Instructions Confundus tablets 25 mg/250 mg blisters No. 100
Composition
active ingredients: carbidopa, levodopa;
Each tablet contains carbidopa monohydrate equivalent to carbidopa 25 mg, levodopa 250 mg;
Excipients: pregelatinized starch, microcrystalline cellulose, crospovidone, hydroxypropylcellulose, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: flat, butterfly-shaped tablets from white to almost white in color, with a deep break line on one side and a normal break line on the other side.
Pharmacotherapeutic group
Antiparkinsonian drugs. Dopaminergic drugs. DOPA and derivatives. Levodopa with decarboxylase inhibitor. ATX code N04B A02.
Pharmacological properties
Pharmacodynamics
Confundus® is a combination antiparkinsonian agent that contains the metabolic precursor of dopamine, levodopa, used as a replacement therapy for Parkinson's disease/syndrome, and the inhibitor of peripheral dopa decarboxylase, carbidopa, which prevents the metabolism of levodopa to dopamine in the peripheral circulation, thus increasing the amount of levodopa that enters the brain and is converted there to dopamine. This combination allows for the use of a lower dose of levodopa, which reduces the frequency and severity of side effects.
The combination of carbidopa/levodopa helps to relieve many of the symptoms of Parkinson's disease/syndrome, especially rigidity and bradykinesia. This combination is often effective for tremor, dysphagia, sialorrhea, and postural instability.
In cases where the clinical response to levodopa monotherapy is variable, and the objective and subjective symptoms of Parkinson's disease/syndrome are not controlled evenly throughout the day, the administration of carbidopa/levodopa usually reduces the fluctuations in the therapeutic effect.
By reducing some of the adverse reactions that occur with levodopa alone, its use in combination with carbidopa allows more patients to obtain adequate relief of the symptoms of Parkinson's disease/syndrome.
Pharmacokinetics
After oral administration, levodopa is rapidly but variably absorbed from the gastrointestinal tract in the absence of a decarboxylase inhibitor. The plasma half-life is about 1 hour. Levodopa is metabolized primarily by decarboxylation to dopamine, some of which is converted to norepinephrine. Up to 30% is converted to 3-O-methyldopa, which has a half-life of 9 to 22 hours. About 80% of levodopa is excreted in the urine within 24 hours, mainly as homovanillic and dihydroxyphenylacetic acids. Less than 1% is excreted unchanged.
Once in the bloodstream, levodopa competes with other neutral amino acids for passage across the blood-brain barrier. Once levodopa enters striatal neurons, it is decarboxylated to dopamine, stored, and released from presynaptic neurons. Because levodopa is rapidly decarboxylated in the gastrointestinal tract and liver, very little of it reaches the brain unchanged. Peripheral decarboxylation reduces the therapeutic efficacy of levodopa and is responsible for many of its side effects. For this reason, levodopa is usually given with a peripheral decarboxylase inhibitor, such as carbidopa, to achieve the same therapeutic effect at lower doses.
After oral administration, carbidopa is rapidly but incompletely absorbed from the gastrointestinal tract in the absence of levodopa. About 50% is recovered in the urine, with approximately 3% of this amount of the drug in unchanged form.
Carbidopa does not cross the blood-brain barrier, but it crosses the placenta and is excreted in breast milk. Carbidopa is rapidly eliminated, with virtually all of the unchanged drug excreted in the urine within 7 hours.
Carbidopa inhibits the peripheral decarboxylation of levodopa to dopamine, but because it does not cross the blood-brain barrier, effective levels of dopamine in the brain are achieved with lower doses of levodopa, thus reducing the likelihood of peripheral side effects, especially nausea, vomiting, and cardiac arrhythmias.
Indication
Parkinson's disease.
Parkinson's syndrome.
Contraindication
Hypersensitivity to the active substances or to any of the excipients of the drug. Concomitant use of non-selective monoamine oxidase inhibitors (MAO) (the use of these drugs should be discontinued at least two weeks before prescribing treatment with Confundus®). The drug can only be used with selective MAO-B inhibitors in recommended doses (for example, with selegiline hydrochloride). Angle-closure glaucoma. Suspicious (for melanoma) pigmented neoplasms on the skin or a history of melanoma. Severe psychoses. Pregnancy. Breastfeeding.
Interaction with other medicinal products and other types of interactions
Caution should be exercised when carbidopa/levodopa is used concomitantly with the following medicinal products.
Postural hypotension may occur when carbidopa/levodopa is added to the treatment of patients receiving antihypertensive drugs. Dosage adjustment of the antihypertensive drug may be necessary.
Antidepressants.
