Ongentys (Opicapone)
Once-Daily COMT Inhibitor Capsule for Parkinson’s Disease with End-of-Dose Motor Fluctuations
Quick Facts About Ongentys
Key Takeaways About Ongentys
- Targeted adjunct to levodopa: Ongentys is used only in combination with levodopa plus carbidopa or benserazide; it is not a monotherapy and does not replace your other Parkinson’s medicines
- Once-daily bedtime dosing: The recommended dose is one 50 mg capsule once daily at bedtime, at least one hour before or one hour after any levodopa combination dose
- Extends each levodopa dose: Pivotal clinical trials (BIPARK-I and BIPARK-II) showed that opicapone 50 mg reduces absolute daily OFF time by approximately 60 minutes compared with placebo
- Dyskinesia is common: Increased involuntary movements occur in more than 1 in 10 patients, especially in the first weeks of treatment, and often resolve when your doctor lowers the levodopa dose
- Some combinations are forbidden: Do not take Ongentys together with non-selective monoamine oxidase inhibitors, or if you have phaeochromocytoma, paraganglioma or a history of neuroleptic malignant syndrome
What Is Ongentys and What Is It Used For?
Ongentys is an oral prescription medicine containing opicapone, a peripheral and highly selective inhibitor of catechol-O-methyltransferase (COMT). It is used as an add-on treatment to levodopa and a dopa decarboxylase inhibitor (DDCI) in adults with Parkinson’s disease who experience end-of-dose motor fluctuations that cannot be controlled by levodopa alone.
Parkinson’s disease is a progressive neurodegenerative disorder characterised by the loss of dopamine-producing neurons in the substantia nigra of the midbrain. This loss of dopamine leads to the classical motor symptoms of bradykinesia (slowness of movement), muscle rigidity, resting tremor and postural instability, alongside a broad range of non-motor symptoms including sleep disturbance, autonomic dysfunction, cognitive changes and mood disorders. Levodopa combined with a peripheral dopa decarboxylase inhibitor – carbidopa or benserazide – remains the single most effective symptomatic therapy and the cornerstone of treatment.
However, after several years of levodopa therapy most patients develop motor fluctuations: the once smooth, predictable response to each dose gives way to alternating ON periods (when mobility and symptom control are good) and OFF periods (when Parkinson’s symptoms re-emerge before the next dose is due). These end-of-dose “wearing-off” phenomena reflect a progressively shorter duration of therapeutic levodopa levels in the blood and brain. OFF time is distressing for patients and families because it disrupts activities of daily living, mobility, self-care and social engagement, and it is one of the strongest predictors of reduced quality of life in Parkinson’s disease.
Opicapone addresses this problem at a pharmacokinetic level. COMT is one of two major enzymes responsible for the metabolic degradation of levodopa in the body; the other is aromatic amino acid decarboxylase (AADC), which is blocked in the periphery by carbidopa or benserazide. When AADC is already inhibited, COMT becomes the dominant peripheral metabolic route for levodopa. By selectively and reversibly binding peripheral COMT, opicapone reduces the conversion of levodopa to its inactive metabolite 3-O-methyldopa, which in turn increases the bioavailability of levodopa and prolongs its plasma half-life. The result is that each levodopa dose lasts longer and produces steadier brain levels of dopamine throughout the day.
The clinical effectiveness of Ongentys has been established in two large, randomised, double-blind clinical trials, collectively known as BIPARK-I and BIPARK-II. In these studies, patients with Parkinson’s disease experiencing motor fluctuations on stable levodopa therapy were randomly assigned to receive opicapone, another COMT inhibitor (entacapone), or placebo. Opicapone 50 mg once daily was shown to reduce absolute daily OFF time by approximately 60 minutes compared with placebo and was at least as effective as entacapone taken with every levodopa dose. Equally important, the benefit was achieved with a simple once-daily bedtime schedule, which is more convenient than the multiple-times-daily dosing required for earlier COMT inhibitors.
Ongentys was first authorised by the European Medicines Agency (EMA) in June 2016 and by the U.S. Food and Drug Administration (FDA) in April 2020. It is now available in many countries as a once-daily adjunct for adult patients whose end-of-dose motor fluctuations cannot be adequately controlled by levodopa/DDCI combinations alone. It is not indicated as initial therapy, nor as monotherapy, and it is not approved for use in children or adolescents.
Opicapone belongs to the third generation of COMT inhibitors. Unlike earlier agents such as tolcapone, it does not cross the blood-brain barrier to any meaningful degree and acts almost exclusively in the periphery. Unlike entacapone, which must be taken with every dose of levodopa because of its very short duration of action, opicapone binds COMT with such high affinity that its enzymatic inhibition persists for about 24 hours – enabling a single evening dose to cover the full levodopa schedule the following day.
What Should You Know Before Taking Ongentys?
Before starting Ongentys, tell your doctor about any heart, liver, kidney or blood pressure problems, any history of hallucinations, impulse control disorders, cancer or rare hormonal tumours, and every medicine you take – including antidepressants, MAO inhibitors and over-the-counter products. Do not take Ongentys if you are pregnant or breastfeeding, or if you have any of the contraindications listed below.
Opicapone is a potent pharmacological agent that acts by amplifying the effect of levodopa. Like all dopamine-enhancing medicines, it should only be used after a careful medical assessment by a physician experienced in the management of Parkinson’s disease. Your doctor will review your full history, your current treatment regimen, your blood pressure and liver function, and your Parkinson’s symptom pattern (especially the amount and pattern of OFF time) before deciding whether Ongentys is appropriate for you.
Contraindications
You must not take Ongentys in any of the following situations:
- Known hypersensitivity to opicapone or to any of the excipients listed in the “What does Ongentys contain?” section, including lactose
- Phaeochromocytoma, paraganglioma or any other catecholamine-secreting neoplasm – rare hormonal tumours in which the combination of COMT inhibition with excess circulating catecholamines could precipitate a hypertensive crisis
- History of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis, conditions that can recur or worsen if dopaminergic therapy is intensified abruptly
- Concomitant treatment with non-selective monoamine oxidase (MAO-A and MAO-B) inhibitors such as phenelzine, tranylcypromine, isocarboxazid or linezolid (used for some bacterial infections). The combination of a non-selective MAO inhibitor and a COMT inhibitor can cause a dangerous rise in blood pressure. Selective MAO-B inhibitors used at standard anti-Parkinson doses (rasagiline 1 mg daily, selegiline up to 10 mg orally or 1.25 mg orodispersible daily, safinamide) are permitted under specialist supervision
If any of these contraindications apply to you, discuss alternative options with your doctor or neurologist. True hypersensitivity reactions to opicapone or its excipients are rare but may present with itching, rash, facial or throat swelling, or breathing difficulty shortly after a dose. Stop the medicine and seek urgent medical advice if any of these signs appear.
Warnings and Precautions
Talk to your doctor, pharmacist or specialist nurse before taking Ongentys if any of the following situations apply, as extra monitoring or a dose change may be needed:
- Worsening dyskinesia after starting Ongentys: Because Ongentys boosts the effect of levodopa, it commonly increases involuntary movements (dyskinesia) in the first weeks of treatment. Your doctor will usually reduce your total daily levodopa dose to regain balance between symptom control and dyskinesia. Do not change the doses of your other Parkinson’s medicines yourself.
- Hallucinations, confusion, impulse control disorders: Dopaminergic medicines can cause or worsen hallucinations, confusional states, vivid dreams, paranoid thinking and impulse control disorders such as pathological gambling, hypersexuality, compulsive shopping or binge eating. These effects can be subtle and develop gradually. Family members are often the first to notice. Report any new or worsening behaviour to your doctor.
- Sudden sleep episodes and excessive daytime sleepiness: Dopaminergic therapy, including Ongentys, can cause sudden sleep onset during the day, sometimes without warning. If you experience daytime sleepiness or sudden sleep episodes, do not drive or operate machinery and inform your doctor; dose adjustment may be required.
- Orthostatic hypotension: Parkinson’s disease itself and dopaminergic treatment can lower blood pressure on standing, leading to dizziness, light-headedness or falls. Rise slowly from sitting or lying, stay well hydrated, and report any episodes of fainting to your doctor.
- Cardiovascular disease: Ongentys has been studied in patients with stable cardiovascular disease, but caution is advised in severe cardiovascular disease or uncontrolled hypertension. Your blood pressure may need to be monitored more closely after starting therapy.
- Moderate hepatic impairment: The recommended dose in patients with moderate hepatic impairment (Child-Pugh B) is reduced to 25 mg once daily. Ongentys is not recommended in severe hepatic impairment (Child-Pugh C), because it has not been studied in this population.
- Abrupt discontinuation: Never stop Ongentys or any other Parkinson’s medicine abruptly without medical guidance. Rapid withdrawal of dopaminergic therapy has been associated with a syndrome resembling neuroleptic malignant syndrome, with high fever, muscle rigidity, altered mental status and elevated creatine kinase.
Use in Children and Adolescents
Ongentys is not licensed for use in children and adolescents under 18 years of age. Parkinson’s disease is extremely rare in this age group and the safety and efficacy of opicapone have not been established in paediatric patients. If your child has been given a diagnosis of juvenile parkinsonism or a related rare movement disorder, care should be delivered by a paediatric neurologist at a specialist centre.
Use in Older Adults
No initial dose adjustment is required on the basis of age alone. Clinical trial populations included a substantial proportion of patients over 65, and pharmacokinetic studies have not shown clinically meaningful differences in opicapone exposure between younger and older adults. However, older patients with Parkinson’s disease often have multiple co-existing conditions (cardiovascular disease, cognitive impairment, postural hypotension) and take several concomitant medicines, all of which can amplify the risk of side effects. Your doctor will weigh these factors individually before starting treatment and may monitor you more closely during the first weeks of therapy.
Pregnancy and Breastfeeding
There are very limited data on the use of Ongentys during human pregnancy. Animal reproduction studies have shown some reproductive toxicity at doses that exceed therapeutic levels. Ongentys is not recommended during pregnancy, nor in women of childbearing potential who are not using effective contraception, unless the potential benefit clearly outweighs the risk. If you are pregnant, think you may be pregnant or are planning a pregnancy, discuss your Parkinson’s treatment with a neurologist experienced in pregnancy management.
It is not known whether opicapone is excreted into human breast milk. A risk to the breastfed infant cannot be ruled out. Ongentys should not be used during breastfeeding. If treatment is essential, alternative feeding methods should be discussed in advance with your doctor, midwife and paediatrician.
Driving and Operating Machinery
Ongentys can cause dizziness, somnolence and, rarely, sudden sleep episodes. Parkinson’s disease itself can also impair reaction time, coordination and vigilance. Do not drive or operate machinery until you know how Ongentys affects you. If you experience daytime sleepiness or a sudden sleep onset, discontinue driving, avoid hazardous activities and contact your doctor without delay. Individual decisions about driving should always take into account national regulations and advice from your treating physician.
Important Information About Excipients
Ongentys capsules contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Each capsule contains less than 1 mmol (23 mg) of sodium, so it is essentially ‘sodium-free’ and may be used by patients on a low-sodium diet. The shell of each capsule also contains small amounts of titanium dioxide and iron oxides as colourings; patients with known sensitivity to these pigments should inform their pharmacist.
How Does Ongentys Interact with Other Drugs?
Ongentys interacts with several important medicine classes, including non-selective MAO inhibitors (contraindicated), drugs metabolised by COMT, tricyclic antidepressants and noradrenaline reuptake inhibitors, and certain statins and other substrates of the OATP1B1 transporter. Always give your doctor and pharmacist a complete list of every medicine, supplement and herbal product you use.
Because opicapone is a potent peripheral enzyme inhibitor, it can alter the disposition of other medicines that are substrates of the same enzymes or transporters. It can also increase the sympathetic effects of drugs that themselves depend on COMT for their inactivation. The table below summarises the most clinically relevant interaction scenarios that your prescriber needs to take into account.
| Interacting Drug or Class | Type of Interaction | Clinical Recommendation |
|---|---|---|
| Non-selective MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid, linezolid) | Risk of hypertensive crisis when combined with a COMT inhibitor | Contraindicated. Do not combine with Ongentys under any circumstances |
| Selective MAO-B inhibitors (rasagiline, selegiline, safinamide) at anti-Parkinson doses | No clinically relevant interaction at approved doses | Permitted under specialist supervision; higher-than-recommended doses should be avoided |
| Catecholamines and drugs metabolised by COMT (adrenaline, noradrenaline, dopamine, dobutamine, isoprenaline, alpha-methyldopa, apomorphine) | Enhanced cardiovascular and CNS effects due to decreased peripheral metabolism | Use with caution, especially in emergency or anaesthetic settings; inform anaesthetists before surgery |
| Tricyclic antidepressants & SNRIs (amitriptyline, nortriptyline, imipramine, clomipramine, venlafaxine, duloxetine, maprotiline) | Potential enhancement of cardiovascular effects of noradrenergic transmission | Use with caution; monitor blood pressure and heart rhythm, especially early in therapy |
| OATP1B1 substrates (rosuvastatin, simvastatin, atorvastatin, pitavastatin, repaglinide) | Opicapone can raise plasma levels of these medicines by inhibiting hepatic uptake | Take Ongentys at least one hour before or after the interacting drug; consider dose adjustment or an alternative statin |
| Other levodopa/DDCI products & dopamine agonists (pramipexole, ropinirole, rotigotine, apomorphine) | Additive dopaminergic effects – increased dyskinesia, hallucinations, postural hypotension | Usually co-prescribed under specialist supervision; the levodopa dose is often reduced when Ongentys is added |
| Iron salts (ferrous sulphate, ferrous fumarate) | Iron can chelate levodopa and COMT inhibitors, reducing absorption | Separate iron supplements and Ongentys by at least 2–3 hours; avoid co-administration with main meals |
| Alcohol | May increase sedation and orthostatic hypotension | Limit alcohol intake, especially when starting or changing the dose |
Some practical considerations further reduce the risk of problematic interactions. Opicapone is not a potent inhibitor or inducer of the major cytochrome P450 enzymes (CYP3A4, CYP2D6, CYP2C9, CYP1A2) at therapeutic doses, so it is not expected to significantly affect the plasma concentrations of most common medicines metabolised by these pathways. However, because Parkinson’s patients often take medicines for sleep, anxiety, depression, pain, hypertension and prostate symptoms, the overall burden of polypharmacy is high. A structured medication review at the start of Ongentys therapy, and at least once a year thereafter, helps detect unnecessary medicines, potential duplications and drug-drug interactions that may have accumulated over time.
