Clozapine

In Aotearoa New Zealand, clozapine is available as tablets which come in different strengths: 25 mg, 50 mg, 100 mg and 200 mg. Liquid is available as 50 mg in 1 mL strength. A 20 mg in 1 mL strength can be made by your pharmacist but it isn't paid for by the government.

• The dose of clozapine is different for different people, depending on your response. Your doctor will start you on a low dose and increase it slowly as your body gets used to it. The following is a guide. 
  • Day 1: Start with 12.5 mg once or twice a day.
  • Day 2: Increase to 25 mg once or twice a day.
  • Over the following 2 to 3 weeks: Your dose would be increased gradually by 25 to 50 mg a day, until you're taking the dose that will give you the most benefit. This is usually 200 to 450 mg a day but can be up to a maximum of 900 mg per day.
• Always take your clozapine exactly as your doctor has told you.
• Dose increases may vary depending on your response to treatment and your medical history. 
• After a while, your doctor might also recommend reducing your dose, depending on how you respond to clozapine.
• The pharmacy label on your medicine will tell you how much clozapine to take, how often to take it and any special instructions.
• Keep a record of when to take your doses on a medicines list.(external link)

• Timing: Clozapine is usually taken 2 times a day. However, if your total daily dose is 200 mg or less, you may be able to take the whole amount in a single dose, usually in the evening. Try to take your clozapine dose(s) at the same times each day.
• Food: You can take clozapine with or without food.
• With fluid: Swallow clozapine tablets with a full glass of water or other liquid.
• Liquid clozapine may be taken alone or in water. Shake the bottle for 10 seconds before use.
• Keep taking clozapine every day: It usually takes a few weeks to start working and it can take a few months before you feel the full benefits. 
• 1 missed dose: If you forget to take your dose, take it as soon as you remember. But if your next dose is due within the next 4 hours or sooner, skip the missed dose and just take the next dose at the right time. Don't take double the dose.
• More than 1 missed dose: If you forget to take clozapine for more than 48 hours, you must contact your doctor or the clinic you normally attend straight away. To stop unwanted side effects your dose may need to be adjusted. Don't start taking clozapine again before you talk to your doctor.
• See tips to help you remember to take your medicines regularly.

Here are some things to know when you're taking clozapine. Other things may be important as well, so ask your healthcare provider what you should know about.

• Stay on the same brand of clozapine:  There are 2 brands available and it’s important not to swap brands without talking with your doctor.
• Other medicines: Clozapine interacts with a number of medicines especially hormonal contraceptives, some antibiotics, anti-seizure medicines, antidepressants and antihistamines. Check with your healthcare provider before starting clozapine and before taking any new medicines. Your dose of clozapine may need to be adjusted.
• It may also interact with herbal supplements, rongoā Māori and medicines that are available without a prescription: So check with your doctor or pharmacist before starting any new products.
• Driving: Be careful when driving or using tools until you know how this medicine affects you.
• Clozapine can make you sweat less: So take care in hot environments or when doing lots of exercise as you can overheat.
• Don't stop taking or reduce the dose of clozapine without talking to your doctor first: The dose will have to be lowered gradually over several weeks.
• Constipation: It's common for clozapine to slow down your gut so you will be prescribed laxatives to help with this. The aim is to have a soft poo at least every second day. See more information on constipation in the side effects section below.
• Your clozapine levels can be affected by the COVID-19 virus: If you test positive for COVID-19 you'll need to have both your blood level of clozapine and a full blood count (FBC) checked. You may need to have your blood tested from home, talk to your healthcare provider.
• Contraception: While you're taking clozapine, use effective contraception to avoid getting pregnant. If you would like to become pregnant, talk to your healthcare provider.
• Pregnancy: If you become pregnant, tell your healthcare provider immediately.
• Breastfeeding: If you want to start breastfeeding your pēpi, talk to your healthcare provider. Clozapine may pass into breast milk and affect your baby.
• Plan ahead: Plan for public holidays and travel so you don’t miss your blood tests or run out of clozapine. Your pharmacy can only give you enough clozapine until the next blood test date.

Alcohol

Avoid alcohol while you are taking clozapine, especially when you first start treatment.

Drinking alcohol while taking clozapine can:

• cause drowsiness and affect concentration, putting you at risk of falls and other accidents
• cause agitation, aggression and forgetfulness.

If you do drink alcohol, drink only small amounts and see how you feel. Don't stop taking your medicine.

Smoking

Smoking (but not nicotine replacement therapy or vaping) affects the way your body breaks down (metabolises) clozapine. If you start or stop smoking, or even make a big change to he number of cigarettes you're smoking while you're taking clozapine, tell your healthcare provider immediately. Your dose of clozapine may need to be adjusted. If you’d like to stop smoking or switch to vaping while you're taking clozapine, your doctor can plan a smoking cessation programme with you and monitor your clozapine levels.

Caffeine

Don't change how much caffeine you have. Sources of caffeine include coffee, cola and energy drinks. Sudden changes in your caffeine intake can alter (increase or decrease) the levels of clozapine in your blood. This can be harmful.

You will need to have regular blood tests while taking clozapine because it can affect your white blood cells (called neutrophils). These cells help to fight infections and keep your immune system healthy.

• For every 100 people taking clozapine, 3 people will get a drop in the number of these white blood cells. This can lead to a condition called neutropenia or a more severe reduction in your white blood cells called agranulocytosis. A drop in neutrophils puts you at greater risk of picking up infections.
• You need to get your white blood cell count checked with regular blood tests because you may not notice any symptoms until you have an infection.
• Checking the number of your white blood cells helps to find any changes before they cause problems.
• You’ll collect your clozapine from a nominated pharmacy. You won’t be allowed to collect your clozapine prescription unless you have an up-to-date blood result.
• You will need to have a blood test within 10 days before starting clozapine treatment, then every week for the first 18 weeks of treatment. Then you will need to have blood tests every 4 weeks throughout treatment.
• Read more about neutropenia.

Other tests

Your healthcare provider will also do some other tests to check for any changes caused by clozapine to your heart, blood glucose and cholesterol levels. You will have your weight, blood pressure, liver and kidney function checked regularly. You may need an ECG test to check your heart rate.

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

Constipation

Constipation is a very common side effect of clozapine (up to 8 in every 10 people taking clozapine). This can be very uncomfortable and if it's not treated, it can lead to serious problems including being life-threatening if left for too long. Most people starting clozapine will be prescribed laxatives.

• You can also prevent constipation by increasing the fluid and fibre intake in your diet and by exercising regularly. Most people will need to take laxatives. Read more about preventing constipation.
• If you have problems with constipation before starting clozapine, tell your doctor. You will be started on a laxative when you start taking clozapine.
• If you develop constipation while taking clozapine, contact your healthcare provider straight away for immediate treatment. Getting treatment as soon as possible is very important. These symptoms include:
  • fewer bowel movements than usual or not having a bowel movement for 2 days or more
  • hard or dry poos
  • tummy pain for more than 1 hour
  • bloating or gas in your tummy
  • feeling sick (nausea) or being sick (vomiting)
  • reduced appetite.
  • diarrhoea (runny poos), especially if bloody. Diarrhoea can also be a symptom of constipation.
• You're at increased risk of constipation:
  • during the first 4 months of starting clozapine
  • if you have an increase in your clozapine dose
  • if you're taking other medicines that are likely to cause constipation
  • if your diet changes
  • if you stop smoking.        

Flu symptoms

• Clozapine can affect your white blood cells which fight infection (a condition called neutropenia). This can put you at greater risk of picking up infections. 
• At the first sign of infection (eg, fever, cold or flu symptoms, muscle aches, headache, or sore throat) you need to contact your doctor or mental health worker for an urgent blood test to check your white blood cells.
• Read more about neutropenia.

Other side effects