Levodopa and carbidopa Hexal

Italy
Brand name Levodopa and carbidopa Hexal
Form tablets, prolonged-release
Active substance / Dosage
LEVODOPA
CARBIDOPA MONOHYDRATE
Prescription type Prescription only
ATC code
N04BA02
Registration number 036514
Manufacturer SANDOZ S.P.A.
Levodopa and carbidopa Hexal tablets, prolonged-release

Table of Contents

Package leaflet: Information for the patient

Levodopa/Carbidopa Hexal 100 mg/25 mg prolonged-release tablets
Levodopa/Carbidopa Hexal 200 mg/50 mg prolonged-release tablets
Generic medicine
Read carefully this leaflet 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 questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
  • If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.4. Contents of this leaflet:
    1. What Levodopa/Carbidopa Hexal is and what it is used for
    2. What you need to know before taking Levodopa/Carbidopa Hexal
    3. How to take Levodopa/Carbidopa Hexal
    4. Possible side effects
    5. How to store Levodopa/Carbidopa Hexal
    6. Contents of the pack and other information

1 WHAT LEVODOPA/CARBIDOPA HEXAL IS AND WHAT IT IS USED FOR
Levodopa/Carbidopa Hexal is used to treat Parkinson's disease. If you are currently being treated with levodopa alone or with immediate-release levodopa/decarboxylase inhibitor tablets (e.g. carbidopa) and experience sudden, uncontrolled movements, Levodopa/Carbidopa Hexal shortens the "off" period (a sudden muscle stiffness that may last several minutes or even hours).
Levodopa/Carbidopa Hexal belongs to a class of drugs used to treat Parkinson's disease. The symptoms of this disorder are likely caused by a deficiency of dopamine, a substance normally produced by the brain that plays an essential role in controlling muscle movements. Dopamine deficiency leads to motor function problems. Levodopa compensates for the lack of dopamine, while carbidopa ensures that sufficient amounts of levodopa reach the brain.

2 WHAT YOU NEED TO KNOW BEFORE TAKING LEVODOPA/CARBIDOPA HEXAL
Do not take Levodopa/Carbidopa Hexal

  • if you are allergic (hypersensitive) to levodopa or carbidopa, or to any of the excipients of the tablets;
  • if you have increased intraocular pressure (closed-angle glaucoma);
  • if you have severe heart failure;
  • if you have severe cardiac arrhythmia;
  • in case of sudden stroke;
  • if you are not allowed to use medicines acting on the central nervous system (sympathomimetic agents);
  • if you are taking non-selective or selective monoamine oxidase inhibitors or MAO inhibitors of type A (medicines used to treat depression). Treatment with these medicines must be discontinued at least two weeks before starting treatment with Levodopa/Carbidopa Hexal;
  • Levodopa/Carbidopa Hexal may be administered concomitantly with the recommended dose of a selective MAO-B inhibitor (e.g. selegiline).

Warnings and precautions
Exercise particular caution with Levodopa/Carbidopa Hexal:

  • if you are currently taking or have previously taken levodopa alone. In this case, you must wait at least 12 hours before starting to take Levodopa/Carbidopa Hexal;
  • if you suffer from motor disorders such as facial muscle spasms, muscle stiffness and soreness, difficulty initiating movement, finger or hand tremors. In such cases, dosage reduction may be necessary;
  • if you have previously experienced involuntary movements;
  • if you have previously suffered from psychotic episodes or psychosis. Psychosis is a severe mental disorder that impairs the ability to control one's own behavior. Very rarely, cases of depression followed by suicidal tendencies have been reported. If you think this may apply to you, you must immediately inform your doctor;
  • if you are in a state of constant fatigue or tend to fall asleep suddenly. In this case, you must not drive or operate machinery: if necessary, your doctor may adjust the dosage or discontinue treatment altogether;
  • if you suffer from severe cardiovascular disorders;
  • if you suffer from severe pulmonary disease or sudden attacks of breathlessness due to muscle spasms and swelling of the mucous membranes in the respiratory tract, often accompanied by cough and phlegm (bronchial asthma);
  • if you have kidney or liver problems, or disorders of the endocrine system (glands that secrete hormones into the bloodstream);
  • if you have previously suffered from stomach or intestinal ulcers, as this increases the risk of gastrointestinal bleeding;
  • if you vomit blood;
  • if you have previously experienced epileptic seizures/convulsions;
  • if you recently had a heart attack and still have irregular heart rhythms;
  • if you suffer from chronic glaucoma (increased intraocular pressure);
  • if your levodopa/carbidopa dosage is suddenly reduced or treatment is discontinued, especially if you are taking medicines to treat psychosis; this may mask changes in your mental condition; muscle stiffness and increased body temperature may occur.
  • if you suffer from a hereditary disorder characterized by sudden, involuntary but coordinated movements (Huntington's chorea). In this case, the use of Levodopa/Carbidopa Hexal is not recommended;
  • if you have ever had malignant melanoma;
  • if you suffer from an undiagnosed skin disorder.
  • Levodopa/Carbidopa Hexal may cause abnormalities in several laboratory tests. These include:
    • liver function tests
    • false positive Coombs test
    • reduced hemoglobin and hematocrit, elevated serum glucose levels, white blood cells, bacteria, and blood in urine.
    • a false positive for ketone bodies in urine may occur if a strip test is used to determine ketonuria. This reaction is not altered by boiling the urine sample
  • a false negative result in the urine glucose test may also occur when using the glucose oxidase method

