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Sinemet (Carbidopa-Levodopa) Side Effects & Adverse Reactions (List)

Sinemet is a pharmaceutical drug engineered by Merck that combines Carbidopa (a peripheral enzymatic inhibitor of DOPA decarboxylase) and Levodopa (an agent that crosses the blood-brain barrier to increase central concentrations of dopamine); hence it is frequently referred to as “Carbidopa-Levodopa.”  The drug was initially approved by the U.S. FDA in 1988 for the treatment of idiopathic Parkinson’s disease.  Individuals with Parkinson’s disease generally exhibit degeneration and ultimately depletion of dopamine-producing neurons in the striatum.

Depletion of striatal dopamine neurons leads to deficits in dopaminergic signaling throughout the entire basal ganglia, causing motor symptoms such as:  bradykinesia (slow movement), postural instability, resting tremor, and rigidity.  Although Sinemet does not interfere with the insidious progression of Parkinson’s disease, it generally improves motor function among most users.  It accomplishes this by increasing dopamine concentrations, thereby enhancing dopaminergic innervation throughout the basal ganglia.

Patients with Parkinson’s disease often attribute significant increases in overall functionality and quality of life to Sinemet (Carbidopa-Levodopa).  Despite the fact that many users find Sinemet therapeutically effective, it is clearly not devoid of side effects.  For many individuals, the side effects associated with Sinemet worsen with continued treatment, eventually outweighing the benefits and rendering the drug intolerable.

Sinemet (Carbidopa-Levodopa) Side Effects & Adverse Reactions (List)

Compiled below is a list of side effects and adverse reactions associated with Sinemet (Carbidopa-Levodopa).  Understand that the total number of side effects, their respective severities, as well as the specific side effects that you experience – will be subject to interindividual variation.  In other words, the side effects you notice during treatment with Sinemet may differ significantly from someone else.

That said, since Sinemet exerts a consistent dopaminergic effect across all users, some side effects are more frequently reported than others.  Examples of the most common Sinemet side effects include: blurred vision, confusion, dizziness, drowsiness, dry mouth, dyskinesia, hallucinations, orthostatic hypotension, nausea, and vomiting.  If you are concerned with any particular side effect or have questions, consult a medical professional.

Anxiety: Though the progression of Parkinson’s disease can induce anxiety, treatments such as Sinemet also may provoke anxious thoughts.  The side effect of anxiety may be more common among those who are taking too potent of a dose, leading to abnormally high dopamine concentrations in certain regions of the brain.  Since the dopaminergic system is often overactive in states of fear and/or anxiety, improper dosing is most likely to trigger anxiety as a side effect.

Do not be surprised if Sinemet makes you feel nervous, jittery, or anxious in situations that were previously relaxing or comfortable.  You may find yourself overthinking things and/or ruminating excessively during treatment.  Some individuals may find themselves becoming excessively anxious to the extent of paranoia; this may be a sign of treatment-induced psychosis.

Other users may experience anxiety as a reactive response to other side effects such as hallucinations or delusions.  If after taking Sinemet you are anxious about specific side effects or have a difficult time coping with the side effect of anxiety, do not hesitate to contact your doctor.  There may be some adjuvant options that’ll help attenuate the disconcerting side effect of anxiety.

Appetite loss: The dopaminergic stimulation provided from Sinemet may affect your appetite.  Specifically, you’re most likely to experience a decreased appetite as a result of elevations in dopamine.  Heightened concentrations of dopamine are understood to potentiate feelings of satiety, thereby resulting in fewer food cravings and urges to eat; you may feel full all the time.

In other cases, a reduced appetite during treatment may stem from several other side effects such as nausea and vomiting.  It’s relatively difficult to maintain an appetite if you’re constantly feeling nauseated.  Be cognizant of this appetite loss and realize that it may promote some weight loss.  Do your best to eat sufficient calories from nutrient-dense foods to maintain your overall health.

Blood pressure changes: Some individuals may find that Sinemet causes fluctuations in blood pressure.  Among the most common side effects of Sinemet is orthostatic hypotension or abrupt decreases in blood pressure while transitioning from a seated position (or lying down) to an upright standing position.  Orthostatic hypotension may lead to feelings of dizziness, lightheadedness, and could cause some users to faint.

If you are taking any blood pressure medications (e.g. antihypertensive agents) along with Sinemet, it is imperative that your doctor rules out contraindications prior to treatment.  Individuals with a history of blood pressure abnormalities (e.g. hypertension) and/or other cardiac conditions should monitor blood pressure regularly during treatment.  Sometimes an adjustment in dosing and/or medical advice can help prevent treatment-induced blood pressure alterations.

Blurred vision: While taking Sinemet, you may notice that your vision becomes blurry.  The side effect of blurred vision may be associated with altered neural activation in the visual processing regions of the brain and/or turnover of neurotransmitters.  Blurred vision is a common side effect of many neuropsychiatric drugs and is likely stems directly from adjustments in neurochemistry.

Fortunately, blurred vision isn’t caused by actual damage to the eyes and often subsides with continued Sinemet administration.  If you are concerned that your eyesight may be worsening as a result of Sinemet, it is recommended to consult an ophthalmologist for an optical assessment.  That said, there is some evidence to suggest that Sinemet could exacerbate preexisting glaucoma; those with narrow-angle glaucoma are recommended against using this drug.

Cold-like symptoms: During treatment with Sinemet, you may feel as if you’ve come down with the “common cold” characterized by headaches, itchiness, sneezing, and a stuffy nose.  Although you may actually have a cold or infection, cold-like symptoms are also reported side effects of Sinemet.  Therefore, it may be difficult to distinguish as to whether you legitimately are sick from some sort of cold virus or whether these effects were induced by the Carbidopa-Levodopa combination.

If you experience cold-like symptoms in your first few weeks of treatment, they are more likely to be a reaction to the treatment.  On the other hand, if you’ve been taking Sinemet for awhile and have developed cold-like symptoms without a change in dosing (or addition of another agent), it’s more likely to be an actual cold.  Always discuss these cold-like symptoms with your doctor to rule out: other medical conditions, allergic reactions, and contraindications.

Confusion: Although neurodegeneration associated with Parkinson’s disease can cause confusion (especially in severe cases), confusion is also a recognized side effect of Sinemet treatment.  The side effect of confusion resulting from Sinemet administration may be characterized by: brain fog (inability to think clearly), disorganized thinking, lack of focus, and memory problems (retrieval difficulties).  Since confusion can interfere with ability to function in social and occupational settings, it should be considered an impairing side effect.

Certain individuals may find that confusion subsides as they adjust to ongoing administration of Carbidopa-Levodopa.  Others may experience confusion as a side effect, regardless of the duration over which they’ve been taking Sinemet.  If you feel extremely confused while taking Carbidopa-Levodopa, discuss possible ways to decrease this side effect with your doctor.

Constipation: Many individuals report constipation as a side effect of Sinemet treatment.  In certain users, the Carbidopa-Levodopa combination may slow the shuttling of food through the gastrointestinal tract and lead to infrequent bowel movements.  This constipation may also be accompanied by indigestion and stomach aches.

If you’ve become constipated as a result of Sinemet, your doctor may recommend increasing: physical activity, dietary fiber, and/or fluid intake – these should all help with constipation.  Additionally, for those with extreme constipation (as a side effect), an oral laxative may help normalize frequency of bowel movements.  Also keep in mind that constipation may be a transient side effect in that it subsides after several weeks of Carbidopa-Levodopa treatment.

Delusions: An unfortunate psychiatric side effect of Sinemet that occurs in a subset of users is deluded thinking.  If a Sinemet user experiences delusions, he/she may develop new beliefs and hold them with 100% conviction, despite the fact that they are inaccurate with no basis in reality.  There are many types of delusions that may plague a Sinemet user such as: that the government is spying on them, that they are suddenly famous, or that a deity (e.g. God) has sent them on a special mission.

These drug-induced delusions are associated with dysfunctional transmission of dopamine and may be accompanied by hallucinations and/or full-blown psychosis.  Delusions are considered a hallmark positive symptom of schizophrenia and may be related to a surplus of dopaminergic signaling in the mesolimbic pathway.  Moreover, delusions often contribute to bizarre, erratic, and unpredictable behaviors.

Family members and friends of those taking Sinemet should be informed of delusions as a potential side effect of the medication.  If delusions are experienced by the user, he/she will necessitate reevaluation by a medical professional.  Sometimes a reduction in dosing and/or medication change may be necessary to avoid delusions.

Depression: While Sinemet may improve symptoms of depression associated with Parkinson’s disease in some users, the antidepressant relief is often difficult to sustain.  Users generally build-up tolerance to the initial mood enhancement provided by Sinemet and end up increasingly depressed throughout treatment.  This is because the brain may downregulate dopaminergic processes as a result of regular Sinemet administration, leading to abnormally low dopamine signaling.

Other individuals may notice that their mood becomes increasingly depressed after just a few days or weeks of treatment.  Since the levodopa within Sinemet alters dopaminergic systems throughout the entire brain (not solely isolated to regions affected by Parkinson’s), regions unaffected by Parkinson’s pathology may not react favorably to the excess dopamine.  As a result, the altered neurochemistry of any particular user may induce depression.

Diarrhea: A very common side effect of Sinemet (Carbidopa-Levodopa) is diarrhea.  Those experiencing diarrhea often notice that the drug causes an upset stomach, thereby irritating their gastrointestinal tract and digestive system.  Irritation of the gastrointestinal tract may expedite the shuttling of food through the digestive tract and lead to frequent bowel movements with loose stools.

One way to potentially decrease likelihood of diarrhea is to take Sinemet along with food or after a big meal; this may reduce gastrointestinal irritation as caused by the medication.  In some cases, diarrhea may subside with ongoing treatment as the body continues to adjust to Sinemet.  However, if diarrhea is unremitting, some individuals may want to consider an over-the-counter antidiarrheal agent such as Imodium.

Dizziness: Another extremely common side effect of Sinemet is mild to moderate dizziness.  Some users report that the dizziness is most extreme when initially starting treatment and that it subsides with time.  Others find that dizziness persists throughout treatment, but that its severity decreases with continued Sinemet administration.

Mild dizziness (possibly accompanied by lightheadedness) may be a normal side effect of the medication that you’ll have to simply accept as part of treatment.  However, if you feel extremely dizzy to the extent that you have difficulty maintaining balance or functioning, it should be discussed with a medical professional.  Also beware of the fact that dizziness may occur as a result of orthostatic hypotension (abrupt decrease in blood pressure) – another side effect that may cause fainting.

