Consumer medicine information

Kinson

Levodopa; Carbidopa

BRAND INFORMATION

Brand name

Kinson

Active ingredient

Levodopa; Carbidopa

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Kinson.

What is in this leaflet

This leaflet answers some common questions about KINSON.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking KINSON against the benefits expected for you.

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

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

What KINSON is used for

KINSON is used to treat some of the symptoms of Parkinson's disease. This is a disease of the nervous system that mainly affects body movement. The three main symptoms are shaking (tremor), muscle stiffness and slow and unsteady movement.

People with Parkinson's disease often walk with a shuffle as they have difficulty in initiating movement. If untreated, Parkinson's disease can cause difficulty in performing normal daily activities.

KINSON is most helpful in improving slow movement and muscle stiffness. It can also be helpful in treating shaking, difficulty in swallowing, drooling and unstable posture.

The symptoms of Parkinson's disease are caused by a lack of dopamine, a naturally occurring chemical produced by certain brain cells. Dopamine sends messages in the part of the brain that controls muscle movement.

When too little dopamine is produced, slowness of movement results.

KINSON contains two active ingredients, levodopa and carbidopa. Levodopa is a chemical closely related to dopamine which allows the body to make its own dopamine. Carbidopa makes sure that enough levodopa gets to the brain where it is needed. In many patients, KINSON reduces some of the symptoms of Parkinson's disease.

Your doctor may have prescribed KINSON for another reason.

Ask your doctor if you have any questions about why KINSON has been prescribed for you. KINSON is available only with a doctor's prescription.

KINSON is available only with a doctor’s prescription.

Before you take KINSON

When you must not take it

Do not take KINSON if you are allergic to medicines containing levodopa, carbidopa or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • wheezing or shortness of breath.
  • skin rash, itching or hives;
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing;

Do not take KINSON if you have:

  • any unusual skin lumps or moles which have not been checked by your doctor
  • a history of melanoma (a type of skin cancer).

Do not take KINSON if you have a type of glaucoma called narrow-angle glaucoma.

Do not take KINSON if you are taking another medicine for depression called a monoamine oxidase inhibitor (MAOI), or you have previously taken a MAOI within the last 14 days. Some examples of MAOIs are phenelzine (Nardil) and tranylcypromine (Parnate).

Do not take KINSON if you are breastfeeding or plan to breastfeed. It has been shown that one of the active ingredients of KINSON passes into breast milk. Therefore, because of the potential harm to the baby, KINSON should not be used during breastfeeding.

Do not give KINSON to a child or teenager below 18 years old, unless advised by the child's doctor. The safety and effectiveness of KINSON in children and teenagers under 18 years old has not been established.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will discuss the risks and benefits of taking KINSON during pregnancy.

Tell your doctor if you wish to breastfeed.

Tell your doctor if you have, or have had, any medical conditions, especially the following:

  • depression, mental illness or psychiatric problems
  • heart disease, including irregular heart beat (arrhythmia)
  • lung disease, including asthma
  • kidney, liver or hormonal problems
  • convulsions or fits
  • glaucoma
  • peptic ulcer disease

Your doctor may want to take special care if you have any of these conditions.

Tell your doctor if you or your family member/caregiver notices you are developing urges to gamble, excessive eating or spending, medicine use or repetitive purposeless activities with other medicines for Parkinson's Disease, and/or other intense urges that could harm yourself or others. These behaviours are called impulse control disorders. Your doctor may need to review your treatments.

Tell your doctor if you are currently taking levodopa or have taken it in the past. Some examples of medicines which contain levodopa are Madopar and Sinemet.

If you have not told your doctor about any of the above, tell them before you start taking KINSON.

Taking other medicines

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

Some medicines may be affected by KINSON, or may affect how well it works. These include:

  • selegiline (Eldepryl, Selgene), another medicine used to treat Parkinson's disease
  • some medicines used to treat high blood pressure
  • some medicines used to treat depression
  • some medicines used to treat mental illness or psychiatric problems
  • some medicines used to treat diseases related to involuntary movements.
  • phenytoin (Dilantin), a medicine used to treat convulsions
  • isoniazid, a medicine used to treat tuberculosis.
  • iron supplements and multivitamins containing iron

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

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking KINSON.

How to take KINSON

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist.

How much to take

Your doctor will tell you how many tablets to take each day. The dose varies considerably from patient to patient.

The usual starting dose is one KINSON 100/25mg tablet three times a day. Your doctor may adjust this dose depending on how you respond to this medicine whether or not you are taking any other medicines.

How to take it

Swallow the tablets whole with a glass of water.

When to take it

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it for

Keep taking KINSON for as long as your doctor recommends.

KINSON helps control some of the symptoms of Parkinson's disease, but does not cure your condition. It is important that you take KINSON every day on a regular basis.

Continue taking KINSON for as long as your doctor prescribed.

Do not stop taking KINSON, or lower the dosage, without checking with your doctor. Your doctor may want you to gradually reduce the amount of KINSON you are using before stopping completely. This may help reduce the possibility of withdrawal symptoms such as muscle stiffness, fever or mental changes.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

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

If you are not sure what to do or have any questions, ask your doctor or pharmacist.

If you have trouble remembering to take your tablets, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much KINSON. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking KINSON

Things you must do

If you feel light-headed, dizzy or faint get up slowly when getting out of bed or standing up. You may feel light-headed or dizzy while taking KINSON. This is because your blood pressure is falling suddenly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, tell your doctor.

Before starting any new medicine, tell your doctor or pharmacist that you are taking KINSON.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking KINSON.

If you become pregnant while taking KINSON, tell your doctor.

If you plan to have surgery, including dental surgery, that needs a general anaesthetic, tell your doctor or dentist that you are taking KINSON.

If you are diabetic, check with your doctor or pharmacist before using urine sugar tests. KINSON may cause false test results with some urine sugar tests.

If you need to have any other blood or urine tests, tell your doctor that you are taking KINSON. KINSON may affect the results of some tests.

Visit your doctor regularly so they can check on your progress. You may need to have tests to make sure that KINSON is not affecting your blood, liver, kidneys and heart.

Tell your doctor if you feel KINSON is not working as well as it did previously. In some people who have been taking KINSON for long periods of time, such as a year or more, sudden and unexpected losses of movement may occur. These may last from a few minutes to several hours. Afterwards, the person can move as before. This may unexpectedly occur again and again. This is called the "on-off" effect. If this happens, your doctor may want to adjust your medicine.

Things you must not do

Do not stop taking KINSON, or lower the dose, without checking with your doctor. Stopping KINSON suddenly may cause muscle stiffness, fever and mental changes. Your doctor may want you to gradually reduce the amount of KINSON you are taking before stopping completely.

Do not use KINSON to treat any other conditions unless your doctor tells you to.

Do not give KINSON to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful when driving or operating machinery until you know how KINSON affects you. KINSON may cause dizziness or lightheadedness in some people. If this occurs, do not drive, operate machinery or do anything else that could be dangerous if you are dizzy or lightheaded. Drinking alcohol can makes dizziness and lightheadedness worse.

In addition, in very rare cases, KINSON may cause excessive sleepiness and sudden onset of sleep.

If you experience these effects, do not drive or operate machinery until these effects are resolved.

Be careful getting up from a sitting or lying position. Dizziness, lightheadedness or fainting may occur, especially when you get up quickly. This is because your blood pressure is suddenly falling. Getting up slowly may help. If this problem continues or gets worse, tell your doctor.

Be careful not to eat a diet high in protein. The amount of levodopa absorbed by your body may be reduced if your diet is high in protein. Ask your doctor, pharmacist or dietician to check your diet.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking KINSON.

KINSON helps most people with Parkinson's disease, but it may have unwanted side effects in some 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.

