Consumer medicine information

Hequinel Tablets 200 mg

Hydroxychloroquine sulfate

BRAND INFORMATION

Brand name

Hequinel

Active ingredient

Hydroxychloroquine sulfate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Hequinel Tablets 200 mg.

SUMMARY CMI

HEQUINEL

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 HEQUINEL?

HEQUINEL contains the active ingredient hydroxychloroquine sulfate. HEQUINEL is used to treat rheumatoid arthritis and may slow down the process of joint damage and relieve the symptoms of the disease.

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

2. What should I know before I use HEQUINEL?

Do not use if you have ever had an allergic reaction to hydroxychloroquine sulfate 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 HEQUINEL? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Hequinel 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 HEQUINEL?

  • Swallow tablets whole with a little water or other liquid at mealtimes.
  • The dosage will depend on why you are being treated with Hequinel

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

5. What should I know while using HEQUINEL?

Things you should doRemind any doctor, dentist or pharmacist you visit that you are using Hequinel.
Things you should not doHequinel should not be used in children under 6 years.
Hequinel should not be used in children over 6 years for long periods.
Driving or using machinesHequinel may cause problems with the eyesight of some people. Make sure you know how you react to Hequinel before you drive a car, operate machinery, or do anything else that could be dangerous with blurred vision.
Looking after your medicineKeep your tablets in the bottle until it is time to take them.
If you take the tablets out of the bottle they will not keep well.
Keep it in a cool dry place where the temperature stays below 25°C.

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

6. Are there any side effects?

Common side effect include nausea, vomiting, diarrhoea, abdominal cramps, loss of appetite, muscle weakness, dizziness, ringing in the ears, headache, nervousness, skin rash and itching, hair loss. The more serious side effects include but are not limited to visual disturbances, hearing loss, suicidal behavior, frequent fevers, severe chills, bruising, sore throat or mouth ulcers (these may be signs of blood reactions), changes in the way your heart beats.

Having thoughts of self-harm or suicide, feeling depressed, feeling nervous or anxious, feeling confused, agitated, difficulty sleeping, delusions, hallucinations, changes in mood, feeling elated or overexcited. More severe side effects include disorientation, seizures, fits or convulsions and loss of consciousness. All of the above are possible side effects and you may need urgent medical attention.

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

HEQUINEL

Active ingredient(s): Hydrochloroquine sulfate


Consumer Medicine Information (CMI)

This leaflet provides important information about using Hequinel. 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 HEQUINEL.

Where to find information in this leaflet:

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

1. Why am I using HEQUINEL?

Hequinel contains the active ingredient hydroxychloroquine sulfate.

Hequinel is used for any of the following conditions:

Rheumatoid arthritis
Rheumatoid arthritis is a form of arthritis with inflammation of the joints, characterised by stiffness, swelling and pain. Hequinel may be used for short or long-term rheumatoid arthritis treatment.

In treating rheumatoid arthritis, Hequinel may slow down the process of joint damage and relieve the symptoms of the disease.

Systemic Lupus Erythematous (SLE)
SLE is a disease in which a person's normal immunity is upset. The body produces an excess of blood proteins called antibodies and these antibodies may cause problems in any organ of the body.

These antibodies may end up, for example, in the skin causing a variety of skin rashes or deposit in the kidney, brain, lung and joints causing injury.

Discoid Lupus Erythematous (DLE)
DLE is similar to SLE except it only affects the skin and is characterised by a scaling, red rash.

Malaria (treatment and control of symptoms)
Malaria is an infectious disease caused by the presence of parasites in red blood cells.

The disease is characterised by chills, fever and sweats.

In malaria, Hequinel destroys the harmful parasite which causes the illness.

Your doctor may have prescribed this medicine for another reason. Ask your doctor if you have any questions about why Hequinel has been prescribed for you.

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

2. What should I know before I use HEQUINEL?

Warnings

Do not use Hequinel if:

  • you are allergic to hydroxychloroquine, chloroquine 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 have previously experienced changes in your eyesight when taking medicines for rheumatoid arthritis or malaria.
  • You have a heart rhythm disorder.
  • Hequinel should not be used in children under 6 years.
  • Hequinel should not be used in children over 6 years for long periods.
  • Do not take Hequinel after the expiry date printed on the bottle.
  • Do not take Hequinel if the bottle is damaged or shows signs of tampering.
  • Do not take Hequinel to treat any other complaint unless your doctor says it is safe. Do not give this medicine to anyone else.

Check with your doctor if you:

  • are taking any other medicines for any medical condition.
  • are allergic to quinine.
  • have allergies to any ingredients listed under "Product Description" at the end of this leaflet.
  • have any pre-existing eye disorders.
  • have experienced low blood sugar levels (hypoglycaemia - a "hypo"). Hequinel may increase the risk of you having a hypo.
  • have or have had any of these medical conditions:
    - Chloroquine-resistant malaria
    - Liver or kidney problems
    - Diabetes
    - Stomach, brain or blood disorders
    - Disease of the heart muscle
    - Skin diseases, in particular psoriasis which is a kind of itchy rash.
    - Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency which is a lack of a chemical substance which causes the breakdown of sugar in the body.
    - porphyria, which is a rare disease of blood pigments.

