day in a way that suits you best. Always wait at least fifteen minutes between each spray.

Do not use more than 12 sprays per day unless your doctor tells you otherwise.
If you use more Sativex than you should
If you accidentally take a larger amount of Sativex than normally required, you may:

• see or hear things that do not exist (hallucinations)
• feel dizzy, drowsy or confused
• notice a change in your heart rate.
• Contact your doctor or pharmacist if you have used more Sativex than you should.

If you forget to use Sativex

• If you forget to take a dose, use one spray as soon as you remember or when you feel the need.
• Do not take a double dose to make up for a forgotten dose.

How to tell if the spray bottle is nearly empty
After using the three priming sprays, the spray bottle contains up to 90 measured sprays. When the spray bottle is nearly empty, the sound you hear when using it may change. You may also notice a difference in the spray when you spray it into your mouth. This occurs because the spray bottle is nearly empty. In this case, you will need to open a new spray bottle.
If you stop using Sativex

If you decide to stop using Sativex for any reason, inform your doctor or pharmacist.
Suddenly stopping this medicine may temporarily affect your sleep, appetite or emotions. If you stop taking Sativex, muscle stiffness usually returns gradually.
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking the medicine and speak to your doctor or go to hospital immediately if you experience any
of the following serious side effects, as you will need to be monitored until the symptoms have
disappeared:

• seeing or hearing things that are not real (hallucinations).
• believing in ideas that are not true.
• believing that others are against you.
• thoughts of suicide.
• feeling depressed or confused.
• severe restlessness or loss of contact with reality.

The following side effects are more likely at the beginning of treatment. In most cases, the side
effects are mild and usually disappear within a few days.

• If you experience any of the following side effects, use fewer sprays or stop using Sativex until you feel normal again.
• When you resume using the medicine, take the number of sprays you used when you did not feel these side effects.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist.

Very common (may affect more than 1 in 10 people)

• Dizziness or tiredness.

Common (may affect up to 1 in 10 people)

• Memory problems or difficulty concentrating.
• Drowsiness or feeling light-headed.
• Blurred vision.
• Difficulty speaking.
• Eating more or less than usual.
• Change in taste sensation or dry mouth.
• Constipation or diarrhoea.
• Feeling unwell or having a general sense of being unwell.
• Mouth problems, including burning, pain or ulcers.
• Lack of energy or feeling weak or generally unwell.
• Feeling abnormal or intoxicated.
• Loss of balance or falling.

Uncommon (may affect up to 1 in 100 people)

• Fainting.
• Changes in pulse rate, heart rate or blood pressure.
• Sore throat or inflamed throat.
• Stomach ache.
• Change in colour of mouth or teeth.
• Irritation at the site where Sativex is sprayed.
• Red, swollen or peeling inside the mouth. Do not continue spraying on these areas.

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sativex

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label and the carton after {EXP}. The expiry date refers to the last day of that month.
• Before being opened, Sativex should be stored upright in the box in a refrigerator (between 2 °C and 8 °C). If not stored in a refrigerator, it becomes unstable and is unlikely to remain effective.
• Once opened, Sativex should be stored upright at a temperature not exceeding 25 °C.
• After opening, Sativex must be used within 42 days.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This measure will help protect the environment.

6. Package contents and other information

What Sativex contains

• The active substances are cannabis extracts. 1 ml contains 38-44 mg and 35-42 mg of two extracts from Cannabis sativa L., leaves and flowers, equivalent to 27 mg/ml of delta-9-tetrahydrocannabinol (THC) and 25 mg/ml of cannabidiol (CBD). Each single spray delivers 100 microlitres containing 2.7 mg of THC and 2.5 mg of CBD.
• The other components are ethanol, propylene glycol and peppermint oil.

Description of the appearance of Sativex and contents of the pack
Sativex is a yellow/brown solution contained in a 10 ml glass spray bottle equipped with a pump. The pump is protected by a plastic cap.
The bottle contains up to 90 metered sprays (after the three priming sprays).
Sativex is available in a pack containing 3 spray bottles.
Marketing Authorisation Holder
Jazz Pharmaceuticals Ireland Ltd, 5th Floor, Waterloo Exchange, Waterloo Road, Dublin,
D04 E5W7, Ireland
Manufacturer
Jazz Pharmaceuticals Netherlands B.V.,
Stationsplein 13A, 3818 LE, Amersfoort
The Netherlands
Marketing Authorisation Holder's representative in Italy: Almirall SpA, via Messina 38 - Torre C, 20154 Milano
Leaflet included in the package.
For a pack containing 3 spray bottles of 10 ml each: