Consumer medicine information

APO-Aripiprazole Tablets

Aripiprazole

BRAND INFORMATION

Brand name

APO-Aripiprazole

Active ingredient

Aripiprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Aripiprazole Tablets.

APO-Aripiprazole

APO-Aripiprazole

 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 APO-Aripiprazole?

APO-Aripiprazole contains the active ingredient aripiprazole. APO-Aripiprazole is used to treat symptoms of schizophrenia. APO-Aripiprazole may be given to treat acute episodes of sustained upward mood swings (mania) in adult patients with Bipolar 1 Disorder. During mania, patients experience episodes of overactivity, elation or irritability.

For more information, see Section 1. Why am I using APO-Aripiprazole? in the full CMI.

 2. What should I know before I use APO-Aripiprazole?

Do not use if you have ever had an allergic reaction to APO-Aripiprazole 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 APO-Aripiprazole? in the full CMI.

 3. What if I am taking other medicines?

Some medicines may interfere with APO-Aripiprazole 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 APO-Aripiprazole?
  • Unless your doctor gives you other directions, you should take APO-Aripiprazole only once a day.
  • Take APO-Aripiprazole at about the same time each day.

More instructions can be found in Section 4. How do I use APO-Aripiprazole? in the full CMI.

 5. What should I know while using APO-Aripiprazole?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using APO-Aripiprazole.
  • If you become pregnant while taking APO-Aripiprazole, tell your doctor immediately.
Things you should not do
  • Do not give APO-Aripiprazole to anyone else, even if their symptoms seem similar or they have the same condition as you.
  • Do not stop taking APO-Aripiprazole or lower the dosage, even if you are feeling better, without checking with your doctor.
Driving or using machines
  • Make sure that you know how you react to APO-Aripiprazole before you drive a car, operate machinery or do anything else that could be dangerous if you are dizzy or light headed or not alert.
Drinking alcohol
  • Be careful when drinking alcohol while taking APO-Aripiprazole.
  • Your doctor may suggest you avoid alcohol while you are being treated with APO-Aripiprazole.
Looking after your medicine
  • Store APO-Aripiprazole in a cool dry place where the temperature will stay below 25°C.

For more information, see Section 5. What should I know while using APO-Aripiprazole? in the full CMI.

 6. Are there any side effects?

Common side effects are headache; indigestion; nausea; vomiting; insomnia; constipation; light-headedness; drowsiness; agitation; anxiety; inability to sit or stand still, restless movement of the arms and legs. Serious side effects include seizure; fits or convulsions; fainting; sudden increase in body temperature; sweating.

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.

APO-Aripiprazole

Active ingredient(s): Aripiprazole (Ari-pip-rah-zol)

 Consumer Medicine Information (CMI)

This leaflet provides important information about using APO-Aripiprazole. 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 APO-Aripiprazole.

Where to find information in this leaflet:

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

 1. Why am I using APO-Aripiprazole?

APO-Aripiprazole contains the active ingredient aripiprazole. APO-Aripiprazole belongs to a group of medicines called antipsychotic agents which improve the symptoms of certain types of mental illness.

APO-Aripiprazole is used to treat symptoms of schizophrenia.

APO-Aripiprazole may be given to treat acute episodes of sustained upward mood swings (mania) in adult patients with Bipolar 1 Disorder. During mania, patients experience episodes of overactivity, elation or irritability.

Schizophrenia is a mental illness with disturbances in thinking, feelings and behaviour.

Bipolar disorder is a condition with symptoms such as feeling "high", having excessive amounts of energy, needing much less sleep than usual, talking very quickly with racing ideas and sometimes severe irritability.

Your doctor may have prescribed APO-Aripiprazole for another reason. Ask your doctor if you have any questions about why APO-Aripiprazole has been prescribed for you.

There is no evidence that APO-Aripiprazole is addictive.

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

APO-Aripiprazole is not recommended for use in children under the age of 18, as safety and efficacy have not been established in this age group.

 2. What should I know before I use APO-Aripiprazole?

Warnings

Do not use APO-Aripiprazole if:

  • you are allergic to aripiprazole, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.

Symptoms of an allergic reaction include:

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

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances such as foods, preservatives or dyes

Do not take APO-Aripiprazole after the expiry or use by date printed on the pack.

If you take this medicine after this date has passed, it may not work as well.

Do not take APO-Aripiprazole if the packaging is torn or shows signs of tampering.

If this is the case, return it to your pharmacist.

If you are not sure whether you should start taking APO-Aripiprazole, talk to your doctor or pharmacist.

Check with your doctor if you:

  • have any other medical conditions especially the following:
    - a reaction to some medicines with a sudden increase in body temperature, sweating, fast heartbeat, muscle stiffness and fluctuating blood pressure, which may lead to coma. This reaction is called neuroleptic malignant syndrome.
    - a reaction to some medicines with abnormal movements of the tongue, or other uncontrolled movements of the mouth, tongue, cheeks or jaw which may progress to the arms and legs. This reaction is called tardive dyskinesia.
    - low blood pressure
    - problems with your heart or blood vessels
    - epilepsy, seizures or fits
    - problems with your oesophagus (food pipe) such as difficulty in swallowing
    - high blood sugar or diabetes mellitus
    - Alzheimer's disease or dementia
    - alcohol or drug abuse or dependence or a history of one of these
    - venous thromboembolism or are at risk of venous thromboembolism
    - have a history of or are at risk of sleep apnea (a sleep disorder where your breathing is interrupted during sleep)
    - lactose intolerance
  • take any medicines for any other condition

Tell your doctor if you have past experience of excessive gambling.

Tell your doctor if you drink alcohol.

Your doctor may advise you to avoid alcohol as it can magnify the side-effects of this medicine.

Aripiprazole may cause sleepiness, fall in blood pressure when standing up, dizziness and changes in your ability to move and balance, which may lead to falls. Caution should be taken.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking APO-Aripiprazole.

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

Check with your doctor if you are pregnant or intend to become pregnant.

APO-Aripiprazole is not recommended for use during pregnancy. If you need to take APO-Aripiprazole during your pregnancy, your doctor will discuss with you the benefits and risks of taking it. Babies exposed to antipsychotics (including APO-Aripiprazole) during the third trimester of pregnancy are at risk of experiencing shaking, muscle stiffness, difficulty in feeding and/or withdrawal symptoms. These symptoms may resolve spontaneously or require additional medical treatment.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

It is recommended that you do not breast-feed while taking APO-Aripiprazole, as it may pass into breast milk and therefore there is a possibility that the breast-fed baby may be affected.

 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 interfere with APO-Aripiprazole and affect how it works. These include:

  • medicines used to treat brain disorders such as, anxiety, depression, mood swings, epilepsy or seizures, Parkinson's disease or insomnia
  • medicines used to treat high blood pressure
  • medicines used to treat fungal infections
  • medicines used to treat heart rhythm disturbances
  • medicines used to treat bacterial or viral infections
  • a medicine called cyclosporin (Neoral®; Sandimmun®)
  • a medicine called cimetidine (Tagamet®; Magicul®)

These medicines may be affected by APO-Aripiprazole, or may affect how well it works. Your doctor may need to adjust your dose of APO-Aripiprazole or of the other medicine.

Eating grapefruit or drinking grapefruit juice may affect how APO-Aripiprazole works.

Your doctor or pharmacist may have more information on medicines to be careful with or avoid while taking APO-Aripiprazole.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect APO-Aripiprazole.

 4. How do I use APO-Aripiprazole?

How much to take / use

  • Unless your doctor gives you other directions, you should take APO-Aripiprazole only once a day.
  • APO-Aripiprazole tablets should be swallowed whole and washed down with a glass of water.
  • Follow the instructions provided and use APO-Aripiprazole until your doctor tells you to stop.
  • APO-Aripiprazole helps to control your condition but does not cure it. Therefore you must take APO-Aripiprazole every day. Improvement in symptoms may take several days to some weeks to occur. Even if you feel better do not stop taking APO-Aripiprazole unless your doctor tells you to.

