Novidin: detailed information

Patient Information Leaflet

Novidin, 400 mg, film-coated tablets
Hydroxychloroquini sulfas
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Novidin is and what it is used for

Novidin contains 400 mg of hydroxychloroquine sulfate.
Hydroxychloroquine is an antimalarial agent belonging to the group of 4-hydroxyquinolines (exhibiting rapid blood schizontocidal and gametocytocidal activity), also classified as a disease-modifying antirheumatic drug with delayed action.
Novidin is indicated for use in adults for:

prevention and treatment of uncomplicated malaria caused by chloroquine-sensitive Plasmodium species, as an alternative to chloroquine (when first-line treatment is inappropriate or unavailable),
symptomatic treatment of rheumatoid arthritis,
treatment of discoid lupus erythematosus and systemic lupus erythematosus,
treatment of skin disorders caused by photosensitivity (photodermatoses).

Novidin is indicated for use in adolescents (aged 12 years and older) 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 treatment is inappropriate or unavailable),
treatment of juvenile idiopathic arthritis in combination with other therapies.

Hydroxychloroquine is not effective against chloroquine-resistant P. falciparum strains and does not exhibit activity against exoerythrocytic forms (hypnozoites) of P. vivax and P. ovale. Therefore, it does not prevent infection caused by these organisms when used prophylactically, nor does it prevent relapses of infection caused by them.

2. What you need to know before you take Novidin

Do not take Novidin:

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

Do not administer Novidin to children under 6 years of age (ideal body weight < 31 kg).

Warnings and precautions

Before taking Novidin, talk to your doctor or pharmacist if:

you have liver or kidney disorders, or if you are taking medicines that may affect the liver and/or kidneys (dose adjustment may be necessary),
you have gastrointestinal disorders,
you have neurological disorders,
you have blood disorders,
you have metabolic disorders,
you have cardiac conduction disorders,
you are hypersensitive to quinine,
you have glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency (an enzyme present in red blood cells),
you have porphyria (a hereditary metabolic disorder),
you have inactive chronic infection with concomitant viral hepatitis B,
you have epilepsy,
you are taking potentially nephrotoxic or hepatotoxic medicines,
you have previously diagnosed psoriasis,
you are pregnant or breastfeeding.

Hydroxychloroquine may cause low blood glucose levels. Ask your doctor to inform you about symptoms of hypoglycemia. Blood glucose levels may need to be monitored.
While taking Novidin, protect yourself from direct exposure to sunlight.
Do not take medicines containing gold salts or phenylbutazone (medicines used in rheumatoid arthritis and gout) at the same time.
Before starting long-term treatment with Novidin, an eye examination is recommended (to assess visual acuity, colour vision, central visual field and fundus) and regular ophthalmological monitoring should be performed at least every 3 months throughout treatment. These follow-up examinations should be appropriately adjusted for patients in the following situations:

patients whose daily dose exceeds 6.5 mg/kg of ideal body weight (lean body mass, see section 3 "How to take Novidin");
patients with renal impairment;
patients whose cumulative dose exceeds 200 g;
elderly patients;
patients with decreased visual acuity.

