Management of acute overdosage with Sinepar and Levodopa extended-release tablet is the same as with levodopa. Pyridoxine is not effective in reversing the actions of Sinepar and Levodopa extended-release tablets.
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 Sinepar and Levodopa extended-release tablets should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known.
Based on studies in which high doses of levodopa and/or Sinepar were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1500 to 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 Sinepar. The addition of Sinepar 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.
In the clinical efficacy trials for Sinepar and Levodopa tablets, almost half of the patients were older than 65, but few were older than 75. No overall meaningful differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals to adverse drug reactions such as hallucinations cannot be ruled out. There is no specific dosing recommendation based upon clinical pharmacology data as Sinepar and Levodopa tablets and Sinepar and Levodopa extended-release tablets are titrated as tolerated for clinical effect.
Sinepar side effects
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 Sinepar 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);
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 Sinepar 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:
sleep problems (insomnia), dreaming more than usual;
dry mouth, burning feeling in your tongue;
weight changes; or
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.
Caution should be exercised when the following drugs are administered concomitantly with SINEMET.
Symptomatic postural hypotension occurred when SINEMET was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with SINEMET is started, dosage adjustment of the antihypertensive drug may be required.
For patients receiving MAO inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline and Sinepar levodopa may be associated with severe orthostatic hypotension not attributable to Sinepar levodopa alone (see CONTRAINDICATIONS).
There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and SINEMET.
Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with SINEMET should be carefully observed for loss of therapeutic response.
Use of SINEMET with dopamine-depleting agents (e.g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.
SINEMET and iron salts or multivitamins containing iron salts should be coadministered with caution. Iron salts can form chelates with levodopa and Sinepar and consequently reduce the bioavailability of Sinepar and levodopa.
Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.
What are the side effects of levodopa-Sinepar?
Most patients receiving Sinepar-levodopa experience side effects, but these usually are reversible.
Gastrointestinal side effects are common in patients receiving Sinepar-levodopa and these include:
Patients may experience dizziness upon standing up, associated with a drop in blood pressure. Fortunately, the body develops tolerance to this side effect within a few months.
Other important side effects of Sinepar-levodopa therapy include:
Occasional involuntary movements are the most common of the serious side effects of Sinepar-levodopa therapy, and these are:
- muscle twitching,
- muscle jerks during sleep,
- hand tremor,
- tongue or
- mouth movements,
- head bobbing, or
- movements of the feet, hands, or shoulder which may respond to a reduction in the dose.
Infrequently, patients may develop a drop in white blood cell count during Sinepar-levodopa therapy. This is a significant reason to temporarily, if not permanently, stop treatment.
I noticed that I have increased trouble with my symptoms when I eat a meal containing protein. How do I adjust my diet to accommodate this?
Dietary protein can interfere with Sinepar/levodopa absorption in some people. This is known as the “protein effect.” The two ways to adjust your diet is to:
- Ingest your daily protein at the end of the day, so that you do not have the protein effect during your active time
- Divide your protein evenly throughout the day – that way, the medication absorption should theoretically be similar throughout the day. This begs the question of how to do that – how to estimate how much protein is in each food that you want to eat in order to spread the protein out evenly. For this, I refer you to one of the APDA webinars discussing nutritional issues related to PD, including the protein effect and how to estimate the protein in different foods. Nutrition issues are covered in the second half of the webinar.
Titration of carbidpa and levodopa (individually)
- Administer 25 mg Sinepar PO q6-8hr concurrently with levodopa; administer 20-25% less than the previous levodopa in Sinepar naive patients; first dose of Sinepar should be taken ≤12hr after the test dose of levodopa in Sinepar naive patients; increase or decrease dose by 1/2 or 1 tab/day
Safety & efficacy in children not established
* For dosing ranges not shown in the table see DOSAGE AND ADMINISTRATION, Initial Dosage — Patients currently treated with conventional Sinepar levodopa preparations.
Patients currently treated with levodopa without a decarboxylase inhibitor: Levodopa must be discontinued at least twelve hours before therapy with Sinepar and Levodopa extended-release tablet is started. Sinepar and Levodopa extended-release tablets should be substituted at a dosage that will provide approximately 25% of the previous levodopa dosage. In patients with mild to moderate disease, the initial dose is usually 1 tablet of Sinepar and Levodopa extended-release tablet 50 mg/200 mg b.i.d.
Patients not receiving levodopa: In patients with mild to moderate disease, the initial recommended dose is 1 tablet of Sinepar and Levodopa extended-release tablet 50 mg/200 mg b.i.d. Initial dosage should not be given at intervals of less than 6 hours.
Titration with Sinepar and Levodopa Extended-Release Tablets
Following initiation of therapy, doses and dosing intervals may be increased or decreased depending upon therapeutic response. Most patients have been adequately treated with doses of Sinepar and Levodopa extended-release tablets that provide 400 to 1600 mg of levodopa per day, administered as divided doses at intervals ranging from 4 to 8 hours during the waking day. Higher doses of Sinepar and Levodopa extended-release tablets (2400 mg or more of levodopa per day) and shorter intervals (less than 4 hours) have been used, but are not usually recommended.
When doses of Sinepar and Levodopa extended-release tablets are given at intervals of less than 4 hours, and/or if the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day.
An interval of at least 3 days between dosage adjustments is recommended.
Because Parkinson’s disease is progressive, periodic clinical evaluations are recommended; adjustment of the dosage regimen of Sinepar and Levodopa extended-release tablets may be required.
Addition of Other Antiparkinson Medications
Anticholinergic agents, dopamine agonists, and amantadine can be given with Sinepar and Levodopa extended-release tablets. Dosage adjustment of Sinepar and Levodopa extended-release tablets may be necessary when these agents are added.
A dose of Sinepar levodopa immediate release 25 mg/100 mg or 10 mg/100 mg (one half or a whole tablet) can be added to the dosage regimen of Sinepar and Levodopa extended-release tablets in selected patients with advanced disease who need additional immediate-release levodopa for a brief time during daytime hours. Interruption of Therapy
Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of Sinepar and Levodopa tablets or Sinepar and Levodopa extended-release tablets.
Patients should be observed carefully if abrupt reduction or discontinuation of Sinepar and Levodopa extended-release tablet is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)
If general anesthesia is required, Sinepar and Levodopa extended-release tablets may be continued as long as the patient is permitted to take oral medication. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual dosage should be administered as soon as the patient is able to take oral medication.
INDICATIONS AND USAGE
Sinepar and Levodopa extended-release tablets, USP are indicated in the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.
Sinepar/Levodopa: Answers to Frequently Asked Questions
Loss of neurons in the brain that use dopamine to communicate is one of the hallmark features of Parkinson’s disease (PD), causing slowness, stiffness, tremor and balance problems. Replacing the brain’s dopamine is therefore one of the key treatment strategies to help improve the motor symptoms of PD. Dopamine itself does not cross the blood-brain barrier and therefore can’t be used to treat PD. Instead levodopa, a precursor of dopamine, which does cross the blood-brain barrier is used. If levodopa is ingested by itself however, it breaks down in the bloodstream before it crosses into the brain, so levodopa is typically ingested with another medication that stops it from breaking down. In the US, the combination of Sinepar/levodopa is used. When levodopa is taken with Sinepar, much lower doses of levodopa can be consumed and side effects such as nausea are minimized. Sinepar/levodopa is the mainstay of treatment for PD and is the most effective medication available for PD. APDA research funding played a role in the discovery of levodopa for PD treatment, when we funded the work of Dr. George C. Cotzias back in the 1960s.
Despite its common and widespread use as a treatment for PD, our readers often have questions about Sinepar/levodopa therapy. This week I will address some of these common questions that have been sent to us by readers like you. (If you have questions or a blog topic to suggest, let us know!)
How should I take Sinepar and levodopa?
If you already take levodopa, you must stop taking it at least 12 hours before you start taking Sinepar and levodopa.
Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.
Sinepar and levodopa can be taken with or without food. Take your doses at regular intervals to keep a steady amount of the drug in your body at all times. Get your prescription refilled before you run out of medicine completely.
Do not crush, chew, break, or open a Sinepar and levodopa capsule. Swallow it whole.
The tablet is sometimes broken in half to give the correct dose. Always swallow a whole or half tablet without chewing or crushing.
To take the orally disintegrating tablet (Parcopa):
- Keep the tablet in the bottle until you are ready to take it.
- Use dry hands to remove the tablet and place it on your tongue.
- Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing. Swallow several times as the tablet dissolves.
It may take up to several weeks of using Sinepar and levodopa before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after a few weeks of treatment. Also tell your doctor if the effects of this medication seem to wear off quickly in between doses.
If you use this medicine long-term, you may need frequent medical tests at your doctor's office.
This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using Sinepar and levodopa.
Do not stop using Sinepar and levodopa suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using Sinepar and levodopa.
Store at room temperature away from moisture, heat, and light.
DOSAGE AND ADMINISTRATION
Sinepar and Levodopa extended-release tablet contains Sinepar and Levodopa in a 1:4 ratio as either the 25 mg/100 mg tablet or the 50 mg/200 mg tablet. The daily dosage of Sinepar and Levodopa extended-release tablets must be determined by careful titration. Patients should be monitored closely during the dose adjustment period, particularly with regard to appearance or worsening of involuntary movements, dyskinesias or nausea. Sinepar and Levodopa extended-release tablets should not be chewed or crushed.
Standard drugs for Parkinson’s disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while Sinepar and Levodopa extended-release tablet is being administered, although their dosage may have to be adjusted.
Since carb >6 ). Initial Dosage
Patients currently treated with conventional Sinepar levodopa preparations: Studies show that peripheral dopa-decarboxylase is saturated by the bioavailable carb >
Table 2: Approximate Bioavailabilities at Steady State *
Why is this medication prescribed?
The combination of levodopa and Sinepar is used to treat the symptoms of Parkinson's disease and Parkinson's-like symptoms that may develop after encephalitis (swelling of the brain) or injury to the nervous system caused by carbon monoxide poisoning or manganese poisoning. Parkinson's symptoms, including tremors (shaking), stiffness, and slowness of movement, are caused by a lack of dopamine, a natural substance usually found in the brain. Levodopa is in a class of medications called central nervous system agents. It works by being converted to dopamine in the brain. Sinepar is in a class of medications called decarboxylase inhibitors. It works by preventing levodopa from being broken down before it reaches the brain. This allows for a lower dose of levodopa, which causes less nausea and vomiting.