When to take / use APO-Aripiprazole

  • Take APO-Aripiprazole at about the same time each day.
Taking the medicine at the same time each day will have the best effect. It will also help you remember when to take it.
  • It does not matter whether you take APO-Aripiprazole with or without food.

If you forget to use APO-Aripiprazole

APO-Aripiprazole should be used regularly at the same time each day. If you miss your dose at the usual time, follow the instructions below:

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

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

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

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

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

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

If you use too much APO-Aripiprazole

If you think that you have used too much APO-Aripiprazole, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), 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 APO-Aripiprazole?

Things you should do

  • If you are about to be started on any new medicine, tell your doctor, dentist and pharmacist that you are taking APO-Aripiprazole.
  • If you plan to have any kind of surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking APO-Aripiprazole.
  • Be sure to keep all of your doctor's appointments so that your progress can be checked.

Call your doctor straight away if you:

  • Become pregnant while taking APO-Aripiprazole.

Remind any doctor, dentist or pharmacist you visit that you are using APO-Aripiprazole.

Things you should not do

  • Do not give APO-Aripiprazole to anyone else, even if their symptoms seem similar or they have the same condition as you.
  • Do not take APO-Aripiprazole to treat any other complaints unless your doctor or pharmacist tells you to.
  • Do not stop taking APO-Aripiprazole or lower the dosage, even if you are feeling better, without checking with your doctor. If you stop taking APO-Aripiprazole suddenly your condition may worsen.
  • Do not take more of this medicine and do not take it more often than your doctor has ordered.

Make sure you keep cool in hot weather and keep warm in cool weather.

APO-Aripiprazole may affect the way your body reacts to temperature changes. It may prevent sweating, even during heatwaves. You may feel dizzy or faint if you are too hot. To stay cool in hot weather, try to do the following:

  • wear light clothing
  • spend time in air-conditioned environments (or keep windows open and use electric fans)
  • drink plenty of water
  • take cool baths or showers and avoid hot baths and saunas
  • try to restrict exercise or heavy work to cool parts of the day

Driving or using machines

Make sure that you know how you react to APO-Aripiprazole before you drive a car, operate machinery or do anything else that could be dangerous if you are dizzy or light headed or not alert.

APO-Aripiprazole may cause some people to become drowsy or less alert than they are normally or cause light-headedness, dizziness or tiredness. If this occurs do not undertake the activity.

If APO-Aripiprazole makes you feel light-headed, dizzy or faint, be careful when getting up from a sitting or lying position.

Getting up slowly may help.

Drinking alcohol

Tell your doctor if you drink alcohol.

Be careful when drinking alcohol while taking APO-Aripiprazole.

Your doctor may suggest you avoid alcohol while you are being treated with APO-Aripiprazole.

Looking after your medicine

Store APO-Aripiprazole in a cool dry place where the temperature stays below 25°C.

Heat and dampness can destroy some medicine

Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

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.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines. Do not keep outdated medicine or medicine no longer needed.

When to discard your medicine

If your doctor tells you to stop taking APO-Aripiprazole or the medicine has passed its expiry date, ask your pharmacist what to do with any leftover medicine.

Be sure that any discarded medicine is out of the reach of children.

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?

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.

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

APO-Aripiprazole is generally well-tolerated and the side effects are often hard to distinguish from disease symptoms. It is important that you tell your doctor as soon as possible about any unwanted effects.

