Levodopa with carbidopa (co-careldopa, Sinemet): Parkinson’s disease treatment explained

Levodopa is the name of one of the main classes of Parkinson’s drugs. Parkinson’s UK explains that it is a chemical building block that the body converts into dopamine in the brain, so taking it boosts the supply and lets nerve cells make more dopamine. It is used at all stages of the condition.

Levodopa on its own is broken down in the bloodstream before much of it reaches the brain. The NHS says it is usually combined with another medicine, such as benserazide or carbidopa, which stops it being broken down before it gets to the brain and reduces side effects such as feeling or being sick, tiredness and dizziness. Co-careldopa is the combination with carbidopa; co-beneldopa (Madopar) is the combination with benserazide.

The manufacturer leaflet for a generic carbidopa and levodopa tablet explains that carbidopa belongs to a group of medicines that slow the speed at which levodopa is broken down in the body, helping it work more effectively. It improves the signs of Parkinson’s disease in adults, such as slowness, stiffness and tremor.

Parkinson’s UK lists the forms of co-careldopa. Standard tablets (Sinemet and Sinemet Plus) are usually taken three or four times a day, though this varies. Modified-release tablets (Lecado, Half Sinemet CR and Sinemet CR) let levodopa enter the body slowly, and taking one before bed can help with stiffness at night; they must be swallowed whole and not broken, crushed or chewed. Duodopa is a gel form pumped through a tube into the small intestine, requiring an operation to place the tube, and is used for advanced and complex Parkinson’s.

There are also combination tablets of co-careldopa with entacapone, a COMT inhibitor that makes the levodopa work better.

Because different brands and release types behave differently, check the exact product on your prescription. The leaflet notes that if you have been given different tablets, you should make sure you take the correct one at the right time, and that if a tablet breaks when removed from the bottle you should throw away the pieces and take another full tablet, because a partial dose may make symptoms worse.

Parkinson’s UK advises taking levodopa on an empty stomach if possible, and says that if it makes you feel sick you can take it with a low-protein snack such as a cracker or a piece of fresh fruit, which still allows it to be absorbed. The manufacturer leaflet says to try to avoid taking tablets with a heavy meal and that too much protein (meat, eggs, milk, cheese) may stop it working as well.

For some people, Parkinson’s UK says, protein can interfere with absorption and a protein redistribution diet, with most daily protein in the evening, can help levodopa work better in the daytime. It stresses that protein is necessary and you should not cut it down without speaking to your specialist or Parkinson’s nurse.

Iron tablets and supplements can mean less levodopa gets into the parts of the body where it is needed, so ask your pharmacist when best to take them. The leaflet lists medicines for low iron among those where the dose may need to change.

The leaflet says it can have an effect after one day but may take up to seven days to work, and that you should take tablets at regular intervals. Do not change the times of your tablets or take other Parkinson’s medicines without speaking to your doctor first. Another page on this site covers why Parkinson’s doses are treated as time-critical in hospital.

Parkinson’s UK explains that taking levodopa for a long time can lead to wearing off, when a dose no longer lasts as long and symptoms return towards the end of a dose. Alongside movement symptoms, anxiety, sleepiness, low mood or pain may appear as medication wears off. If symptoms affect daily life, your specialist or Parkinson’s nurse should review your medication.

On-off changes are when well-controlled periods (on) alternate with return of symptoms (off), sometimes suddenly. Parkinson’s UK says apomorphine may be suggested if wearing off and on-off changes are not controlled by other medicines. Involuntary movements, called dyskinesia, can appear after long-term use and may include twitches, jerks, twisting or writhing movements.

The NHS says levodopa can produce a dramatic improvement at first, but its effects can be less long-lasting in the following years, so the dose may need to be increased from time to time, and long-term use is linked to dyskinesias and on-off effects. Parkinson’s UK says people with Parkinson’s will benefit from medicines containing levodopa throughout their lifetime.

Impulsive and compulsive behaviours can happen with any Parkinson’s drug. The leaflet asks you and your family or carers to tell the doctor about urges such as gambling, excessive eating or spending, or an abnormally high sex drive, so treatment can be reviewed.

Other common side effects listed by Parkinson’s UK include nausea and vomiting, low blood pressure on standing, loss of appetite, anxiety and depression, sleep problems and hallucinations. The leaflet says it can cause sleepiness or sudden sleep attacks, and that you should not drive or use machines if this happens.

The leaflet says not to take it if you have narrow-angle glaucoma, a severe mental disorder, a history of skin cancer or unexamined unusual moles, or if you are taking MAOI antidepressants, which must be stopped at least two weeks before. It also says not to take it if you are pregnant or breastfeeding. Tell your doctor if you have a history of fits, gut ulcers, heart or circulation problems, kidney, liver or hormonal problems, depression or wide-angle glaucoma, which needs regular eye pressure checks.

When switching from another levodopa medicine the leaflet says to wait 12 hours after a normal-release product and 24 hours after a slow-release product. Anticholinergics, phenytoin, papaverine and several others can interact. The leaflet also says it can affect some laboratory tests, so remind staff.

If you stop suddenly the leaflet warns of stiff muscles, high temperature and mental changes, and Parkinson’s UK says withdrawal symptoms such as depression, anxiety or pain can occur and in the most serious cases lead to hospitalisation. If you are admitted to hospital, tell staff that your Parkinson’s medicines are time-sensitive.

Levodopa is prescribed on the NHS by neurologists, geriatricians and Parkinson’s specialist nurses, with GPs continuing prescriptions. Private specialists use the same medicines. The key practical points, regular review, a clear dose-time chart and a named Parkinson’s nurse or specialist, are worth asking for in either setting.