There have been rare reports of reactions, including hypertension and dyskinesia, occurring with concomitant use of tricyclic antidepressants (see Contraindications).
Anticholinergic drugs.
Anticholinergics may affect the absorption of the drug and, consequently, its therapeutic effect.
Iron.
Studies have shown a decrease in the bioavailability of carbidopa and/or levodopa when taken with ferrous sulfate or ferrous gluconate.
Other medicines.
To date, there have been no signs of interactions that would preclude the concomitant use of standard antiparkinsonian drugs.
Dopamine D2 receptor antagonists (e.g. phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effect of levodopa. Patients should be carefully monitored for loss of antiparkinsonian effect.
Phenytoin and papaverine have been reported to counteract the beneficial effects of levodopa in Parkinson's disease. Patients taking these drugs concomitantly with carbidopa/levodopa should be monitored for loss of therapeutic efficacy.
The use of carbidopa/levodopa with agents that destroy dopamine (e.g. tetrabenazine) or other drugs that reduce monoamines is not recommended.
Concomitant use of selegiline with carbidopa/levodopa may result in severe orthostatic hypotension not seen with levodopa/carbidopa alone (see section 4.3).
Because levodopa competes with certain amino acids, some patients on a high-protein diet may experience impaired absorption of the drug.
The effect of co-administration of antacids with carbidopa/levodopa on the bioavailability of levodopa has not been studied.
The drug can be used in patients with Parkinson's disease/syndrome who are taking vitamin preparations containing pyridoxine hydrochloride (vitamin B6).
Application features
General.
Carbidopa/levodopa is not recommended for the treatment of drug-induced extrapyramidal reactions.
Carbidopa/levodopa should be used with caution in patients with bronchial asthma, cardiovascular disease, lung, kidney, liver, endocrine system disease, or a history of peptic ulcer (due to the risk of upper gastrointestinal bleeding).
Patients with a history of seizures should be treated with caution.
Since Confundus® contains levodopa, if its long-term use is necessary, it is recommended to periodically examine the function of the liver, kidneys, cardiovascular system and hematopoietic organs.
Cardiac arrhythmias.
Carbidopa/levodopa should be used with caution in patients with myocardial infarction and residual sinoatrial or ventricular arrhythmias. In such patients, cardiac function should be closely monitored during the initial dose adjustment period.
Drowsiness or sudden falling asleep.
Levodopa has been associated with episodes of somnolence or sudden sleep onset. Very rare cases of sudden sleep onset during daytime activities have been reported, in some cases without awareness or warning. Patients should be advised of the possibility of such symptoms and advised to exercise caution when driving or operating machinery during treatment with levodopa. Patients who experience somnolence and/or episodes of sudden sleep onset during treatment with levodopa should refrain from driving or operating machinery. In addition, dose reduction or discontinuation of treatment may be considered.
Dyskinesia.
In patients previously treated with levodopa alone, dyskinesia may occur because carbidopa allows more levodopa to reach the brain and thus more dopamine to be formed. Dyskinesia should prompt a dose reduction.
Mental disorders.
All patients receiving carbidopa/levodopa therapy should be closely monitored for the development of psychiatric changes, depression with suicidal ideation, and other serious manifestations of antisocial behavior. Patients with pre-existing psychosis should be treated with caution.
Since Confundus® contains levodopa, its use may cause involuntary movements and mental disorders. Patients who have had severe involuntary movements and psychotic episodes while taking levodopa in the past require special attention when switching to Confundus®. It is believed that since these reactions are associated with an increase in dopamine levels in the brain due to levodopa therapy, the use of Confundus® may cause their recurrence.
There have been reports of a syndrome resembling neuroleptic malignant syndrome, with clinical manifestations including muscle rigidity, fever, mental changes and elevated serum creatine phosphokinase, following abrupt withdrawal of antiparkinsonian drugs. Therefore, patients should be closely monitored during any abrupt dose reduction or withdrawal of Confundus®, especially in patients also receiving neuroleptics.
Dopamine dysregulation syndrome.
Dopamine dysregulation syndrome (DDS) is an addictive disorder caused by excessive drug use in some patients treated with carbidopa/levodopa. Before initiating treatment with carbidopa/levodopa, patients and their caregivers should be informed of the potential risk of developing DDS (see section 4.8).
Impulse control disorders.
Patients should be monitored closely for the development of impulse control disorders (ICD). Patients and caregivers should be made aware of the potential for behavioral changes suggestive of ICD (pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating, compulsive eating) when treated with dopamine agonists and/or other dopaminergic drugs containing levodopa, including Confundus®. If such symptoms occur, the treatment regimen should be reviewed.
Glaucoma.