Treatment with Novidin should be discontinued if any visual disturbances occur (e.g. decreased visual acuity or loss of ability to see red colour), and the patient should consult a doctor for a repeat eye examination. The risk of retinal disease is primarily dose-dependent. With daily doses below 6.5 mg/kg body weight, the risk is low. If this dose is exceeded, the risk of retinal disease significantly increases.
During long-term treatment, regular blood tests and muscle and tendon function assessments should also be performed. If abnormalities occur (e.g. blood changes or muscle weakness), your doctor will decide whether to discontinue Novidin.
Cases of cardiomyopathy, some fatal, have been reported in patients treated with hydroxychloroquine. Your doctor will monitor for symptoms and signs of cardiomyopathy. Treatment with Novidin should be discontinued if cardiomyopathy occurs.
In patients treated with hydroxychloroquine who have conduction disorders (bundle branch block, atrioventricular block) and biventricular hypertrophy, chronic toxicity should be suspected.
Novidin may cause cardiac arrhythmias in some patients. Exercise caution when taking Novidin if you have congenital QT prolongation (visible on ECG, which is an electrical recording of heart activity) or a family history of QT prolongation, if you have acquired QT prolongation, if you have heart disease or a history of myocardial infarction, or if you have electrolyte imbalances in the blood (especially low potassium or magnesium levels, see section "Novidin with other medicines"). If palpitations or irregular heartbeat occur during treatment, inform your doctor immediately. Follow the recommended dosage, as increasing the dose may increase the risk of cardiac disorders.
The duration of therapy should not exceed 3 years.
Patients with seizure disorders should be regularly monitored by a doctor.
Hydroxychloroquine has a cumulative effect; therefore, it may take several weeks before therapeutic effects appear in the treatment of rheumatoid arthritis or systemic lupus erythematosus. Consequently, adverse effects may occur very quickly. Treatment efficacy can be assessed after at least 4 to 12 weeks.
If no improvement is observed after 6 months, treatment should be discontinued.
When treating malaria, consider that in countries with known chloroquine resistance, hydroxychloroquine should be used in combination with other antimalarial drugs.
Movement disorders (extrapyramidal symptoms) may occur during treatment with Novidin.
Some patients treated with Novidin may experience psychiatric disorders such as irrational thoughts, anxiety, hallucinations, feelings of disorientation or depression, including suicidal thoughts or self-harming behaviour, even in individuals who previously had no such disorders. If you or someone close to you notices such adverse effects (see section 4), seek medical help immediately.
Serious skin rashes have been reported with the use of hydroxychloroquine (see section 4 "Possible side effects"). Often, the rash may involve ulceration of the oral cavity, throat, nose, genital organs and conjunctivitis (redness and swelling of the eyes). Such serious skin rashes are often preceded by flu-like symptoms such as fever, headache and body aches. The rash may progress to extensive blistering and skin peeling. If such skin symptoms occur, discontinue hydroxychloroquine and contact your doctor immediately.

Renal and hepatic impairment
Patients with renal or hepatic impairment, or those taking medicines affecting these organs, may require dose reduction.

Children
Children are highly sensitive to the class of medicines to which Novidin belongs. Therefore, extreme caution should be exercised, and this medicine should be stored out of sight and reach of children to prevent poisoning.

Elderly patients
There are no data available comparing the use of hydroxychloroquine in elderly patients with other age groups.

Novidin with other medicines
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Some medicines may interact with hydroxychloroquine. It is important to inform your doctor if you are taking the following medicines:

So-called basic therapeutics (used in the treatment of rheumatoid arthritis). These medicines, when used concomitantly with Novidin, may increase the risk of adverse effects; therefore, their concomitant use with hydroxychloroquine should be avoided.
Digoxin (a medicine used in heart failure). Concomitant use with Novidin may increase digoxin effects. Your doctor should monitor treatment carefully.
Antacids (medicines used to treat excessive stomach acid secretion) may reduce the absorption of Novidin. A minimum interval of 4 hours should always be maintained between taking Novidin and antacids.
Cimetidine (a gastric acid secretion inhibitor) may delay the elimination of Novidin.
Neostigmine or pyridostigmine (medicines used to treat muscle weakness). Concomitant use with Novidin may reduce the effect of neostigmine or pyridostigmine.
Aminoglycosides (medicines used to treat infections). Concomitant use with Novidin may enhance neuromuscular blockade.
Pyrimethamine/sulfadoxine (antimalarial medicines): concomitant use of Novidin with pyrimethamine/sulfadoxine significantly increases the risk of skin reactions.
Insulin: Novidin may enhance the effect of medicines used to treat diabetes (e.g. insulin), and a reduction in insulin or other antidiabetic medicine dosage may be necessary.
Inform your doctor if you are taking any medicines affecting heart rhythm. These include medicines used for cardiac arrhythmias (antiarrhythmics), depression (tricyclic antidepressants), psychiatric disorders (antipsychotics), bacterial infections or malaria (e.g. halofantrine).
Cyclosporine (a medicine used after organ transplantation). Concomitant use with Novidin may increase cyclosporine blood levels.
Mefloquine, bupropion (medicines that lower the seizure threshold): hydroxychloroquine may lower the seizure threshold. Concomitant use with Novidin may increase the risk of seizures.
Antiepileptic medicines: the effectiveness of some antiepileptic medicines may be reduced when used concomitantly with Novidin.
Agalsidase (used in the treatment of α-galactosidase deficiency). Concomitant use with Novidin may reduce the effect of agalsidase.
Praziquantel (an antiparasitic medicine). Concomitant use with Novidin may lead to decreased praziquantel blood levels.
Phenylbutazone (an analgesic medicine). Concomitant use with Novidin increases the risk of exfoliative dermatitis (inflammatory skin disease with skin peeling).
Hepatotoxic substances (avoid excessive alcohol consumption) and MAO inhibitors (medicines used to treat depression) should not be used with Novidin.
Tamoxifen (a medicine used in breast cancer treatment). It is known that concomitant use with Novidin causes toxic effects on the retina.
Probenecid (a medicine preventing increased uric acid levels) and indomethacin (an anti-inflammatory agent). Concomitant use with Novidin may increase the risk of hypersensitivity and retinopathy.
Corticosteroid derivatives (medicines used to treat allergies and inflammatory conditions). Concomitant use with Novidin may exacerbate myopathy (muscle disease) or cardiomyopathy (heart muscle disease).
Folic acid antagonists, such as methotrexate (used in cancer treatment). Concomitant use with Novidin may enhance the effect of folic acid antagonists.
Ampicillin (an antibiotic used to treat infections). Concomitant use with Novidin may reduce ampicillin absorption.
Chloroquine phosphate (an antimalarial medicine). Concomitant use with Novidin may lead to interactions, as this substance has a structure similar to hydroxychloroquine. Therefore, the following adverse effects cannot be excluded.
Metronidazole (a medicine used to treat infections). Acute dystonic reactions (muscle tone changes and altered movement) have been observed after metronidazole administration.
Penicillamine (an antirheumatic medicine) may increase the risk of hematological and/or renal adverse effects and skin reactions.
Vaccinations: antibody response to the HDC rabies vaccine may be reduced (intramuscular vaccination is recommended for rabies prophylaxis). The effect on routine vaccinations (tetanus, diphtheria, measles, polio, typhoid and tuberculosis) has not been monitored.
Hydroxychloroquine inhibits the CYP2D6 enzyme. Therefore, CYP2D6 inhibitors should not be taken concomitantly with Novidin.

Novidin and alcohol
Avoid drinking large amounts of alcohol.

Pregnancy, breastfeeding and fertility
If you are pregnant, breastfeeding, think you may be pregnant or are planning to have a baby, consult your doctor or pharmacist before taking this medicine. Your doctor will discuss whether Novidin is suitable for you.

Pregnancy
Novidin should not be used in high daily doses during pregnancy unless your doctor determines it is necessary because the risk of discontinuing treatment is greater than the risk posed by the medicine to the fetus. A small increased risk of serious congenital malformations may be associated with Novidin.

Breastfeeding
Hydroxychloroquine passes into breast milk. There is insufficient information on the effects of hydroxychloroquine in newborns and infants. Depending on the patient's condition and duration of treatment, your doctor will decide whether this medicine can be used during breastfeeding.
If you take this medicine once a week, e.g. for malaria prophylaxis, breastfeeding does not need to be interrupted. However, this dose is not sufficient to prevent malaria in the infant.

Rheumatoid arthritis, lupus erythematosus:
Due to the long half-life and high daily dose of hydroxychloroquine, a cumulative effect should be expected.

Fertility
There are no data on the effect of hydroxychloroquine on human fertility. In rat studies, chloroquine, the parent compound of hydroxychloroquine, reduced testosterone secretion, testicular and epididymal weight, and caused formation of abnormal sperm.

Driving and using machines
Do not drive, use tools or operate machinery until you know how this medicine affects you. Side effects such as dizziness and visual disturbances may occur.
In some people, Novidin may cause side effects affecting the ability to drive and use machinery. Caution is advised, as hydroxychloroquine may cause reduced vision and blurred vision. These side effects may occur especially at the beginning of treatment.
The use of hydroxychloroquine together with alcohol or sedative medicines may affect the ability to drive and use machinery.

3. How to take Novidin

This medicine should always be taken as directed by a doctor or pharmacist. If in
doubt, consult a doctor or pharmacist.
For oral use only. Take the tablet with food or a glass of milk.
The tablet may be divided into equal doses.
The dose should be adjusted according to body weight. In overweight individuals, the dose should be
based not on actual body weight, but on ideal body weight. If dosing is based on the patient's actual
body weight, this may lead to overdosing in overweight individuals.