Less serious side effects

Less serious side effectsWhat to do
Gastrointestinal related:
  • indigestion
  • vomiting
  • constipation
Pain related:
  • headache
  • chest pain
General well-being related:
  • insomnia
  • light-headedness
  • drowsiness
  • agitation
  • anxiety
  • inability to sit or stand still; restless movement of the arms and legs such as tapping, marching in places, rocking, crossing and uncrossing the legs.
  • feeling dizzy especially when getting up from a lying or sitting position
  • altered or increased sexual interest
  • high blood sugar (excessive thirst, hunger and weakness) or the onset or worsening of diabetes
  • weight gain
  • weight loss
  • loss of appetite
  • excessive sweating
  • drowsiness
  • high blood pressure
  • difficulty swallowing
  • hiccups
  • nausea
Infection related:
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
Bleeding related:
  • bleeding or bruising more easily than normal
Speech related
  • speech disorder
Bladder related
  • urinary incontinence
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
Pain related:
  • muscle pain, muscle weakness or muscle stiffness
  • painful irreversible erection
General well-being-related
  • seizure, fits or convulsions
  • fainting
  • abnormal movements of the tongue, or other uncontrolled movements of the tongue, mouth, cheeks, eyes or jaw which may progress to the arms and legs
  • sudden increase in body temperature, sweating, fast heart beat, muscle stiffness, high blood pressure and convulsions
  • disorder of body temperature regulation resulting in low body temperature or high body temperature
  • yellowing of the skin and/or eyes, also called jaundice with or without nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching and dark coloured urine
Allergy related
  • rash
  • allergic reaction (rash, itching or hives on the skin; shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body) with or without fever
Inflammation related
  • inflammation of the pancreas, severe upper stomach pain often with nausea and vomiting
Infection related
  • serious lung infection with fever, chills, shortness of breath, cough, chest pain and blood streaked phlegm
Bladder related
  • difficulty in passing urine
Mental related
  • thoughts or talk about death or suicide; thoughts or talk about self-harm or doing harm to others; any recent attempts at self-harm; an increase in aggressive behaviour, irritability or agitation. If you or someone you know is showing these signs contact your doctor or a mental health advisor right away or go to the nearest hospital for treatment.
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 if you have obsessive (recurring) thoughts or behaviours or trouble controlling impulsive urges or while taking APO-Aripiprazole.

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.

Also, while taking APO-Aripiprazole, some elderly patients with dementia have suffered serious side effects such as a "mini" stroke, stroke, pneumonia or heart problems. These serious side effects can be life threatening.

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

You may not experience any or only some of them.

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. 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 APO-Aripiprazole contains

Active ingredient
(main ingredient)		aripiprazole
Other ingredients
(inactive ingredients)
  • Microcrystalline Cellulose
  • Tartaric Acid
  • Magnesium Stearate
  • Croscarmellose Sodium
  • Indigo Carmine aluminium lake (2 mg and 5 mg strength only)
  • Iron Oxide Yellow (2 mg and 15 mg strength only)
  • Iron Oxide Red (10 mg and 30 mg strength only)
Potential allergensAPO-Aripiprazole is gluten-free, lactose-free, sucrose-free, tartrazine-free and free of other azo dyes.

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

What APO-Aripiprazole looks like

2 mg tablets:

Green, rectangular, slightly biconvex tablets engraved “2” on one side, “A” on the other side. AUST R 152903. AUST R 152917.

5 mg tablets:

Blue, rectangular, slightly biconvex tablets engraved “5” on one side, “A” on the other side. AUST R 152904. AUST R 152911.

10 mg tablets:

Pink, rectangular, slightly biconvex tablets, engraved “10” on one side, “A” on the other side. AUST R 152908. AUST R 152920.

15 mg tablets:

Yellow, round, slightly biconvex tablets, engraved “ARI” over “15” on one side, “APO” on the other side. AUST R 152924. AUST R 152898.

20 mg tablets:

White to off-white, round, slightly biconvex tablets, engraved “ARI” over “20” on one side, “APO” on the other side. AUST R 152899. AUST R 152932.

30 mg tablets:

Pink, round, slightly biconvex tablets, engraved “ARI” over “30” on one side, “APO” on the other side. AUST R 152905. AUST R 152929.

Available in blister packs of 30 tablets, or bottles of 30 or 100 tablets.

* Not all strengths, pack types and/or pack sizes may be available.

Who distributes APO-Aripiprazole

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113
Australia
Tel: (02) 8877 8333
Web: www1.apotex.com/au

APO and APOTEX are registered trademarks of Apotex Inc.

This leaflet was last updated in May 2022.

Published by MIMS July 2022

BRAND INFORMATION

Brand name

APO-Aripiprazole

Active ingredient

Aripiprazole

Schedule

S4

 

1 Name of Medicine

Aripiprazole.

2 Qualitative and Quantitative Composition

Each tablet contains 2 mg, 5 mg, 10 mg, 15 mg, 20 mg and 30 mg aripiprazole as the active ingredient.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

2 mg tablets. Green, rectangular, slightly biconvex tablets, engraved "2" on one side, "A" on the other side.
5 mg tablets. Blue, rectangular, slightly biconvex tablets, engraved "5" on one side, "A" on the other side.
10 mg tablets. Pink, rectangular, slightly biconvex tablets, engraved "10" on one side, "A" on the other side.
15 mg tablets. Yellow, round, slightly biconvex tablets, engraved "ARI" over "15" on one side, "APO" on the other side.
20 mg tablets. White to off-white, round, slightly biconvex tablets, engraved "ARI" over "20" on one side, "APO" on the other side.
30 mg tablets. Pink, round, slightly biconvex tablets, engraved "ARI" over "30" on one side, "APO" on the other side.

