Serious Warnings and Precautions

Studies with various medicines of the group to which ZELDOX belongs, when used in the elderly patients with dementia, have been associated with an increased rate of death. ZELDOX is not indicated in elderly patients with dementia.

BEFORE you use ZELDOX talk to your doctor or pharmacist if you:

• are taking or have recently taken any prescription medicines
• are taking any over-the-counter medicines you can buy without a prescription, including natural/herbal remedies
• have had any problems with your heart or any family history of heart disease
• are taking any medications for heart disease or blood pressure that makes you prone to low blood pressure
• have a history of stroke or “mini-stroke”
• have had any problems with your liver
• have had any problem with fainting or dizziness
• have ever had blackouts or seizures
• have diabetes or a family history of diabetes
• are pregnant, might be pregnant, or plan to get pregnant
• are breast-feeding
• are allergic to any medicines
• drink alcohol or use recreational drugs
• abuse drugs
• have ever had an allergic reaction to ziprasidone or any of the other ingredients of ZELDOX capsules
• exercise vigorously or work in hot or sunny places
• suffer from lactose intolerance because ZELDOX capsules contain lactose
• have low white blood cell counts
• have low levels of potassium or magnesium in your blood
• are dehydrated
• have risk factors for developing blood clots such as: a family history of blood clots, age over 65, smoking, obesity, recent major surgery (such as hip or knee replacement), immobility due to air travel or other reason, or take oral contraceptives (“The Pill”).

If you are a woman of child bearing potential and receiving ZELDOX you should use a reliable method of birth control.

Effects on Newborns:

In some cases, babies born to a mother taking ZELDOX during pregnancy have experienced symptoms that are severe and require the newborn to be hospitalized. Sometimes, the symptoms may resolve on their own. Be prepared to seek immediate emergency medical attention for your newborn if they have difficulty breathing, are overly sleepy, have muscle stiffness, or floppy muscles (like a rag doll), are shaking, or are having difficulty feeding.

Like any medication, ZELDOX may cause some side effects. The most common side effects of ZELDOX are:

• feeling unusually tired or sleepy
• nausea or upset stomach
• constipation
• dizziness
• restlessness
• abnormal movements
• diarrhea
• rash
• increased cough/runny nose.

Tell your doctor immediately if you experience muscle twitching or abnormal movements of the face or tongue.

It is important to tell your doctor or pharmacist if you have diarrhea, vomiting, or any other illness that can cause you to lose fluids. Your doctor may want to check your blood to make sure that you have the right amount of important salts (“electrolytes”) after such illnesses, because an imbalance in electrolytes is a risk factor for heart problems, which may occur more frequently with ZELDOX than with other anti-psychotics. Disordered eating, alcoholism, and water intoxication are also risk factors for imbalance in electrolytes.

Your doctor should check your body weight before starting ZELDOX and continue to monitor it for as long as you are being treated.

Your doctor should take blood tests before starting ZELDOX. They will monitor blood sugar, and the number of infection fighting white blood cells. Your doctor should continue to monitor your blood for as long as you are being treated.

If you have high levels of prolactin (measured with a blood test) and a condition called hypogonadism you may be at increased risk of breaking a bone due to osteoporosis. This occurs in both men and women.

If you experience any symptoms of a possible heart rhythm disturbance, such as dizziness, palpitations (sensation of rapid, pounding, or irregular heart beat), fainting, or seizures, you should seek immediate medical attention.

Since medications of the same drug class as ZELDOX may interfere with the ability of the body to adjust to heat, it is best to avoid becoming overheated or dehydrated (for example with vigorous exercise or exposure to extreme heat) while taking ZELDOX.

Because some people experience sleepiness with ZELDOX, you should avoid driving a car or operating machinery until you know how ZELDOX affects you.

Because some medicines can affect how ZELDOX works, and some medicines may increase the risk of heart rhythm problems, it is important to tell your physician, pharmacist or other healthcare professional that you are taking ZELDOX before you start taking any other drugs, including over-the-counter medications and natural/herbal remedies.

The effects of alcohol could be made worse while taking ZELDOX. It is recommended that you do not drink alcohol while taking ZELDOX.

In order for ZELDOX to help you feel better, it is very important to take it every day, exactly as your doctor has prescribed. Your doctor has decided on the best dosage for you based on your individual needs. Your doctor may increase or decrease your dose depending on your response.

Overdose

If you have taken more ZELDOX capsules than your doctor has recommended, contact your regional Poison Control Centre and talk to your doctor right away or go to your nearest hospital emergency department. Take the medication package with you.

Missed dose:

If you miss a dose of ZELDOX by only a few hours, take it as soon as possible. If most of the day has passed since your missed dose, skip that dose and wait until your next scheduled dose. Do not take 2 doses at once.

Serious Warnings for Asthma Patients

Formoterol, one of the medicines in ZENHALE, may increase the risk of asthma-related death. It may increase the risk of asthma-related hospitalization in pediatrics and adolescent patients. Therefore:

• Your doctor will assess your asthma control at regular intervals. ZENHALE should only be used when your doctor decides that other asthma medications (e.g. inhaled glucocorticosteroids along with an as needed relief medication) are not helping you enough, or that you need two maintenance medications to control your asthma.
• ZENHALE should not be the first medication you use, unless advised by your doctor.

Once asthma control has been achieved and maintained, your doctor will assess you at regular intervals. ZENHALE should only be used when an inhaled corticosteroid does not adequately control your asthma symptoms.

BEFORE you use ZENHALE talk to your doctor or pharmacist if you:

• you are diabetic
• have high blood pressure
• have ever had a heart problem, such as rapid or irregular heart beat or abnormal electrical signal called “prolongation of the QT interval”
• have liver disease or cirrhosis
• have problems with your thyroid or adrenal glands
• have low levels of potassium in your blood
• have or have ever had tuberculosis
• have a fungal infection (thrush) in your mouth or throat
• have eye disorders such as glaucoma or cataracts
• have hypoprothrombinemia (a blood clotting problem) and are taking acetylsalicylic acid (aspirin)
• have an aneurysm (area where an artery is swollen like a sack because the wall of the artery is weak)
• have pheochromocytoma (a tumor of the adrenal gland that can affect blood pressure)
• are pregnant, planning to get pregnant or are breastfeeding.

Important things to remember when using ZENHALE:

• If symptoms get worse (increased use of a 'reliever' medication, peak flow measurement falls, your symptoms are waking you up at night) or do not get better after using ZENHALE, you should contact your doctor as soon as possible.
• ZENHALE should not be used to treat sudden asthma symptoms.
• Do not stop taking ZENHALE on your own, even if you feel better. Your doctor can direct you on how to discontinue ZENHALE slowly to avoid asthma flare-ups.
• If you are transferring to ZENHALE from steroid tablets or syrup and your doctor is slowly decreasing the dose, you may notice that you develop symptoms of allergies such as itchy, watery eyes or rash, which had been controlled by your steroid. Your doctor will tell you how to control these symptoms. During this time, if you begin to notice joint or muscle pain, feelings of depression, tiredness or lethargy, you should tell your doctor.
• You may need to also take steroid tablets or syrup during a severe asthma attack, during other illnesses or during times of stress. Your doctor may give you some steroid tablets or a syrup to carry with you as well as a steroid warning card, which will give you advice on when and how to use them.
• Adolescents 12 years and older treated with ZENHALE may grow more slowly than others.
• You should avoid coming into contact with anyone who has measles or chicken pox. If you or your child are exposed, tell your doctor right away.
• While using inhaled corticosteroids, patients should be monitored for signs of cataracts, glaucoma (see your eye doctor regularly) or of osteoporosis (decreased bone density).
• When using drugs like ZENHALE for long term treatment, you may be at risk of:
  • Breaking a bone (bone fractures);
  • Osteoporosis (increased risk of bone fractures);
  • Take extra care to avoid any injury, especially falls.
• Drugs like ZENHALE can cause eye disorders:
  • Cataracts: clouding of the lens in the eye, blurry vision, eye pain;
  • Glaucoma: An increased pressure in your eyes, eye pain. Untreated, it may lead to permanent vision loss.
  • You should therefore have regular eye exams.
• If you notice the following symptoms: a flu-like illness, rash, pins and needles or numbness of arms or legs, severe sinusitis and worsening lung or breathing problems, this can be a sign of Churg-Strauss syndrome. This can happen in people with asthma who are using inhaled corticosteroids. Tell your healthcare provider right away if these symptoms occur.

Like all medicines, ZENHALE can cause side effects, although not everybody gets them. Side effects may include:

• nausea
• headache
• hoarseness
• tremor
• shakiness
• nervousness
• dizziness
• disturbed sleep
• muscle cramps
• sore throat
• rounded face
• loss of bone density
• fainting
• dry mouth.

Tell your doctor or pharmacist if you are taking or have recently taken any other medications.

Drugs that may interact with ZENHALE include:

• Beta-blocker medicines ( such as atenolol or propranolol used for high blood pressure) including eye drops (such as timolol eyedrops for glaucoma)
• Ketoconazole, itraconazole (an antifungal medicine)
• Corticosteroids (by mouth or by injection)
• Diuretics (water pills)
• Xanthine medicines (such as theophylline and aminophylline) used to treat asthma
• Medicines for a fast or uneven heartbeat (such as quinidine)
• Tricyclic anti-depressants
• Monoamine oxidase inhibitors (MAOIs)
• Terfenadine or astemizole (an antihistamine used to treat allergies)
• Other medicines containing a long-acting beta2-agonist (i.e. formoterol, salmeterol)
• Disopyramide, procainamide or phenothiazines
• Ritonavir, atazanavir, indinavir, nelfinavir, saquinavir (an anti-HIV medicine)
• Macrolide antibiotics (e.g. erythromycin, azithromycin, clarithromycin)
• Inhaled anaesthetics such as halogenated hydrocarbons (e.g. halothane), used during surgery. Inform your doctor that you use ZENHALE if you are to have surgery under anaesthesia
• Acetylsalicylic acid (aspirin) if you have hypoprothrombinemia

Make sure that your doctor or pharmacist knows what other medications you are taking, including those you can buy without a prescription and as natural health products.

Always take ZENHALE exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

When to replace your ZENHALE inhaler:

When the counter reads 20, you should refill your prescription or ask your doctor if you need a new prescription for ZENHALE.

Discard ZENHALE after the counter reaches 0, indicating that you have used the number of actuations on the product label and box. Your inhaler may not feel empty and it may continue to operate, but you will not get the right amount of medicine if you keep using it.

Never try to change the numbers on the counter or remove the counter from the actuator.

Warning:

Do not use the inhaler after the expiration date. The expiry date refers to the last day of that month.

How to clean your ZENHALE inhaler:

The mouthpiece should be cleaned using a dry wipe after every 7 days of use.

Routine cleaning instructions:

• Remove the cap off the mouthpiece. Wipe the inside and outside surfaces of the actuator mouthpiece with a clean, dry lint-free tissue or cloth. Do not wash or put any parts of your inhaler in water. Put the cap back on the mouthpiece after cleaning.
• Do not remove the canister from the actuator.
• Do not attempt to unblock the actuator with a sharp object, such as a pin.

Use with a spacer:

If necessary, your doctor will prescribe the use of a spacer to help you properly take this medication. Instructions provided with the spacer device should be consulted prior to use.

Overdose:

If you use more ZENHALE than you should, contact your doctor or pharmacist.

The most common symptoms that may occur if you use more ZENHALE than you should are nausea, vomiting, headache, trembling, drowsiness, low potassium levels, high sugar levels, high blood pressure or a rapid or irregular heart beat.

If you have used larger doses for a long period of time, you should talk to your doctor or pharmacist for advice. This is because larger doses of ZENHALE may reduce the amount of steroid hormones produced by the adrenal gland.

In case of drug overdose, contact a healthcare practitioner, hospital emergency department or regional poison control centre, even if there are no symptoms.

Missed dose:

If you miss a dose, take it as soon as you remember. However, if it is nearly time for your next dose, skip the missed dose. Do not take a double dose to make up for the forgotten dose.

Do not suddenly stop using this medicine even if your asthma seems to be better. Speak with your doctor first.

Your symptoms may come back if you stop using this medicine before your doctor has told you to do so. If you think that your asthma is not getting any better or seems to be getting worse, after you have started using ZENHALE go back and see your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Serious Warnings and Precautions

Lactic acidosis and severe liver enlargement: Lactic acidosis (severe increase of lactic acid in the blood) and severe liver enlargement, including deaths, have been reported among patients taking ZERIT. Symptoms of lactic acidosis may include:

If you notice these symptoms or if your medical condition has suddenly changed, stop taking ZERIT and call your doctor right away. Lactic acidosis is a medical emergency that must be treated in a hospital.

Talk to your doctor before using ZERIT if:

• You are using other medications including those you can buy without a prescription, as they may interfere with ZERIT .

• You are pregnant or planning on becoming pregnant. It is not known if ZERIT can harm a human fetus. Also, pregnant women have experienced serious side effects when taking ZERIT in combination with didanosine and other HIV medicines. ZERIT should be used during pregnancy only after discussion with your doctor.

• You are breast-feeding. Studies have shown ZERIT is in the breast milk of animals receiving the drug, so it may be present in human breast milk. The Centers for Disease Control and Prevention (CDC) recommends that HIV-infected mothers not breast-feed to reduce the risk of passing HIV infection to their babies and the potential for serious adverse reactions in nursing infants. Therefore, do not nurse a baby while taking ZERIT.

• You have kidney, liver problems or history of heavy alcohol use.

• You have had pancreatitis, gallstones.

• You have had peripheral neuropathy.

Other medicines, including those you can buy without a prescription, may interfere with the actions of ZERIT. You should not use ZERIT in combination with zidovudine (AZT). You should talk to your doctor if you are taking doxorubicin or ribavarin as these drugs may interfere with ZERIT. Do not take any medicine, vitamin, supplement, or other health preparation without first checking with your doctor. (Taking ZERIT with other drugs that also may cause peripheral neuropathy may increase your risk of getting this serious side effect.)

Before using this product, tell your doctor or pharmacist if you are allergic to ipratropium or albuterol (salbutamol); or to tiotropium; or to atropine or other belladonna-type drugs; or to levalbuterol; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details. Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood pressure, heart disease (such as chest pain, heart attack, irregular heartbeat), personal or family history of glaucoma (angle-closure type), difficulty urinating (for example, due to enlarged prostate), seizure, overactive thyroid (hyperthyroidism), diabetes. This drug may make you dizzy or cause blurred vision or other vision changes. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages. Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). Older adults may be more sensitive to the side effects of this drug, especially problems urinating or constipation. During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

See also How to Use section. Headache, dizziness, cough, nausea, dry mouth, shaking (tremors), nervousness, or constipation may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high. Infrequently, this medication may cause severe sudden worsening of breathing problems right after use. If you have sudden worsening of breathing, get medical help right away. Tell your doctor right away if you have any serious side effects, including: difficult/painful urination, muscle cramps. Get medical help right away if you have any very serious side effects, including: chest pain, fast/pounding/irregular heartbeat, rapid breathing, confusion, eye pain/swelling/redness, vision changes (such as seeing rainbows around lights at night, blurred vision). A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing. This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. In the US - Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor\'s approval. Albuterol is very similar to levalbuterol. Do not use medications containing levalbuterol while using albuterol.