Drowsiness: Among the most common side effects of Sinemet treatment is drowsiness.  You may notice that you feel drowsier than usual throughout the day, possibly leading to fatigue, lethargy, or sleepiness.  New users of Sinemet are encouraged to refrain from operating a motor vehicle and/or heavy machinery due to the fact that the side effect of drowsiness may impair psychomotor vigilance and reaction times.

It is understood that drowsiness may compromise your ability to perform cognitively-demanding tasks and/or function in occupational settings.  If you dislike the drowsiness resulting from Sinemet, you may wish to discuss dosage adjustments and/or attenuators with a medical professional.  In some cases, drowsiness may improve as a user’s neurophysiology adapts to the drug.

Dry mouth: A side effect that many Sinemet users report is dry mouth.  Your neurophysiology may respond to the drug by decreasing oral salivary production, thereby leaving the mucous membranes within your mouth completely parched.  While dry mouth may be modestly uncomfortable, it is usually not considered a problematic side effect.

However, it is important to realize that ongoing extreme cases of dry mouth may allow for the proliferation of bad bacteria.  Bacterial proliferation in oral cavities due to lack of saliva may lead to halitosis and/or compromise dental health.  If Sinemet dries out your mouth, you may want to discuss the implications with a dentist.

Dyskinesia: Sinemet is regarded as an effective agent in correcting motor dysfunction resulting from Parkinson’s disease, however, it may also trigger dyskinesia as a side effect.  Dyskinesia is characterized by involuntary, abnormal muscle movements and/or lack of voluntary muscle control.  Levodopa-induced dyskinesia (LID) is estimated to occur in 9% to 80% of levodopa users.

If you notice dyskinesia at any time during treatment, it should be immediately reported to a medical professional.  Once levodopa-induced dyskinesia is fully established, it is highly-difficult to treat.  Various mitigation strategies may be employed to decrease and/or prevent levodopa-induced dyskinesia including: dosage reduction (with possible adjunct of a dopamine agonist), administration of amantadine, usage of atypical neuroleptics, and/or neurosurgery.

Hallucinations: A common, yet troubling side effect of Sinemet is hallucinations.  Hallucinations are characterized as bizarre sensory perceptions with no legitimate basis in reality.  They are typically caused by dopaminergic dysregulation, particularly in the mesolimbic region and may be accompanied by delusions.

The hallucinations experienced by Sinemet users are most likely to be auditory (e.g. hearing voices) and/or visual (e.g. seeing creatures), but may involve other senses as well such as touch, taste, or smell.  Hallucinations generally subside with recalibration of Sinemet dosing, but may persist if they aren’t recognized and/or reported to a medical professional.  Realize that hallucinations may provoke feelings of fear and distress.

Headaches: Upon initiation of Sinemet treatment, many users experience headaches.  Headaches may result from initial adjustments in neurochemistry in attempt to accommodate the drug, but may also be related to excessive dopaminergic signaling (from suboptimal dosing).  While mild headaches are recognized as a side effect of Sinemet, if you’re experiencing severe headaches (e.g. migraines), they should be discussed with a doctor.

Sometimes headaches diminish with continued Sinemet treatment, becoming less severe over time.  In other cases, a dosage adjustment will provide benefit in alleviation of levodopa-induced headaches.  If the headaches are considered severe, you may want to discuss some safe over-the-counter headache relief options with your doctor.

Hot flashes: Many Sinemet users report sudden feelings of feverish heat accompanied by flushing of the skin and possibly sweating.  If you experience hot flashes while taking Sinemet, you may mistakenly believe that you are running a fever or getting sick.  After a hot flash, you may find yourself drenched in sweat and/or feeling more chilled than usual.

While this may be an uncomfortable side effect, hot flashes may decrease in occurrence and/or intensity with continued Sinemet treatment.  In the early stages of treatment, your neurophysiology may not have adapted to regular Sinemet administration, leading to thermoregulatory alterations that trigger a hot flash.  Sometimes a dosage adjustment and/or adjuvant treatment for hot flashes may be helpful if they’re severe.

Impulse control disorder (ICD): Usage of any medication containing levodopa puts a person at risk to develop an impulse control disorder (ICD).  While risk of an impulse control disorder with levodopa is lower than a dopamine agonist (e.g. pramipexole), approximately 7-8% of levodopa users will develop an impulse control disorder in which they have difficulty resisting urges to gamble, shop, or have sex.

Prior to using Sinemet, family and friends of patients with Parkinson’s should be informed to recognize changes in behaviors, particularly those associated with impulse control.  Any suspected impulse control disorders should be discussed with a medical professional as soon as possible, as these may lead to severe deterioration of health and/or financial well-being.  Risks for impulse control disorders are higher among those who are: single, younger, smokers, from the United States, and/or have a family history of gambling addiction.

Insomnia: Although Sinemet may make you feel drowsy during the daytime, it may also interfere with your ability to fall asleep at night.  A documented side effect of Sinemet is insomnia, or inability to transition from a state of wakefulness to sleep at night.  You may find yourself lying in bed for hours, wondering why you cannot fall asleep.

One could suspect that the dopaminergic stimulation provided by Sinemet interferes with the circadian rhythm, leading to insomnia.  If you experience insomnia, it may be beneficial to discuss possible adjuvant sleeping medications (hypnotics) to offset the levodopa-induced insomnia.  In other cases, something as simple as a dosage adjustment or better stress management may help combat insomnia.

Irregular heartbeat: During treatment with Sinemet, many patients report changes in their heartbeat.  You may notice that your heartbeat is uneven, abnormally fast, or seems irregular.  Some individuals may experience palpitations or a noticeably rapid, strong, or fluttering heartbeat.

Any irregular heartbeat or rhythm should be immediately reported to a medical professional to rule out underlying cardiovascular abnormalities, premorbidities, and/or disease.  Assuming your cardiovascular function is considered normal by a cardiologist and no problems are discovered, you may need to accept the uncomfortable irregular heart rhythms as part of Sinemet treatment. While an adjustment in dosing may prove helpful in normalizing heart rhythms, this is not always viable nor effective.

Itchiness: Reports indicate that Sinemet can provoke feelings of itchiness throughout the body.  The itchiness may be accompanied by a skin rash, but not always.  If you start to feel itchy, it is necessary to report this side effect to your doctor – as this could be a sign of a contraindication, allergic reaction, or more serious medical diagnosis.

Some medical professionals believe that the itchiness experienced among Sinemet users may not always be a result of the drug.  In some cases, feelings of tingling, itching, and crawling sensations could be directly attributed to progression of Parkinson’s disease.  In other cases, itchiness may be attributed to some sort of Sinemet-induced dopaminergic tactile hallucination; leading to excessive scratching of the skin.

Assuming you develop severe itchiness after taking Sinemet, it could be a sign that you’re allergic to an ingredient in the formulation.  Certain users report being itchy to the dyes within Sinemet and/or other ingredients; whether these reports are accurate is unknown.  Discuss some potential attenuation strategies with your doctor and do your best to avoid scratching, as this may worsen the itch.

Lightheadedness: You may begin taking Sinemet and feel extremely lightheaded to the extent that you also feel dizzy and as if the room is spinning.  In many cases, lightheadedness is most prominent in early phases of treatment and usually subsides as dosing is optimized and treatment is continued.  Lightheadedness is usually a byproduct of alterations in neurochemistry elicited by Sinemet treatment; as users adapt to these neurochemical changes, lightheadedness decreases.

That said, lightheadedness may also occur often upon transition from lying down or a seated position to standing upright.  If you feel lightheaded as you stand up, it may be a sign that your blood pressure suddenly plummeted due to orthostatic hypotension.  In this case, lightheadedness should be taken as a warning sign that your blood pressure has dropped and that you may faint. To avoid the lightheadedness associated with orthostatic hypotension, slowly transition from being seated to standing rather than jumping up quickly.

Memory deficits: As Parkinson’s disease progresses, memory typically worsens.  This is because the disease affects more regions of the brain than just the striatum and areas responsible for motor control.  However, agents such as Sinemet may also interfere with cognitive processes by disrupting homeostatic neurotransmission, thereby contributing to memory impairment.

If you experience some memory loss or deficits during treatment, you are certainly not alone.  Many individuals report difficulty with memory retrieval, storage, and learning throughout their treatment.  Assuming you discontinue Sinemet or take a break from treatment, and healthy memory performance is restored, you can know for sure that memory deficits were triggered as a side effect of the drug.

Muscle or joint pain: Many individuals with Parkinson’s disease have difficulty walking and exercising.  As a result of these difficulties, they avoid physical activity altogether and their muscles atrophy, becoming weaker in time.  During treatment with Sinemet, motor function may be restored, but individuals may experience muscle or joint pain.

It is unclear as to whether this joint pain is directly a result of the drug, if it is caused by a worsening of Parkinson’s, and/or resuming physical activity after a hiatus; it could be a combination of the three.  If you develop muscle stiffness, joint pain, and/or experience difficulty walking, discuss these side effects with your doctor.  Your doctor may recommend an adjuvant medication to combat the pain and/or reduce inflammation.

Nervousness: It is understood that abnormally high concentrations of dopamine can provoke anxiety and nervousness.  If you feel nervous while taking Sinemet, realize that this is a common side effect and may be a sign that your dosage is too high.  Sometimes the nervousness resulting from Sinemet treatment may not be a direct side effect (per se), but a psychological reaction to another side effect (e.g. hallucinations, heart palpitations, insomnia, etc.).

Mild feelings of nervousness can usually be dealt with by most users.  However, if you constantly feel nervous to the point that you’re having full-blown panic attacks and/or a nervous breakdown, you’ll want to discuss this with your doctor.  Sometimes a lower dosage of Sinemet may help decrease nervousness, while other times it may be helpful to utilize an anxiolytic adjunct and/or pursue psychotherapy.

Orthostatic hypotension:  During treatment with Sinemet, you may notice that you feel dizzy, lightheaded, and/or as if you may faint each time you stand up (from a seated position).  The cause of this dizziness, lightheadedness, and possibly fainting upon standing upright is orthostatic hypotension, or a sudden decrease in blood pressure.  Orthostatic hypotension is regarded as a very common side effect of Sinemet and agents containing levodopa.

There are certain documented risk factors that may increase your likelihood of experiencing orthostatic hypotension including: excessive bed rest, elderly age (above age 65), alcohol, and heat exposure.  To cope with and/or prevent orthostatic hypotension, medical literature recommends: abdominal compression, drinking enough water, counter-maneuvers (e.g. leg elevation), certain medications, and salt intake.  If you’ve experienced this side effect, talk to your doctor about ways in which you can decrease it.

Psychosis: Advanced-stage Parkinson’s disease is associated with atrophy of many areas of the brain, leading to disarray in the signaling of neurotransmitters and the function of various regions.  As a result, it is understood that some patients can develop psychosis, a psychiatric condition characterized by loss of contact with reality.  Additionally, some individuals can develop psychosis during treatment with Sinemet.

The drug-induced psychosis resulting from Sinemet may be related to excess dopaminergic transmission, particularly in the mesolimbic pathway.  During a psychotic episode, individuals may become paranoid, hallucinate, and experience delusions.  Families, friends, and caregivers of those with Parkinson’s should be informed of psychosis as a possible side effect of Sinemet.

Skin rash: A small percentage of Sinemet users end up developing a skin rash as a result of treatment.  The skin rash may be widespread (throughout various regions of the body) or isolated to a particular region.  It may provoke sensations of itchiness, causing patients to claw their skin – which may lead to a worsening of the rash.

If you develop a rash at any point during treatment with Sinemet, you’ll want to discuss the possibility of an allergic reaction with your doctor.  A rash that worsens with continued treatment should be taken as a sign that your body isn’t compatible with Sinemet.  Those that experience rashes may need to pursue alternative pharmacological interventions.

Sleep attacks: A dangerous side effect that can occur during Sinemet treatment is that of sleep attacks.  Although sleep attacks are less common among users of levodopa than dopamine agonists (e.g. pramipexole), they are a well-documented adverse reaction.  Due to the risk of sleep attacks, it is recommended that users of Sinemet avoid operating motor vehicles and/or heavy machinery until they’ve stabilized on treatment.

Literature documents 2 specific types of sleep attacks that can occur: those of sudden onset (without any warning signs) and those of gradual onset (with prodromal drowsiness).  If you experience sleep attacks, you may want to discuss possible interventions with your doctor.  Usage of an adjunct eugeroic (wakefulness-promoting agent) may be helpful for those who need to maintain wakefulness for a particular occupation.

Sleep disturbances: As you use Sinemet, you may find that your sleep becomes disturbed or chaotic.  You may struggle to fall asleep at night (as a result of insomnia), but may also wake up several times throughout the night.  Furthermore, you could end up experiencing nightmares and possibly even sleep-related hallucinations (e.g. hypnagogic or hypnopompic phenomena).

These sleep disturbances are likely generated by changes in neurochemistry as induced by the Sinemet.  They could also result from the simultaneous progression of Parkinson’s – which is also documented to interfere with sleep.  If you find yourself getting poor sleep during treatment, talk to your doctor about possible usage of a hypnotic (e.g. Z-drug) to offset the Sinemet-induced sleep alterations.

Stomach aches: Sinemet is known to disturb the gastrointestinal (GI) tract, especially when taken on an empty stomach.  As a result, users may experience stomach aches, possibly accompanied by constipation, diarrhea, and/or indigestion.  Stomach aches may be most prevalent among those who just began treatment with Sinemet and may subside after awhile.

If you find yourself experiencing ongoing stomach aches throughout treatment, you may want to consider only taking Sinemet after a large meal and/or along with food.  If taking it with food doesn’t seem to help, discuss possible over-the-counter agents to offset the GI and digestive distress induced by treatment.  Your doctor will be able to provide you with some recommendations.

Suicidal thoughts: The combination of Parkinson’s disease and Sinemet treatment may alter neurochemistry to a significant extent, possibly causing depression.  For certain Sinemet users, the depression may become so severe that they experience suicidal thoughts.  If at any point throughout treatment you are feeling suicidal, it is necessary to seek immediate medical attention.

You may need to utilize additional pharmacology to attenuate the depressive thinking and/or pursue psychotherapy.  In the event that suicidal thoughts are a direct side effect of Sinemet, your doctor may recommend decreasing the dosage and/or testing an alternative medication.  Friends and family of patients should monitor those being treated with Sinemet for suicidal ideation.

Sweating: Numerous reports from Sinemet users document sweating as a side effect of treatment.  The sweating may be mild, but could also be profuse to the extent that you may find your daytime clothes completely drenched.  You may also wake up in the middle of the night to feeling chilled from night sweats, leaving your bed sheets soaked.

Many users will need to accept that sweating or “hyperhidrosis” is a fairly tolerable side effect of Sinemet.  A subset of those who sweat profusely from treatment may realize that the color of their sweat is particularly dark (reddish, brownish, or blackish) and stains their clothing and/or bed sheets.  Sweat discoloration is generally not regarded as problematic, but may be worth discussing with your doctor.

Numbness / Tingling sensations: As you continue to use Sinemet, you may feel numbness and/or tingling in random places.  In other words, certain parts of your body may become noticeably numb and tingle simultaneously.  These tactile sensations may not be isolated to a single area, you may feel numbness and tingling in your arms one minute and your eyebrows the next.

Since tingling can be a symptom of Parkinson’s disease, it may be unclear to a doctor as to whether it was caused by the underlying pathology or the Sinemet.  Medication-induced tingling may be accompanied by itchiness and may seem to drive some users (proverbially) crazy.  Fortunately, dosage adjustments and/or continuation of treatment may decrease these unwanted tactile sensations.

Vomiting: It is understood that Sinemet is a potent neurological medication.  As a result of its potency, it may cause users to vomit – especially when high doses are required.  Vomiting is understood to be a common side effect of treatment and is often provoked by stomach aches and/or nausea.

To avoid vomiting during treatment, consider taking Sinemet only after a large meal.  Taking Sinemet on an empty stomach may provoke greater irritation of the stomach lining, which could cause users to feel nauseated and ultimately vomit.  If the vomiting is incessant and fails to improve with continued Sinemet usage, you may want to discuss adjuvant antiemetic agents with your doctor.

Weakness: For certain individuals, Sinemet may cause feelings of weakness throughout the body.  Sudden weakness is a side effect of the medication, and may be related to the drug’s impact on motor function within the basal ganglia.  The weakness could be associated with the side effect of dyskinesia (involuntary movements and/or lack of control over voluntary motor functions) and/or muscle pain.

Those who feel noticeably weak during treatment should talk to their doctor about a potential dosing change.  Understand that mild weakness may subside as you continue using Sinemet, but may also worsen if the dosing is increased.  Regular physical therapy should be encouraged among Parkinson’s patients experiencing weakness to help build strength and improve gait.

Weight loss: Many individuals report changes in body weight throughout treatment with Sinemet.  Experiencing weight loss is relatively common for multiple reasons, including: appetite suppression, BMR increase, diarrhea, and/or vomiting.  Some individuals may also lose muscle as their Parkinson’s disease worsens, which contributes to weight loss.

The weight loss experienced while taking Sinemet may not be extreme, but should be noted as a side effect.  Usually once dosage of the medication is optimized, any weight loss at the beginning of treatment will be regained.  Assuming you take Sinemet for several months, your body weight should begin to normalize – even after an initial fluctuation.

Weird dreams: Due to the fact that Sinemet affects neurotransmission, it may affect your sleep – particularly your dreams.  You may experience particularly bizarre, vivid, or nightmarish dreams throughout your treatment.  These changes in dreams may not only be caused by altered neurotransmission, but altered neural activation and REM (latency, density, duration).

Some individuals may find the dreams to be an entertaining aspect of treatment, others may dread experiencing nightmares each time they sleep.  If your dreams have become problematic, you may want to consult a sleep specialist to determine how Sinemet is affecting your sleep.  Additionally, your doctor may recommend a sleeping medication that may be helpful for reducing nightmares.

  • Source: https://www.nlm.nih.gov/medlineplus/druginfo/meds/a601068.html

Note: Most users are unlikely to experience every last side effect listed above.  If you are concerned with a particular side effect and/or have further questions about an unlisted side effect, consult your doctor.

Variables that influence Sinemet side effects

Those taking Sinemet should understand variables that may influence specific side effects as well as side effect severities.  Influential variables include: Sinemet dosage (and Carbidopa-Levodopa ratio), co-administered agents, duration of administration, and individual factors (e.g. Parkinson’s severity).  Keep these variables in mind when contemplating the side effects you’re experiencing during treatment.

  1. Sinemet dosage + Carbidopa-Levodopa ratio

The dosage of Sinemet that you administer on a daily basis will influence the likelihood that you are to experience side effects, as well as the severity of side effects experienced.  Medical documentation suggests that dosages of Sinemet (Carbidopa-Levodopa) should be carefully optimized by a medical doctor to fit the needs of each particular patient.  The tablets are manufactured in a multiple Carbidopa to Levodopa ratios including 1:4 and 1:10.

If dosage of Sinemet is too high for the particular needs of the patient, side effects are more likely to occur.  This is because when given at unnecessarily high doses, the brain becomes flooded with excess concentrations of dopamine.  Abnormally high concentrations of dopamine may trigger anxiety, delusions, hallucinations, insomnia, sleep disturbances, etc.

If the proper dosage is given to fit the needs of a particular patient, he/she will receive sufficient dopamine to correct neurological dysfunction associated with Parkinson’s, yet shouldn’t experience as extreme of side effects.  The goal of a medical doctor should be to determine the particular dopaminergic needs based on severity of Parkinson’s symptoms.  Initial starting dosage of Sinemet is usually 25 mg/100 mg (Carbidopa-Levodopa), given three times daily (t.i.d.).

This provides 75 mg Carbidopa to offset side effects related to peripheral metabolism of dopamine, while simultaneously increasing the amount of levodopa that crosses the blood-brain-barrier.  If a dosage of 10 mg/100 mg (Carbidopa-Levodopa) is administered (a 1:10 ratio), side effects may be more likely.  This is because there is less Carbidopa relative to Levodopa, provoking more side effects as a result of peripheral Levodopa metabolism.

Those taking the lowest effective dosage to decrease symptoms of Parkinson’s, particularly at the 1:4 ratio, are least likely to experience Sinemet side effects.  This is because lower dosages exert less influence over homeostatic neurophysiological processes and because there’s more Carbidopa to metabolize the peripheral Levodopa.  High-dose users, particularly those using the 1:10 ratio (Carbidopa-Levodopa) should be considered most susceptible to side effects.

