Consumer medicine information

What is in this leaflet?

Please read this leaflet carefully before you start Wellvone Suspension.

This leaflet answers some common questions about Wellvone Suspension. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Wellvone Suspension against the benefits this medicine is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Wellvone Suspension is used for

Atovaquone the active ingredient in Wellvone Suspension belongs to a group of medicines called anti-infectives.

Wellvone 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).

Wellvone Suspension works by interfering with important functions within Pneumocystis carinii.

Your doctor may have prescribed Wellvone Suspension for another reason.

Ask your doctor if you have any questions about why Wellvone Suspension has been prescribed for you.

This medicine is available only with a doctor’s prescription. Wellvone Suspension is not addictive.

Before you take Wellvone Suspension

When you must not take it

• Do not take Wellvone Suspension if you have ever had an allergic reaction to atovaquone or any of the ingredients listed at the end of this leaflet.
  Symptoms of an allergic reaction may be mild or severe. They usually include some or all of the following: wheezing, swelling of the lips/mouth, difficulty in breathing, hayfever, lumpy rash ("hives") or fainting.
• Do not take Wellvone Suspension if you are pregnant, trying to become pregnant or breastfeeding, unless your doctor says you should.
  Your doctor will discuss the risks and benefits of using Wellvone Suspension if you are pregnant or breastfeeding.
• Do not take Wellvone Suspension after the expiry date (EXP) printed on the pack.
  If you take it after the expiry date has passed, it may not work as well.
• Do not take Wellvone Suspension if the packaging is torn or shows signs of tampering.
  If you're not sure whether you should be taking Wellvone Suspension, talk to your doctor.

Before you start to take it

You must tell your doctor if:

• you are allergic to foods, dyes, preservatives or any other medicines.
• you have or have had diarrhoea or any other stomach or bowel problem.
• you have or have had kidney or liver disease.
• you have taken or are taking any medicine containing rifampicin (for example, Rifadin),rifabutin (for example Mycobutin), tetracycline (for example, Achromycin), zidovudine (f or example, Retrovir) or metoclopramide (for example, Maxolon), indinavir (for example Crixivan).

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

Make sure you tell your doctor if you have taken or are taking any medicine containing rifampicin, rifabutin, tetracycline, zidovudine, indinavir or metoclopramide. Example of branded medicines containing these active ingredients are given under the “Before you start to take it” section above.

Some medicines may affect the way others work. Your doctor or pharmacist will be able to tell you what to do when taking Wellvone Suspension with other medicines.

Use in children

There is insufficient information to recommend that children can take Wellvone Suspension.

How to take Wellvone Suspension

The Pharmacist's label on the pack will tell you how to take Wellvone Suspension. If there is something you do not understand, ask your doctor or pharmacist.

How much to take

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.

How to take it

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

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

Wellvone Suspension should not be diluted.

When to take it

It is very important that you take Wellvone Suspension with food.

How long to take it

The usual course of treatment with Wellvone Suspension is 21 days.

If you forget to take it

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, then go back to taking it as you would normally.

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

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 131126) for advice, if you think you or anyone else may have taken too much Wellvone Suspension, even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

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

While you are taking Wellvone Suspension

Things you must do

Tell your doctor or pharmacist that you are taking Wellvone 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 must not do

Do not stop taking Wellvone 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 Wellvone Suspension to treat any other complaints unless your doctor says to.

Things to be careful of

Be careful driving or operating machinery until you know how Wellvone Suspension affects you. Wellvone Suspension generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, Wellvone Suspension may cause headache in some people.

Side-Effects

Check with your doctor as soon as possible if you have any problems while taking Wellvone Suspension, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

In clinical studies, Wellvone 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 Wellvone Suspension or taking Wellvone Suspension with other medicines. Some of these symptoms may occur as part of advanced HIV disease.

Like other medicines, Wellvone 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.

The most commonly reported side-effects are:

• rash
• nausea, vomiting
• diarrhoea
• headache
• fever
• difficulty in sleeping

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist immediately if you notice any of the following:

• weakness
• itchiness
• oral thrush
• abdominal pain
• constipation
• dizziness
• cough
• anxiety
• anorexia
• difficulty swallowing
• taste disturbance
• hay fever
• sinusitis
• abnormal blood sugar
• low blood pressure
• insomnia

A small number of patients have had other unwanted effects after taking Wellvone. These include unwanted effects on the liver and blood.

Ask your doctor or pharmacist to answer any questions you may have.

If you think you are having an allergic reaction to Wellvone Suspension, TELL YOUR DOCTOR IMMEDIATELY or go to the casualty department at your nearest hospital. Symptoms usually include some or all of the following:

• wheezing
• swelling of the lips/mouth
• difficulty in breathing
• hay fever
• lumpy rash ("hives")
• fainting

This is not a complete list of all possible side-effects. Others may occur in some people and there may be some side-effects not yet known.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

Ask your doctor or pharmacist if you don't understand anything in this list.

Do not be alarmed by this list of possible side-effects. You may not experience any of them.

After taking Wellvone Suspension

Storage

Keep this medicine 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.

Keep Wellvone Suspension in a cool, dry place where it stays below 25°C.

Wellvone Suspension should not be frozen.

Do not store it, or any other medicine, in a bathroom or near a sink.

Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep your Wellvone Suspension in its pack until it is time to take it. If you take the Wellvone Suspension out of its pack it may not keep well.

Disposal

If your doctor tells you to stop taking Wellvone Suspension, or the Product has passed its expiry date, ask your pharmacist what to do with any Wellvone Suspension left over.

Product description

What Wellvone Suspension looks like.

Wellvone Suspension is a bright yellow liquid with a sweet, fruity odour. The plastic bottle contains 210 mL of suspension and is packed in a box with a plastic spoon.

Ingredients

Active ingredient:

Wellvone Suspension contains the active ingredient atovaquone.

Inactive ingredients:

Wellvone Suspension also contains benzyl alcohol, xanthan gum, poloxamer 188, saccharin sodium, Tutti Frutti flavour 51880 A (PI 965) and purified water.

Wellvone Suspension does not contain gluten or lactose.

Sponsor

Aspen Pharmacare Australia Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Australia.

Further Information

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your doctor or pharmacist is the best person to give you advice on the treatment of your condition. You may also be able to find general information about your disease and its treatment from books, for example in public libraries.

Do not throw this leaflet away. You may need to read it again.

The information provided applies only to: Wellvone Suspension.

Australian registration number:
AUST R 66688.

This leaflet was revised in March 2020.

Published by MIMS May 2020

1 Name of Medicine

Atovaquone.

2 Qualitative and Quantitative Composition

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

Excipient with known effect.

3 Pharmaceutical Form

Wellvone suspension is bright yellow with a sweet fruity odour.

4 Clinical Particulars

4.1 Therapeutic Indications

Wellvone 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 (Pa0₂) ≥ 60 mmHg (8 kPa) breathing room air) in adult patients with AIDS who are intolerant of trimethoprim/sulphamethoxazole therapy.

4.2 Dose and Method of Administration

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

Dosage in adults.

Pneumocystis carinii pneumonia.

Dosage in children.

Dosage in elderly.

4.3 Contraindications

Wellvone suspension is contraindicated 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. Gastrointestinal 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 Wellvone 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).

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 Wellvone 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, antidiarrhoeals 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, nonsteroidal anti-inflammatory drugs, antiemetics (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 Wellvone and indinavir results in a significant decrease in the Cmin of indinavir (23% decrease; 90% CI 8 to 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.
Table 1 summarises common adverse experiences (frequency ≥ 10%) reported in a pharmacokinetic study of atovaquone suspension for the treatment of PCP in adult patients with AIDS.
Table 2 summarises common adverse experiences (frequency ≥ 5%), regardless of attributability, reported in a comparative study of atovaquone tablets and trimethoprim-sulphamethoxazole for the treatment of PCP in adult patients with AIDS. Laboratory test abnormalities (frequency ≥ 5%) during the treatment period are summarised in Table 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.
Table 4 summarises common adverse experiences (frequency ≥ 5%), regardless of attributability, reported in a comparative study of atovaquone tablets and intravenous pentamidine for the treatment of PCP in adult patients with AIDS. Laboratory test abnormalities (frequency ≥ 5%) during the treatment period are summarised in Table 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

Each 5 mL of suspension contains benzyl alcohol, xanthan gum, poloxamer 188, saccharin sodium, tutti frutti flavour 51880 A (PI 965) and purified water.

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.

6.4 Special Precautions for Storage

Store below 25°C. Do not freeze.

6.5 Nature and Contents of Container

Supplied in a plastic HDPE bottle with child-resistant screw cap and plastic spoon. Pack size 210 mL.

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 < 2x10^-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