Inform your doctor if you or someone in your family or caregiver notices that you are developing urges or desires to behave in ways that are unusual for you and that you cannot resist the impulse or temptation to perform certain activities that could harm yourself or others. These behaviors are called impulse control disorders and may include gambling addiction, excessive eating or spending, abnormally increased sexual desire, or increased sexual thoughts or feelings. Your doctor may consider it necessary to reassess your treatment.
Inform your doctor if you or a family member/caregiver notices the development of symptoms resembling addiction, leading to a desire for high doses of levodopa/carbidopa Hexal and other medicines used to treat Parkinson's disease.

Children and adolescents
The safety and efficacy of Levodopa/Carbidopa Hexal in neonates and children/adolescents under 18 years of age have not been established; therefore, the use of Levodopa/Carbidopa Hexal in patients under 18 years of age is not recommended.
If any of the above warnings apply to you or have applied in the past, inform your doctor.

Other medicines and Levodopa/Carbidopa Hexal
Levodopa/Carbidopa Hexal may interfere with the effects/side effects of other medicines and vice versa. This particularly occurs with the following medicines:

  • medicines used to treat high blood pressure (your doctor may need to adjust the dosage);
  • medicines used to treat depression (see also section "Do not take Levodopa/Carbidopa Hexal");
  • medicines acting on the central nervous system (anticholinergics, bronchodilators used for asthma treatment), such as ipratropium and tiotropium. These medicines may reduce the effects of levodopa; your doctor will adjust the dosage as needed;
  • medicines used to treat psychosis
  • isoniazid (a medicine used to treat tuberculosis);
  • benzodiazepines (certain sleeping pills and tranquilizers), such as diazepam, oxazepam, and lormetazepam, which may reduce the effects of Levodopa/Carbidopa Hexal;
  • phenytoin (a medicine used to treat epilepsy), which may reduce the effects of Levodopa/Carbidopa Hexal;
  • papaverine (a medicine used to treat gastrointestinal spasms), which may reduce the effects of Levodopa/Carbidopa Hexal;
  • selegiline (a medicine used to treat Parkinson's disease); when used concomitantly with Levodopa/Carbidopa Hexal, a severe drop in blood pressure may occur;
  • COMT inhibitors (used to treat Parkinson's disease); when administered concomitantly with Levodopa/Carbidopa Hexal, the levels of levodopa reaching the brain may increase. Therefore, adjustment of the Levodopa/Carbidopa Hexal dosage may be necessary;
  • amantadine (used to treat Parkinson's disease); side effects of levodopa may increase. Therefore, adjustment of the Levodopa/Carbidopa Hexal dosage may be necessary;
  • metoclopramide (a gastrointestinal drug);
  • medicines acting on the central nervous system (sympathomimetics, bronchodilators used to treat asthma), such as apraclonidine, dipivefrin, and brimonidine; cardiovascular side effects may increase;
  • medicines that reduce dopamine (e.g. tetrabenazine, which reduces dopamine in the central nervous system by inhibiting specific transporter proteins called monoamine transporters that transport monoamines (e.g. dopamine) into or out of cells) or other medicines known to reduce monoamine reserves.
  • ferrous sulfate. Levodopa absorption may decrease.

If you are taking or have recently taken any other medicines, including those without a prescription, inform your doctor or pharmacist.

Taking Levodopa/Carbidopa Hexal with food and drinks
The effects of levodopa may sometimes be compromised in patients following a high-protein diet.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

  • Women of childbearing potential treated with Levodopa/Carbidopa 100 mg/25 mg / 200 mg/50 mg should use effective contraceptive methods.
  • Data on the use of Levodopa/Carbidopa Hexal during pregnancy are not known. Animal studies have shown the substance to be harmful.
  • Do not take Levodopa/Carbidopa Hexal during pregnancy or if you are planning a pregnancy.
  • Levodopa is excreted in breast milk. Therefore, breastfeeding must not be performed during treatment with Levodopa/Carbidopa Hexal.

Driving and using machines
Levodopa/Carbidopa Hexal may cause side effects such as

  • dizziness,
  • somnolence,
  • double vision, which may impair your reaction abilities. Therefore, these effects must be considered if you intend to drive or operate machinery. Patients who tend to fall asleep or fall asleep suddenly must not drive or operate machinery.

Levodopa Carbidopa Hexal contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per prolonged-release tablet, i.e. essentially "sodium-free".

3 HOW TO TAKE LEVODOPA/CARBIDOPA HEXAL
Dosage
Adults and elderly
Your doctor has prescribed the correct dosage of Levodopa/Carbidopa Hexal for you.
Generally, the following dosages apply.
If you have never been treated with levodopa:
Take this medicine exactly as directed by your doctor or pharmacist. If you have doubts, consult your doctor or pharmacist.
Initial dosage
1 tablet of Levodopa/Carbidopa Hexal 100 mg/25 mg twice daily or 1 tablet of Levodopa/Carbidopa Hexal 200 mg/50 mg twice daily.
Maximum initial dosage
6 tablets of Levodopa/Carbidopa Hexal 100 mg/25 mg per day or 3 tablets of Levodopa/Carbidopa Hexal 200 mg/50 mg per day (600 mg of levodopa per day).
Doses should be taken at intervals of at least six hours.
If switching from standard Levodopa/Carbidopa Hexal tablets to prolonged-release tablets:
This switch must be performed gradually and under medical supervision.
If you are currently undergoing treatment with levodopa alone:
Treatment with levodopa must be discontinued at least 12 hours before administration of Levodopa/Carbidopa Hexal.
Initial dosage for patients with mild to moderate Parkinson's disease:
1 tablet of Levodopa/Carbidopa Hexal 200 mg/50 mg twice daily or 2 tablets of Levodopa/Carbidopa Hexal 100 mg/25 mg twice daily.
Maintenance dose:
Your doctor will regularly monitor you and adjust the dosage if necessary. At least three days should elapse between dosage adjustments.
Swallow the tablets whole with a glass of water, regardless of meals; do not break or chew the tablets.
If you feel that the effects of Levodopa/Carbidopa Hexal are too strong or too weak, consult your doctor or pharmacist.
Use in children and adolescents (under 18 years)
The use of Levodopa/Carbidopa Hexal in patients under 18 years of age is not recommended (see section "Exercise particular caution with Levodopa/Carbidopa Hexal especially in the following cases").
Duration of treatment
Your doctor will tell you how long you should take Levodopa/Carbidopa Hexal. Do not stop treatment prematurely; symptoms may reappear.
If you take more Levodopa/Carbidopa Hexal than you should
If you have taken an excessive dose of Levodopa/Carbidopa Hexal, contact your doctor or pharmacist immediately. Symptoms of overdose may include: spasms of the orbicularis muscle surrounding the eye (see also section 4: "Possible side effects").
If you forget to take Levodopa/Carbidopa Hexal
Do not take a double dose of Levodopa/Carbidopa Hexal to make up for a missed dose. If you have forgotten to take a dose, you may take it, unless it is almost time for the next dose. If this is the case, continue with the prescribed dosage schedule.
If you stop taking Levodopa/Carbidopa Hexal
If your dosage is suddenly reduced or treatment stopped, your doctor will keep you under regular observation. Read section: "Exercise particular caution with Levodopa/Carbidopa Hexal especially in the following cases", particularly if you are using medicines to treat psychosis (antipsychotic agents).
If you have any doubts about using Levodopa/Carbidopa Hexal, consult your doctor or pharmacist.

4 POSSIBLE SIDE EFFECTS
Like all medicines, Levodopa/Carbidopa Hexal can cause side effects, although not everyone gets them.
The side effects that may occur are:
Infections and infestations
Very common: may affect up to 1 in 10 people

  • urinary tract infections

Disorders of the blood and lymphatic system
Rare: may affect 1 in 1,000 people

  • deficiency of white blood cells, accompanied by increased risk of infection (leukopenia)
  • anemia (hemolytic and non-hemolytic)
  • deficiency of platelets, accompanied by bruising and tendency to bleed (thrombocytopenia) Very rare: may affect 1 in 10,000 people
  • severe deficiency of white blood cells, accompanied by sudden high fever, severe sore throat, and mouth ulcers (agranulocytosis)

Metabolism and nutrition disorders
Common: may affect 1 in 10 people

  • loss of appetite (anorexia) Uncommon: may affect 1 in 100 people
  • weight loss
  • weight gain

Psychiatric disorders
Common: may affect 1 in 10 people

  • seeing things that are not there (hallucinations)
  • confusion
  • dizziness
  • nightmares
  • somnolence
  • fatigue
  • insomnia
  • depression with (very rare) suicidal tendencies
  • feeling of well-being (euphoria)
  • episodes of severe mental disorder, during which control over one's own behavior is lost (psychosis)
  • irritability Rare: may affect 1 in 1,000 people
  • excitement (agitation)
  • anxiety
  • reduced ability to concentrate
  • disorientation
  • headache
  • increased sexual desire
  • numbness
  • seizures

Frequency not known: frequency cannot be estimated from available data

  • dementia
  • inability to resist the impulse or temptation to perform actions that could be harmful to oneself or others, which may include: o strong impulse to gamble excessively, despite severe personal or family consequences o altered or increased sexual interest and behavior causing significant concern to you or others, e.g., increased sexual desire. o uncontrollable shopping or excessive spending o compulsive eating (eating large amounts of food in a short period of time) o bulimia (eating more food than normal and more than needed to satisfy your hunger) Desire for excessive doses of Levodopa/Carbidopa Hexal beyond what is required to control motor symptoms, known as dopamine dysregulation syndrome. Some patients experience severe abnormal involuntary movements (dyskinesias), mood changes, or other side effects after taking high doses of Levodopa/Carbidopa Hexal.

Inform your doctor if any of these behaviors occur, so he can decide how to intervene to manage or reduce symptoms.
Nervous system disorders
Common: may affect 1 in 10 people

  • movement disorders (dyskinesia)
  • disorder characterized by sudden irregular movements (chorea)
  • alteration of muscle tone (dystonia)
  • movement alterations caused by factors external to the nervous system (extrapyramidal)
  • sudden changes in Parkinson's disease symptoms ("on-off" symptoms)
  • slowing of movements during "on-off" periods (bradykinesia) Uncommon: may affect 1 in 100 people
  • ataxia
  • increased hand tremor Rare: may affect 1 in 1,000 people
  • a severe disorder caused by neuroleptics, which may manifest as muscle rigidity, marked inability to sit still, high fever, sweating, increased salivation, and altered consciousness (neuroleptic malignant syndrome)
  • sensations of tingling, prickling, and itching without apparent cause (paresthesia)
  • seizures
  • gait disturbances
  • trismus

Frequency not known: frequency cannot be estimated from available data

  • Somnolence and (very rarely) constant daytime fatigue/sudden sleep attacks.

Eye disorders
Rare: may affect 1 in 1,000 people

  • blurred vision
  • spasms of the orbicularis muscle surrounding the eye (this may be a sign of overdose)
  • activation of pre-existing Horner's syndrome (an eye disorder)
  • double vision
  • dilated pupils
  • altered eye movements

Cardiac disorders
Common: may affect 1 in 10 people

  • palpitations
  • irregular heartbeat

Vascular disorders
Common: may affect 1 in 10 people

  • decrease in blood pressure, e.g. when rising quickly from sitting or lying down, sometimes accompanied by dizziness (orthostatic hypotension)
  • tendency to faint
  • sudden loss of consciousness Uncommon: may affect 1 in 100 people
  • increase in blood pressure Rare: may affect 1 in 1,000 people
  • inflammation of veins (phlebitis)

Respiratory, thoracic and mediastinal disorders
Uncommon: may affect 1 in 100 people