Read the Patient Information Leaflet if available from your pharmacist before you start using this product and each time you get a refill. Learn how to use this inhaler properly. If you have any questions, ask your doctor or pharmacist. Follow the instructions for priming the inhaler if you are using it for the first time or if you have not used it for more than 3 days or for more than 21 days. When priming the inhaler, make sure to spray away from the face so that you do not get the medication into your eyes. Inhale this medication by mouth as directed by your doctor, usually 4 times daily. Your doctor may also direct you to use this medication as needed for wheezing and shortness of breath. Follow your doctor\'s instructions carefully. However, the manufacturer recommends that you do not use more than 6 inhalations in a 24-hour period. Doing so may increase the risk of serious side effects. The dosage is based on your medical condition and response to treatment. Avoid getting this medication into your eyes. It may cause eye pain/irritation, temporary blurred vision, and other vision changes. Therefore, when using the inhaler, put your lips tightly around the mouthpiece. Rinse your mouth after using the inhaler to prevent dry mouth and throat irritation. If you are using other inhalers at the same time, wait at least 1 minute between the use of each medication. Use this medication regularly to get the most benefit from it. This medication works best if used at evenly spaced intervals. To help you remember, use it at the same times each day. Do not increase your dose, use this medication more often, or stop using it without first consulting your doctor. Clean the mouthpiece of the inhaler at least once a week as directed. Learn which of your inhalers you should use every day and which you should use if your breathing suddenly worsens (quick-relief drugs). Ask your doctor ahead of time what you should do if you have new or worsening cough or shortness of breath, wheezing, increased sputum, waking up at night with trouble breathing, if you use your quick-relief inhaler more often, or if your quick-relief inhaler does not seem to be working well. Learn when you can treat sudden breathing problems by yourself and when you must get medical help right away. Tell your doctor if your symptoms do not improve or if they worsen.

Like all medicines, ZIAGEN can have side effects. When treating HIV infection, it is not always possible to tell whether some of the undesirable effects that occur are caused by ZIAGEN, by other medicines you are taking at the same time or by the HIV infection. For this reason it is very important that you inform your doctor about any changes in your health.

A hypersensitivity reaction (serious allergic reaction) has been reported in patients who have been treated with ZIAGEN. This is described in the section on Hypersensitivity Reaction in the beginning of this leaflet. It is important that you read and understand the information about this serious reaction.

The most common side effects (could affect at least 1 in 10 in every 100 people) are nausea (feeling of sickness), vomiting, lethargy (unusual lack of energy), fatigue, anorexia (loss of appetite), fever (high temperature), headache, diarrhea, hyperlactatemia (high blood lactate level) and skin rash (without any other illness). If these symptoms persist or become bothersome, contact your doctor.

Other side effects include: Rare (could affect <1 in 1000 people): lactic acidosis (excess of lactic acid in your blood) and inflammation of the pancreas (pancreatitis). This may result in increasing pain and discomfort in the upper abdomen and may be accompanied by nausea and vomiting. However, it is not known whether this is caused by ZIAGEN, other medicines you may be taking or your HIV infection.

Very rare (could affect less <1 in 10 000 people): serious skin reactions which include erythema multiforme (a skin condition characterized by a red rash), Stevens-Johnson syndrome (a severe and sometimes fatal skin rash) and toxic epidermal necrolysis (a life-threatening skin disorder characterized by blistering and peeling of the skin).

Changes in body fat have been seen in patients taking antiretroviral therapy. These changes may include increased amount of fat on the upper back and neck (“buffalo hump”), breasts, and around the trunk. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effect of these conditions is not known at this time.

Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time, or you could develop an autoimmune disease in which your immune system reacts against your own body (e.g. Graves' disease (which affects the thyroid gland), Guillain-Barré syndrome (which affects the nervous system) or polymyositis (which affects the muscles) and it may develop at any time, sometimes months later after the start of HIV therapy). Sometimes symptoms can be severe, so if you develop high temperature (fever), joint or muscle pain, redness, rash, swelling, or fatigue or any new symptoms contact your doctor straight away.

ZIAGEN is unlikely to interact with other medicines you are being treated with; however, it is important that you tell your doctor or pharmacist about all the medicines listed below or any that you are taking or have recently taken, including those you have bought yourself:

• Methadone

• Retinoids

If you are taking methadone, your doctor may need to adjust your methadone dose, as abacavir increases the rate at which methadone leaves your body. This is unlikely to affect most methadone users.

In men, alcohol does increase the amount of abacavir in your blood. However, the meaning of this is unknown. This interaction has not been studied in women.