Lodosyn

LODOSYN is indicated for use with carbidopa-levodopa or with levodopa in the treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism, which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.

LODOSYN is for use with carbidopa-levodopa in patients for whom the dosage of carbidopa-levodopa provides less than adequate daily dosage (usually 70 mg daily) of carbidopa.

LODOSYN is for use with levodopa in the occasional patient whose dosage requirement of carbidopa and levodopa necessitates separate titration of each medication.

LODOSYN is used with carbidopa-levodopa or with levodopa to permit the administration of lower doses of levodopa with reduced nausea and vomiting, more rapid dosage titration, and with a somewhat smoother response. However, patients with markedly irregular (“on-off”) responses to levodopa have not been shown to benefit from the addition of carbidopa.

Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, supplemental pyridoxine (vitamin B6), can be given to patients when they are receiving carbidopa and levodopa concomitantly or as carbidopa-levodopa.

Although the administration of LODOSYN permits control of parkinsonism and Parkinson's disease with much lower doses of levodopa, there is no conclusive evidence at present that this is beneficial other than in reducing nausea and vomiting, permitting more rapid titration, and providing a somewhat smoother response to levodopa.

Certain patients who responded poorly to levodopa alone have improved when carbidopa and levodopa were given concurrently. This was most likely due to decreased peripheral decarboxylation of levodopa rather than to a primary effect of carbidopa on the peripheral nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa.

In deciding whether to give LODOSYN with carbidopa-levodopa or with levodopa to patients who have nausea and/or vomiting, the physician should be aware that, while many patients may be expected to improve, some may not. Since one cannot predict which patients are likely to improve, this can only be determined by a trial of therapy. It should be further noted that in controlled trials comparing carbidopa and levodopa with levodopa alone, about half the patients with nausea and/or vomiting on levodopa alone improved spontaneously despite being retained on the same dose of levodopa during the controlled portion of the trial.

It is important that LODOSYN with levodopa be taken at regular intervals according to the schedule outlined by the health care provider. Caution patients not to change the prescribed dosage regimen and not to add any additional antiparkinson medications, including other carbidopa-levodopa preparations without first consulting a physician.

Advise patients that sometimes a 'wearing-off' effect may occur at the end of the dosing interval. Tell patients to notify the prescriber if such response poses a problem to lifestyle.

Patients should be advised that occasionally dark color (red, brown, or black) may appear in saliva, urine, or sweat after ingestion of LODOSYN and levodopa. Although the color appears to be clinically insignificant, garments may become discolored.

The patient should be advised that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying thus delaying the absorption of levodopa. Iron salts (such as in multivitamin tablets) may also reduce the amount of levodopa available in the body. The above factors may reduce the clinical effectiveness of the LODOSYN and levodopa therapy.

Alert patients to the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including levodopa. Advise patients to exercise caution while driving or operating machinery and that if they have experience somnolence and/or sudden sleep onset, they must refrain from these activities. (See WARNINGS, Falling Asleep During Activities of Daily Living and Somnolence General.)

There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson's disease, including LODOSYN and levodopa. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges, or other intense urges while taking LODOSYN and levodopa. Physicians should consider dose reduction or stopping Lodosyn and levodopa if a patient develops such urges while taking Lodosyn with carbidopa/levodopa (See PRECAUTIONS, Impulse Control/Compulsive Behaviors).

Your pharmacist can provide more information about carbidopa.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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You should not use carbidopa if you have narrow-angle glaucoma.

Do not use this medicine if you have used an MAO inhibitor in the past 14 days, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

The following side effects may occur when carbidopa is taken with levodopa.

Call your doctor at once if you have:

• uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);

• worsening of tremors (uncontrolled shaking);

• severe nausea, vomiting, or diarrhea;

• confusion, hallucinations, unusual changes in mood or behavior;

• depression or suicidal thoughts;

• seizure (convulsions); or

• severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Some people taking carbidopa with levodopa have fallen asleep during normal daytime activities such as working, talking, eating, or driving. Tell your doctor if you have any problems with daytime sleepiness or drowsiness.

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medicine. Talk with your doctor if this occurs.

You may notice that your sweat, urine, or saliva appears dark in color, such as red, brown, or black. This is not a harmful side effect, but it may cause staining of your clothes or bed sheets.