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

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

Tell your doctor if you notice any of the following and they worry you:

  • abnormal uncontrolled movements including muscle twitching or spasms, which may or may not be like your Parkinson's symptoms
  • dizziness, lightheadedness when getting up quickly
  • nausea (feeling sick), vomiting, loss of appetite
  • discolouration of urine, sweat and/or saliva
  • dark saliva
  • sudden episodes of sleep onset, excessive drowsiness
  • slow movements
  • dream abnormalities, sleepiness or sudden onset of sleep
  • twitching or spasm of the eyelids
  • hair loss
  • diarrhoea

Tell your doctor if you experience any of these behaviours:

You may experience an inability to resist the impulse to perform an action that could be harmful, which may include:

  • strong impulses to gamble
  • increased sexual drive
  • uncontrollable excessive shopping
  • spending, binge/compulsive eating
  • taking medicines and repetitive purposeless activities
  • and/or other urges

These are possible side effects of KINSON. For the most part, the above side effects have been mild.

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

  • blood in the urine
  • difficulty or pain in passing urine
  • skin rash, itching
  • pinkish, itchy swellings on the skin, also called hives or nettlerash
  • changes in mood such as depression
  • forgetfulness
  • signs of anaemia such as tiredness, headaches, being short of breath, dizziness and looking pale
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • bruising or bleeding more easily than normal, nose bleeds
  • numbness or tingling in the hands or feet
  • fainting
  • signs of melanoma, such as new skin spots or changes to the size, shape, colour or edges of an existing skin spot, freckle or mole.

The above list includes serious side effects which may require medical attention. Serious side effects are rare.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • difficulty breathing, wheezing or shortness of breath
  • bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea
  • vomiting blood or material that looks like coffee grounds
  • chest pain
  • fast or irregular heartbeats, also called palpitations
  • muscle stiffness accompanied by fever
  • mental changes such as feeling very fearful or paranoid, hallucinations

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Contact your doctor as soon as possible if you or someone you know is showing signs of unusual behaviour while taking KINSON.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some patients. Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

After taking KINSON

Storage

Keep KINSON where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep 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 your tablets in a cool dry place where the temperature stays below 30°C.

Do not store KINSON or any other medicine in the bathroom or near a sink.

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

Disposal

If your doctor tells you to stop taking KINSON, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

KINSON is a 9mm flat bevelled-edged yellow tablet debossed LC/2 on one side and 'alpha' on the reverse.

Each bottle contains 100 tablets.

Ingredients

The active ingredients in KINSON are levodopa and carbidopa (as monohydrate). Each KINSON tablet contains 100 mg of levodopa and 25 mg of carbidopa.

The tablets also contain the following inactive ingredients:

  • maize starch
  • povidone
  • microcrystalline cellulose
  • magnesium stearate
  • purified talc
  • sodium starch glycollate
  • quinoline yellow aluminium lake

KINSON contains sulfites.

Manufacturer

KINSON is made in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in April 2023.

Australian registration number:
KINSON - AUST R 49481

KINSON_cmi\Apr23/00

Published by MIMS May 2023

BRAND INFORMATION

Brand name

Kinson

Active ingredient

Levodopa; Carbidopa

Schedule

S4

 

1 Name of Medicine

Levodopa and carbidopa (as monohydrate).

2 Qualitative and Quantitative Composition

Kinson is a combination of levodopa, the metabolic precursor of dopamine, and carbidopa, an aromatic amino acid decarboxylase inhibitor, for the treatment of Parkinson's disease and syndrome.
Each tablet contains 100 mg of levodopa and 25 mg of carbidopa (as monohydrate) as the active ingredients.

Excipients with known effect.

Sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Kinson tablet: 9 mm flat bevelled-edged yellow tablet debossed LC/2 on one side and 'alpha' on the reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of Parkinson's disease and syndrome. It is useful in relieving many of the symptoms of Parkinsonism, particularly rigidity and bradykinesia. Levodopa/ carbidopa is frequently helpful in the management of tremor, dysphagia, sialorrhoea, and postural instability associated with Parkinson's disease and syndrome.

4.2 Dose and Method of Administration

The optimum daily dosage of Kinson must be determined by careful titration in each patient. Kinson tablets are available in a 1:4 ratio of carbidopa to levodopa (25 mg/100 mg).

General considerations.

Dosage should be titrated to individual patient needs and this may require adjusting both the individual dose and the frequency of administration.
Studies show that the peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg daily. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.
Standard antiparkinsonian drugs, other than levodopa alone, may be continued while Kinson is being administered, although dosage may have to be adjusted.

Usual initial dosage.

Dosage is best initiated with one tablet of Kinson three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage equivalent of eight tablets of Kinson a day is reached.
Response has been observed in one day, and sometimes after one dose. Fully effective doses usually are reached within seven days as compared to weeks or months with levodopa alone.

How to transfer patients from levodopa.

Because both therapeutic and adverse responses occur more rapidly with Kinson than when levodopa is given, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly with Kinson than with levodopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.
Levodopa should be discontinued at least 12 hours before Kinson is started (24 hours for slow release preparations of levodopa). A daily dosage of Kinson should be chosen that will provide approximately 20% of the previous levodopa daily dosage.
Patients who are taking less than 1500 mg of levodopa a day should be started on one tablet of Kinson 25/100 three or four times a day.

Maintenance.

Therapy should be individualised and adjusted according to the desired therapeutic response. At least 70 to 100 mg of carbidopa per day should be provided for optimal inhibition of extracerebral decarboxylation of levodopa.
Usual dose is 3 tablets daily. Dosage may be increased by one tablet every day or every other day, as necessary, up to a maximum of 8 tablets daily. Experience with total daily dosages of carbidopa greater than 200 mg is limited. For dosage beyond this recommendation, other brands of levodopa/ carbidopa may have to be used. (Patients may require more levodopa but no advantage will be gained by increasing the amount of carbidopa above 200 mg/day.)
Most patients can be maintained on 3 to 6 tablets a day and none should receive more than 8 tablets a day. No advantage will be gained by increasing the dosage of carbidopa beyond that provided by 8 tablets of Kinson. Patients may require additional levodopa. Dosage ranges recommended should usually not be exceeded.
Adjustment in the dosage of Kinson may be necessary.
Patients taking Kinson should be instructed not to take additional levodopa unless prescribed.

4.3 Contraindications

Monoamine oxidase inhibitors (MAOIs) and combination levodopa/ carbidopa monohydrate tablet should not be given concomitantly. MAOIs must be discontinued at least 2 weeks prior to initiating therapy with combination levodopa/ carbidopa monohydrate.
Kinson may be administered concomitantly with the manufacturer's recommended dose of a MAO inhibitor with selectivity for MAO type B, e.g. selegiline (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Other drugs).
Kinson is contraindicated in patients with known hypersensitivity to this drug or any component of this medication, and in patients with narrow angle glaucoma.
Because levodopa may activate a malignant melanoma, it should not be used in patients with suspicious undiagnosed skin lesions or history of melanoma.

4.4 Special Warnings and Precautions for Use

Combination levodopa/ carbidopa monohydrate tablet may be given to patients already receiving levodopa alone; however, the levodopa must be discontinued 12 hours before combination levodopa/ carbidopa monohydrate is started. Combination levodopa/ carbidopa monohydrate should be substituted at a dosage that will provide approximately 20% of the previous levodopa daily dosage (see Section 4.2 Dose and Method of Administration). Patients taking combination levodopa/ carbidopa monohydrate should be instructed not to take additional levodopa unless prescribed.
Combination levodopa/ carbidopa monohydrate is not recommended for the treatment of drug induced extrapyramidal reactions.
All patients should be monitored carefully for the development of mental changes, depression with suicidal tendencies, or other serious antisocial behaviour.
Dyskinesia may occur in patients previously treated with levodopa alone because carbidopa permits more levodopa to reach the brain and thus more dopamine to be formed. The occurrence of dyskinesia may require dosage reduction.
Patients with a history of severe involuntary movements or psychotic episodes when treated with levodopa alone should be observed carefully when combination levodopa/ carbidopa monohydrate is substituted. These reactions are thought to be due to increased brain dopamine following administration of levodopa and use of combination levodopa/ carbidopa monohydrate may cause a recurrence.
If concomitant administration of psychoactive drugs is necessary, such drugs should be administered with caution and patients carefully observed for loss of antiparkinsonian effect.
Patients with a history of convulsions should be treated with caution.
Levodopa has been associated with somnolence and episodes of sudden sleep onset. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with levodopa. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.
Patients with chronic wide angle glaucoma may be treated cautiously with combination levodopa/ carbidopa monohydrate, provided the intraocular pressure is well controlled and the patient monitored carefully for changes in intraocular pressure during therapy.
Care should be exercised in administering combination levodopa/ carbidopa monohydrate to patients who have atrial, nodal or ventricular arrhythmia. In such patients, cardiac function should be monitored continuously during the period of initial dosage adjustment.
Symptomatic postural hypotension has been reported occasionally. Therefore combination levodopa/ carbidopa monohydrate should be given cautiously to patients taking antihypertensive drugs. When combination levodopa/ carbidopa monohydrate tablet is started, dosage adjustment of the antihypertensive drug may be required. (For patients receiving pargyline, see Section 4.3 Contraindications on MAOIs.)
A symptom complex resembling the neuroleptic malignant syndrome including muscular rigidity, elevated body temperature, mental changes, and increased serum creatinine phosphokinase has been reported when antiparkinsonian agents were withdrawn abruptly. Therefore, patients should be observed carefully when the dosage of levodopa/ carbidopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
If general anaesthesia is required, therapy with combination levodopa/ carbidopa monohydrate may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the usual daily dosage may be administered as soon as the patient is able to take oral medication.
Combination levodopa/ carbidopa monohydrate tablet should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, as well as ulcer diseases or haematemesis. Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function are recommended during extended therapy.
As with levodopa, there is a possibility of upper gastrointestinal haemorrhage in patients with a history of peptic ulcer.

