Usual Initial Dosage
Dosage is best initiated with one tablet of SINEMET 25-100 three times a day. This dosage schedule provides 75 mg of Antiparkin per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of SINEMET 25-100 a day is reached.
If SINEMET 10-100 is used, dosage may be initiated with one tablet three or four times a day. However, this will not provide an adequate amount of Antiparkin for many patients. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (2 tablets q.i.d.) is reached.
As with levodopa, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended therapy.
Patients with chronic wide-angle glaucoma may be treated cautiously with Antiparkin and Levodopa extended-release tablets provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.
Levodopa alone, as well as Antiparkin and Levodopa extended-release tablets, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction.
Hallucinations / Psychotic-Like Behavior
Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In general, hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. Hallucinations may be accompanied by confusion and to a lesser extent sleep disorder (insomnia) and excessive dreaming.
Antiparkin and Levodopa extended-release tablets may have similar effects on thinking and behavior. This abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.
Ordinarily, patients with a major psychotic disorder should not be treated with Antiparkin and Levodopa extended-release tablets, because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effectiveness of Antiparkin and Levodopa extended-release tablets.
Impulse Control / Compulsive Behaviors
Reports of patients taking dopaminergic medications (medications that increase central dopaminergic tone), suggest that patients may experience an intense urge to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or the caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with Antiparkin and Levodopa extended-release tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking Antiparkin and Levodopa extended-release tablets .
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 Antiparkin and Levodopa extended-release tablets for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
Antiparkin levodopa drug interactions
Symptomatic postural hypotension has occurred when Antiparkin, given with levodopa or Antiparkin-levodopa combination products, was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with Antiparkin, given with or without levodopa or Antiparkin-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
For patients receiving monoamine oxidase inhibitors (Type A or B). Concomitant therapy with selegiline or rasigiline and Antiparkin and Antiparkin-levodopa may be associated with severe orthostatic hypotension not attributable to Antiparkin-levodopa alone.
There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and Antiparkin-levodopa preparations.
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 Antiparkin and levodopa or Antiparkin-levodopa combination products should be carefully observed for loss of therapeutic response.
Antiparkin and iron salts or multi vitamins containing iron salts should be co administered with caution. Iron salts can form chelates with levodopa and Antiparkin and consequently reduce the bioavailability of Antiparkin 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.
Droxidopa: Antiparkin may diminish the therapeutic effect of Droxidopa. Antiparkin may decrease serum concentrations of the active metabolite(s) of Droxidopa. Antiparkin may increase the serum concentration of Droxidopa. Monitor therapy
Spiramycin: May decrease the serum concentration of Antiparkin. And thus may decrease the effectiveness of levodopa. Monitor therapy
False-positive reaction for urinary glucose with Clinitest®; false-negative reaction using Clinistix®; false-positive urine ketones with Acetest®, Ketostix®, Labstix®.
When SINEMET is to be given to patients who are being treated with levodopa, levodopa must be discontinued at least twelve hours before therapy with SINEMET is started. In order to reduce adverse reactions, it is necessary to individualize therapy. See DOSAGE AND ADMINISTRATION section before initiating therapy.
The addition of Antiparkin with levodopa in the form of SINEMET reduces the peripheral effects (nausea, vomiting) due to decarboxylation of levodopa; however, Antiparkin does not decrease the adverse reactions due to the central effects of levodopa. Because Antiparkin permits more levodopa to reach the brain and more dopamine to be formed, certain adverse central nervous system (CNS) effects, e.g., dyskinesias (involuntary movements), may occur at lower dosages and sooner with SINEMET than with levodopa alone.
All patients should be observed carefully for the development of depression with concomitant suicidal tendencies.
SINEMET should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.
As with levodopa, care should be exercised in administering SINEMET to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care.
As with levodopa, treatment with SINEMET may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.
Are there any negatives to consider if I want to postpone starting Antiparkin/levodopa? The only symptom that I currently notice is tremor which affects my non-dominant hand and does not affect my daily functioning. I have no problems with my walking or balance and I exercise every day.
In general, there is no downside to postponing levodopa to treat a tremor that is not affecting function. Please discuss with your neurologist or physical therapist to determine if you are able to exercise effectively and up to your maximal capabilities while unmedicated. If you are not able to exercise maximally when untreated, then you should consider starting medication.
INDICATIONS AND USAGE
Antiparkin 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.
Hyperpyrexia and Confusion
Sporadic cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have been reported in association with dose reductions or withdrawal of certain antiparkinsonian agents such as levodopa, Antiparkin-levodopa, or Antiparkin-levodopa extended-release. Therefore, patients should be observed carefully when the dosage of levodopa or Antiparkin-levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
Neuroleptic malignant syndrome (NMS) is an uncommon but life-threatening syndrome characterized by fever or hyperthermia. Neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper-or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin, have been reported.
The early diagnosis of this condition is important for the appropriate management of these patients. Considering neuroleptic malignant syndrome (NMS) as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.
The management of neuroleptic malignant syndrome (NMS) should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene, are often used in the treatment of neuroleptic malignant syndrome (NMS); however, their effectiveness has not been demonstrated in controlled studies.
I have had PD for about 10 years. Over the years, the length of time that a particular dose of Antiparkin/levodopa works has gotten shorter. One dose used to last five hours, but recently, it lasts closer to three hours. In addition, sometimes my dose does not work at all. What is going on?
This shifting response to medication is known as motor fluctuations and can be a very significant challenge in the treatment of PD as the disease progresses. There are many strategies that your doctor can use to try to lengthen a dose of medication and even out your response to medication throughout the day. These strategies include changing the timing or strength of a dose, using different formulations of Antiparkin/levodopa, or adding other medications. All of these strategies are summarized in a recent APDA webinar on enhancing communication.
What is Sinemet?
Sinemet is a combination medicine used to treat symptoms of Parkinson's disease, such as muscle stiffness, tremors, spasms, and poor muscle control. Parkinson's disease may be caused by low levels of a chemical called dopamine (DOE pa meen) in the brain.
Levodopa is converted to dopamine in the brain. Antiparkin helps prevent the breakdown of levodopa before it can reach the brain and take effect.
Sinemet is also used to treat Parkinson symptoms caused by carbon monoxide poisoning or manganese intoxication.
Sinemet may also be used for purposes not listed in this medication guide.
In controlled clinical trials, patients predominantly with moderate to severe motor fluctuations while on Antiparkin and Levodopa tablets were randomized to therapy with either Antiparkin and Levodopa tablets or Antiparkin and Levodopa extended-release tablets. The adverse experience frequency profile of Antiparkin and Levodopa extended-release tablets did not differ substantially from that of Antiparkin and Levodopa, as shown in Table 1.
Table 1: Clinical Adverse Experiences Occurring in 1% or Greater of Patients
Nervous system side effects
Symptoms related to neuroleptic malignant syndrome are characterized by fever or hyperthermia. Other findings include neurological symptoms such as muscle rigidity, involuntary movements, altered consciousness, mental status changes, other disturbances such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper- or hypotension, and laboratory findings such as elevated creatine phosphokinase, leukocytosis, myoglobinuria, and increased serum myoglobin.
A causal relationship with concomitant Antiparkin and levodopa and the reported side effect of convulsions has not been established.
Frequency not reported: Bradykinetic episodes (“on-off” phenomenon), convulsions, dizziness, dyskinesias such as choreiform, dystonic and other involuntary movements, headache, neuroleptic malignant syndrome, oculogyric crises, paresthesia, peripheral neuropathy, somnolence, syncope, taste alterations
* For dosing ranges not shown in the table see DOSAGE AND ADMINISTRATION, Initial Dosage — Patients currently treated with conventional Antiparkin levodopa preparations.
Patients currently treated with levodopa without a decarboxylase inhibitor: Levodopa must be discontinued at least twelve hours before therapy with Antiparkin and Levodopa extended-release tablet is started. Antiparkin 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 Antiparkin 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 Antiparkin 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 Antiparkin 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 Antiparkin 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 Antiparkin 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 Antiparkin 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 Antiparkin and Levodopa extended-release tablets may be required.
Addition of Other Antiparkinson Medications
Anticholinergic agents, dopamine agonists, and amantadine can be given with Antiparkin and Levodopa extended-release tablets. Dosage adjustment of Antiparkin and Levodopa extended-release tablets may be necessary when these agents are added.
A dose of Antiparkin 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 Antiparkin 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 Antiparkin and Levodopa tablets or Antiparkin and Levodopa extended-release tablets.
Patients should be observed carefully if abrupt reduction or discontinuation of Antiparkin and Levodopa extended-release tablet is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)
If general anesthesia is required, Antiparkin 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.
Dizziness, lightheadedness, nausea, vomiting, loss of appetite, trouble sleeping, unusual dreams, or headache may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.
This medication may cause saliva, urine, or sweat to turn a dark color. This effect is harmless, but your clothes may be stained.
To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Some people taking this medication have fallen asleep suddenly during their usual daily activities (such as talking on the phone, driving). In some cases, sleep occurred without any feelings of drowsiness beforehand. This sleep effect may occur anytime during treatment with Antiparkin/levodopa even if you have used this medication for a long time. If you experience increased sleepiness or fall asleep during the day, do not drive or do other possibly dangerous activities until you have discussed this effect with your doctor. Your risk of this sleep effect is increased by using alcohol or other medications that can make you drowsy. See also Precautions section.
Tell your doctor right away if you have any serious side effects, including: new/worsening movements you can't control/spasms, greatly increased eye blinking/twitching, fainting, vision changes (such as blurred vision, double vision), eye pain, severe stomach/abdominal pain, black/tarry stools, vomit that looks like coffee grounds, mental/mood changes (such as agitation, hallucinations, depression, thoughts of suicide), signs of infection (such as sore throat that doesn't go away), easy bleeding/bruising, unusual tiredness, tingling of the hands/feet, unusual strong urges (such as increased gambling, increased sexual urges).
Get medical help right away if you have any very serious side effects, including: chest pain.
Abruptly stopping or reducing the dose of this medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, unusual muscle stiffness, severe confusion, sweating, fast/irregular heartbeat, rapid breathing.
A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
How should I take Antiparkin?
Follow all directions on your prescription label. Do not take Antiparkin in larger or smaller amounts or for longer than recommended.
Take both Antiparkin and levodopa at the same time.
If you already take levodopa but have never taken Antiparkin before, start taking both medicines at least 12 hours after you last took levodopa by itself.
Use Antiparkin with levodopa regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.
While using this medicine, you may need frequent blood tests. Your heart, kidney function, and liver function may also need to be checked.
It may take up to several weeks of using Antiparkin with 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.
Do not stop using Antiparkin suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using this medicine.
This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using Antiparkin with levodopa.
Store at room temperature away from moisture and heat.