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

Hequinel should be avoided in pregnancy except when, in the judgement of the physician, the potential benefits outweigh the potential hazards.

Ask your doctor about the risks and benefits or taking Hequinel while you are breastfeeding.

When Hequinel is taken for long periods of time, there is an increased risk to the unborn child. It may cause problems with brain function, hearing, balance and vision.

There is very limited data on the safety in the breastfed infant during long-term treatment with Hequinel. The active ingredient (hydroxychloroquine) is excreted in breast milk and it is known that infants are extremely sensitive to the toxic effects.

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 Hequinel and affect how it works, these include:

  • Any medicine to treat depression, including the herbal product St John's wort
  • Digoxin - a medicine used to treat heart disease
  • Medicines to treat diabetes
  • Medicines used to suppress the immune system such as ciclosporin
  • Antiarrythmic drugs such as amiodarone and moxifloxacin
  • Other antimalarial drugs
  • Medicines to treat epilepsy, such as carbamazepine and phenobarbital
  • Tamoxifen (a medicine used to treat breast cancer)
  • Anti-infective medicines
  • Medicines that may affect your blood
  • Medicines that may affect your eyes
  • Antacids containing magnesium or kaolin or cimetidine, used to neutralise stomach acid
  • Itraconazole, an antifungal medication
  • Clarithromycin and rifampicin (antibiotics)
  • Grapefruit juice
  • Anticoagulant drugs such as dabigatran and clopidogrel
  • Medicines to treat high cholesterol, such as gemfibrozil
  • Ritonavir (a medicine used to treat HIV)

These medicines may be affected by Hequinel or affect the way Hequinel works.

Your doctor or pharmacist can tell you what to do if you are taking any of these medicines.

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

4. How do I use HEQUINEL?

How much to take

The usual doses are:

Rheumatoid arthritis

Adults

  • 2-3 tablets daily. Your doctor may later reduce this to 1-2 tablets daily.

SLE and DLE

Adults

  • 2-4 tablets daily. Your doctor may later reduce this to 1-2 tablets daily.

Control of Malaria Symptoms

Adults

  • 2 tablets once a week. The tablets should be taken on exactly the same day of each week.
  • For example, if your first dose is taken on a Monday, then each weekly dose should be taken on a Monday.

Treatment of malaria

Adults

  • The starting dose is 4 tablets. Take another 2 tablets six to eight hours later and two further tablets on each of the next 2 days.

Always follow the instructions given to you by your doctor.

Dosages for children are calculated according to the child's body weight.

Your doctor will work out the correct dose for you or your child.

HEQUINEL should not be used in children for long periods.

Your doctor may ask you to take a different dose. You should follow the instructions on the label.

If you are unsure what dose to take, ask your pharmacist or doctor.

When to take HEQUINEL

  • Swallow tablets whole with a little water or other liquid.
  • It is best to take Hequinel at meal times.
  • The dosage will depend on why you are being treated with Hequinel.

If you forget to take HEQUINEL

If you are being given Hequinel for rheumatoid arthritis, SLE or DLE, do not take a double dose to make up for the dose missed. Just continue with the appropriate dose on the next day.

If you are being given Hequinel for suppression or treatment of malaria, you should take your tablets as soon as you remember, and go back to taking it as you would normally.

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

If you take too much Hequinel

If you think that you have taken too much Hequinel, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre in Australia by calling 13 11 26, or 0800 POISON or 0800 764766 in New Zealand, 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.

If you take too many tablets you may experience headaches, drowsiness, visual disturbances or fits.

These symptoms may occur within 30 minutes of overdose.

5. What should I know while using HEQUINEL?

Things you should do

Remind any doctor, dentist or pharmacist you visit that you are using Hequinel.

Call your doctor straight away if you:

  • Are about to start taking any new medicines, tell your doctor and pharmacist that you are taking Hequinel.
  • Experience any of the following symptoms including; weakness, trembling or shaking, sweating, lightheadedness, headache, dizziness, lack of concentration, tearfulness or crying, irritability, hunger and numbness around the lips and fingers. These symptoms may be associated with hypoglycaemia.
  • If you experience any of the symptoms of hypoglycaemia, you need to raise your blood glucose urgently. You can do this by taking one of the following:
    - 5-7 jelly beans
    - 3 teaspoons of sugar or honey
    - 1/2 can of ordinary (non-diet) soft drink
    - 2-3 concentrated glucose tablets
    - unless you are within 10 to 15 minutes of your next meal or snack, follow up with extra carbohydrates e.g. plain biscuits, fruit or milk - when over the initial symptoms. Taking this extra carbohydrate will prevent a second drop in your blood glucose level.
  • Make sure you, your friends, family and work colleagues can recognise the symptoms of hypoglycaemia and know how to treat them.
  • Your doctor will need to perform the following tests during treatment with Hequinel.

Eye Tests

  • Your doctor will need to perform some eye tests every few months to check that your eyesight is not changing.
  • In extremely rare cases, Hequinel has been associated with blindness. This can be avoided by having regular eye tests.
  • It is recommended you wear sunglasses when out in the sun.

Blood Tests

  • Your doctor will need to perform occasional blood tests to check for any blood reactions.
  • Your doctor may monitor your blood sugar levels if you have experienced hypoglycaemia while taking Hequinel.

Mental health problems

  • Some people being treated with Hequinel can experience mental health problems such as irrational thoughts, anxiety, hallucinations, feeling confused or feeling depressed, including thoughts of self-harm or suicide, even those who have never had similar problems before. If you or others around you notice any of these side effects (see section Side effects) seek medical advice straight away, and stop your treatment if you have thoughts of self-harm or suicide.

Driving or using machines

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

Hequinel may cause dizziness in some people.

Hequinel may cause problems with the eyesight of some people. Make sure you know how you react to Hequinel before you drive a car, operate machinery, or do anything else that could be dangerous with blurred vision.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep your tablets in the bottle until it is time to take them.
  • If you take the tablets out of the bottle they will not keep well.
  • Keep it in a cool dry place where the temperature stays below 25°C.
  • Heat and dampness can destroy some medicines. Do not leave Hequinel in the car on hot days.

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.

Children are particularly sensitive to the unwanted effects of Hequinel.

When to discard your medicine

If your doctor tells you to stop taking the tablets, ask your pharmacist what to do with any tablets 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. Hequinel helps most people with rheumatoid arthritis, SLE, DLE, treatment of malaria and the control of malaria symptoms, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

Less serious side effects

Less serious side effectsWhat to do
Stomach problems such as:
  • Nausea
  • Vomiting
  • Diarrhoea
  • Abdominal cramps
Other problems such as:
  • Loss of appetite
  • Muscle weakness
  • Dizziness
  • Ringing in the ears
  • Headache
  • Nervousness
  • Skin rash and itching
  • Hair loss

If you already have psoriasis, you are more likely to experience skin reactions than other people when taking Hequinel.

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
  • Visual disturbances
  • Any hearing loss
  • Suicidal behaviour
  • Having thoughts of self-harm or suicide
  • Feeling depressed, feeling nervous or anxious, feeling confused, agitated, difficulty sleeping, delusions, hallucinations, changes in mood, feeling elated or overexcited,
  • Frequent fevers, severe chills, bruising, sore throat or mouth ulcers (these may be signs of blood reactions)
  • Changes in the way your heart beats
  • More severe symptoms of hypoglycaemia, including:
    - disorientation
    - seizures, fits or convulsions
    - loss of consciousness
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.

These are serious side effects. You may need urgent medical attention.

Serious side effects are rare.

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 HEQUINEL contains

Active ingredient
(main ingredient)
Contains 200 mg of hydroxychloroquine sulfate as the active ingredient
Other ingredients
(inactive ingredients)
  • Anhydrous Calcium hydrogen phosphate
  • Pregelatinised maize startch
  • hypromellose
  • magnesium stearate
  • colloidal anhydrous silica
  • polysorbate 80
  • Opadry II White 85F18422.

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

This medicine is gluten-free, lactose free and free of other azo dyes.

What HEQUINEL looks like

White to off-white, capsule-shaped tablets, embossed “HCQS” on one side, plain on the other side. AUST R 223696.

Packaged in bottles of 100 tablets.

Sponsor

Arrow Pharma Pty Ltd
15 – 17 Chapel street
VIC 3121
www.arrowpharma.com.au

This leaflet was prepared in August 2021

Published by MIMS October 2021

BRAND INFORMATION

Brand name

Hequinel

Active ingredient

Hydroxychloroquine sulfate

Schedule

S4

 

1 Name of Medicine

Hydroxychloroquine sulfate.

2 Qualitative and Quantitative Composition

Each tablet contains 200 mg hydroxychloroquine sulfate, which is equivalent to 155 mg base.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White to off-white, capsule-shaped tablets, embossed "HCQS" on one side, plain on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Rheumatoid arthritis; mild systemic and discoid lupus erythematosus; the suppression and treatment of malaria.

4.2 Dose and Method of Administration

Hequinel tablets 200 mg are intended for oral administration.

Rheumatoid arthritis.

Hydroxychloroquine is cumulative in action and will require several weeks to exert its beneficial therapeutic effects, whereas minor side effects may occur relatively early. Several months of therapy may be required before maximum effects can be obtained.

Initial dosage.

In adults, a suitable initial dosage is from 400-600 mg daily, preferably taken at meal times. In a few patients the side effects may require temporary reduction of the initial dosage. Generally, after 5-10 days the dose may be gradually increased to the optimum response level, frequently without return of side effects.

Maintenance dosage.

When a good response is obtained (usually in 4-12 weeks) the dose can be reduced to 200-400 mg daily (but should not exceed 6 mg/kg per day) and can be continued as maintenance treatment. The minimum effective maintenance dose should be employed. The incidence of retinopathy has been reported to be higher when the maintenance dose is exceeded.
If objective improvement (such as reduced joint swelling or increased mobility) does not occur within six months the drug should be discontinued.
If a relapse occurs after medication is withdrawn, therapy may be resumed or continued on an intermittent schedule if there are no ocular contraindications.
Safe use of hydroxychloroquine for the treatment of juvenile rheumatoid arthritis has not been established.

Use in combination therapy.

Hydroxychloroquine may be used safely and effectively in combination with corticosteroids, salicylates, NSAIDs and methotrexate and other second line therapeutic agents. Corticosteroids and salicylates can generally be decreased gradually in dosage or eliminated after hydroxychloroquine has been used for several weeks. When gradual reduction of steroid dosage is suggested, it may be done by reducing every 4-5 days the dose of cortisone by no more than 5-15 mg; of methylprednisolone from 1-2 mg and dexamethasone from 0.25-0.5 mg. Treatment regimens using agents other than corticosteroids and NSAIDs are under development. No definitive dose combinations have been established.

Lupus erythematosus.

In mild systemic and discoid cases, antimalarials are the drugs of choice.
The dose of hydroxychloroquine depends on the severity of the disease and the patient's response to treatment. For adults, an initial dose of 400-800 mg daily is recommended. This level can be maintained for several weeks and then reduced to a maintenance dose of 200-400 mg daily.

Malaria.

Hydroxychloroquine is active against the erythrocytic forms of P. vivax and P. malariae and most strains of P. falciparum (but not the gametocytes of P. falciparum).
Hydroxychloroquine does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exo-erythrocytic forms, nor will it prevent vivax or malariae infection when administered as a prophylactic.
It is effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.

Malaria suppression.

Suppressive therapy should begin two weeks prior to exposure. Failing this, in adults an initial loading dose of 800 mg (620 mg base), or in children 10 mg base per kg, may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.

Adults.

400 mg (310 mg base) on exactly the same day of each week.

Children.

The weekly suppressive dose is 5 mg (base) per kg bodyweight, but should not exceed the adult dose regardless of weight.

Treatment of the acute attack.

Adults.

An initial dose of 800 mg followed by 400 mg 6-8 hours later and then 400 mg on each of two consecutive days (total dose of 2 g or 1.55 g base). A single dose of 800 mg (620 mg base) has also proved effective.

Children.

The dosage is calculated on the basis of bodyweight (total dose of 25 mg base per kg).
First dose: 10 mg base per kg (not exceeding a single dose of 620 mg base).
Second dose: 5 mg base per kg (not exceeding 310 mg base), six hours after first dose.
Third dose: 5 mg base per kg eighteen hours after second dose.
Fourth dose: 5 mg base per kg twenty four hours after third dose.
For radical cure of vivax and malariae malaria, concomitant therapy with an 8-aminoquinoline is necessary.

4.3 Contraindications

Hydroxychloroquine is contraindicated in:
patients with pre-existing maculopathy of the eye;
patients with known hypersensitivity to 4-aminoquinoline compounds;
long-term therapy in children;
children under 6 years of age.

4.4 Special Warnings and Precautions for Use

Hydroxychloroquine is not effective against chloroquine-resistant strains of P. falciparum.
Patients should be warned to keep hydroxychloroquine out of the reach of children, as small children are particularly sensitive to 4-aminoquinolines.
Hydroxychloroquine should be used with caution, or not at all, in patients with severe gastrointestinal, neurological or blood disorders. If such severe disorders occur during therapy, hydroxychloroquine should be stopped. Periodic blood counts are advised.
When used in patients with porphyria or psoriasis, these conditions may be exacerbated. Hydroxychloroquine should not be used in these conditions unless in the judgement of the physician, the benefit to the patient outweighs the possible risk.

Chronic cardiac toxicity.

Cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcome, have been reported in patients treated with hydroxychloroquine. Clinical monitoring for signs and symptoms of cardiomyopathy is advised and hydroxychloroquine should be discontinued if cardiomyopathy develops. Chronic toxicity should be considered when conduction disorders (bundle branch block/ atrio-ventricular heart block) as well as biventricular hypertrophy are diagnosed.

Hypoglycaemia.

Hydroxychloroquine has been shown to cause severe hypoglycaemia including loss of consciousness that could be life threatening in patients treated with and without anti-diabetic medications. Patients treated with hydroxychloroquine should be warned about the risk of hypoglycaemia and the associated clinical signs and symptoms. Patients presenting with clinical symptoms suggestive of hypoglycaemia during treatment with hydroxychloroquine should have their blood glucose level checked and treatment reviewed as necessary.

QT interval prolongation.

Hydroxychloroquine prolongs the QTc interval and should not be used in patients receiving drugs known to prolong the QT interval, e.g. class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, some anti-infectives due to increased risk of ventricular arrhythmia (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.9 Overdose).
Hydroxychloroquine should be used with caution in patients with congenital or documented acquired QT prolongation and/or known risk factors for prolongation of the QT interval such as:
cardiac disease, e.g. heart failure, myocardial infarction;
proarrhythmic conditions, e.g. bradycardia (< 50 bpm);
a history of ventricular dysrhythmias;
uncorrected hypokalaemia and/or hypomagnesaemia.
The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

Ophthalmological.

Irreversible retinal damage has been observed in some patients who had received long-term or high dosage 4-aminoquinolone therapy for discoid and systemic lupus erythematosus or rheumatoid arthritis. Retinopathy has been reported to be dose related. Exceeding the recommended daily dose sharply increases the risk of retinal toxicity.
If there is any indication of abnormality in the visual field or retinal macular areas (such as pigmentary changes, loss of foveal reflex), or any visual symptoms (such as light flashes and streaks) which are not fully explainable by difficulties of accommodation or corneal opacities, hydroxychloroquine should be discontinued immediately and the patient closely observed for possible progression. Retinal changes (and visual disturbances) may progress after cessation of therapy (see Section 4.8 Adverse Effects (Undesirable Effects)).
Concomitant use of hydroxychloroquine with drugs known to induce retinal toxicity, such as tamoxifen, is not recommended.
Before starting treatment with hydroxychloroquine, all patients should have a careful complete examination of both eyes which includes slit lamp microscopy for corneal changes, fundoscopy, visual acuity, central visual field and colour vision. A complete eye examination before treatment will determine the presence of any visual abnormalities, either coincidental or due to the disease and establish a baseline for further assessment of the patient's vision.
Ophthalmological testing should be conducted at 6 monthly intervals in patients receiving hydroxychloroquine at a dose of not more than 6 mg per kg body weight per day.
Ophthalmological testing should be conducted at 3-4 monthly intervals in the following circumstances:
dose exceeds 6 mg/kg ideal (lean) body weight per day. Using absolute body weight, as a guide to dosage, could result in an over dosage in the obese;
significant renal impairment;
significant hepatic impairment;
elderly;
complaints of visual disturbances;
duration of treatment exceeds 8 years.
Corneal changes often subside on reducing the dose or on interrupting therapy for a short period of time, but any suggestion of retinal change or restriction in the visual field is an indication for complete withdrawal of the drug.
The use of sunglasses in patients exposed to strong sunlight is recommended, as this may be an amplifying factor in retinopathy.

Skin reactions.

Pleomorphic skin eruptions (morbilliform, lichenoid, purpuric), itching, dryness and increased pigmentation sometimes appear after a few months of therapy. The rash is usually mild and transient. If a rash appears, hydroxychloroquine should be withdrawn and only started again at a lower dose.
Patients with psoriasis appear to be more susceptible to severe skin reactions than other patients.

Other monitoring on long term treatments.

Patients on long-term therapy should have periodic full blood counts. If evidence of abnormalities such as agranulocytosis, aplastic anaemia, thrombocytopenia or leukopenia becomes apparent, and cannot be attributed to the disease being treated, hydroxychloroquine should be discontinued.
All patients on long-term therapy with this preparation should be questioned and examined periodically, including the testing of knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs discontinue the drug.

Miscellaneous.

Gastrointestinal disturbances such as nausea, anorexia, abdominal cramps or rarely vomiting, occur in some patients. The symptoms usually stop on reducing the dose or temporarily stopping the drug.
Muscle weakness, vertigo, tinnitus, nerve deafness, headache and nervousness have been reported less frequently.
In the treatment of rheumatoid arthritis, if objective improvement (such as reduced joint swelling, increased mobility) does not occur within six months, hydroxychloroquine should be discontinued. Safe use of hydroxychloroquine in the treatment of juvenile rheumatoid arthritis has not been established.
Suicidal behaviour has been reported in very rare cases in patients treated with hydroxychloroquine.
Psychiatric side effects typically occur within the first month after the start of treatment with hydroxychloroquine sulfate and have been reported also in patients with no prior history of psychiatric disorders. Patients should be advised to seek medical advice promptly if they experience psychiatric symptoms during treatment.
Extrapyramidal disorders may occur with hydroxychloroquine.
Also observe caution in patients with gastrointestinal, neurological, or blood disorders, in those with a sensitivity to quinine, and in glucose-6-phosphate dehydrogenase deficiency.

Use in hepatic and renal impairment.

Observed caution in patients with hepatic or renal disease, in whom a reduction in dosage may be necessary, as well as in those taking medicines known to affect these organs.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, Ophthalmological.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacodynamic interactions.

Drugs known to prolong QT interval/ with potential to induce cardiac arrhythmia.

Hydroxychloroquine should not be used in patients receiving drugs known to prolongs the QT interval e.g. Class I A and III antiarrhythmics, tricyclic antidepressants, antipsychotics, some anti-infectives due to increased risk of ventricular arrhythmia (see Section 4.4 Special Warnings and Precautions for Use; Section 4.9 Overdose). Halofantrine should not be administered with hydroxychloroquine.

Antidiabetic drugs.

As hydroxychloroquine may enhance the effects of a hypoglycaemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required.

Antimalarials.

Hydroxychloroquine can lower the convulsive threshold. Co-administration of hydroxychloroquine with other antimalarials known to lower the convulsion threshold (e.g. mefloquine) may increase the risk of convulsions.

Antiepileptic drugs.

The activity of antiepileptic drugs might be impaired if co-administered with hydroxychloroquine.

Others.

There is a theoretical risk of inhibition of intra-cellular α-galactosidase activity when hydroxychloroquine is co-administered with agalsidase.
Concurrent use with drugs with oculotoxic or haemotoxic potential should be avoided if possible.
It has been suggested that 4-aminoquinolines are pharmacologically incompatible with monoamine oxidase inhibitors.
Hydroxychloroquine sulphate may also be subject to several of the known interactions of chloroquine even though specific reports have not appeared. These include: potentiation of its direct blocking action at the neuromuscular junction by aminoglycoside antibiotics; inhibition of its metabolism by cimetidine which may increase plasma concentration of the antimalarial; antagonism of effect of neostigmine and pyridostigmine; reduction of the antibody response to primary immunisation with intradermal human diploid-cell rabies vaccine.

Effects of other medicinal products on hydroxychloroquine.

Antacids.

Concomitant administration with magnesium-containing antacids or kaolin may result in reduced absorption of chloroquine. Per extrapolation, hydroxychloroquine should therefore be administered at least two hours apart from antacids or kaolin.

CYP inhibitors or inducers.

Concomitant use of cimetidine, a moderate CYP2C8 and CYP3A4 inhibitor, resulted in a 2-fold increase of chloroquine exposure. Per extrapolation, due to the similarities in structure and metabolic elimination pathways between hydroxychloroquine and chloroquine, a similar interaction could be observed for hydroxychloroquine. Caution is advised (e.g. monitoring for adverse reactions) when CYP2C8 and CYP3A4 strong or moderate inhibitors (such as gemfibrozil, clopidogrel, ritonavir, itraconazole, clarithromycin, grapefruit juice) are concomitantly administered.
Lack of efficacy of hydroxychloroquine was reported when rifampicin, a CYP2C8 and CYP3A4 strong inducer, was concomitantly administered. Caution is advised (e.g. monitoring for efficacy) when CYP2C8 and CYP3A4 strong inducers (such as rifampicin, St John's Wort, carbamazepine, phenobarbital (phenobarbitone)) are concomitantly administered.

Effects of hydroxychloroquine on other medicinal products.

P-gp substrates.

The inhibitory potential of hydroxychloroquine on P-gp substrates has not been evaluated. In vitro observations show that all other aminoquinolines tested inhibit P-gp. Therefore, there is a potential for increased concentrations of P-gp substrates when hydroxychloroquine is concomitantly administered.
Increased plasma ciclosporin levels have been reported when ciclosporin and hydroxychloroquine are co-administered.
Increased digoxin serum levels were reported when digoxin and hydroxychloroquine were coadministered. Caution is advised (e.g. monitoring for adverse reactions or for plasma concentrations as appropriate) when P-gp substrates with narrow therapeutic index (such as digoxin, ciclosporin, dabigatran) are concomitantly administered.

Praziquantel.

In a single-dose interaction study, chloroquine has been reported to reduce the bioavailability of praziquantel. It is not known if there is a similar effect when hydroxychloroquine and praziquantel are co-administered. Per extrapolation, due to the similarities in structure and pharmacokinetic parameters between hydroxychloroquine and chloroquine, a similar effect may be expected for hydroxychloroquine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no animal data on hydroxychloroquine action on fertility.
Animals studies showed an impairment of male fertility for chloroquine, a parent drug (see Section 5.3 Preclinical Safety Data).
There are no data in humans.
(Category D)
Hydroxychloroquine crosses the placenta. It should be noted that 4-aminoquinolines in therapeutic doses have been associated with central nervous system damage, including ototoxicity (auditory and vestibular toxicity, congenital deafness), retinal haemorrhages and abnormal retinal pigmentation. Literature review of observational data and meta-analyses, on the use of hydroxychloroquine in women with autoimmune disease during pregnancy excluded a large risk of congenital malformations (RR > 3). However, the statistical power to detect modest risks was limited and various limitations of observational data do not allow robust exclusion of causality.
Due to lack of studies, no conclusions can be made from the epidemiologic literature about paternal exposure to hydroxychloroquine affecting fertility or birth outcomes.
Hydroxychloroquine should be avoided in pregnancy except when, in the judgement of the physician, the potential benefits outweigh the potential hazards.
The use of this drug in the treatment of malaria or suppression of malaria in high risk situations may be justified if the treating physician considers the risk to the foetus is outweighed by the benefits to the mother and foetus.
Hydroxychloroquine is excreted in breast milk and it is known that infants are extremely sensitive to the toxic effects of 4-aminoquinones. In one study, the daily HCQ exposures to infant from breast milk were estimated to be less than 2% of the maternal dose (after bodyweight correction).
Although hydroxychloroquine is excreted in breast milk, the amount is insufficient to confer any protection against malaria to the infant. Separate chemoprophylaxis for the infant is required.
There are very limited data on the safety in the breastfed infant during long-term hydroxychloroquine treatment; the prescriber should assess the potential risks and benefits of use during breastfeeding, according to indication and duration of treatment.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned about driving and operating machinery since hydroxychloroquine can impair visual accommodation and cause blurring of vision. If the condition is not self-limiting, the dosage may need to be temporarily reduced.

4.8 Adverse Effects (Undesirable Effects)

Very common ≥ 1/10 (≥ 10%); common ≥ 1/100 and < 1/10 (≥ 1% and < 10%); uncommon ≥ 1/1000 and < 1/100 (≥ 0.1% and < 1.0%); rare ≥ 1/10,000 and < 1/1000 (≥ 0.01% and < 0.1%); very rare < 1/10,000 (< 0.01%); not known, frequency cannot be estimated from available data.

Blood and lymphatic system disorders.

Rare: bone marrow depression, anaemia, aplastic anaemia, leucopenia, thrombocytopenia.
Very rare: agranulocytosis.

Immune system disorders.

Not known: urticaria, angioedema, bronchospasm.

Metabolism and nutrition disorders.

Common: anorexia.
Not known: hypoglycaemia.
Hydroxychloroquine may exacerbate porphyria.

Psychiatric disorders.

Common: affect lability.
Very rare: psychosis, suicidal behavior, nightmares, depression, hallucinations, anxiety, agitation, confusion, delusions, mania and sleep disorders.

Nervous system disorders.

Common: headache.
Uncommon: dizziness, nerve deafness, nervousness.
Rare: convulsions, neuromyopathy.
Very rare: nystagmus, ataxia.
Not known: extrapyramidal disorders such as dystonia, dyskinesia, tremor.

Eye disorders.

Common: blurring of vision.
Uncommon: corneal changes, retinal changes, retinopathy with changes in pigmentation and visual field defects. In its early form, it appears reversible on discontinuation of hydroxychloroquine. If allowed to develop, there may be a risk of progression even after treatment withdrawal.
Patients with retinal changes may be asymptomatic initially, or may even have scotomatous vision with paracentral, pericentral ring types, temporal scotomas and abnormal colour visions.
Corneal changes including oedema and opacities have occurred from three weeks (infrequently) to some years after the beginning of therapy. They are either symptomless or may cause disturbances such as halos, blurring of vision or photophobia. They may be transient or are reversible on stopping treatment. Should these types of corneal changes occur with hydroxychloroquine, it should be either stopped or temporarily withdrawn.
Not known: Cases of maculopathies and macular degeneration have been reported and may be irreversible.
Reversible extra-ocular muscle palsies and temporary blurring of vision due to interference with accommodation have also been noted.
Retinal changes such as abnormal macular pigmentation and depigmentation (sometimes described as a "bull's eye"), pallor of the optic disc, optic atrophy and narrowing of the retinal arterioles have been reported.
Originally, the condition was thought to be progressive and irreversible, but more recent evidence suggests that routine ophthalmological examinations may detect retinal changes, especially pigmentation, at an early and reversible stage when there is no apparent visual disturbance.
Much evidence suggests that there is a threshold of dosage above which retinopathy appears. These results seem to correlate more with daily dosage than with a cumulative dose, although the risk increases with increased duration of treatment.
Before starting treatment with hydroxychloroquine, all patients should have a careful complete examination of both eyes which included slit lamp microscopy for corneal changes, fundoscopy, visual acuity, central visual field and colour vision, repeated at six month intervals during therapy (see Section 4.4 Special Warnings and Precautions for Use, Ophthalmological).
Any adverse changes in the ocular findings or the appearance of scotoma, night blindness or other retinal changes require immediate discontinuation of hydroxychloroquine; these patients should not subsequently receive any pharmacologically similar drugs.

Ear and labyrinth disorders.

Uncommon: vertigo, tinnitus.
Not known: hearing loss.

Cardiac disorders.

Rare: cardiomyopathy which may result in cardiac failure, and in some cases a fatal outcome (see Section 4.4 Special Warnings and Precautions for Use).
Chronic toxicity should be considered when conduction disorders (bundle branch block/ atrio-ventricular heart block) as well as biventricular hypertrophy are diagnosed.
Not known: QT interval prolongation in patients with specific risk factors, which may lead to arrhythmia (torsade de pointes, ventricular tachycardia) (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Gastrointestinal disorders.

Very common: abdominal pain, nausea.
Common: diarrhoea, vomiting.

Hepatobiliary disorders.

Uncommon: abnormal liver function tests.
Very rare: fulminant hepatitis.

Skin and subcutaneous tissue disorders.

Common: skin rashes, alopecia, pruritus.
Uncommon: pigmentary changes, bleaching of hair.
Very rare: bullous eruptions such as acute generalized exanthematous pustulosis (AGEP), exfoliative dermatitis and erythema multiforme, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), toxic epidermal necrolysis, photosensitivity.

Musculoskeletal and connective tissue disorders.

Uncommon: sensory-motor disorders.
Not known: absent or hypoactive deep tendon reflexes, muscle weakness or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups (muscle weakness may be reversible after drug discontinuation, but recovery may take many months). Depression of tendon reflexes and abnormal nerve conduction studies.
Very rare: extraocular muscle palsies.

Miscellaneous.

Rare: exacerbation or precipitation of porphyria and attacks of psoriasis.
Very rare: weight loss, lassitude.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdosage with 4-aminoquinolines is dangerous. Children are particularly sensitive to these compounds and a number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 or 1 gram in one 3 year old child).
The 4-aminoquinolines are very rapidly and completely absorbed after ingestion and toxic symptoms following overdosage may occur within 30 minutes. Toxic symptoms consist of headache, drowsiness, visual disturbances, hypokalaemia, cardiovascular collapse and convulsions.
The ECG may reveal rhythm and conduction disorders including QT prolongation, torsade de pointe, ventricular tachycardia, ventricular fibrillation, width-increased QRS complex, bradyarrhythmias (including bradycardia), nodal rhythm, atrioventricular block, followed by sudden potentially fatal respiratory and cardiac arrest. Immediate medical attention is required as these effects may appear shortly after the overdose.

Treatment.

Treatment is symptomatic and must be prompt. Emesis is not recommended because of the potential for CNS depression, convulsions and cardiovascular instability. Activated charcoal should be administered. The dose of activated charcoal should be at least five times the estimated amount of hydroxychloroquine ingested.
Consideration should be given to using diazepam parentally as there have been reports that it may decrease cardiotoxicity.
Respiratory support and management of shock should be instituted as necessary.
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.

Hydroxychloroquine is an anti-malarial. It also exerts a beneficial effect in mild systemic and discoid lupus erythematosus and rheumatoid arthritis. The precise mechanism of action is not known.

Malaria.

Like chloroquine phosphate, hydroxychloroquine is highly active against the erythrocytic forms of Plasmodium vivax and P. malariae and most strains of P. falciparum (but not the gametocytes of P. falciparum).
Hydroxychloroquine does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exo-erythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria, it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Reproductive toxicity.

Only limited preclinical data are available for hydroxychloroquine, therefore chloroquine data are considered due to the similarity of structure and pharmacological properties between the 2 products.
In animal studies on chloroquine, embryo-foetal developmental toxicity was shown at very high, supratherapeutic doses (ranging from 250 to 1500 mg/kg bodyweight).
A study in male rats showed a decrease in testosterone levels, weight of testes, epididymis, seminal vesicles and prostate after 30 days of oral treatment with chloroquine at 5 mg/day. In another rat study with chloroquine the male fertility rate was decreased after 14 days of intraperitoneal treatment at 10 mg/kg/day.

Genotoxicity.

There are limited data on hydroxychloroquine genotoxicity. Chloroquine is reported in the literature to elicit both gene mutations and chromosomal/DNA breaks in some in vitro systems but not others and in in vivo studies using rodents when dosed via the intraperitoneal route. Chromosomal effects were not observed in vivo when chloroquine was administered orally.

Carcinogenicity.

No carcinogenicity studies are available on hydroxychloroquine. A dietary carcinogenicity study in rats with the parent drug chloroquine was negative. No other carcinogenicity study was conducted in mice or other species. In the absence of sufficient human and animal data an increased risk of cancer in patients receiving long term treatment cannot be ruled out.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hequinel tablets contains the following excipients: anhydrous calcium hydrogen phosphate, pregelatinised maize starch, hypromellose, magnesium stearate, polysorbate 80, colloidal anhydrous silica and Proprietary Ingredient Opadry II White 85F18422.

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. Protect from light.

6.5 Nature and Contents of Container

200 mg: Packaged in HDPE bottles of 100 tablets.

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

Hydroxychloroquine sulfate is a colourless crystalline solid, soluble in water to at least 20%.

Chemical structure.

Chemical name: (RS)-2-N-[4-(7-chloro-4-quinolylamino) pentyl]-N-ethylaminoethanol sulfate.
Molecular formula: C18H26ClN3O.H2SO4.
Molecular weight of 433.95.

CAS number.

Cas No.: 747-36-4.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes