Actions of Nakom Mite in details
Nakom Mite is a combination of Carbidopa (Nakom Mite), an aromatic amino acid decarboxylase inhibitor, and Levodopa (Nakom Mite), the metabolic precursor of dopamine, in a polymer-based controlled-release tablet formulation, for use in the treatment of Parkinson's disease and syndrome. Nakom Mite is particularly useful to reduce "off" time in patients treated previously with a conventional Levodopa (Nakom Mite)/decarboxylase inhibitor combination who have had predictable peak-dose dyskinesias and unpredictable motor fluctuations.
Patients with Parkinson's disease treated with preparations containing Levodopa (Nakom Mite) may develop motor fluctuations characterized by end-of-dose failure, peak-dose dyskinesia and akinesia. The advanced form of motor fluctuations ("on-off" phenomenon) is characterized by unpredictable swings from mobility to immobility. Although the causes of the motor fluctuations are not completely understood, it has been demonstrated that they can be attenuated by treatment regimens that produce steady-plasma levels of Levodopa (Nakom Mite).
Levodopa (Nakom Mite) relieves the symptoms of Parkinson's disease by being decarboxylated to dopamine in the brain. Carbidopa (Nakom Mite), which does not cross the blood brain barrier inhibits only the extracerebral decarboxylation of Levodopa (Nakom Mite), making more Levodopa (Nakom Mite) available for transport to the brain and subsequent conversion to dopamine. This normally obviates the necessity for large doses of Levodopa (Nakom Mite) at frequent intervals. The lower dosage reduces or may help eliminate gastrointestinal and cardiovascular side effects, especially those which are attributable to dopamine being formed in extracerebral tissues.
Nakom Mite is designed to release the active ingredients over a 4- to 6-hr period. With this formulation, there is less variation in plasma Levodopa (Nakom Mite) levels and the peak plasma level is 60% lower than with conventional Nakom Mite.
In clinical trials, patients with motor fluctuations experienced reduced "off" time with Nakom Mite when compared with Nakom Mite. Global ratings of improvement and activities of daily living in the "on" and "off" state, as assessed by both patient and physician, were better during therapy with Nakom Mite than with Nakom Mite. Patients considered Nakom Mite to be more helpful for their clinical fluctuations and preferred it over Nakom Mite. In patients without motor fluctuations, Nakom Mite, under controlled conditions, provided the same therapeutic benefit with less frequent dosing than with Nakom Mite.
How should I take Nakom Mite?
Take Nakom Mite exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.
If you already take Levodopa (Nakom Mite), you must stop taking it at least 12 hours before you start taking Nakom Mite.
Nakom Mite can be taken with or without food. Take your doses at regular intervals to keep a steady amount of the drug in your body at all times. Get your prescription refilled before you run out of medicine completely.
The tablet is sometimes broken in half to give the correct dose. Always swallow a whole or half tablet without chewing or crushing.
It may take up to several weeks of using Nakom Mite before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after a few weeks of treatment. Also tell your doctor if the effects of this medication seem to wear off quickly in between doses.
If you use Nakom Mite long-term, you may need frequent medical tests at your doctor's office.
This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using Nakom Mite.
Do not stop using Nakom Mite suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using this medicine.
Store at room temperature away from moisture, heat, and light.
Nakom Mite administration
Intestinal suspension (Duopa): Remove one cassette from refrigerator 20 minutes prior to use (failure to use at room temperature may result in inaccurate dosage). Administer as a 16-hour infusion through either a nasojejunal tube (temporary administration) or through a percutaneous endoscopic gastrostomy-jejunostomy (PEG-J) tube (long-term administration) connected to the CADD-Legacy 1400 pump. At the end of administration, disconnect the tube from the pump at the end of the infusion and flush with room-temperature drinking water with a syringe. Following discontinuation of the daily infusion, patients should administer their routine night-time dosage of oral immediate-release Nakom Mite.
Intestinal gel (Duodopa [Canadian product]): Gel is administered directly to the jejunum via a portable infusion pump (CADD-legacy Duodopa pump). Administer through a temporary nasojejunal tube for a short-term test period to evaluate patient response and for dose optimization. Long-term administration requires placement of PEG-J tube for intestinal infusion. Continuous maintenance dose is infused throughout the day for up to 16 hours if necessary, may administer at night (eg, nocturnal akinesia). Disconnect PEG-J tube from infusion pump at end of infusion and flush with room temperature water to prevent occlusion of tubing. Following discontinuation of the daily infusion, patients should administer their routine night-time dosage of oral Levodopa (Nakom Mite)/Carbidopa (Nakom Mite).
Oral:
ER capsule: Administer with or without food; a high-fat, high-calorie meal may delay the absorption of Levodopa (Nakom Mite) by ~2 hours. Swallow capsules whole; do not chew, divide, or crush capsules. Patients who have difficulty swallowing intact capsules may open the capsule, sprinkle entire contents on a small amount of applesauce (1 to 2 tablespoons) and consume immediately (do not store for future use).
Oral tablet formulations: Space doses evenly over the waking hours. Administer with meals to decrease GI upset. Controlled release product should not be chewed or crushed.
Orally disintegrating tablets do not require water; the tablet should disintegrate on the tongue's surface before swallowing.
Bariatric surgery: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to IR formulation (tablet or orally disintegrating tablet) or capsule may be opened and contents sprinkled onto soft food of choice. Patient should be instructed to swallow the mixture without biting down or chewing.
Nakom Mite pharmacology
Mechanism Of Action
Carbidopa (Nakom Mite)
When Levodopa (Nakom Mite) is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa (Nakom Mite) inhibits the decarboxylation of peripheral Levodopa (Nakom Mite), making more Levodopa (Nakom Mite) available for delivery to the brain.
Levodopa (Nakom Mite)
Levodopa (Nakom Mite) is the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby Levodopa (Nakom Mite) relieves symptoms of Parkinson's disease.
Pharmacodynamics
Because its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of Carbidopa (Nakom Mite) with Levodopa (Nakom Mite) makes more Levodopa (Nakom Mite) available to the brain. The addition of Carbidopa (Nakom Mite) to Levodopa (Nakom Mite) reduces the peripheral effects (nausea, vomiting) due to decarboxylation of Levodopa (Nakom Mite);
however, Carbidopa (Nakom Mite) does not decrease the adverse reactions due to the central effects of Levodopa (Nakom Mite). Patients treated with Levodopa (Nakom Mite) therapy for Parkinson's disease may develop motor fluctuations characterized by end-of-dose failure, peak dose dyskinesia, 'on-off' phenomenon, and akinesia.
Pharmacokinetics
Absorption
Carbidopa (Nakom Mite)
Following oral dosing of Nakom Mite the maximum concentration occurred at approximately 3 hours. The bioavailability of Carbidopa (Nakom Mite) from Nakom Mite relative to immediate-release Carbidopa (Nakom Mite)-Levodopa (Nakom Mite) tablets was approximately 50%.
Levodopa (Nakom Mite)
The pharmacokinetics of Nakom Mite were evaluated following single doses in healthy subjects and following single and multiple doses in patients with Parkinson's disease. The bioavailability of Levodopa (Nakom Mite) from Nakom Mite in patients was approximately 70% relative to immediate-release carbidopalevodopa. Following an initial peak at about one hour, plasma concentrations are maintained for about 4 to 5 hours before declining.
Distribution
Carbidopa (Nakom Mite) is approximately 36% bound to plasma proteins. Approximately 10-30% of Levodopa (Nakom Mite) is bound to plasma protein.
Metabolism And Elimination
Carbidopa (Nakom Mite)
The terminal phase elimination half-life of Carbidopa (Nakom Mite) is approximately 2 hours.
Carbidopa (Nakom Mite) is metabolized to two main metabolites: α-methyl-3-methoxy-4-hydroxyphenylpropionic acid and α-methyl-3,4-dihydroxy-phenylpropionic acid. These two metabolites are primarily eliminated in the urine unchanged or as a glucuronide. Unchanged Carbidopa (Nakom Mite) accounts for 30% of the total urinary excretion.