Melanoma.

Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2 to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear.
For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using combination levodopa/ carbidopa monohydrate tablet for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g. dermatologists).

Compulsive behaviour.

Patients should be regularly monitored for the development of impulse control disorders. Patients and caregivers should be made aware that behavioural symptoms of impulse control disorders (such as pathological gambling, hypersexuality, increased libido, compulsive spending/ buying, and binge eating, medication use and punding (repetitive purposeless activity)) has been reported in patients taking dopamine agonists for the treatment of Parkinson's disease, especially at high doses. In some patients, dopamine dysregulation syndrome (DDS), an addictive disorder which leads to excessive use of the medication, was observed during treatment with carbidopa/ levodopa. Review of treatment is recommended if such symptoms develop. Prescribers, patients and caregivers should be alert to the possibility of such behaviour, which may have serious financial and social consequences.

Use in hepatic impairment.

No data available.

Use in renal impairment.

No data available.

Use in the elderly.

No data available.

Paediatric use.

The safety of combination levodopa/ carbidopa monohydrate tablet in patients under 18 years of age has not been established.

Effects on laboratory tests.

Abnormalities in laboratory tests may include elevations of blood urea nitrogen, creatinine, SGOT, SGPT, LDH, bilirubin, alkaline phosphatase or protein bound iodine. More commonly, levels of blood urea nitrogen and uric acid are lower during the administration of combination levodopa/ carbidopa monohydrate than with levodopa.
Decreased haemoglobin and haematocrit; elevated serum glucose, white blood cells and bacteria; and blood in the urine have been reported.
Levodopa-carbidopa preparations may cause a false positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False negative tests may result with the use of glucose oxidase methods of testing for glycosuria.
Positive Coombs' tests have been reported both with combination levodopa/ carbidopa monohydrate and with levodopa alone, but haemolytic anaemia is rare.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Caution should be exercised when the following drugs are administered concomitantly with combination levodopa/ carbidopa monohydrate tablet.

Antihypertensive agents.

Symptomatic postural hypotension has occurred when levodopa/ decarboxylase inhibitor combinations were added to the treatment regimen of patients receiving some antihypertensive drugs. Therefore, when therapy with combination levodopa/ carbidopa monohydrate is started, dosage adjustment of the antihypertensive drug may be required.

Antidepressants.

For patients receiving monoamine oxidase inhibitors, (see Section 4.3 Contraindications). There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and levodopa-carbidopa preparations.
MAOIs and combination levodopa/ carbidopa monohydrate tablet should not be given concomitantly (see Section 4.3 Contraindications). The MAOIs must be discontinued at least 2 weeks prior to initiating therapy with combination levodopa/ carbidopa monohydrate.

