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Sinemet: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Feb 2, 2021.

1. How it works

  • Sinemet is a brand (trade) name for a combination tablet containing carbidopa and levodopa which may be used to treat Parkinson's disease.
  • Research has shown that Parkinson's disease is related to the depletion of dopamine in the brain. Administering dopamine to treat Parkinson's disease is ineffective because it does not cross the blood-brain barrier. But levodopa, a precursor of dopamine, does cross the blood-brain barrier, and appears to be converted to dopamine in the brain. However, large amounts of levodopa are decarboxylated before it even reaches the brain so carbidopa is added which inhibits the decarboxylation of peripheral levodopa. Carbidopa does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system. Administering Sinemet increases levels of dopamine in the brain which helps to relieve the symptoms of Parkinson's disease.
  • Sinemet belongs to the class of medicines known as dopaminergic antiparkinsonism agents. It may also be called a dopamine antiparkinsonian agent or a dopamine agonist.

2. Upsides

  • May be used to treat Parkinson's disease.
  • May also be used to treat post-encephalitic parkinsonism and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.
  • The presence of carbidopa in Sinemet means that more levodopa reaches the brain and less is converted into dopamine in the periphery which may also reduce the incidence of nausea and vomiting and permit faster dosage increases of Sinemet.
  • Available as a generic under the name of carbidopa/levodopa.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Dyskinesias (abnormal involuntary movements, including erratic writhing movements of the face, arms, legs, or trunk, and rapid jerking or slow and extended muscle spasms) and nausea are the most common side effects reported with Sinemet. These side effects may occur sooner and at lower dosages with Sinemet compared with levodopa alone. This is because the addition of carbidopa only reduces decarboxylation of levodopa in the periphery, not the CNS. A dosage reduction may be required to reduce the severity of dyskinesias.
  • Other adverse effects include chest pain, cardiac irregularities, low blood pressure, lack of energy, vein inflammation, gastrointestinal effects (eg, vomiting, diarrhea, dyspepsia), pain, cramps, rash, increased sweating, weight gain, or weight loss.
  • Sinemet has also been associated with psychotic-like behavior and hallucinations that may be accompanied by confusion and sleep disorders. Sinemet may also affect thinking and behavior and cause agitation, delirium, delusions, and paranoia. Usually, people with a preexisting psychotic disorder should not be treated with Sinemet.
  • Sinemet may affect impulse control and people may experience intense urges to gamble, spend money, eat, or have sex. These urges may decrease on dosage reduction or stopping the medication.
  • The risk of melanoma is two to six times higher in people taking Sinemet than in the general population. Periodic skin evaluations should be performed by appropriately qualified individuals.
  • Not recommended in children or adolescents under the age of 18 years.
  • For patients converting from levodopa to Sinemet, levodopa must be discontinued at least twelve hours before therapy with Sinemet is started. Start a dosage of Sinemet that will provide approximately 25% of the previous levodopa dosage. For example, people taking levodopa less than 1500mg/day should be started on Sinemet 25-100 three or four times a day and those taking more than 1500mg should be started on Sinemet 25-250 three or four times per day.
  • Should not be given within two weeks of nonselective monoamine oxidase (MAO) inhibitors such as isocarboxazid, phenelzine, and tranylcypromine. Sinemet may be administered with the manufacturer's recommended dose of a selective MAO type B inhibitor such as selegiline.
  • Contraindicated in people with a known hypersensitivity to any component of Sinemet, and in patients with narrow-angle glaucoma, unless the intraocular pressure is well controlled and the person is monitored carefully. Regular blood tests and monitoring of liver, renal, and cardiovascular function is recommended in people taking Sinemet for long periods.
  • There is an increased risk of depression in people taking Sinemet. Monitor people taking Sinemet for the development of depression with concomitant suicidal tendencies.
  • Administer cautiously to people with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic, or endocrine disease. This includes people with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. Cardiac function may need to be monitored in a facility with provisions for intensive cardiac care during the initial dosage titration.
  • May increase the risk of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.
  • There are reports of people suddenly falling asleep without prior warning of sleepiness while engaged in daily activities, including driving resulting in road traffic accidents. May occur soon after treatment initiation but has been reported as long as one year after the initiation of treatment.
  • The dosage of Sinemet needs to be individualized. The usual; recommended starting dose is one tablet of Sinemet 25-100 three times a day. This may be increased by one tablet every day or every other day until a dosage of eight tablets of Sinemet 25-100 a day is reached. Sinemet 10-100 tablets may be used; however, these do not provide an adequate amount of carbidopa for many patients. The dosage may be increased by one tablet every day or every other day until a dosage of eight tablets of Sinemet 10-100 a day is reached.
  • Dose reductions or discontinuation of Sinemet has been uncommonly associated with a symptom complex resembling neuroleptic malignant syndrome (NMS), which may be fatal. Symptoms include fever, hyperthermia, muscle rigidity, involuntary movements, altered consciousness, confusion, fast heartbeat, sweating, low or high blood pressure, and altered laboratory values, such as creatine phosphokinase. Observe patients when the dosage of Sinemet is reduced abruptly or discontinued, especially if the patient is also receiving antipsychotics.
  • Sinemet may cause laboratory test abnormalities such as elevations in liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN) and positive Coombs test have also been reported. May cause false-positive reactions for urinary ketone bodies, false-negative tests using glucose-oxidase methods of testing for glucosuria, and rarely falsely diagnosed pheochromocytoma.
  • The use of Sinemet during pregnancy has not been adequately studied but there is evidence it crosses the human placental barrier, enters the fetus, and is metabolized. Animal studies have revealed both visceral and skeletal malformations. Weigh up the risks versus benefits before using during pregnancy. Use caution when using Sinemet during breastfeeding as levodopa has been detected in human milk.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Sinemet is a medication that may be used for the treatment of Parkinson's disease that is available in three different strengths: Sinemet 25-100, Sinemet 25-250, and Sinemet 10-100. Dyskinesias (abnormal involuntary movements) and nausea are the main side effects and it may discolor saliva, urine, and sweat a dark red, brown, or black. It may increase the risk of depression, melanoma, and affect impulse control. Tablets need to be taken frequently throughout the day and dosage reductions or discontinuations have been uncommonly associated with a symptom complex resembling NMS).