Rheumatoid arthritis
Adults:
Initial dose: 400 to 600 mg daily. Maintenance dose: 200 to 400 mg daily.

Juvenile idiopathic arthritis
Children and adolescents:
The minimum effective dose should be used, which must not exceed 6.5 mg/kg body weight
daily based on ideal body weight or 400 mg daily (whichever of these values is lower).

Treatment of systemic and discoid lupus erythematosus
Adults and adolescents:
Initial dose: 400 to 600 mg daily. Maintenance dose: 200 to 400 mg daily.

Maintenance dose:
Body weight mg hydroxychloroquine daily
31–49 kg 200 mg
50–64 kg 200 mg one day, 400 mg the next day, then 200 mg again the following day, etc.
≥ 65 kg 400 mg

Children and adolescents:
The minimum effective dose should be used, which must not exceed 6.5 mg/kg body weight
daily 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 during weekly therapy.
In areas endemic for Plasmodium ovale and (or) Plasmodium vivax, concomitant prophylaxis with
primaquine phosphate during the last two weeks of therapy or immediately after completion of
hydroxychloroquine prophylaxis is recommended (see section 4.4).

Adults:
400 mg (1 tablet) once weekly.
Prophylaxis should begin one week before entering a malaria-endemic area and continue for at least
four weeks after leaving the area.

Children and adolescents:
Prophylaxis should begin two weeks before entering a malaria-endemic area and continue for at least
four weeks after leaving the area. Long-term use for malaria prophylaxis in children should be avoided.
The weekly prophylactic dose is 6.5 mg per kg body weight, but must not exceed the maximum adult
dose regardless of body weight.

Treatment of uncomplicated malaria
In documented infections with Plasmodium ovale and (or) Plasmodium vivax, treatment should also
include primaquine phosphate for complete radical cure (see section 4.4).

Adults:
Initial dose: 800 mg (2 tablets), then 400 mg (1 tablet) after 6 hours, followed by 400 mg (1 tablet) daily
for the next 2 or 3 days, depending on body weight (3 days for individuals weighing over 60 kg).

Children and adolescents
Adolescents (aged 12 years and older) and children aged ≥ 6 years (≥ 31 kg):
Over 2 days of treatment, administer the maximum therapeutic dose of 30 mg/kg body weight
based on ideal body weight, following these instructions:
Initial dose: 13 mg/kg body weight (not exceeding 800 mg).
Second dose: 6.5 mg/kg body weight (not exceeding 400 mg), after 6 hours.
Third dose: 6.5 mg/kg body weight (not exceeding 400 mg), 24 hours after the first dose.
Fourth dose: 6.5 mg/kg body weight (not exceeding 400 mg), 48 hours after the first dose.

Special patient groups
Patients with impaired renal or hepatic function
Dose adjustment may be necessary when treating patients with impaired kidney or liver function.

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

Taking more Novidin than you should
If you take more Novidin than recommended, you must immediately inform your doctor or go to a
hospital emergency department.
Overdose of 4-aminoquinolines is particularly dangerous in infants, as ingestion of just 1 to 2 g has
been fatal.
Symptoms of overdose may include headache, visual disturbances, cardiovascular collapse, seizures,
and rhythm and conduction abnormalities, followed by sudden and early cardiac and respiratory arrest.
Given that these symptoms may occur after ingestion of a large dose, treatment must be immediate.

If you forget to take Novidin
Do not take a double dose to make up for a missed dose.

Stopping Novidin
Continue taking Novidin as long as your doctor has not advised otherwise. Do not stop taking Novidin
even if you feel better. Premature discontinuation of therapy may result in disease progression.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Gastrointestinal side effects are the most common side effects, observed in 10-20% of patients. Side effects may resolve spontaneously or after dose reduction, and they can usually be prevented by performing the recommended monitoring tests.
Usually observed side effects are reversible, but irreversible side effects (e.g. deafness, visual field changes) have also been reported.
Patients with psoriasis appear to have an increased risk of developing severe skin reactions.
You should immediately stop taking Novidin and consult a doctor if any of the following serious side effects occur — urgent medical treatment may be required:

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

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

Nausea
Abdominal pain

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

Decreased appetite
Emotional instability, e.g. irritability, nervousness, and restlessness
Headache
Visual disturbances such as seeing rings in the field of vision, blurred vision, photophobia, disturbances of visual acuity, and double vision
Diarrhea with weight loss
Flatulence
Vomiting
Rash
Itching (observed in approximately 40% of patients with systemic lupus erythematosus)
Sensory-motor disturbances

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

Nervousness, insomnia or drowsiness, confusion, or paresthesia
Dizziness
Changes in the retina causing deterioration of vision, visual field changes, irregular pigmentation of the retina, and retinal damage
Tinnitus
Abnormal liver function test results
Induction or worsening of liver function disorders
Hair loss
Changes in skin and mucous membrane pigmentation
Hair discoloration and hair loss

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

Suppression of new blood vessel formation (bone marrow)
Blood disorders such as decreased white blood cells (leukopenia and agranulocytosis), decreased platelets (thrombocytopenia), and anemia (anemia and aplastic anemia)
Heart disorders (cardiomyopathy)
Skin and (or) mucous membrane swelling
Bullous rash
Urticaria

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

Reversible phospholipidosis (increased intracellular accumulation of phospholipids)
Liver function disorders

Frequency not known (cannot be estimated from available data)

Bronchospasm leading to shortness of breath
Metabolic disorders (porphyria)
Low blood sugar levels
Feelings of depression or suicidal thoughts, hallucinations, feelings of nervousness or anxiety, disorientation, restlessness, sleep disturbances, feelings of euphoria or excessive excitement.
Seizures, epileptic fits, extrapyramidal disorders such as muscle tone disturbances, involuntary movements, inability to sit still, tremor
Corneal opacity, corneal edema, visual field restriction, blurred vision, photophobia
Maculopathy and macular degeneration
Hearing loss
Effects on the liver and liver failure
Worsening of psoriasis
Muscle weakness or reduced nerve function (myopathy or neuromyopathy), which may be reversible after discontinuation of treatment
Diminished tendon reflexes
Impaired nerve conduction
Changes in heart rhythm (your doctor may check the electrical activity of the heart using an electrocardiogram)
Photosensitivity reactions
Skin peeling (exfoliative dermatitis)
Erythema multiforme (fever, rash on face, arms, and legs).

Reporting of side effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw,
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Novidin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the pack following "EXP".
The expiry date refers to the last day of the specified month.
There are no special storage instructions for this medicinal product.
Medicines must not be disposed of via the sewage system or household waste. Please ask
your pharmacist how to dispose of medicines no longer required. Such measures will help
protect the environment.

6. Contents of the package and other information

What Novidin contains
The active substance is hydroxychloroquine sulfate. Each coated tablet contains 400 mg of
hydroxychloroquine sulfate (equivalent to 310 mg of hydroxychloroquine).
The other ingredients are:
Tablet core:
Calcium hydrogen phosphate (E 341)
Corn starch
Povidone (E 1201)
Magnesium stearate (E572)
Tablet coating (Opadry 85F18422 White)
Polyvinyl alcohol (E 1203)
Titanium dioxide (E 171)
Macrogol (E 1521)
Talc (E 553b)
What Novidin looks like and contents of the pack
White, elongated, biconvex coated tablets 400 mg, with a break line.
Length: approximately 14 mm
Width: approximately 7 mm
Height: approximately 6 mm
Novidin coated tablets are packed in PVC/Aluminium blisters, placed in a cardboard box.
Pack size: 30 tablets.
Marketing Authorisation Holder
Gebro Pharma GmbH
Bahnhofbichl 13
6391 Fieberbrunn
Austria
Manufacturer
Recipharm Parets, S.L.U
C/ Ramón y Cajal, 2
08150 Parets del Vallès, Barcelona
Spain
For further information about this medicinal product, contact the local representative of the
Marketing Authorisation Holder:
medac GmbH Sp. z o.o.
Branch in Poland
ul. Postępu 21 B
02-676 Warszawa
tel. +48 22 430 00 30
fax +48 22 430 00 31
email: [email protected]
This medicinal product is authorised in the European Economic Area countries under the
following trade names:
Spain: Duplaxil
Poland: Novidin