Iron.

Studies demonstrate a decrease in the bioavailability of carbidopa and/or levodopa when it is ingested with ferrous sulfate or ferrous gluconate.

Anticholinergics.

Anticholinergic medications can act synergistically with levodopa to improve a tremor. However, concomitant use can worsen involuntary movement disorders by delaying absorption. Therefore, a dose adjustment of levodopa/ carbidopa may be necessary.

Other drugs.

Dopamine D2-receptor antagonists (e.g. phenothiazines, butyrophenones and risperidone), benzodiazepines and isoniazid may reduce the therapeutic effects of levodopa. The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with combination levodopa/ carbidopa monohydrate tablet should be observed carefully for loss of therapeutic response.
Use of combination levodopa/ carbidopa monohydrate tablet with dopamine depleting agents (e.g. reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.
Concomitant therapy with selegiline and levodopa/ carbidopa may be associated with severe orthostatic hypotension not attributable to levodopa/ carbidopa alone (see Section 4.3 Contraindications).
Sympathomimetics can exacerbate the cardiovascular adverse reactions to levodopa.
Since levodopa competes with certain amino acids the absorption of levodopa may be impaired in some patients on a high protein diet.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.
Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
Although the effects of combination levodopa/ carbidopa monohydrate on human pregnancy and lactation are unknown, levodopa caused visceral and skeletal malformations in rabbits at doses of 125 and 250 mg/kg/day. With combinations of levodopa and carbidopa in doses ranging from 250/50 to 500/100 mg/kg/day, there was no evidence of teratogenicity in mice but in rabbits, visceral and skeletal malformations occurred similar to those seen with levodopa alone. Carbidopa alone showed no evidence of teratogenicity in mice and rabbits at doses up to 120 mg/kg/day.
Combinations of levodopa and carbidopa in doses up to 100/10 mg/kg/day had no adverse effects on the reproductive performance of male or female rats or on the growth and survival of the pups.
Therefore, use of combination levodopa/ carbidopa monohydrate tablet in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards, should pregnancy occur.
 It is not known whether carbidopa is excreted in human milk. In a study of one nursing mother with Parkinson's disease, excretion of levodopa in human breast milk was reported. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in infants, combination levodopa/ carbidopa monohydrate tablet should not be used by breastfeeding mothers. A decision should be made either to discontinue breastfeeding or to discontinue levodopa/ carbidopa monohydrate tablet.

4.7 Effects on Ability to Drive and Use Machines

Patients being treated with levodopa and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such recurrent episodes and somnolence have resolved.

4.8 Adverse Effects (Undesirable Effects)

Side effects that occur frequently in patients receiving levodopa/ carbidopa are those due to the central neuropharmacological activity of dopamine. These reactions can usually be diminished by dosage reduction. The most common side effects are dyskinesias, including choreiform, dystonic, and other involuntary movements. Muscle twitching and blepharospasm may be taken as early signs to consider dosage reduction.
Other serious side effects are mental changes, including paranoid ideation and psychotic episodes including delusions, hallucinations; depression with or without development of suicidal tendencies; and dementia. A common, but less serious side effect is nausea.
Less frequent side effects are cardiac irregularities and/ or palpitations, orthostatic effects including hypotensive episodes, bradykinetic episodes (the "on-off" phenomenon), anorexia, vomiting, somnolence and dizziness.
Gastrointestinal bleeding, development of duodenal ulcer, hypertension, phlebitis, leucopoenia, haemolytic and non-haemolytic anaemia, thrombocytopenia, agranulocytosis, chest pain, dyspnoea and paraesthesia have occurred rarely.
Rarely, convulsions have occurred; however, a causal relationship with levodopa/ carbidopa has not been established.
Haemolytic anaemia is extremely rare.
Other side effects that have been reported include:

Body as a whole.

Syncope.

Nervous system.

Ataxia, increased hand tremor, muscle twitching, muscle cramps, trismus, activation of latent Horner's syndrome, oculogyric crises, peripheral neuropathy.

Psychiatric.

Confusion, insomnia, nightmares and dream abnormalities, hallucinations, delusions, agitation, anxiety, euphoria, lethargy, sedation, increased libido. Levodopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes. Dopamine dysregulation syndrome (DDS) has also been observed in some patients treated with carbidopa/ levodopa.

Gastrointestinal.

Dry mouth, bitter taste, sialorrhoea, dysphagia, bruxism, hiccups, epigastric and abdominal pain and distress, constipation, diarrhoea, flatulence, burning sensation of tongue, difficulty in swallowing, dark saliva.

Hypersensitivity.

Angioedema, urticaria, pruritus, Henoch-Schonlein purpura.

Investigations.

Weight gain, weight loss.

Metabolism and nutrition disorders.

Oedema, anorexia.

Integumentary.

Flushing, increased sweating, dark sweat, rash, hair loss, bad odour.

Genitourinary.

Urinary retention, urinary incontinence, dark urine, priapism, haematuria, urinary tract infection.

Special senses.

Diplopia, blurred vision, dilated pupils.

Miscellaneous.

Weakness, faintness, fatigue, headache, hoarseness, malaise, hot flushes, breast pain, sense of stimulation, bizarre breathing patterns, neuroleptic malignant syndrome, malignant melanoma (see Section 4.3 Contraindications).
Other side effects that have been associated with controlled release formulations and may therefore be potential side effects with immediate release formulations such as Kinson are:

Gastrointestinal.

Dyspepsia.

Nervous system/ psychiatric.

Asthenia, decreased mental acuity, disorientation, falling, gait abnormalities.

Post-marketing data.

In post marketing use, pathological (compulsive) gambling, increased libido, hypersexuality, compulsive spending/ buying, and binge/ compulsive eating have been reported with dopamine agonists and/or other dopaminergic treatments, and in patients treated with levodopa, including combination levodopa/ carbidopa monohydrate (see Section 4.4 Special Warnings and Precautions for Use).

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 the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Treatment.

Management of acute overdosage with combination levodopa/ carbidopa monohydrate is basically the same as management of acute overdosage with levodopa; however, pyridoxine is not effective in reversing the actions of levodopa/ carbidopa monohydrate.
In the event of overdosage, general supportive measures should be employed. Intravenous fluids should be administered judiciously and an adequate airway maintained. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as combination levodopa/ carbidopa monohydrate should be taken into consideration. To date, no experience has been reported with dialysis; hence its value in overdosage is not known.
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.

Symptoms of Parkinson's disease have been related to depletion of dopamine in the corpus striatum of the brain. Levodopa, the metabolic precursor of dopamine, relieves the symptoms of Parkinson's disease presumably by being converted to dopamine in the brain. Following oral administration, levodopa is rapidly decarboxylated and converted to dopamine in extracerebral tissues and only a small amount of unchanged levodopa reaches the central nervous system. Thus, large doses of levodopa are required at frequent intervals for adequate therapeutic effect and are often attended by many adverse reactions, some of which are attributable to dopamine being formed in extracerebral tissue.
Carbidopa, which does not cross the blood brain barrier, inhibits only extracerebral decarboxylation of levodopa, making more levodopa available for transport to the brain and conversion to dopamine. The lower dosage reduces or eliminates certain adverse reactions attributable to dopamine being formed in extracerebral tissues.
Following co-administration of levodopa and carbidopa in man, plasma levels of levodopa were markedly increased over those found when the same dosage of levodopa is given alone, while plasma levels of dopamine and homovanillic acid, two principal metabolites of levodopa, were markedly reduced.
Pyridoxine hydrochloride (vitamin B6) in oral doses of 10 mg to 25 mg have been noted to rapidly reverse the antiparkinsonian effect of levodopa. Carbidopa prevents this action of pyridoxine. In a study of patients who received 100 mg to 500 mg of pyridoxine a day whilst being treated with levodopa and carbidopa in combination there was no reversal of therapeutic effect.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Levodopa.

Levodopa is rapidly absorbed from the gastrointestinal tract and extensively metabolised. Although more than 30 metabolites may be formed, levodopa is mainly converted to dopamine and, in lesser amounts, to adrenaline (epinephrine) and noradrenaline (norepinephrine). These are ultimately metabolised to the principal excretion products, dopacetic acid, homovanillic acid and vanillylmandelic acid.
When single test doses of radioactive levodopa are given to fasting patients with Parkinson's disease, plasma levels of radioactivity peak at 0.5 to 2 hours and remain measurable for 4 to 6 hours. At peak levels, about 30% of the radioactivity appears as catecholamines, 15% as dopamine and 10% as dopa. The radioactive compounds are rapidly excreted in the urine, one-third of the dose appearing in the urine in 2 hours. 80 to 90% of urinary metabolites are phenylcarboxylic acids, principally homovanillic acid. Over 24 hours, 1 to 2% of recovered radioactivity is dopamine and less than 1% is adrenaline (epinephrine), noradrenaline (norepinephrine) and unchanged levodopa.

Carbidopa.

Following an oral dose of radioactive labelled carbidopa to healthy subjects and to patients with Parkinson's disease, maximum plasma levels of radioactivity were reached in 2 to 4 hours in the subjects and in 1.5 to 5 hours in the patients. Approximately equal quantities were excreted in the urine and the faeces by both groups.
A comparison of the urinary metabolites in healthy subjects and patients indicated that carbidopa is metabolised to the same degree in both. Urinary excretion of unchanged drug was essentially complete in 7 hours and represented 35% of the total urinary radioactivity. Only metabolites were present thereafter.
Among the metabolites excreted by humans are α-methyl-3- methoxy-4- hydroxy-phenylpropionic acid and α-methyl-3,4- dihydroxyphenylpropionic acid. These accounted for approximately 14% and 10%, respectively, of the radioactive metabolites excreted. Two minor metabolites were also found. One was identified as 3,4-dihydroxyphenylacetone and the other tentatively identified as N-methylcarbidopa. They each accounted for less than 5% of the urinary metabolites. Unchanged carbidopa is also present in urine. No conjugates were found.

Effect of carbidopa on levodopa metabolism.

Carbidopa consistently increased plasma levels of levodopa by statistically significant amounts, as measured against placebo, in healthy subjects. This has been demonstrated when carbidopa is given before levodopa and when the 2 drugs are given simultaneously. In one study, pre-treatment with carbidopa increased plasma levels of a single dose of levodopa about 5 times and extended the duration of measurable plasma concentrations of levodopa from 4 to 8 hours. When the 2 drugs were given simultaneously in other studies, similar results were obtained.
In a study in which a single dose of stem labelled levodopa was given to patients with Parkinson's disease who had been pre-treated with carbidopa, there was an increase in the half-life of total plasma radioactivity derived from the levodopa from 3 to 15 hours. The proportion of radioactivity remaining as unmetabolised levodopa was increased at least 3 times by carbidopa. Plasma and urinary dopamine and homovanillic acid were both decreased by carbidopa pre-treatment.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Kinson tablets contain the following inactive ingredients: microcrystalline cellulose, maize starch, sodium starch glycollate, purified talc, povidone, magnesium stearate, quinoline yellow, aluminium lake.

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 30°C.

6.5 Nature and Contents of Container

Container type: HDPE bottle with PP Child-resistant cap.
Pack sizes: 100 tablets.

Australian register of therapeutic goods (ARTG).

AUST R 49481 - Kinson levodopa 100 mg with carbidopa (as monohydrate) 25 mg tablet bottle.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Active ingredient: levodopa.

Chemical name: (-)-3-(3,4-dihydroxyphenyl)-L-alanine.
Structural formula:
Molecular formula: C9H11NO4. Molecular weight: 197.2.

Active ingredient: carbidopa.

Chemical name: L-(-)-2-(3,4-dihydroxybenzyl)-2-hydrazino-propionic acid monohydrate.
Structural formula:
Molecular formula: C10H14N2O4.H2O. Molecular weight: 244.3.
Levodopa, an aromatic amino acid, is a colourless, crystalline compound, slightly soluble in water and insoluble in alcohol.
Carbidopa, an inhibitor of aromatic amino acid decarboxylase, is a white, crystalline compound, slightly soluble in water.

CAS number.

Levodopa: 59-92-7.
Carbidopa: 28860-95-9.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes