SUMMARY CMI

ATOVACUE^®

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 ATOVACUE?

ATOVACUE contains the active ingredient atovaquone. ATOVACUE is used to treat a type of pneumonia (lung infection) caused by Pneumocystis carinii.

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

2. What should I know before I use ATOVACUE?

Do not use if you have ever had an allergic reaction to atovaquone 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 ATOVACUE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ATOVACUE 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 ATOVACUE?

• It is very important that you take ATOVACUE oral suspension with food. It has been shown that taking ATOVACUE Suspension with a high fat meal helps your medicine to work more effectively.
• Shake well before use. Do not dilute.

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

5. What should I know while using ATOVACUE?

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

6. Are there any side effects?

Common side effects include fever, headache, abdominal pain, asthenia, nausea, diarrhoea, vomiting, dyspepsia, insomnia, rash and sinusitis.

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.

FULL CMI

ATOVACUE^®

Active ingredient: Atovaquone

Consumer Medicine Information (CMI)

This leaflet provides important information about using ATOVACUE. 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 ATOVACUE.

Where to find information in this leaflet:

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

1. Why am I using ATOVACUE?

ATOVACUE contains the active ingredient atovaquone. ATOVACUE belongs to a group of medicines called anti-infectives.

ATOVACUE oral suspension is used to treat a type of pneumonia (lung infection) caused by Pneumocystis carinii.

Pneumocystis carinii is a parasite that can lie dormant in the airways unless the body's immune system becomes weakened, for example in human immunodeficiency virus (HIV) infection. This can lead to Pneumocystis carinii pneumonia (PCP).

ATOVACUE suspension works by interfering with important functions within Pneumocystis carinii.

Your doctor may have prescribed ATOVACUE suspension for another reason.

Ask your doctor if you have any questions about why ATOVACUE suspension has been prescribed for you.

This medicine is available only with a doctor's prescription. ATOVACUE suspension is not addictive.

2. What should I know before I use ATOVACUE?

Warnings

Do not use ATOVACUE if:

• you are allergic to atovaquone, or any of the ingredients listed at the end of this leaflet.
• Always check the ingredients to make sure you can use this medicine.
• you are pregnant, trying to become pregnant or breastfeeding, unless your doctor says you should.

This medicine contains 50.00 mg benzyl alcohol in each 5 mL.

Benzyl alcohol may cause allergic reactions.

Check with your doctor if you:

• are allergic to foods, dyes, preservatives or any other medicines.
• have or have had diarrhoea or any other stomach or bowel problem.
• have or have had kidney or liver disease.

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.

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

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 ATOVACUE and affect how it works.

Medicines that may increase the effect of ATOVACUE include:

• Indinavir, medicines used to treat HIV/ AIDS.
• Warfarin, a medicine used to prevent blood clots.

Medicines that may reduce the effect of ATOVACUE include:

• Metoclopramide, a medicine used for nausea and vomiting.
• Rifampicin (for example Rifadin)
• tetracycline (for example Doxylin)
• rifabutin (for example Mycobutin)
• cephalosporins (for example cefuroxime)
• medicines used to treat bacterial infections.
• anti-diarrhoeals and laxatives
• Paracetamol
• Benzodiazepines, medicines used to treat anxiety, seizures and insomnia.
• Aciclovir, a medicine used to treat viral infections.
• Opiates,(for example morphine, codeine and oxycodone).

Drugs that get affected by Atovacue Suspension: Zidovudine

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

4. How do I use ATOVACUE?

How much to take / use

Dosage in adults

The usual dose in adults is one 5 mL spoonful (750 mg), taken twice a day with food, for 21 days.

It is important to take the recommended dose (5 mL: 750 mg) twice a day because this dosing schedule provides the optimum drug concentration in your blood. However, if you have difficulty with swallowing or are only able to eat one meal a day, then the dose is two 5 mL spoonfuls (1500 mg) taken with a meal, for 21 days.

When to take / use ATOVACUE

It is very important that you take ATOVACUE suspension with food. It has been shown that taking ATOVACUE Suspension with a high fat meal helps your medicine to work more effectively.

Make sure you shake the bottle of ATOVACUE Suspension before measuring your dose.

ATOVACUE Suspension should not be diluted.

If you forget to use ATOVACUE

ATOVACUE should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember.

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

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

If you use too much ATOVACUE

If you think that you have used too much ATOVACUE, 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 ATOVACUE?

Things you should do

Tell your doctor or pharmacist that you are taking ATOVACUE suspension if you are about to be started on any new medicines.

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

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.

Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Things you should not do

• Do not stop taking ATOVACUE suspension or change the dose without first checking with your doctor.
• Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
• Do not use ATOVACUE suspension to treat any other complaints unless your doctor says to.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ATOVACUE suspension affects you.