  • hoarseness
  • chest pain Rare: may affect 1 in 1,000 people
  • breathlessness
  • irregularity in breathing rhythm

Gastrointestinal disorders
Common: may affect 1 in 10 people

  • nausea
  • vomiting
  • dry mouth
  • bitter taste

Uncommon: may affect 1 in 100 people

  • constipation
  • diarrhea
  • increased salivation
  • difficulty swallowing (dysphagia)
  • flatulence Rare: may affect 1 in 1,000 people
  • digestive difficulties, with symptoms such as fullness in the upper abdomen, upper abdominal pain, tendency to burp, nausea, vomiting, and heartburn (dyspepsia)
  • stomach and intestinal pain
  • dark saliva
  • bruxism (teeth grinding)
  • hiccups
  • gastrointestinal bleeding
  • burning sensation on the tongue
    • duodenal ulcers

Skin and subcutaneous tissue disorders
Uncommon: may affect 1 in 100 people

  • fluid accumulation (edema) Rare: may affect 1 in 1,000 people
  • sudden accumulation of fluid in the skin and mucous membranes (e.g. throat and tongue), breathing difficulties and/or itching and skin rash, often as an allergic reaction (angioedema)
  • skin rashes with intense itching and wheal formation (urticaria)
  • itching
  • facial flushing
  • hair loss
  • skin rash
  • increased sweating
  • dark sweat
  • in children, bleeding (due to allergy) of the skin and gastrointestinal tract wall (Schönlein-Henoch purpura) Frequency not known: frequency cannot be estimated from available data
  • malignant skin tumor (melanoma)
  • Musculoskeletal and connective tissue disorders Uncommon: may affect 1 in 100 people
  • muscle spasms

Renal and urinary disorders
Uncommon: may affect 1 in 100 people

  • dark urine Rare: may affect 1 in 1,000 people
  • urinary retention
  • involuntary passage of urine
  • persistent erection (priapism)

General disorders and administration site conditions
Uncommon: may affect 1 in 100 people

  • weakness
  • malaise
  • hot flushes

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5 HOW TO STORE LEVODOPA/CARBIDOPA HEXAL
Keep Levodopa/Carbidopa Hexal out of the sight and reach of children.
Do not use Levodopa/Carbidopa Hexal after the expiry date, which is stated on the packaging and blister after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6 CONTENTS OF THE PACK AND OTHER INFORMATION
What Levodopa/Carbidopa Hexal contains
The active substances are: Levodopa and Carbidopa.
Each prolonged-release tablet contains 100 mg of levodopa and 25 mg of carbidopa (as carbidopa monohydrate).
Each prolonged-release tablet contains 200 mg/50 mg contains 200 mg of levodopa and 50 mg of carbidopa (as carbidopa monohydrate).
The excipients are: hypromellose, anhydrous colloidal silica, fumaric acid, sodium stearyl fumarate, macrogol 6000, quinoline yellow (E104), yellow and red iron oxides (E172), titanium dioxide (E171).
Description of the appearance of Levodopa/Carbidopa Hexal and contents of the pack
Appearance:
Levodopa/Carbidopa Hexal 100mg/25 mg prolonged-release tablets: round, orange-brown tablets.
Levodopa/Carbidopa Hexal 200mg/50 mg prolonged-release tablets: round, orange-brown tablets.
The prolonged-release tablets are packed in blisters containing 30, 50, 60 or 100 tablets, which are in turn packaged in cardboard boxes.
Not all pack sizes may be marketed.
Marketing Authorization Holder
Sandoz S.p.A.
Viale Luigi Sturzo 43
20154 Milan
Italy
Responsible manufacturers for batch release
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben
Germany
Lek S.A.
Ul. Domaniewska 50 C
02-672 Warsaw
Poland
This medicinal product has been authorized in EEA member states under the following
names:
Netherlands Levodopa/Carbidopa Sandoz retard 100/25 mg, tablets with prolonged release
Levodopa/Carbidopa Sandoz retard 200/50 mg, tablets with prolonged release
Germany Levocomp® retard 100/25 mg Retardtabletten
Levocomp® retard 200/50 mg Retardtabletten
Italy Levodopa/Carbidopa Hexal 100/25 mg prolonged-release tablets
Levodopa/Carbidopa Hexal 200/50 mg prolonged-release tablets
Sweden Levocar
This leaflet was last approved on