Peripheral dopa-decarboxylase may be saturated by Carbidopa (Nakom Mite) in other Carbidopa (Nakom Mite)-Levodopa (Nakom Mite) products at 70 to 100 mg per day, which produces equivalent exposure to 140 to 200 mg of Carbidopa (Nakom Mite) provided by Nakom Mite.
Levodopa (Nakom Mite)
The terminal phase elimination half-life of Levodopa (Nakom Mite), the active moiety of antiparkinsonian activity, is approximately 2 hours in the presence of Carbidopa (Nakom Mite).
Levodopa (Nakom Mite) is extensively metabolized to various metabolites. The two major metabolic pathways are decarboxylation by dopa decarboxylase (DDC) and O-methylation by catechol-O-methyltransferase (COMT).
Dose Proportionality
Nakom Mite shows approximately dose proportional pharmacokinetics for both Nakom Mite over the Levodopa (Nakom Mite) dosage strength range of 95 mg to 245 mg.
Effect Of Food
In healthy adults, oral administration of Nakom Mite after a high-fat, high-calorie meal reduced C approximately 13% for Levodopa (Nakom Mite) compared to administration in the fasted state. There may be a delay by 2 hours in the absorption of Levodopa (Nakom Mite) when Nakom Mite is taken with a high-fat, high-calorie meal. In addition, absorption of Levodopa (Nakom Mite) may be decreased by a high protein meal.
Specific Populations
Elderly
In pharmacokinetics studies following a single dose of Nakom Mite, the peak concentrations of Nakom Mite are generally similar between younger (45-60 years) and older (60-75 years) subjects.
Gender
In pharmacokinetics studies following a single dose of Nakom Mite:
- Carbidopa (Nakom Mite)
At comparable doses females are reported to have higher Carbidopa (Nakom Mite) peak concentrations and systemic exposure (approximately 33%) compared to males. Median time to peak concentration and terminal half-life are comparable between males and females.
- Levodopa (Nakom Mite)
At comparable doses females are reported to have higher Levodopa (Nakom Mite) peak concentrations (approximately 23% to 33%) and systemic exposure (approximately 33% to 37%) compared to males. Median time to peak concentration and terminal half-life are comparable between males and females.
Clinical Studies
Patients With Early Parkinson's Disease
The effectiveness of Nakom Mite in patients with early Parkinson's disease was established in a randomized, double-blind, placebo-controlled, fixed-dose, parallel-group, 30-week clinical trial (Study 1). Patients enrolled in Study 1 (n=381) were Hoehn and Yahr Stage I–III with a median disease duration of 1 year, and had limited or no prior exposure to Levodopa (Nakom Mite) and dopamine agonists. Patients continued taking concomitant selective monoamine oxidase B (MAO-B) inhibitors, amantadine, and anticholinergics provided the doses were stable for at least 4 weeks before screening. Eligible patients were randomized (1:1:1:1) to placebo or one of three fixed doses of Nakom Mite (Nakom Mite doses of 36.25 mg / 145 mg, 61.25 mg / 245 mg, or 97.5 mg / 390 mg, three times a day). Patients were not allowed to receive supplemental Levodopa (Nakom Mite) or catechol-O-methyl transferase (COMT) inhibitors. Patients receiving Nakom Mite initiated treatment at 23.75 mg / 95 mg three times daily (TID). The dose was increased on Day 4 and the maximum study dose (97.5 mg / 390 mg TID) was achieved by Day 22.
The clinical outcome measure in Study 1 was the mean change from baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (activities of daily living) score, and UPDRS Part III (motor score) for Nakom Mite, compared to placebo at Week 30 (or early termination). The mean score decrease (i.e., improvement) from baseline to Week 30 for each of the three Nakom Mite dosage groups was significantly greater than for placebo. The results of Study 1 are shown in Table 4.
Table 4: Study 1: Change from Bas eline in UPDRS Part II plus Part III Score at Week 30 (or at early termination) in Levodopa (Nakom Mite)-Naïve Patients with Early Parkins on's Dis eas e
| Treatment | Mean UPDRS (Part II and Part III) Score* | ||
| Baseline† | Week 30 Change from Bas eline at Week 30‡ | ||
| Placebo | 36.5 | 35.9 | –0.6 |
| Nakom Mite 36.25 mg / 145 mg TID | 36.1 | 24.4 | –11.7§ |
| Nakom Mite 61.25 / 245 mg TID | 38.2 | 25.3 | –12.9§ |
| Nakom Mite 97.5 mg / 390 mg TID | 36.3 | 21.4 | –14.9§ |
| *For the UPDRS, higher scores indicate greater severity of impairment †All values based on 361 patients who had valid End-of-Study values ‡Negative numbers indicate improvement as compared with the baseline value §P-value is less than 0.05 |
Patients With Advanced Parkinson's Disease
Study 2 was a 22-week trial consisting of a 3-week dose adjustment of current Levodopa (Nakom Mite) treatment prior to a 6-week conversion to Nakom Mite, which was followed by a 13-week, randomized, multicenter, double-blind, Levodopa (Nakom Mite)-containing active control, double-dummy, parallel group trial. The study enrolled 471 (393 randomized) patients (Hoehn & Yahr Stages I-IV) who had been maintained on a stable regimen of at least 400 mg per day of Levodopa (Nakom Mite) prior to entry into the trial. Patients were continued on concomitant dopamine agonists, selective monoamine oxidase B (MAO-B) inhibitors, amantadine, and anticholinergics provided the doses were stable for at least 4 weeks prior to screening. Patients were randomized to receive either Nakom Mite or immediate-release Carbidopa (Nakom Mite)-Levodopa (Nakom Mite) at the dose determined during the adjustment or conversion phases. Patients were not allowed to receive supplemental Carbidopa (Nakom Mite)-Levodopa (Nakom Mite) or catechol-O-methyl transferase (COMT) inhibitor products during the trial.
In Study 2, approximately 60% of patients required further up titration and approximately 16% of patients required down titration compared to the recommended starting dose of Nakom Mite. The final total daily dose of Levodopa (Nakom Mite) from Nakom Mite was approximately double that of the final total daily dose of Levodopa (Nakom Mite) from immediate-release tablets. The majority (88%) of patients in Study 2 received less than 2400 mg; the median dose was 1365 mg.
The clinical outcome measure in Study 2 was the percentage of "off" time during waking hours at Week 22 (or at early termination), as assessed by the patient's Parkinson's Disease Diary. The "off" time was significantly improved in Nakom Mite-treated patients compared to immediate-release carbidopalevodopa- treated patients (Table 5). The decrease in "off" time observed with Nakom Mite occurred with a concomitant increase in "on time" without troublesome dyskinesia.
Table 5: Study 2: Parkinson's Disease Diary Measures in Patients with Advanced Parkinson's Disease
| Baseline | Week 22 (or early termination) | |
| Percentage of waking hours spent in "Off" | ||
| Nakom Mite | 36.9% | 23.8%* |
| Immediate-release Carbidopa (Nakom Mite)-Levodopa (Nakom Mite) | 36.0% | 29.8% |
| "Off" Time (hours ) | ||
| Nakom Mite | 6.1 hours | 3.9 hours* |
| Immediate-release Carbidopa (Nakom Mite)-Levodopa (Nakom Mite) | 5.9 hours | 4.9 hours |
| "On" Time with no or non-troublesome dyskinesia (hours) | ||
| Nakom Mite | 10.0 hours | 11.8 hours* |
| Immediate-release Carbidopa (Nakom Mite)-Levodopa (Nakom Mite) | 10.1 hours | 10.9 hours |
| *P-value is less than 0.05 |
References
- DailyMed. "CARBIDOPA; ENTACAPONE; LEVODOPA: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Carbidopa Anhydrous: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- NCIt. "Levodopa: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Nakom Mite are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Nakom Mite. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