ATOVACUE suspension generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, ATOVACUE suspension may cause headache in some people.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

Follow the instructions in the carton on how to take care of your medicine properly.

Store below 25°C. Do not refrigerate. Do not freeze.

Unused product should be discarded 21 days after opening.

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.

When to discard your medicine

If your doctor tells you to stop taking it or the suspension have passed their expiry date, ask your pharmacist what to do with any that are left over.

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.

In clinical studies, atovaquone suspension has been used to treat pneumocystis carinii pneumonia in patients with underlying HIV infection. Therefore, it is not known whether many of these side-effects are due to taking atovaquone suspension or taking atovaquone suspension with other medicines. Some of these symptoms may occur as part of advanced HIV disease.

Like other medicines, ATOVACUE suspension can cause some side-effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

Less serious side effects

Serious side effects

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.

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 ATOVACUE contains

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

What ATOVACUE looks like

ATOVACUE is 210 mL bright yellow flavoured suspension filled in 250 mL plastic bottle (HPDE) with 28 mm child resistance (CR) clean peel closure and polypropylene double sided spoon (2.5 ml and 5 ml). (AUST R 407150).

Who distributes ATOVACUE

Glenamrk Pharmaceuticals Australia Pty Ltd
Suite 1503, Level 15
14 Martin Place
Sydney, NSW 2000
Australia
Phone number: 1800 371 274
Email ID: [email protected]

This leaflet was prepared in April 2024.

Published by MIMS January 2025

1 Name of Medicine

Atovaquone.

2 Qualitative and Quantitative Composition

Atovacue oral liquid suspension contains the active atovaquone 750 mg in 5 mL.

Excipient with known effect.

3 Pharmaceutical Form

Atovacue oral suspension is a bright yellow liquid.

4 Clinical Particulars

4.1 Therapeutic Indications

Atovacue oral suspension is indicated for:
Acute treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) (difference of alveolar and arterial oxygen tensions [(A-a) DO₂] ≤ 45 mmHg (6 kPa) and oxygen tension in arterial blood (PaO₂) ≥ 60 mmHg (8 kPa) breathing room air) in adult patients with AIDS who are intolerant of trimethoprim/sulfamethoxazole therapy.

4.2 Dose and Method of Administration

The importance of taking the full prescribed dose of Atovacue with food should be stressed to patients. The presence of food, particularly high-fat food, increases bioavailability two to three fold.
Shake well before use. Do not dilute.

Dosage in adults.

Pneumocystis carinii pneumonia.

Dosage in children.

Dosage in elderly.

4.3 Contraindications

Atovacue oral suspension is contra-indicated in individuals with known hypersensitivity to atovaquone or to any components of the formulation.

4.4 Special Warnings and Precautions for Use

Atovaquone has not been systematically evaluated i) in patients failing other PCP therapy, ii) for the treatment of severe episodes of PCP [(A-a) DO₂ > 45 mmHg (6 kPa)], or iii) as a prophylactic agent for PCP.
Absorption of atovaquone is limited but can be significantly increased when the drug is taken with food. In clinical studies using atovaquone tablets, atovaquone plasma concentrations have been shown to correlate generally with the likelihood of successful treatment and survival. There is limited efficacy data on atovaquone suspension that examined the correlation between plasma concentration and treatment success rate. Gastro-intestinal disorders may further reduce absorption of orally administered drugs and patients may not achieve plasma levels of atovaquone associated with response to therapy. Therefore, alternative therapies should be considered for such patients and for patients who have difficulty taking atovaquone with food.
The prescriber must be aware that diarrhoea at the start of treatment has been shown to be correlated with higher incidences of therapy failures and a lower survival rate. Therefore, alternative therapies should be considered for such patients.
Patients with pulmonary disease should be carefully evaluated for causes of disease other than PCP and treated with additional agents as appropriate. Atovaquone is not expected to be effective therapy for concurrent bacterial, viral, fungal or mycobacterial diseases.
The concomitant administration of atovaquone and rifampicin is not recommended. A potential drug interaction has been reported for concomitant administration of zidovudine and rifabutin with atovaquone (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
This medicine contains 50 mg benzyl alcohol in each 5 mL. Benzyl alcohol may cause allergic reaction.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

As experience is limited, care should be taken when combining other drugs with atovaquone. The causal relationship between the change in plasma concentrations of atovaquone and the administration of the drugs mentioned below is unknown.
Concomitant treatment with metoclopramide and rifampicin has been associated with significant decreases in plasma concentrations of atovaquone (mean decreases of 4.0 and 7.6 microgram/mL, respectively). Concomitant administration of tetracycline with atovaquone is associated with approximately 40% lower plasma atovaquone concentration. Caution should be exercised in prescribing either of these drugs with atovaquone until the potential interaction has been further studied.
Concomitant administration of rifabutin and atovaquone has been associated with a moderate reduction in the steady state plasma concentrations of both atovaquone (on average by 34%) and rifabutin (on average by 19%).
In clinical trials of atovaquone, small decreases in plasma concentrations of atovaquone (mean < 3 microgram/mL) were associated with concomitant administration of paracetamol, benzodiazepines, aciclovir, opiates, cephalosporins, anti-diarrhoeals and laxatives. The causal relationship between the change in plasma concentrations of atovaquone and the administration of these drugs is unknown.
Zidovudine does not appear to affect the pharmacokinetics of atovaquone. However, pharmacokinetic data have shown that atovaquone appears to decrease the rate of metabolism of zidovudine to its glucuronide metabolite (steady state AUC of zidovudine was increased by 33% and peak plasma concentration of the glucuronide was decreased by 19%). At zidovudine dosages of 500 or 600 mg/day it would seem unlikely that a three week, concomitant course of atovaquone for the treatment of acute PCP would result in an increased incidence of adverse reactions attributable to higher plasma concentrations of zidovudine. Extra care should be taken in monitoring patients receiving prolonged atovaquone therapy. There are no data available for other antiretrovirals.
In clinical trials of atovaquone the following medications were not associated with a change in steady state plasma concentrations of atovaquone: fluconazole, clotrimazole, ketoconazole, antacids, systemic corticosteroids, non-steroidal anti-inflammatory drugs, anti-emetics (excluding metoclopramide) and H₂-antagonists.
Atovaquone is highly bound to plasma proteins and caution should be used when administering concurrently with other highly plasma protein bound drugs with narrow therapeutic indices. e.g. warfarin. There is no plasma protein binding interaction between atovaquone and quinine, or phenytoin in vitro.
Concomitant administration of atovaquone and indinavir results in a significant decrease in the C_min of indinavir (23% decrease; 90% CI 8-35%). Caution should be exercised in prescribing atovaquone with indinavir due to the decrease in trough levels of indinavir.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

There have been no studies to investigate the effect of atovaquone on driving performance or the ability to operate machinery but a detrimental effect on such activities is not predicted from the pharmacology of the drug.

4.8 Adverse Effects (Undesirable Effects)

Patients participating in clinical trials with atovaquone have often had complications of advanced human immunodeficiency virus (HIV) disease and therefore the causal relationship between the adverse experiences and atovaquone is difficult to evaluate. No life-threatening or fatal adverse experiences have been specifically attributed to atovaquone. See Tables 1, 2 and 3.
Nine percent of patients discontinued atovaquone as the result of an adverse experience. Of the most common adverse experiences, only rash, which occurred at a rate of 23% was shown to be related to plasma atovaquone concentration. The most common reasons for discontinuation of atovaquone were rash and vomiting. The incidence of adverse experiences with atovaquone suspension at the recommended dose was similar to that seen with the tablet formulation. See Table 4 and 5.
Hypersensitivity reactions including angioedema, bronchospasm and throat tightness have also been commonly reported.
Although experience is limited, adverse experiences reported in children with AIDS (Acquired Immune Deficiency Syndrome) do not appear to differ significantly from those of adults with AIDS receiving atovaquone.

Reporting suspected adverse effects.

4.9 Overdose

Acute toxicity of atovaquone was not obvious in rats and mice given the highest practicable dose level.
There is insufficient experience to predict the consequences, or suggest specific management, of atovaquone overdose. If overdose occurs the patient should be monitored and standard supportive treatment administered.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

Clinical trials.

Atovaquone suspension open label study.

Comparative study - atovaquone tablets versus trimethoprim-sulphamethoxazole (TMP-SMX).

Comparative study - atovaquone versus pentamidine.

5.2 Pharmacokinetic Properties

Pharmacokinetics in adults.

Absorption and distribution.

Metabolism and excretion.

Pharmacokinetics in children.

5.3 Preclinical Safety Data

Genotoxicity and carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Benzyl alcohol, xanthan gum, poloxamer 188, hypromellose, saccharin sodium, citric acid monohydrate, sodium citrate dihydrate, purified water, tutti frutti flavour (051880 AP0551).

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.
Unused product should be discarded 21 days after opening.

6.4 Special Precautions for Storage

Store below 25°C. Do not refrigerate. Do not freeze.

6.5 Nature and Contents of Container

210 mL in a plastic bottle (HDPE) with child resistant closure (polypropylene).
A measuring double sided spoon (2.5 mL and 5 mL) (polypropylene) is included.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Atovaquone is an extremely insoluble yellow crystalline powder. Solubility at 25°C in water and 0.1 M hydrochloric acid is < 2 x 10^-4 mg/mL; in 0.1 M sodium hydroxide it is 1.7 mg/mL.
The chemical name of atovaquone is trans-2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4- naphthoquinone, with a molecular formula C₂₂H₁₉ClO₃ and a relative molecular mass of 366.84.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes