Duplaxil 400 mg film-coated tablets EFG: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Duplaxil 400 mg film-coated tablets EFG

Hydroxychloroquine sulfate

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

What Duplaxil is and what it is used for
What you need to know before taking Duplaxil
How to take Duplaxil
Possible side effects
How to store Duplaxil
Contents of the pack and other information

1. What Duplaxil is and what it is used for

Each film-coated tablet of Duplaxil contains 400 mg of hydroxychloroquine sulfate.

Hydroxychloroquine is an antimalarial drug belonging to the 4-hydroxyquinoline family, which combines rapid blood schizonticidal activity with gametocytocidal activity, and is also classified as a disease-modifying antirheumatic drug.

Duplaxil is indicated in adults for:

The prevention and treatment of uncomplicated malaria caused by chloroquine-sensitive Plasmodium species, as an alternative to chloroquine (when first-line treatments are not suitable or not available).
Symptomatic treatment of rheumatoid arthritis.
Treatment of discoid lupus erythematosus and systemic lupus erythematosus.
Treatment of skin disorders that are sensitive to sunlight (photodermatoses).

Duplaxil is indicated in adolescents (from 12 years of age) and children aged 6 to 11 years (ideal body weight ≥ 31 kg) for:

Treatment of discoid lupus erythematosus.
Treatment of systemic lupus erythematosus.
Prevention and treatment of uncomplicated malaria caused by chloroquine-sensitive Plasmodium species, as an alternative to chloroquine (when first-line treatments are not suitable or not available).
Treatment of juvenile rheumatism in combination with other therapies (juvenile idiopathic arthritis).

Hydroxychloroquine is not effective against chloroquine-resistant P. falciparum strains, and it is not active against the pre-erythrocytic forms of P. vivax and P. ovale. Therefore, it does not prevent infection caused by these organisms when administered prophylactically, nor does it prevent relapse of infection due to these organisms.

2. What you need to know before taking Duplaxil

Do not take Duplaxil:

if you are allergic to hydroxychloroquine or any of the other ingredients of this medicine (listed in section 6);
if you have retinopathy, maculopathy;
if you are allergic to other 4-aminoquinoline compounds (antimalarial agents);

Do not administer hydroxychloroquine to a child under 6 years of age (ideal body weight < 31 kg).

Warnings and precautions

Consult your doctor or pharmacist before starting hydroxychloroquine, if you have:

Liver or kidney disorders, or if you are taking medicines that may affect the liver and/or kidneys (a dose adjustment may be necessary);
Gastrointestinal disorders;
Disorders of the nervous system;
Blood disorders;
Metabolic disorders;
Cardiac conduction disorders;
Hypersensitivity to quinine;
Deficiency of an enzyme called glucose-6-phosphate dehydrogenase (the enzyme found in red blood cells);
Porphyria (an inherited metabolic disease);
Inactive chronic hepatitis B virus infection;
Epilepsy;
Concomitant use of potentially nephrotoxic or hepatotoxic drugs;
Pre-existing psoriasis;
Pregnancy and breastfeeding period.

Hydroxychloroquine may cause a decrease in blood glucose levels. Ask your doctor to inform you about the signs and symptoms of low blood glucose. It may be necessary to monitor your blood glucose levels.

When using hydroxychloroquine, you should protect yourself from direct sunlight.

You should not take medicines containing gold salts or phenylbutazone (agents for rheumatoid arthritis and gout) at the same time.

Before starting long-term treatment with hydroxychloroquine, an eye examination is recommended (to assess visual acuity, central visual field, color vision, and fundus) and regular vision checks should be maintained at least every 3 months throughout treatment. These checks should be individualized in the following cases:

for patients whose daily dose exceeds 6.5 mg/kg of ideal body weight (lean body mass, see section 3 "How to take Duplaxil");
in patients with renal impairment;
in patients with cumulative doses exceeding 200 g;
in elderly patients;
in patients with visual disturbances.

If visual problems occur (e.g., reduced visual acuity or loss of ability to see red colors), you must stop your treatment with hydroxychloroquine and consult your doctor for a new eye examination. The risk of retinal disease mainly depends on the dose. At daily doses up to 6.5 mg/kg body weight, the risk is low. If this dose is exceeded, the risk of retinal disease increases significantly.

During long-term treatment, regular blood tests, as well as muscle and tendon function tests, should also be performed. If abnormalities occur (e.g., blood changes or muscle weakness), your doctor will decide whether to discontinue your treatment with hydroxychloroquine.

Cases of cardiomyopathy, some of them fatal, have been reported in patients treated with hydroxychloroquine. Your doctor will monitor you for signs and symptoms of cardiomyopathy. Treatment with hydroxychloroquine should be discontinued if cardiomyopathy develops.

If you are diagnosed with conduction disorders (bundle branch block, AV block) and biventricular hypertrophy, chronic toxicity should be suspected.

Hydroxychloroquine may cause cardiac rhythm disorders in some patients: caution should be exercised when using hydroxychloroquine if you were born with or have a family history of prolonged QT interval, if you have developed QT interval prolongation (by ECG, an electrical recording of the heart), if you have heart conditions or a history of heart attack (myocardial infarction), or if you have an electrolyte imbalance in the blood (especially low levels of potassium and magnesium, see section “Other medicines and Duplaxil”). If you experience palpitations or irregular heartbeats during treatment, you must inform your doctor immediately. The risk of heart problems may increase with higher doses. Therefore, the recommended dose should be followed.

The duration of treatment should not exceed 3 years.

Patients with seizures should be regularly monitored by their doctor.

Hydroxychloroquine has a cumulative effect and may take several weeks for therapeutic effects to occur in the treatment of rheumatoid arthritis or systemic lupus erythematosus. Therefore, side effects may appear rapidly. The effectiveness of treatment will be evaluated after at least 4 to 12 weeks.

If there is no improvement after 6 months, treatment should be discontinued.

In the treatment of malaria, it should be noted that hydroxychloroquine should be used in combination with other medicines in countries with known chloroquine resistance.

Movement disorders (extrapyramidal disorders) may occur during treatment with hydroxychloroquine.

Some people treated with hydroxychloroquine may experience mental health problems such as irrational thoughts, anxiety, hallucinations, confusion, or depression, including thoughts of self-harm or suicide, even those who have never previously had similar problems. If you or people around you notice any of these adverse effects (see section 4), consult a doctor immediately.

Severe skin rashes have been reported with the use of hydroxychloroquine (see section 4 possible adverse effects). Often, the rash may consist of ulcers in the mouth, throat, nose, genitals, and conjunctivitis (red and inflamed eyes). These severe skin rashes are often preceded by flu-like symptoms such as fever, headache, and body aches. The skin rash may progress to widespread blisters and skin peeling. If you experience these skin symptoms, stop taking hydroxychloroquine and contact your doctor immediately.

Renal and hepatic impairment

Patients with hepatic or renal impairment, as well as those taking medicines that affect these organs, may require a reduced dose of the drug.

Paediatric population

Children are highly sensitive to the group of medicines to which hydroxychloroquine belongs. Therefore, you must be very careful and keep the product out of sight and reach of children to prevent poisoning.

Elderly patients

There is no specific information on the comparison of hydroxychloroquine use between elderly patients and other age groups.

Other medicines and Duplaxil

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Some medicines may interact with hydroxychloroquine. It is important that you inform your doctor if you are taking the following medicines:

Medicines called disease-modifying antirheumatic drugs (DMARDs) (medicines for the treatment of rheumatoid arthritis). When used together with hydroxychloroquine, these medicines may increase side effects and should therefore be avoided with hydroxychloroquine.
Digoxin (a medicine for impaired heart function). If used together with hydroxychloroquine, it may increase the effect of digoxin. Your doctor must carefully monitor your treatment.
Antacids (medicines used to treat excess stomach acid) may reduce the absorption of hydroxychloroquine. There should always be at least a 4-hour interval between taking hydroxychloroquine and antacids.
Cimetidine (a gastric acid inhibitor) may delay the excretion of hydroxychloroquine.
Neostigmine or pyridostigmine (medicines used to treat unwanted muscle relaxation). If used together with hydroxychloroquine, the effect of neostigmine or pyridostigmine may be reduced.
Aminoglycosides (medicines for the treatment of infections). If used together with hydroxychloroquine, they may increase neuromuscular blockade.
Pyrimethamine/sulfadoxine (antimalarial medicines): The combination of hydroxychloroquine with pyrimethamine/sulfadoxine significantly increases the risk of skin reactions.
Insulin: If you have diabetes, hydroxychloroquine may increase the effect of medicines used for diabetes (e.g., insulin), and it may be necessary to reduce the dose of insulin or other antidiabetic medicines.
Inform your doctor if you are taking any medicine that may affect heart rhythm. This includes medicines used for abnormal heart rhythm (antiarrhythmics), for depression (tricyclic antidepressants), for psychiatric disorders (antipsychotics), for bacterial infections or malaria (e.g., halofantrine).
Cyclosporine (a medicine used after organ transplantation). If used together with hydroxychloroquine, blood levels of cyclosporine may increase.
Mefloquine, bupropion (medicines that may reduce the seizure threshold): hydroxychloroquine may lower the seizure threshold. If used together with hydroxychloroquine, the risk of seizures may increase.
Anticonvulsants: The effectiveness of certain anticonvulsants may be reduced by concomitant administration of hydroxychloroquine.
Agalsidase (α-galactosidase treatment). If used together with hydroxychloroquine, the effect of agalsidase may be reduced.
Praziquantel (an antihelminthic medicine). If used together with hydroxychloroquine, blood levels of praziquantel may be reduced.
Phenylbutazone (an analgesic). If used together with hydroxychloroquine, the likelihood of exfoliative dermatitis (inflammatory skin disease with skin scaling) increases.
Hepatotoxic substances (avoid drinking large amounts of alcohol) and MAO inhibitors (medicines used for depression) should not be used with hydroxychloroquine.
Tamoxifen (a medicine used to treat breast cancer): if used together with hydroxychloroquine, retinal toxicity may occur.
Probenecid (a medicine that prevents increased uric acid levels) and indomethacin (an anti-inflammatory inhibitor). If used together with hydroxychloroquine, the risk of sensitization and retinopathy may increase.
Corticosteroid derivatives (medicines to treat allergies and inflammation). If used together with hydroxychloroquine, myopathy (muscle disease) or cardiomyopathy (heart muscle disease) may increase.
Folic acid antagonists, such as methotrexate (used to treat cancer). If used together with hydroxychloroquine, the effect of folic acid antagonists will be increased.
Ampicillin (an antibiotic for infections). If used together with hydroxychloroquine, the absorption of ampicillin may be reduced.
Chloroquine phosphate (an antimalarial medicine). When used together with hydroxychloroquine, interactions have been observed, as this substance has a similar structure to hydroxychloroquine. Therefore, these side effects cannot be excluded.
Metronidazole (a medicine for the treatment of infections). After ingestion of metronidazole, an acute dystonic reaction (change in muscle tone and movement disturbance) has been observed.
Penicillamine (an antirheumatic medicine) may increase the risk of haematological and/or renal side effects, as well as skin reactions.
Vaccination. Antibody production may be reduced by rabies vaccination with HDC vaccines (intramuscular vaccination is recommended for rabies prophylaxis). No effect has been monitored on routine vaccinations (tetanus, diphtheria, measles, poliomyelitis, typhus, and tuberculosis).

Hydroxychloroquine inhibits the CYP2D6 enzyme. Therefore, medicines that inhibit CYP2D6 should not be administered concomitantly with hydroxychloroquine.

Duplaxil with alcohol

Avoid consuming large amounts of alcohol.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will advise you whether this medicine is suitable for you.

Pregnancy

Do not use hydroxychloroquine during pregnancy at high daily doses unless your doctor indicates it is necessary because the risk of stopping treatment is greater than the potential risk to the fetus. Hydroxychloroquine may be associated with a small increased risk of major malformations.

Breastfeeding

Hydroxychloroquine passes into breast milk. There is insufficient information regarding the effects of hydroxychloroquine on newborns/infants. Depending on the disease and duration of treatment, your doctor will decide whether you can use this medicine during breastfeeding. If you take this medicine once a week, as in malaria prevention, you do not need to interrupt breastfeeding.

However, this amount is insufficient to prevent malaria in the infant.

Rheumatoid arthritis, systemic lupus erythematosus:

Due to the long half-life and high daily dose of hydroxychloroquine, accumulation should be expected.

Fertility

There are no data on hydroxychloroquine and human fertility. In rat studies, chloroquine, a substance related to hydroxychloroquine, reduced testosterone secretion, testicular and epididymal weight, and caused abnormal sperm.

Driving and using machines

Do not drive or operate tools or machinery until you know how this medicine affects you. Adverse effects such as dizziness and visual disturbances may occur.

In some people, hydroxychloroquine may cause adverse effects that affect their ability to drive or use machines. Caution is advised as hydroxychloroquine may reduce vision and cause blurred vision. These adverse effects may occur especially at the beginning of treatment.

The ability to drive or use machines may be impaired if hydroxychloroquine is taken together with alcohol or sedatives.

3. How to take Duplaxil

Follow exactly the dosing instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

For oral use only. The tablets should be taken with food or a glass of milk. The tablet may be divided into equal doses.

The dose should be based on body weight. In overweight individuals, the dose must not be based on actual body weight, but on ideal body weight. If the dose is based on the patient's actual weight, it may lead to overdose in overweight individuals.

Rheumatoid arthritis

Adults:

Initially 400–600 mg daily. Maintenance dose: 200–400 mg daily.

Juvenile idiopathic arthritis

Paediatric population:

The lowest effective dose should be used, and doses must not exceed 6.5 mg/kg/day, based on ideal body weight or 400 mg per day (whichever is lower).

Systemic and discoid lupus erythematosus

Adults and adolescents:

Initially 400–600 mg daily. Maintenance dose: 200–400 mg daily.

Maintenance dose:

Body weight Hydroxychloroquine mg/day

31–49 kg 200 mg

50–64 kg 200 mg one day – 400 mg the next day – then 200 mg the following day, and so on

≥ 65 kg 400 mg

Paediatric population:

The lowest effective dose should be used, and doses must not exceed 6.5 mg/kg/day, based on ideal body weight.

Photodermatoses

Adults:

400 mg daily as a single dose.

Treatment should only be administered during periods of maximum light exposure.

Malaria prophylaxis

The medicine should be taken on the same day each week.

In areas endemic for Plasmodium ovale and/or Plasmodium vivax, concomitant prophylaxis with primaquine phosphate during the last two weeks or immediately after completion of hydroxychloroquine prophylaxis may be advisable.

Adults:

400 mg (1 tablet) weekly.

Prophylaxis should begin one week before arrival in the endemic area and continue for at least 4 weeks after leaving the malaria zone.

Paediatric population:

Prophylaxis should begin two weeks before arrival and continue for at least 4 weeks after leaving the malaria zone. Prolonged use as malaria prophylaxis in children should be avoided.

The weekly prophylactic dose is 6.5 mg per kg of body weight, but must not exceed the maximum adult dose regardless of body weight.

Treatment of uncomplicated malaria

In cases of malaria caused by Plasmodium ovale and/or Plasmodium vivax, primaquine phosphate may be added for complete radical treatment.

Adults:

Initially 800 mg (2 tablets), followed 6 hours later by 400 mg (1 tablet), then 400 mg (1 tablet) daily for 2 or 3 days in individuals weighing more than 60 kg.

Paediatric population

Adolescents (from 12 years) and children ≥ 6 years (≥ 31 kg):

A maximum treatment dose of 30 mg/kg based on ideal body weight should be administered over 2 days according to the following regimen:

Initial dose: 13 mg/kg (not exceeding 800 mg)

Second dose: 6.5 mg/kg (not exceeding 400 mg), 6 hours later

Third dose: 6.5 mg/kg (not exceeding 400 mg), 24 hours after the first dose

Fourth dose: 6.5 mg/kg (not exceeding 400 mg), 48 hours after the first dose

Special populations

Patients with reduced renal and hepatic function

Dosage adjustment may be necessary during treatment in patients with renal or hepatic impairment.

Paediatric population

The lowest effective dose should be used, and the maximum adult dose must not be exceeded regardless of body weight. Hydroxychloroquine is contraindicated in children < 6 years (ideal body weight < 31 kg) (see section 2).

If you take more Duplaxil than you should:

If you take more hydroxychloroquine than you should, inform a doctor or go to the hospital emergency department immediately.

Overdose with 4-aminoquinolines is particularly dangerous in infants, as only 1–2 g have been fatal.

Symptoms of overdose may include headache, visual disturbances, cardiovascular collapse, seizures, and disturbances in rhythm and conduction, followed by sudden and early cardiorespiratory arrest. Since these effects may occur after ingestion of a massive dose, treatment must be immediate.

If you forget to take Duplaxil

Do not take a double dose to make up for forgotten doses.

If you stop taking Duplaxil

Continue taking hydroxychloroquine until your doctor tells you to stop. Do not stop taking hydroxychloroquine even if you feel better. If you do, your condition may worsen.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Gastrointestinal disorders are the most common side effects, observed in 10–20% of patients. Side effects may resolve spontaneously or with dose reduction, and can generally be prevented with the recommended monitoring.

Side effects are usually reversible, but irreversible side effects have been observed (e.g., deafness, visual field defects).

Patients with psoriasis appear to have a higher risk of severe skin reactions.

Stop taking Duplaxil and see a doctor immediately if you notice any of the following serious adverse effects; you may need urgent medical treatment:

Severe skin reactions (see section 2, Warnings and precautions), such as:
rash with fever and flu-like symptoms and swollen lymph nodes. This could be a condition called drug reaction with eosinophilia and systemic symptoms (DRESS).
blisters, widespread scaly skin, pus-filled spots accompanied by fever. This could be a condition called acute generalized exanthematous pustulosis (AGEP).
blisters or peeling of the skin around the lips, eyes, mouth, nose, and genitals, flu-like symptoms, and fever. This could be a condition called Stevens-Johnson syndrome (SJS).
multiple skin lesions, itchy skin, joint pain, fever, and general malaise. This could be a condition called toxic epidermal necrolysis (TEN).
skin reaction, including painful, raised, plum-colored ulcers, especially on the arms, hands, fingers, face, and neck, which may also be accompanied by fever. This could be a condition called Sweet's syndrome.
Liver problems. Symptoms may include general malaise, with or without jaundice (yellowing of the skin and eyes), dark urine, nausea, vomiting, and/or abdominal pain. Rare cases of liver failure (including fatal cases) have been reported.

Very common adverse effects (may affect more than 1 in 10 people):

Nausea
Abdominal pain

Common adverse effects (may affect up to 1 in 10 people):

Loss of appetite
Emotional instability, e.g., irritability, nervousness, and restlessness
Headache
Visual disturbances such as halos, blurred vision, light sensitivity, visual acuity problems, and double vision
Diarrhea with weight loss
Flatulence
Vomiting
Rash
Pruritus (reported in approximately 40% of patients with systemic lupus erythematosus)
Sensory-motor function disorders

Uncommon adverse effects (may affect up to 1 in 100 people):

Nervousness, insomnia or somnolence, confusion, or paresthesia
Dizziness
Changes in the retina causing decreased vision, visual field changes, irregular pigmentation, and retinal detachment
Tinnitus
Abnormal liver function tests
Activation or increased liver function
Alopecia
Pigmentation changes in skin and mucous membranes
Hair discoloration and hair loss

Rare adverse effects (may affect up to 1 in 1,000 people):

Inhibition of blood vessel formation (in the bone marrow)
Blood disorders such as reduced number of white blood cells (leukopenia and agranulocytosis), reduced platelet count (thrombocytopenia), and anemia (anemia and aplastic anemia)
Heart diseases (cardiomyopathy)
Inflammation of the skin and/or mucosa
Vesicular rash
Urticaria

Very rare adverse effects (may affect up to 1 in 10,000 people):

Reversible phospholipidosis (increased accumulation of intracellular phospholipids)
Liver failure

Adverse effects with unknown frequency (cannot be estimated from available data):

Bronchospasm leading to shortness of breath
Metabolic disorder (porphyria)
Reduction in blood sugar levels
Depression or thoughts of self-harm or suicide, hallucinations, nervousness or anxiety, confusion, agitation, difficulty sleeping, euphoria, or overexcitement
Seizures, epileptic attacks, extrapyramidal disorders such as altered muscle tone, involuntary movements, inability to sit still due to tremor
Corneal opacity, corneal edema, poor visual fields, blurred vision, light sensitivity
Maculopathy and macular degeneration
Hearing loss
Hepatic effects and liver failure
Psoriasis rash
Reduction in nerve or muscle function (myopathy or neuromyopathy), which may resolve when treatment is discontinued
Diminished tendon reflexes
Nerve conduction abnormalities
Changes in heart rhythm (your doctor may monitor the electrical activity of your heart using an electrocardiogram)
Photosensitivity reaction
Skin peeling (exfoliative dermatitis)
Erythema multiforme (fever, rash on face, arms, and legs)

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Duplaxil

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused containers and medicines at the SIGRE Point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Duplaxil

The active substance is hydroxychloroquine sulfate. Each film-coated tablet contains 400 mg of hydroxychloroquine sulfate (equivalent to 310 mg of hydroxychloroquine base).

The other excipients are:

Excipients, core:

Calcium hydrogen phosphate (E 341)

Corn starch

Povidone (E 1201)

Magnesium stearate (E 572)

Excipients, coating (Opadry 85F18422 White):

Polyvinyl alcohol (E 1203)

Titanium dioxide (E 171)

Macrogol (E 1521)

Talc (E 553b)

Appearance of the product and contents of the container

Duplaxil 400 mg film-coated tablets are white, oblong-shaped, and have a score line.

Length: approximately 14 mm
Width: approximately 7 mm
Height: approximately 6 mm

Duplaxil 400 mg film-coated tablets are supplied in PVC-aluminum blisters within printed cardboard boxes.

Pack sizes: 10, 30, 60, 100 tablets. Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Laboratorios Gebro Pharma, S.A.
Avenida Tibidabo, 29
08022 Barcelona, Spain

Manufacturer:

Recipharm Parets, S.L.U.
C/ Ramón y Cajal, 2
08150 Parets del Vallès (Barcelona), Spain

Date of the most recent review of this leaflet: May 2023

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)