Before any surgery or dental procedure, tell your anaesthetist, surgeon or dentist that you take Ongentys. Anaesthetic agents and vasopressors (such as noradrenaline or adrenaline) used during surgery may have amplified effects in the presence of COMT inhibition. Your care team may select different agents or different doses to account for this. Never stop taking Ongentys or your Parkinson’s medicines ahead of surgery without a specific instruction from your specialist team.
What Is the Correct Dosage of Ongentys?
The recommended dose of Ongentys is one 50 mg capsule taken by mouth once daily at bedtime, at least one hour before or after any levodopa combination. Do not exceed the prescribed dose. Patients with moderate liver impairment should take 25 mg once daily; Ongentys is not recommended in severe liver impairment.
Always take Ongentys exactly as your doctor or pharmacist has instructed. The aim of treatment is to reduce the amount of daily OFF time, lengthen ON time with good motor control and limit troublesome dyskinesia. Achieving this balance often requires adjusting the levodopa dose during the first weeks of Ongentys therapy. Regular follow-up – by your neurologist, specialist nurse or general practitioner – is the most important factor for long-term success.
Adults with Parkinson’s Disease
Standard Adult Dose
Dose: One capsule of 50 mg once daily
Timing: At bedtime, at least one hour before or after your levodopa combination dose
Duration: Long-term, for as long as the benefit-risk balance remains favourable and under regular medical review
Swallow the capsule whole with water. Do not open, break or crush the capsule. Ongentys is given as an adjunct to your existing levodopa/DDCI combinations and any other Parkinson’s medicines your doctor has prescribed. Do not stop or reduce your other Parkinson’s treatments on your own initiative.
Patients with Liver Impairment
Moderate Hepatic Impairment (Child-Pugh B)
Dose: One 25 mg capsule once daily at bedtime
Opicapone exposure is increased in patients with moderate liver impairment, so a lower starting dose is recommended. Your doctor will assess liver function before treatment and may recheck it during therapy.
Severe Hepatic Impairment (Child-Pugh C)
Not recommended. Ongentys has not been studied in severe hepatic impairment. Alternative strategies to manage motor fluctuations should be discussed with a specialist.
Patients with Kidney Impairment
No Dose Adjustment Required
Opicapone is eliminated almost entirely by the biliary-faecal route, and less than 1% of the dose is excreted unchanged in urine. As a result, no dose adjustment is required for any degree of renal impairment, including end-stage renal disease. However, patients on dialysis should still inform their nephrologist about their complete Parkinson’s treatment regimen.
Elderly Patients
No Initial Dose Adjustment Required
There is no specific dose adjustment for patients over 65 years, but older adults are more likely to have coexisting cardiovascular disease, cognitive vulnerability or multiple medicines, all of which can increase the likelihood of dopaminergic side effects. Your doctor will monitor blood pressure, mental status and overall function more closely at the start of therapy and will often be cautious about combining Ongentys with other dopamine agonists in this group.
How to Take the Capsule
Correct administration helps maximise benefit and reduces the risk of side effects. Follow these steps every day:
- Take Ongentys once daily at bedtime, on an empty stomach. Food significantly reduces absorption, so avoid taking Ongentys within one hour of a meal
- Swallow the capsule whole with a glass of water. Do not open, chew, crush or dissolve the capsule
- Ensure there is a gap of at least one hour between your last levodopa dose and your Ongentys capsule, and the same gap before your first levodopa dose the next morning
- Do not change the timing, dose or number of your levodopa-containing medicines unless your doctor has explicitly instructed you to do so
- Use a pill organiser or reminder app if you find it difficult to remember your bedtime dose – consistency matters more than the exact clock time
In the first few weeks of Ongentys treatment, your doctor may ask you to keep a simple diary of ON and OFF periods, dyskinesia and sleep. Patients and caregivers are often the best source of information on response to a dose change. Bring your diary to every follow-up appointment so that the levodopa dose can be titrated precisely against your individual pattern.