Patients with chronic open-angle glaucoma should use carbidopa/levodopa with caution and with careful monitoring of intraocular pressure before and during treatment.
Anesthesia.
If general anesthesia is required, carbidopa/levodopa therapy may be continued as long as the patient is able to take fluids and oral medications. If therapy must be temporarily discontinued, carbidopa/levodopa may be resumed as soon as oral medications can be taken at the same daily dose as before.
Melanoma.
Epidemiological studies have shown that patients with Parkinson's disease have a higher risk of developing melanoma than the general population (approximately 2-6 times higher). It is not known whether this risk is related to Parkinson's disease or to other factors, such as the use of antiparkinsonian drugs. Therefore, patients and their caregivers are advised to have regular skin examinations for melanoma while taking carbidopa/levodopa. Periodic skin examinations by a dermatologist are considered the best option.
Laboratory studies.
Typically, blood urea nitrogen, creatinine, and uric acid levels are lower with carbidopa/levodopa than with levodopa alone. Transient metabolic disturbances include increases in blood urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, and alkaline phosphatase.
Decreased hemoglobin, hematocrit, increased blood glucose levels, and increased white blood cell, bacterial, and red blood cell counts in urine have been reported.
Cases of positive Coombs' test have been reported with both carbidopa/levodopa and levodopa alone.
The use of carbidopa/levodopa may cause a false-positive reaction for ketone bodies in urine using test strips. This reaction is not altered by boiling urine samples. The use of glucose oxidase methods may give false-negative results for glycosuria.
Ability to influence reaction speed when driving vehicles or other mechanisms
Since individual response to carbidopa/levodopa may vary, some adverse reactions during therapy with Confundus® may affect the ability to drive or use machines.
Patients who have experienced episodes of somnolence and/or sudden sleep onset while taking levodopa should be advised to avoid driving or engaging in any other activity that requires mental alertness, as this could put themselves and others at risk of injury, including death (e.g. operating machinery). This should continue until such episodes of somnolence and/or sudden sleep onset have resolved (see section 4.4).
Use during pregnancy or breastfeeding
Pregnancy.
Although the effects of carbidopa/levodopa on pregnancy are unknown, both levodopa and its combination with carbidopa have been shown to cause internal organ and skeletal malformations in rabbits. Therefore, the use of Confundus® in women of reproductive age requires that the expected benefit of the drug outweighs the potential risk to the pregnancy.
It is not known whether carbidopa is excreted in human milk. In a study in a breast-feeding woman with Parkinson's disease, levodopa was reported to be excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue Confundus®, taking into account the importance of the drug to the mother.
Method of administration and doses
The drug is intended for oral administration.
The optimal daily dose of carbidopa/levodopa should be determined by careful titration for each individual patient.
Confundus® contains carbidopa and levodopa in a ratio of 1:10 (25 mg/250 mg); the tablets of this medicinal product are used whole. Since the tablet is not divided, if it is necessary to prescribe carbidopa/levodopa in a dose of 12.5 mg/125 mg, preparations with these active substances with the possibility of such a dosage should be used.
During the titration of the dose, close monitoring of the patient's condition should be established. Involuntary movements, including blepharospasm, are early symptoms of overdose in some patients.
Patients who were not receiving levodopa.
For patients starting Confundus®, the starting dose of carbidopa/levodopa should be 12.5 mg/125 mg once or twice daily.
If necessary, the dose of carbidopa/levodopa can be gradually increased by another 12.5 mg/125 mg daily or 25 mg/250 mg every other day until the optimal therapeutic effect is obtained.
The therapeutic effect of the drug is manifested within one day, sometimes after a single dose. The full effective dose of the drug is achieved within seven days, compared to weeks and months of levodopa alone.
Patients receiving levodopa.
Levodopa should be discontinued at least 12 hours (24 hours for sustained-release formulations) before starting therapy with Confundus®.
The daily dose of Confundus® should provide approximately 20% of the previous daily dose of levodopa.
Initial dose.
For patients receiving less than 1500 mg of levodopa per day, the initial daily dose should be 75–100 mg of carbidopa and 300–400 mg of levodopa in 3–4 doses (a drug with a carbidopa/levodopa ratio of 1:4 is used).
For patients receiving more than 1500 mg of levodopa per day, the initial dose of Confundus® should be 1 tablet 3–4 times a day.
Maintenance dose. When using the combined drug Confundus®, it is necessary to take into account the individual characteristics of patients, the dosage can be gradually changed depending on the therapeutic effect.
If more levodopa is required, the dose of carbidopa/levodopa can be increased by a further 12.5 mg/125 mg daily or by 25 mg/250 mg every other day to a maximum daily dose of 200 mg carbidopa and 2 g levodopa (8 tablets in 3–4 divided doses) for patients weighing 70 kg.