  1. Co-administered agents

If you’re taking other drugs and/or supplements along with Sinemet, it is necessary to consider that side effects may occur as a result of an interaction or contraindication.  Those that are taking other medications (or supplements) should discuss safety with a medical professional to rule out contraindications.  Realize that co-administered substances, specifically those with dopaminergic effects (e.g. pramipexole) may exacerbate certain side effects (e.g. impulse control disorder).

Even seemingly unrelated agents such as antihypertensive drugs may increase your risk for orthostatic hypotension, a well-documented side effect resulting from Sinemet.  For this reason, your doctor may recommend using Sinemet as a standalone (without any other substances) for awhile until dosage is adjusted and side effects decrease.  If you are taking another agent with Sinemet, it is also important to recognize that side effects you perceive as stemming from Sinemet, may actually be from the other agent.

Be sure to review the side effect profile(s) of any co-administered substance to ensure that what you are experiencing is legitimately from the Sinemet.  That said, some adjuvant medications may act as attenuators to side effects of Sinemet.  In other words, they may reduce likelihood that you’ll experience common side effects associated with Sinemet administration.

As an example, you may be taking a eugeroic (e.g. modafinil) to enhance psychomotor vigilance and decrease daytime sleepiness.  Had you not been taking the modafinil, you may have experienced cognitive deficits, drowsiness, sleepiness or sleep attacks – resulting from treatment.  Strategically prescribed adjunct interventions may improve tolerability to Sinemet, thereby decreasing side effect severity.

  1. Term of administration

How long you’ve been taking Sinemet may affect the side effects that you experience.  In particular, new users may be more prone to side effects than those who’ve used for a moderate term due to the fact that their dosage hasn’t been properly optimized.  On the other hand, long-term users may experience side effects that hadn’t been present during a short-term due to tolerance to levodopa (requiring a dosage increase).  Think about how long you’ve been using Sinemet and how certain side effects may have improved and/or worsened over time.

  • Short-term: When initially starting Sinemet (Carbidopa-Levodopa) treatment, you’re very likely to experience side effects. At this point, your neurophysiology may react oddly to the exogenous administration of Carbidopa-Levodopa.  Additionally, with short-term treatment, your dosing may not be properly calibrated – it often takes awhile to find the right dose.  The combination of unadjusted neurophysiology to Sinemet, as well as possible suboptimal dosing – may contribute to short-term side effects.
  • Moderate-term: After several months of Sinemet treatment, your neurophysiology will likely have adapted to the drug. Your doctor will have likely found an optimal dose for management of Parkinson’s symptoms and side effects are unlikely to be as severe.  While you may still be experiencing some side effects, you may have even discovered some ways in which you can reduce them and/or have had your doctor prescribe some attenuators to help you cope (e.g. sleeping pills for insomnia).
  • Long-term: After years of treatment, you may have significantly increased the dosage of Sinemet since you first started. The increase in dosing may have been necessary due to the progression of Parkinson’s, as well as the tolerance you developed to treatment.  You may end up experiencing new unwanted long-term effects such as dyskinesia, hallucinations, and impulsivity – resulting from the necessary increase in dosing.
  1. Individual factors

It is necessary to consider that two individuals may take the same Sinemet dosage, without any co-administered substances, and use the drug for the exact same duration – yet one individual may experience markedly different side effects than the other.  Individual factors such as: age, diet, dosing specifics, genetics, Parkinson’s severity, sleep, and stress – may explain these differences.

  • Age: In general, the younger you are, the less likely you are to experience severe side effects. The physiology of younger individuals tends to exhibit more robust function than that of elderly individuals.  Individuals over the age of 65 may be subject to age-related atrophy (e.g. muscle loss), neural deficits, etc., and as a result, experience more side effects from Sinemet than younger patients.
  • Diet: Your diet may help increase or decrease susceptibility and/or severity of certain side effects. For example, someone experiencing Sinemet-related insomnia may also be drinking caffeine in the afternoon – which could exacerbate this reaction.  Had the individual cut out caffeine consumption, he/she may not experience overwhelming insomnia.  Proper nutrition and nutrient timing is known to affect biological processes and may serve to increase or decrease Sinemet side effects.
  • Dosing specifics / format: The specifics of your Sinemet dosing, as well as the format of Sinemet (standard vs. controlled-release) may alter side effects. For example, someone taking standard Sinemet several times per day after meals may experience fewer side effects than a person taking Sinemet CR on an empty stomach.  Also consider that timing of dose (morning, afternoon, evening) and adherence to a consistent dosing schedule may influence side effects.
  • Genetics / epigenetics: How you react to Sinemet may be partially determined by your genetics and epigenetics. Users with a particular gene (or set of genes) may be less prone to experiencing certain side effects (e.g. nervousness) than those with a different gene.  Consider that certain genes and epigenetic signatures may be protective against Sinemet-induced side effects, while others may make you more susceptible.
  • Parkinson’s severity: The severity of your underlying Parkinson’s disease and pre-treatment neurochemistry may predict how you’ll respond to treatment. Individuals with more severe forms of Parkinson’s disease (e.g. Stage 4/5) tend to require higher doses than those in earlier stages (e.g. Stage 2/3).  For this reason, side effects should be expected among those with greater neurodegeneration.
  • Sleep / Stress: The amount and quality of sleep that you’re getting during Sinemet treatment may also influence the side effects that you experience. Those who are well-rested and make a conscious effort to practice good sleep hygiene may be less susceptible to anxiety, cognitive deficits, and daytime drowsiness.  Effectively managing stress with techniques such as deep breathing, psychotherapy, and/or adjuvant pharmacology – may also reduce certain side effects (e.g. palpitations).

Sinemet (Carbidopa-Levodopa): Do the benefits outweigh the side effects?

Though Sinemet (Carbidopa-Levodopa) is a groundbreaking treatment for those with Parkinson’s disease, its side effect profile can be highly problematic for certain individuals.  For this reason, it is necessary to regularly evaluate (with the help of a medical professional) whether the symptomatic improvement derived from treatment outweighs side effects.  If the Sinemet is causing severe side effects (e.g. dyskinesia) and benefits are minimal, another treatment may be pursued.

A rare subset of Sinemet users may report significant benefits without any significant side effects.  Those who don’t experience many side effects from treatment are usually taking a low dose and in an early stage of treatment.  For these users, efforts should be made to maintain the lowest possible therapeutic dose to prevent tolerance to high doses.

Most users will experience a blending of therapeutic effects (e.g. improved motor function) and side effects.  For these users, as long as side effects do not significantly compromise quality of life, treatment is usually continued.  To help these individuals, a medical doctor may slightly adjust dosage and/or recommend adjuvant pharmacology with the impetus to improve tolerability and Sinemet adherence.

In less common cases, users may experience an equipotent blend of severe adverse effects and therapeutic effects.  Even if the Carbidopa-Levodopa combination improves motor symptoms of Parkinson’s, patients who: become uncontrollably psychotic, and/or constantly vomit – may need to pursue alternative treatments.  If you are taking Sinemet, you may want to consider keeping a daily journal to document Sinemet efficacy and tolerability over time; this will help you determine whether treatment is worth continuing.

Possible ways to reduce Sinemet (Carbidopa-Levodopa) side effects

If you’re experiencing side effects from Sinemet, below are some possible strategies to consider employing for side effect reduction.  Prior to implementation of these strategies, both safety and hypothesized efficacy should be confirmed with a medical professional.  Side effect mitigation strategies include: dosage adjustment, adjunct interventions, dosing specifics, elimination of other drugs, and/or continued treatment.

  1. Dosage reduction: Sometimes a reduction in dosing of Sinemet is necessary to decrease severity of certain side effects. For example, in cases of treatment-related dyskinesia, a reduction in Sinemet dosing is often helpful. This reduction may be accompanied by addition of an adjuvant medication (to help manage Parkinson’s symptoms).  However, if initial dosage was too high at the start of treatment, a reduction may decrease side effects and still manage Parkinson’s symptoms.
  2. Adjunct medications: Throughout treatment with Sinemet, an effective way to help patients cope with side effects is via addition of a safe adjunct. For example, those experiencing incessant nausea and/or vomiting may benefit from an adjunct antiemetic. Patients prone to excessive daytime sleepiness may benefit from a eugeroic.  A strategically-prescribed adjunct may increase quality of life and function among those with levodopa-related side effects.
  3. Dosing specifics: Altering the specifics of Sinemet dosing may be effective for reducing side effects. For example, a patient who is taking the standard version may benefit from a switch to Sinemet CR (controlled-release). In addition, patients taking Sinemet on an empty stomach experience fewer side effects when taking it after a meal.  Another variable to consider is the time of dosing (e.g. morning vs. afternoon or night) as influencing side effects.
  4. Eliminate unnecessary agents: Anyone taking drugs, supplements, or over-the-counter agents other than Sinemet should have their “stack” evaluated by a medical professional. If complaining of side effects, any agents deemed unnecessary for the treatment of a medical condition should be discontinued. Discontinuation of these agents may decrease side effects stemming from the particular agent and/or interactions with Sinemet.
  5. Continued treatment: Those new to taking Sinemet may experience some side effects during the early days and/or weeks of treatment. Usually, continuing treatment allows the user’s neurophysiology to adjust to Sinemet and side effects may abate upon adjustment. Those who haven’t been taking Sinemet for very long may find that initial side effects diminish and/or subside completely several months later.

Have you experienced Sinemet (Carbidopa-Levodopa) side effects?

If you take Sinemet (Carbidopa-Levodopa), share a comment mentioning any side effects you’ve experienced throughout your treatment.  Discuss how long it took into your treatment to notice side effects, as well as whether certain side effects subsided over time.  Also note whether any short-term effects worsened over time and/or if any long-term effects emerged with continued usage.

To help others get a better understanding of your situation, include some specifics in your comment such as your: Parkinson’s severity (e.g. Stage 3), Sinemet dosage and format (e.g. 50/200 mg, CR), duration of Sinemet usage, and whether you take other medications (or supplements) along with it.  Do you believe that the therapeutic benefits derived from ongoing Sinemet usage outweigh the side effects and/or adverse reactions? (Why or why not?)

Realize that there are no perfect treatments for Parkinson’s disease – nearly all interventions yield unwanted side effects, especially when taken for an extended duration.  If you’re taking Sinemet, you’ve likely accepted the fact that it is the best available option for the management of your Parkinson’s symptoms.  Continue working with your doctor to brainstorm ways in which Sinemet side effects can be minimized, yet its efficacy can be maintained.

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