Missed Dose
If you forget your bedtime dose, skip the missed dose entirely and take your next dose at the usual time the following evening. Do not take a double dose to make up for a forgotten one; this would not provide extra benefit but could increase the risk of dyskinesia and other dopaminergic side effects. If you frequently forget doses, discuss strategies with your pharmacist or specialist nurse.
Overdose
If you or someone you care for has accidentally taken too many capsules of Ongentys, seek immediate medical advice. Contact your local poison information service, attend the nearest emergency department, or call an ambulance if the person is unwell. Take the medicine packaging with you. There is no specific antidote to opicapone, so management is supportive: cardiovascular and neurological monitoring, symptomatic treatment of any severe dyskinesia, hypotension or arrhythmia, and general measures such as intravenous fluids. The risk of severe toxicity from a single excess dose is low, but individual responses vary, particularly in frail or elderly patients.
Stopping Treatment
Do not stop taking Ongentys suddenly without consulting your doctor. Like other dopamine-enhancing treatments, abrupt discontinuation can lead to a rapid worsening of Parkinson’s symptoms and, in rare cases, to a syndrome resembling neuroleptic malignant syndrome (fever, muscle rigidity, altered mental state and elevated creatine kinase). If you and your doctor decide that Ongentys should be stopped – for example, because of side effects, surgery or a change in overall strategy – the withdrawal will usually be planned, with careful adjustment of levodopa or other anti-Parkinson medicines.
What Are the Side Effects of Ongentys?
The most common side effect of Ongentys is dyskinesia (involuntary movements), which affects more than 1 in 10 patients. Other frequent effects include constipation, dry mouth, insomnia, dizziness, abnormal dreams and a modest drop in body weight. Seek urgent medical attention if you develop high fever with muscle rigidity, new severe chest pain, breathing difficulty, signs of an allergic reaction or sudden uncontrollable urges.
Like all medicines, Ongentys can cause side effects, but not everyone will experience them. The list below is derived from the EMA Summary of Product Characteristics and FDA Prescribing Information and reflects pooled data from pivotal trials and long-term post-marketing surveillance. Most effects relate to the dopaminergic action of levodopa that Ongentys amplifies, rather than to opicapone itself, so some side effects can be mitigated by carefully reducing the daily levodopa dose.
- A high fever together with muscle rigidity, confusion or profuse sweating (possible neuroleptic malignant-like syndrome)
- Sudden severe chest pain, palpitations, shortness of breath or fainting
- Uncontrollable urges to gamble, spend, eat or engage in sexual activity that are new or unlike your usual behaviour
- Severe hallucinations, delusions, paranoia or disorientation
- A widespread rash, blistering of the skin, swelling of the face, lips or throat, or breathing difficulty (possible severe allergic reaction)
Very Common
May affect more than 1 in 10 people
- Nervous system: Dyskinesia (involuntary movements, often jerky or writhing, typically appearing or worsening in the first weeks of treatment)
Common
May affect up to 1 in 10 people
- Psychiatric: Abnormal dreams, hallucinations (visual or auditory), confusional state, depression, insomnia
- Nervous system: Dizziness, headache, somnolence (daytime sleepiness)
- Cardiovascular: Orthostatic hypotension (drop in blood pressure on standing)
- Gastrointestinal: Constipation, dry mouth, vomiting, abdominal discomfort
- Musculoskeletal: Muscle spasms, muscle twitching
- Metabolism: Decreased appetite, weight decreased
- Investigations: Elevated blood creatine phosphokinase (a marker of muscle activity)
Uncommon
May affect up to 1 in 100 people
- Psychiatric: Anxiety, nightmares, agitation, impulse control disorders (pathological gambling, hypersexuality, compulsive shopping or eating)
- Nervous system: Dysgeusia (altered taste), balance disorder
- Eye: Eye pain, blurred vision
- Ear and labyrinth: Tinnitus
- Cardiovascular: Palpitations, hypertension, increased or decreased heart rate
- Respiratory: Dyspnoea (shortness of breath)
- Gastrointestinal: Dyspepsia, flatulence, dry throat
- Skin: Rash, pruritus (itching), muscle weakness
- Metabolism: Hypertriglyceridaemia (elevated blood triglycerides)
- Investigations: Raised liver enzymes (ALT, AST)
Not Known
Frequency cannot be estimated from available data
- General: Withdrawal-emergent hyperpyrexia and confusion following abrupt discontinuation of dopaminergic therapy
- Musculoskeletal: Rhabdomyolysis in very rare cases, particularly in association with rapid medication changes or underlying disease
Dyskinesia deserves a separate mention because it is by far the most frequent reason for dose adjustment after starting Ongentys. Involuntary movements usually reflect excess dopaminergic stimulation and tend to occur during ON periods. In most cases, the response is not to stop Ongentys but to reduce the total daily levodopa dose in small, incremental steps while keeping the once-daily opicapone dose unchanged. Many patients find that their OFF time is still improved even after this levodopa reduction, so the net effect on quality of life is positive.
Impulse control disorders are increasingly recognised as a group of dopaminergic adverse effects that can have serious personal, social and financial consequences. They include pathological gambling, hypersexuality, compulsive shopping or internet use, binge eating and other repetitive reward-seeking behaviours. Because patients may feel embarrassed to report these symptoms, doctors, nurses and family members should actively and non-judgementally ask about them at each review. Early recognition and a gradual reduction in the dose of the offending dopaminergic therapy (often a dopamine agonist) usually reverse the behaviour.
Reporting suspected side effects is essential to the ongoing safety monitoring of medicines. Healthcare professionals and patients are encouraged to report suspected adverse reactions to their national pharmacovigilance authority. In the United Kingdom, reports are made via the Yellow Card Scheme; in the United States, via the FDA MedWatch programme; in the European Union, via national competent authorities or EudraVigilance. Other countries have their own national systems.
How Should You Store Ongentys?
Store Ongentys capsules in the original blister and outer carton to protect them from moisture, at a temperature below 30°C. Keep them out of the sight and reach of children. Do not use the medicine after the expiry date printed on the packaging, and return unused or expired capsules to your pharmacy for safe disposal.
Proper storage helps preserve the pharmaceutical quality of Ongentys throughout its shelf-life. Opicapone is sensitive to moisture, so the blister strip and outer carton are designed to provide a stable micro-environment for each capsule. Follow these practical rules to ensure that every dose you take is as effective and safe as when it left the manufacturer:
- Keep out of the sight and reach of children and vulnerable adults. Accidental ingestion of even a small number of capsules could cause dopaminergic effects in someone who does not take the medicine regularly
- Store below 30°C (86°F). Avoid leaving capsules in a hot car, in direct sunlight or near radiators, stoves or other heat sources
- Keep the capsules in the original blister and outer carton until immediately before use. This protects the capsules from moisture and light
- Do not transfer the capsules to a plastic pill organiser more than 24–48 hours in advance, unless your pharmacist has specifically recommended this as part of a multi-compartment medication system
- Check the expiry date (EXP) printed on the outer carton and on each blister strip. Do not use any capsule after the last day of the stated month
- Inspect each capsule before use. Do not take capsules that are broken, cracked, chipped, discoloured or that appear damp; return them to your pharmacy
- Do not dispose of unused capsules in household waste or wastewater. Return leftover or expired medicine to your pharmacy for proper disposal. This protects waterways and soil from pharmaceutical residues
If you are travelling, carry Ongentys in its original packaging with a copy of your prescription. Keep the medicine in your hand luggage rather than in checked baggage, where temperatures can exceed the recommended storage range. For overnight or cross-time-zone travel, plan how you will adjust the timing of your bedtime dose with the help of your pharmacist or specialist nurse, so that your Parkinson’s regimen remains as stable as possible.
What Does Ongentys Contain?
The active substance is opicapone. Each capsule contains either 25 mg or 50 mg of opicapone, together with a range of inactive excipients, including lactose monohydrate, magnesium stearate and the gelatin capsule shell coloured with titanium dioxide and iron oxides.
Understanding what is in your medicine is important, especially if you have allergies or intolerances. Below is the complete composition of Ongentys hard capsules, divided between the active ingredient, the main excipients of the capsule contents and the components of the capsule shell.
| Ingredient | Role | Notes |
|---|---|---|
| Opicapone | Active substance | 25 mg or 50 mg per capsule |
| Lactose monohydrate | Filler (diluent) | Not suitable for patients with rare hereditary galactose intolerance or lactase deficiency |
| Magnesium stearate | Lubricant | Aids uniform dosing during capsule filling |
| Pregelatinised maize starch | Binder / disintegrant | Helps maintain capsule structure and dissolution |
| Gelatin | Capsule shell | Patients who avoid animal-derived ingredients should speak to their doctor |
| Titanium dioxide (E171) | Capsule shell colourant | Present in both 25 mg and 50 mg capsules to give a pale or dark colour |
| Red iron oxide (E172) | Capsule shell colourant | Distinguishes the different strengths by colour |
| Yellow or black iron oxide (E172) | Capsule shell colourant (strength-dependent) | Contributes to the finished capsule colour and print ink |
Ongentys is supplied as hard gelatin capsules packed in aluminium-aluminium blister strips within a cardboard outer carton. Pack sizes typically include 10 or 30 capsules; not every pack size is marketed in every country. The marketing authorisation holder in the European Union is Bial – Portela & Ca., S.A. (Portugal); in the United States, opicapone is distributed by Neurocrine Biosciences under the Ongentys brand. For country-specific labelling, consult the official patient leaflet supplied with your pack or published by your national regulatory authority.
How Does Opicapone Work in the Body?
Opicapone is a peripheral, selective and reversible inhibitor of catechol-O-methyltransferase (COMT). By blocking this enzyme outside the central nervous system, it reduces the breakdown of levodopa, increases its bioavailability, prolongs its plasma half-life and leads to smoother, longer-lasting dopaminergic stimulation of the brain.
Levodopa remains the most effective medicine for the motor symptoms of Parkinson’s disease, but it has a very short plasma half-life of about 60–90 minutes. A substantial proportion of an oral levodopa dose is metabolised in the intestine, liver and blood before it reaches the brain. Carbidopa or benserazide – the dopa decarboxylase inhibitors (DDCIs) combined in every levodopa formulation – prevent the peripheral conversion of levodopa to dopamine, which increases the fraction of each dose reaching the brain and reduces peripheral side effects. However, once the AADC pathway is blocked, COMT becomes the dominant metabolic route of levodopa in the periphery.
COMT uses S-adenosyl-L-methionine as a methyl donor to convert levodopa into 3-O-methyldopa (3-OMD), an inactive metabolite that competes with levodopa for transport across the blood-brain barrier. Over time, higher 3-OMD levels and a shorter effective plasma half-life of levodopa combine to produce the wearing-off phenomena so familiar to patients with advanced Parkinson’s disease. By inhibiting peripheral COMT, opicapone reduces 3-OMD formation and extends the duration of therapeutic levodopa concentrations in the blood, which in turn gives the brain more time to maintain adequate dopamine replacement.
Opicapone is distinct from earlier COMT inhibitors in three important ways. First, it acts predominantly in the periphery: it does not meaningfully cross the blood-brain barrier, so its pharmacological effect is confined to peripheral tissues. This reduces the likelihood of central side effects such as visual changes and contributes to a favourable hepatic safety profile. Second, it binds COMT with very high affinity, producing an enzymatic inhibition that outlasts the drug’s own plasma half-life. Measured COMT activity remains substantially suppressed for 24 hours after a single dose, which underpins once-daily dosing. Third, its overall liver-safety profile has been favourable in clinical trials compared with tolcapone, a first-generation COMT inhibitor that required regular liver function monitoring.
Pharmacokinetically, opicapone reaches peak plasma concentrations within 1–3 hours of an oral dose on an empty stomach. Food significantly reduces its absorption, which is why it is taken at bedtime, away from meals and from levodopa. Opicapone is extensively metabolised, mainly by sulphation, and is excreted almost entirely in the faeces via the bile. Renal excretion of the parent compound is negligible, so renal impairment does not require dose adjustment. Plasma elimination is rapid (half-life less than 3 hours), but because the drug is locked onto COMT by a slow dissociation, the pharmacodynamic half-life is much longer than the pharmacokinetic half-life – a phenomenon sometimes called “slow off-rate” pharmacology.
The net clinical effect is a more even, sustained stimulation of dopamine receptors in the striatum throughout the day. Patients typically experience fewer and shorter OFF periods, longer ON periods with good motor control, and often a reduction in the total daily levodopa dose required to achieve the same symptomatic benefit. Because motor fluctuations are closely linked to quality of life, reducing OFF time has been shown in clinical trials and patient-reported outcome studies to translate into measurable improvements in activities of daily living, self-perceived health status and caregiver burden.
Frequently Asked Questions About Ongentys
Ongentys (opicapone) is a catechol-O-methyltransferase (COMT) inhibitor used as an add-on treatment to levodopa combinations (with carbidopa or benserazide) in adults with Parkinson’s disease and end-of-dose motor fluctuations. It prolongs the effect of each levodopa dose, reducing daily OFF time and lengthening the ON time during which movement, balance and daily activities are better controlled. It is not a monotherapy and must always be taken with a levodopa/DDCI combination.
Take one 50 mg Ongentys capsule by mouth once daily at bedtime, on an empty stomach. Swallow the capsule whole with a glass of water. Keep a gap of at least one hour between your last levodopa dose and your Ongentys capsule, and the same gap before your first levodopa dose the next morning. Do not open, break or crush the capsule, and do not change the timing or dose without talking to your doctor.
The most commonly reported side effect is dyskinesia (involuntary movements), affecting more than 1 in 10 patients, particularly during the first weeks of therapy. Other common effects include constipation, dry mouth, insomnia, dizziness, abnormal dreams, headache and a modest drop in body weight. Most side effects are dose-dependent and improve when your doctor slightly reduces the daily levodopa dose. Seek immediate medical attention for high fever with muscle rigidity, chest pain, severe hallucinations or signs of an allergic reaction.
Ongentys must not be taken with non-selective monoamine oxidase (MAO) inhibitors such as phenelzine, tranylcypromine or linezolid, because the combination can cause dangerous rises in blood pressure. It should be used with caution alongside tricyclic antidepressants (amitriptyline, imipramine) and noradrenaline reuptake inhibitors (venlafaxine, duloxetine, maprotiline); your doctor may monitor your blood pressure more closely in these cases. Selective serotonin reuptake inhibitors (SSRIs) are generally compatible with Ongentys, but always tell every prescriber about every medicine you take.
The main practical difference is dosing frequency. Entacapone has to be taken with every levodopa dose (often 5–8 times a day) because of its very short duration of action. Ongentys is taken only once daily at bedtime, as its inhibition of peripheral COMT persists for about 24 hours due to very high-affinity binding to the enzyme. Clinical trials have shown that opicapone 50 mg is at least as effective as entacapone in reducing daily OFF time, with a broadly comparable safety profile. Your neurologist will decide which agent is best suited to your pattern of motor fluctuations, other medicines and individual preferences.
Yes. Ongentys is not a substitute for levodopa; it is an adjunct that extends the effect of each levodopa dose. You must continue to take your levodopa/DDCI combinations and any other Parkinson’s medicines exactly as prescribed. However, because Ongentys amplifies the effect of levodopa, your doctor may reduce the total daily levodopa dose during the first few weeks to prevent or treat dyskinesia. Do not change the dose or timing of levodopa yourself.
Moderate alcohol intake is not formally contraindicated with Ongentys, but alcohol can add to somnolence, orthostatic hypotension and balance problems, all of which are already more common in Parkinson’s disease and with dopaminergic therapy. If you choose to drink, do so in moderation and not close to bedtime dosing. Discuss any concerns with your doctor, especially if you have liver disease, cognitive symptoms or a history of alcohol misuse.
No. Ongentys is a symptomatic treatment: it improves motor fluctuations by prolonging the effect of each levodopa dose, but it does not modify the underlying neurodegeneration of Parkinson’s disease. No current medicine has been conclusively shown to halt or reverse disease progression. Long-term management therefore combines symptomatic medicines like Ongentys with lifestyle interventions (exercise, speech and physiotherapy, occupational therapy), advanced therapies for selected patients (such as deep brain stimulation or levodopa/carbidopa intestinal gel) and psychological support.
References
This article is based on international medical guidelines, regulatory documentation and peer-reviewed scientific sources. All clinical claims reflect current best-practice guidance and evidence-based medicine.
- European Medicines Agency (EMA). Ongentys (opicapone) – Summary of Product Characteristics (SmPC). EMA product information database. Accessed December 2025.
- U.S. Food and Drug Administration (FDA). Ongentys (opicapone) Capsules – Prescribing Information. FDA label repository. Accessed December 2025.
- British National Formulary (BNF). Opicapone. NICE BNF monograph, London. Accessed December 2025.
- Ferreira JJ, Lees A, Rocha JF, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial (BIPARK-I). Lancet Neurology. 2016;15(2):154–165. doi:10.1016/S1474-4422(15)00336-1
- Lees AJ, Ferreira J, Rascol O, et al. Opicapone as adjunct to levodopa therapy in patients with Parkinson disease and motor fluctuations: a randomized clinical trial (BIPARK-II). JAMA Neurology. 2017;74(2):197–206. doi:10.1001/jamaneurol.2016.4703
- Rocha JF, Santos A, Gama H, et al. Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: a multiple-ascending-dose study. Clinical Pharmacokinetics. 2014;53(1):71–82. doi:10.1007/s40262-013-0118-3
- Fabbri M, Ferreira JJ, Lees A, et al. Opicapone for the treatment of Parkinson’s disease: a review of a new licensed medicine. Movement Disorders. 2018;33(10):1528–1539. doi:10.1002/mds.27475
- Fox SH, Katzenschlager R, Lim SY, et al. International Parkinson and Movement Disorder Society evidence-based medicine review: update on treatments for the motor symptoms of Parkinson’s disease. Movement Disorders. 2018;33(8):1248–1266. doi:10.1002/mds.27372
- Bloem BR, Okun MS, Klein C. Parkinson’s disease. The Lancet. 2021;397(10291):2284–2303. doi:10.1016/S0140-6736(21)00218-X
- National Institute for Health and Care Excellence (NICE). Parkinson’s disease in adults: diagnosis and management (NG71). London: NICE; 2017 (updated).
- European Academy of Neurology (EAN). Guideline on the Treatment of Parkinson’s Disease. EAN; 2023.
- World Health Organization (WHO). Parkinson disease: a public health approach. Geneva: WHO; 2022.
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This article has been written and reviewed by the iMedic Medical Editorial Team, a multidisciplinary group of licensed specialist physicians with documented expertise in neurology, movement disorders and clinical pharmacology.
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