Patients receiving other decarboxylase inhibitors. When transferring a patient from levodopa to the combination drug Confundus® is combined with the use of other decarboxylase inhibitors, their use should be discontinued at least 12 hours before the start of the drug. The use of Confundus® should be initiated with a dose corresponding to the amount of levodopa in the levodopa/decarboxylase inhibitor combination in the previous drugs.
Patients receiving other antiparkinsonian drugs: the combination of Confundus® with monoamine oxidase-B inhibitors (MAO-B) may increase the effectiveness of the drug in controlled cases of akinesia and/or dyskinesia.
For patients who use other antiparkinsonian drugs simultaneously with Confundus®, it may be necessary to adjust the dose of these drugs.
Elderly patients.
The drug is used in elderly patients.
Children
The safety and effectiveness of the drug in children have not been established, so it is not recommended for use in patients under 18 years of age.
Overdose
Treatment of acute overdose with carbidopa/levodopa is generally the same as for acute overdose with levodopa, however, pyridoxine is ineffective in reversing the effects of the components of Confundus®. The patient's ECG should be monitored for arrhythmias. In the event of arrhythmias, appropriate antiarrhythmic agents should be used. Consideration should be given to whether the patient is taking other medications with carbidopa/levodopa. There is no experience with dialysis, and its value in the treatment of overdose with carbidopa/levodopa is unknown. In the presence of carbidopa, the terminal half-life of levodopa is approximately two hours.
Adverse reactions
Adverse reactions commonly observed with carbidopa/levodopa are due to the central neuropharmacological activity of dopamine. These reactions usually disappear or are attenuated by reducing the dose. The most common manifestations are dyskinesia, including choreic, dystonic and other involuntary movements, and nausea. Muscle spasms and blepharospasm may be early signs that the dose should be reduced.
Skin and subcutaneous tissue disorders: alopecia, rash, dark sweat, redness, increased sweating, melanoma.
From the blood and lymphatic system: leukopenia, anemia, hemolytic anemia, thrombocytopenia, agranulocytosis.
Cardiovascular system: cardiac arrhythmias and/or palpitations, orthostatic effects, including episodes of arterial hypotension, hot flashes, arterial hypertension, phlebitis, chest pain.
Respiratory: dyspnea, respiratory disorders, hoarseness.
Gastrointestinal: vomiting, gastrointestinal bleeding, duodenal ulcer, diarrhea, dark saliva, dyspepsia, dry mouth, bitter taste in the mouth, drooling, dysphagia, bruxism, hiccups, abdominal pain, constipation, flatulence, burning sensation on the tongue.
From the urinary system: dark urine, urinary retention, urinary incontinence, priapism.
From the organs of vision: diplopia, blurred vision, dilated pupils, oculogyric crisis.
Metabolic disorders: weight loss or gain, edema.
Benign, malignant and unspecified neoplasms (including cysts and polyps): melanoma (see sections "Contraindications" and "Special instructions").
Nervous system: dyskinesia, including choreic, dystonic and other involuntary movements; blepharospasm, headache, syncope, neuroleptic malignant syndrome (see section "Contraindications"); episodes of bradykinesia ("on-off" phenomenon); dizziness; paresthesia; sleep disorders, including drowsiness, excessive daytime sleepiness and episodes of sudden sleep onset; convulsions; asthenia, ataxia, numbness, increased hand tremor, muscle twitching, trismus, activation of latent Horner's syndrome, insomnia, falls, gait disturbance, dopamine dysregulation syndrome1.
Psychiatric disorders: anorexia, dysphoria, psychotic episodes (including delusions, hallucinations and paranoid thoughts); depression with or without suicidal ideation; dementia; agitation; feeling irritable, confusional state; increased libido; decreased acuity of thinking, disorientation, anxiety, euphoria, impulse control disorders2.
Others: general weakness, pathological fatigue.
1Dopamine dysregulation syndrome (DDS) is an addictive disorder that occurs in some patients treated with carbidopa/levodopa. Patients with this syndrome exhibit compulsive behavior towards the abuse of dopaminergic agents at doses higher than those required for adequate control of motor symptoms, which may in some cases lead to the development of severe dyskinesia (see section 4.4).
2Impulse control disorders.
Pathological gambling, increased libido, hypersexuality, impulsive desire to spend money or make purchases, overeating, impulsive eating when using dopamine agonists and/or other dopamine-containing drugs containing carbidopa and levodopa (see section "Special instructions").
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Kusum Healthcare Pvt Ltd.
Location of the manufacturer and its business address
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India/SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.