4 Clinical Particulars

4.9 Overdose

Symptoms. In clinical studies and postmarketing experience, accidental or intentional acute overdosage of aripiprazole alone was identified in adult patients with estimated doses up to 1260 mg with no fatalities. The potentially medically important signs and symptoms seen in adult patients who overdosed with aripiprazole alone at doses up to 1260 mg included somnolence, lethargy, tachycardia, blood pressure increased, and vomiting. In addition, reports of accidental overdose with aripiprazole alone (up to 195 mg) in children have been established. The potentially medically serious signs and symptoms reported include transient loss of consciousness and somnolence. There were no reported observations indicating a clinically significant adverse change in vital signs, laboratory assessments, or ECG in patients who were evaluated in hospital settings.
Treatment. No specific information is available on the treatment of overdose with aripiprazole. The chance of multiple drug involvement should be considered. Accordingly, cardiovascular monitoring should begin immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. Otherwise, management of overdose should focus on supportive therapy, oxygenation and ventilation, maintaining an adequate airway, and management of symptoms. Close medical supervision and monitoring should continue until recovery.
Charcoal. In the event of an overdose of aripiprazole, the early administration of charcoal may assist in partially preventing the absorption of aripiprazole. In a single-dose study in which 15 mg of aripiprazole was administered to fully compliant, fully conscious, healthy, male volunteers and followed by activated charcoal (50 g), administered one hour after aripiprazole, aripiprazole AUC and Cmax was decreased by 51 and 41%, respectively, compared to historic controls, suggesting that charcoal may be effective for overdose management.
Haemodialysis. Although there is no information on the effect of haemodialysis in treating an overdose with aripiprazole, haemodialysis is not likely to be of assistance in overdose management, since aripiprazole is not eliminated unchanged by the kidneys and is highly bound to plasma proteins.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Aripiprazole was tested using a standard range of assays for chromosomal damage, gene mutation, and DNA damage and repair. Aripiprazole was non-genotoxic in the in vitro bacterial DNA repair assay, the in vitro forward gene mutation assay in mouse lymphoma cells, the in vitro bacterial reverse-mutation assay, and the unscheduled DNA synthesis assay in rat hepatocytes. However, aripiprazole and its minor metabolite 2,3-DCPP were clastogenic in the in vitro chromosomal aberration assay in Chinese hamster lung (CHL) cells in both the presence and absence of metabolic activation. A positive response for aripiprazole in 1 of 6 in vivo mouse micronucleus tests was attributed to drug-induced hypothermia.
Carcinogenicity. Lifetime carcinogenicity studies were conducted in ICR mice and in Sprague-Dawley (SD) and Fischer (F344) rats. For 2 years aripiprazole was administered in the diet at doses of 1, 3, 10, and 30 mg/kg/day to ICR mice and 1, 3, and 10 mg/kg/day to F344 rats (0.2 to 5 and 0.3 to 3 times the maximum recommended human dose [MRHD] based on mg/m2, respectively). SD rats were dosed orally by gavage for 2 years at 10, 20, 40, and 60 mg/kg/day (3 to 18 times the MRHD based on mg/m2). In male mice and rats, there was no evidence of tumorigenesis. In female mice, the incidences of pituitary gland adenomas and mammary gland adenocarcinomas and adenoacanthomas were increased at dietary doses of 3 to 30 mg/kg/day (0.1 to 0.9 times MRHD based on AUC and 0.5 to 5 times the MRHD based on mg/m2). In female rats, the incidence of mammary gland fibroadenomas was increased at a dietary dose of 10 mg/kg/day (< 0.1 times MRHD based on AUC and 3 times the MRHD based on mg/m2) and the incidences of adrenocortical carcinomas and combined adrenocortical adenomas/carcinomas were increased at an oral gavage dose of 60 mg/kg/day (10 times the MRHD based on AUC and 18 times MRHD based on mg/m2). In male rats, the incidence of benign and combined benign/malignant phaeochromocytomas were also increased at an oral gavage dose of 60 mg/kg/day (10 times the MRHD based on AUC and 18 times the MRHD based on mg/m2).
Proliferative changes in the pituitary and mammary gland of rodents have been observed following chronic administration of other antipsychotic agents and are considered prolactin-mediated. Serum prolactin was not measured in the aripiprazole carcinogenicity studies. Hyperprolactinaemia was observed in female mice in a 13-week dietary study at doses associated with mammary gland and pituitary tumours, but not in female rats in 4- and 13-week dietary studies at doses associated with mammary gland tumours. Hyperprolactinaemia was observed in female rats after 5 and 13 weeks of oral administration at doses up to that associated with adrenocortical tumours, but serum prolactin was decreased at this dose in male rats. The relationship between tumourigenic findings with aripiprazole and prolactin is unclear and the relevance for human risk of prolactin-mediated endocrine tumours is unknown. The adrenocortical response in female rats is considered a consequence of increased adrenocortical cell proliferation secondary to chronic drug-related adrenocortical cytotoxicity; the no-effect exposure (plasma AUC) was about fold 7 clinical exposure at the MRHD.
Animal toxicology. Choleliths (gallsand and/or gallstones) were observed in the bile of monkeys given aripiprazole orally for 4-52 weeks at doses of 25-125 mg/kg/day (1-3 times the MRHD based on plasma AUC and 15-76 times the MRHD based on mg/m2) and were attributed to precipitation of sulfate conjugates of hydroxy metabolites, which exceeded their solubility limits in bile. After repeated daily administration of the MRHD, human biliary concentrations of these sulfate conjugates are substantially lower (0.2-14% of their in vitro solubility limits).
Bilateral retinal degeneration was observed in albino rats given oral aripiprazole for 6 months or two years at exposures of 6-13 times the clinical exposure at the MRHD (based on plasma AUC). The exposure at the NOEL dose was 3 times that at the MRHD. A subsequent 18-month study reported this finding in albino but not pigmented rats, possibly due to lack of photoprotective ocular melanin in the albino rats, although it is unknown whether pigmentation prevented or merely delayed retinal degeneration in the pigmented rats. The clinical relevance of this finding is uncertain.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Aripiprazole is an off-white to white powder. Aripiprazole melts between 139.0 and 139.5°C. It is practically insoluble in water and its solubility is pH dependent.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSARIPIP.gif Chemical Name: 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2(1H)-quinolinone.
Molecular Formula: C23H27Cl2N3O2.
Molecular Weight: 448.39 g/mol.
CAS number. 129722-12-9.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes

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