Common side effects may include:

• nausea, upset stomach;

• headache, dizziness;

• sleep problems (insomnia), dreaming more than usual;

• dry mouth, burning feeling in your tongue;

• weight changes; or

• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Manifestations of parkinsonian syndrome related to depletion of dopamine in the corpus striatum.104 105 106 107

• Levodopa relieves symptoms of parkinsonism presumably by increasing dopamine concentrations in the brain.104 105 106 107

• It is used to treat Parkinson's disease.
• It is used to treat signs like Parkinson's disease caused by other health problems.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Headache.
• Dry mouth.
• Feeling sleepy.
• Not able to sleep.
• Upset stomach or throwing up.
• Change in taste.
• Hard stools (constipation).
• Loose stools (diarrhea).
• Not hungry.
• Strange or odd dreams.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Lodosyn is contraindicated in patients with known hypersensitivity to any component of this drug.

Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with levodopa or carbidopa-levodopa combination products with or without Lodosyn. These inhibitors must be discontinued at least two weeks prior to initiating therapy with levodopa. Carbidopa-levodopa, or levodopa may be administered concomitantly with the manufacturer’s recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (see PRECAUTIONS, Drug Interactions).

Levodopa or carbidopa-levodopa products, with or without Lodosyn, are contraindicated in patients with narrow-angle glaucoma.

No reports of overdose with Lodosyn have been received. Management of overdosage with carbidopa is the same as that with levodopa or carbidopa-levodopa preparations.

In the event of overdosage, general supportive measures should be employed, along with immediate gastric lavage. 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 Lodosyn should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known. Pyridoxine is not effective in reversing the actions of Lodosyn.

Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1500-2000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3360 mg/kg.

Whether given with carbidopa-levodopa or with levodopa, the optimal daily dose of

Lodosyn must be determined by careful titration. Most patients respond to a 1:10

proportion of carbidopa and levodopa, provided the daily dosage of carbidopa is 70 mg or

more a day. The maximum daily dosage of carbidopa should not exceed 200 mg, since

clinical experience with larger dosages is limited. If the patient is taking carbidopa-levodopa,

the amount of carbidopa in carbidopa-levodopa should be considered when calculating the

total amount of Lodosyn to be administered each day.

Patients Receiving Carbidopa-Levodopa Who Require Additional Carbidopa

Some patients taking carbidopa-levodopa may not have adequate reduction in nausea and

vomiting when the dosage of carbidopa is less than 70 mg a day, and the dosage of levodopa

is less than 700 mg a day. When these patients are taking carbidopa-levodopa, 25 mg of Lodosyn may be given with the first dose of carbidopa-levodopa each day. Additional doses of 12.5 mg or 25 mg may be given during the day with each dose of carbidopa-levodopa. Lodosyn may be given with any dose of carbidopa-levodopa as required for optimum therapeutic response. The maximum daily dosage of carbidopa, given as Lodosyn

and as carbidopa-levodopa, should not exceed 200 mg.

Patients Requiring Individual Titration of Carbidopa and Levodopa Dosage

Although carbidopa-levodopa is the most frequently used of carbidopa and levodopa

administration, there may be an occasional patient who requires individually titrated doses of

these two drugs. In these patients, Lodosyn (carbidopa) should be initiated at a dosage

of 25 mg three or four times a day. The two drugs should be given at the same time,

starting with no more than one-fifth (20%) to one-fourth (25%) of the previous or

recommended daily dosage of levodopa when given without Lodosyn (carbidopa). In

patients already receiving levodopa therapy, at least twelve hours should elapse between

the last dose of levodopa and initiation of therapy with Lodosyn (carbidopa) and

levodopa. A convenient way to initiate therapy in these patients is in the morning

following a night when the patient has not taken levodopa for at least twelve hours.

Health care providers who prescribe separate doses of Lodosyn and levodopa should be

thoroughly familiar with the directions for use of each drug.

Dosage Adjustment

Dosage of Lodosyn may be adjusted by adding or omitting one-half or one tablet a day. Because both therapeutic and adverse responses occur more rapidly with combined therapy than when only levodopa is given, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly when Lodosyn and levodopa are given concomitantly than when levodopa is given without Lodosyn. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.

Current evidence indicates other standard antiparkinsonian drugs may be continued while carbidopa and levodopa are being administered. However, the dosage of such other standard antiparkinsonian drugs

may require adjustment.

Interruption of Therapy

Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and

withdrawal of carbidopa-levodopa) or carbidopa-levodopa extended release. Patients should

be observed carefully if abrupt reduction or discontinuation of carbidopa-levodopa or

carbidopa-levodopa extended release is required, especially if the patient is receiving

neuroleptics. (See WARNINGS.)

If general anesthesia is required, therapy may be continued as long as the patient is permitted to take fluids and medication by mouth. When therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual daily dosage may be resumed as soon as the patient is able to take medication orally.