5. Tips

  • Sinemet is available in different ratios of carbidopa to levodopa, for example, Sinemet 25-100 (carbidopa 1: levodopa 4), Sinemet 25-250 (carbidopa 1: levodopa 10), and Sinemet 10-100 (carbidopa 1: levodopa 10). Tablets of two ratios may be used to produce the optimum dosage for you. Always check the label to ensure you are taking the right strength of Sinemet. It may take a while for your doctor to find the right dosage for you.
  • Sinemet is a quick but short-acting formulation that needs to be taken regularly. Take Sinemet exactly as prescribed by your doctor; do not increase or decrease the dosage without their advice. Tell your doctor if you experience a "wearing-off" effect just before your next dose of Sinemet.
  • The absorption of levodopa may be affected by a change to a high protein diet, excessive acidity, or by some supplements, such as iron salts (may be contained in multivitamin tablets). Try to keep your diet consistent and talk to your doctor or pharmacist before taking any other medications or supplements.
  • Be cautious when driving or operating machinery because Sinemet may cause people to suddenly fall asleep without any prior warning, or prior feeling of drowsiness. Avoid alcohol or other medications, such as sedating antihistamines, that may also cause sedation.
  • Sinemet may cause your saliva, urine, or sweat to become discolored to red, brown, or black. Although this does not seem to have a clinically meaningful effect, garments may become discolored.
  • Sinemet may affect your impulse control and you may experience intense urges to gamble, spend money, eat, or have sex. Tell your doctor if this happens to you because a dosage reduction may decrease these urges.
  • Sinemet may increase your risk of developing skin cancers, such as melanoma. Protect your skin when going outside by wearing a hat and protective clothing, apply sunblock to exposed areas of skin. Ensure you get your skin checked for skin cancer at least once a year by an appropriately qualified individual.
  • If you require surgery, Sinemet may be continued as long as fluids and medication by mouth are permitted. If you have to temporarily discontinue treatment of Sinemet, then you should be monitored for the appearance of NMS; symptoms include fever, hyperthermia, muscle rigidity, involuntary movements, altered consciousness, confusion, fast heartbeat, or sweating. Restart Sinemet as soon as you are able.
  • If you are of child-bearing age you should use adequate contraception to ensure you do not become pregnant while taking Sinemet. If you inadvertently become pregnant, tell your doctor straight away so that you can be monitored throughout your pregnancy.

6. Response and Effectiveness

  • The absorption of levodopa may be impaired in some patients on a high protein diet because levodopa competes with certain amino acids for transport across the gut wall.
  • The presence of carbidopa in Sinemet allows patients treated for Parkinson's disease to use much lower doses of levodopa (about 75% lower). Some people who have responded poorly to levodopa have improved on Sinemet; most likely due to a decreased breakdown of levodopa caused by administration of carbidopa rather than by a primary effect of carbidopa on the nervous system. Carbidopa does not enhance the intrinsic efficacy of levodopa.
  • The decarboxylase inhibiting activity of carbidopa is limited to extracerebral tissues, which makes more levodopa available for transport to the brain.
  • The incidence of levodopa-induced nausea and vomiting is less with Sinemet than with levodopa, which may permit a more rapid dosage increase.
  • The half-life of levodopa is about 50 minutes without carbidopa. With carbidopa the half-life of levodopa is increased to about 1.5 hours.
  • Sinemet is available in different ratios of carbidopa to levodopa, for example, Sinemet 25-100 (carbidopa 1: levodopa 4), Sinemet 25-250 (carbidopa 1: levodopa 10), and Sinemet 10-100 (carbidopa 1: levodopa 10). Studies have shown that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. People who receive less than this amount are more at risk of side effects such as nausea and vomiting.

7. Interactions

Medicines that interact with Sinemet may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Sinemet. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Sinemet include:

  • 5-hydroxytryptophan
  • amisulpride
  • antidepressants, such as tricyclic antidepressants (eg, amitriptyline) or monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine)
  • any medication that lowers blood pressure, such as beta-blockers (eg, atenolol or sotalol), ACE inhibitors (such as captopril or enalapril), or diuretics (such as bendrofluazide or furosemide
  • any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), or opioids (such as codeine, morphine)
  • cholesterol-lowering agents such as atorvastatin or simvastatin
  • dopamine D2 receptor antagonists such as butyrophenones, phenothiazines, or thioxanthenes and atypical antipsychotics (eg, olanzapine, quetiapine, risperidone, ziprasidone)
  • dopamine-depleting agents, such as reserpine or tetrabenazine
  • iron salts or multivitamins that contain iron (can form chelates with Sinemet and reduce its absorption)
  • metoclopramide (has dopamine antagonistic properties)
  • selegiline
  • sodium oxybate
  • vincristine.

Avoid drinking alcohol or taking illegal or recreational drugs while taking Sinemet.

Sinemet may be given to people receiving supplemental pyridoxine (vitamin B6) because carbidopa inhibits the pyridoxine-increased decarboxylation of levodopa.

Note that this list is not all-inclusive and includes only common medications that may interact with Sinemet. You should refer to the prescribing information for Sinemet for a complete list of interactions.

References

Further information

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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