Ajuben Tablet 6 mg
Ajuben Tablet 6 mg Uses, Dosage, Side Effects, Food Interaction and all others data.
Ajuben Tablet 6 mg is a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the management of chorea associated with Huntington’s disease. It is a hexahydro-dimethoxybenzoquinolizine derivative and a deuterated Tetrabenazine . The presence of deuterium in deutetrabenazine increases the half-lives of the active metabolite and prolongs their pharmacological activity by attenuating CYP2D6 metabolism of the compound . This allows less frequent dosing and a lower daily dose with improvement in tolerability . Decreased plasma fluctuations of deutetrabenazine due to attenuated metabolism may explain a lower incidence of adverse reactions associated with deutetrabenazine . Ajuben Tablet 6 mg is a racemic mixture containing RR-Ajuben Tablet 6 mg and SS-Ajuben Tablet 6 mg .
Huntington's disease (HD) is a hereditary, progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and neuropsychiatric disturbances that interfere with daily functioning and significantly reduce the quality of life. The most prominent physical symptom of HD that may increase the risk of injury is chorea, which is an involuntary, sudden movement that can affect any muscle and flow randomly across body regions . Psychomotor symptoms of HD, such as chorea, are related to hyperactive dopaminergic neurotransmission . Ajuben Tablet 6 mg depletes the levels of presynaptic dopamine by blocking VMAT2, which is responsible for the uptake of dopamine into synaptic vesicles in monoaminergic neurons and exocytotic release . As with other agents for the treatment of neurodegenerative diseases, deutetrabenazine is a drug to alleviate the motor symptoms of HD and is not proposed to halt the progression of the disease . In clinical trials of patients with HD, 12 weeks of treatment of deutetrabenazine resulted in overall improvement in mean total maximal chorea scores and motor signs than placebo . It was approved by FDA in April 2017 and is marketed under the trade name Austedo as oral tablets.
In clinical trials, there was an evidence of clinical effectiveness of deutetrabenazine in improving the symptoms of involuntary movements in patient with tardive dyskinesia by reducing the mean Abnormal Involuntary Movement Scale (AIMS) score . In a randomized, double-blind, placebo-controlled crossover study in healthy male and female subjects, single dose administration of 24 mg deutetrabenazine results in an approximately 4.5 msec mean increase in QTc . Effects at higher exposures to deutetrabenazine or its metabolites have not been evaluated . Ajuben Tablet 6 mg and its metabolites were shown to bind to melanin-containing tissues including eyes, skin and fur in pigmented rats. After a single oral dose of radiolabeled deutetrabenazine, radioactivity was still detected in eye and fur at 35 days following dosing .
| Trade Name | Ajuben Tablet 6 mg |
| Availability | Prescription only |
| Generic | Deutetrabenazine |
| Deutetrabenazine Other Names | Deutetrabenazine |
| Related Drugs | Ingrezza, Austedo, vitamin e, tetrabenazine, valbenazine, Xenazine, Alpha E |
| Weight | 6 mg |
| Type | Tablet |
| Formula | C19H27NO3 |
| Weight | Average: 323.466 Monoisotopic: 323.236754209 |
| Protein binding | At doses ranging from 50 to 200 ng/mL in vitro, tetrabenazine protein binding ranged from 82% to 85%, α-HTBZ binding ranged from 60% to 68%, and β-HTBZ binding ranged from 59% to 63% . Similar protein binding pattern is expected for deutetrabenazine and its metabolites. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Incepta Pharmaceuticals Ltd. |
| Available Country | Bangladesh |
| Last Updated: | October 19, 2023 at 6:27 am |
Uses
Ajuben Tablet 6 mg is a vesicular monoamine transporter 2 inhibitor used for the symptomatic treatment of chorea in Huntington's disease and tardive dyskinesia.
Indicated for the treatment of chorea associated with Huntington’s disease .
Ajuben Tablet 6 mg is also used to associated treatment for these conditions: Huntington's Disease (HD)
How Ajuben Tablet 6 mg works
The precise mechanism of action of deutetrabenazine in mediating its anti-chorea effects is not fully elucidated. Ajuben Tablet 6 mg reversibly depletes the levels of monoamines, such as dopamine, serotonin, norepinephrine, and histamine, from nerve terminals via its active metabolites. The major circulating metabolites are α-dihydrotetrabenazine [HTBZ] and β-HTBZ that act as reversible inhibitors of VMAT2. Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic terminal and depletion of monoamine stores from nerve terminals .
Ajuben Tablet 6 mg contains the molecule deuterium, which is a naturally-occurring, nontoxic hydrogen isotope but with an increased mass relative to hydrogen . Placed at key positions, deuterium forms a stronger hydrogen bond with carbon that requires more energy for cleavage, thus attenuating CYP2D6-mediated metabolism without having any effect on the therapeutic target .
Toxicity
Adverse reactions associated with overdosage include acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor . In case of an overdose, general supportive and symptomatic measures are recommended while monitoring cardiac rhythm and vital signs. In managing overdosage, the possibility of multiple drug involvement should always be considered .
No carcinogenicity studies were performed with deutetrabenazine. In p53+/– transgenic mice, there were no detectable tumors following oral administration of deutetrabenazine at doses of 0, 5, 15, and 30 mg/kg/day for 26 weeks . Findings from in vitro assays and in vivo mice micronucleus assay suggest that deutetrabenazine and its metabolites are unlikely to be mutagenic . The effects of deutetrabenazine on fertility have not been evaluated. Oral administration of tetrabenazine had no effects on mating and reproductive systems of male and female rats .
Food Interaction
- Avoid alcohol. Additive sedative effects may occur from co-administration of deutetrabenazine with alcohol.
- Take with food. Taking deutetrabenazine with food increases its Cmax.
Ajuben Tablet 6 mg Alcohol interaction
[Moderate] GENERALLY AVOID:
Alcohol may potentiate some of the pharmacologic effects of central nervous system (CNS)-active agents.
Use in combination may result in additive CNS depression and/or impairment of judgment, thinking, and psychomotor skills.
Patients receiving CNS-active agents should be advised to avoid or limit consumption of alcohol.
Ambulatory patients should be counseled against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
Ajuben Tablet 6 mg Drug Interaction
Major: chlorpromazineModerate: diazepamUnknown: sacubitril / valsartan, empagliflozin, clopidogrel
Ajuben Tablet 6 mg Disease Interaction
Major: depression, hepatic dysfunction, QT prolongationModerate: NMS, parkinson
Volume of Distribution
The median volume of distribution (Vc/F) of the α-HTBZ, and the β-HTBZ metabolites of deutetrabenazine are approximately 500 L and 730 L, respectively . Human PET-scans of tetrabenazine indicate rapid distribution to the brain, with the highest binding in the striatum and lowest binding in the cortex . Similar distribution pattern is expected for deutetrabenazine.
Elimination Route
The extent of absorption is 80% with oral deutetrabenazine. As deutetrabenazine is extensively metabolized to its main active metabolites following administration, linear dose dependence of peak plasma concentrations (Cmax) and AUC was observed for the metabolites after single or multiple doses of deutetrabenazine (6 mg to 24 mg and 7.5 mg twice daily to 22.5 mg twice daily) . Cmax of deuterated α-HTBZ and β-HTBZ are reached within 3-4 hours post-dosing . Food may increase the Cmax of α-HTBZ or β-HTBZ by approximately 50%, but is unlikely to have an effect on the AUC .
Half Life
The half-life of total (α+β)-HTBZ from deutetrabenazine is approximately 9 to 10 hours .
Clearance
In patients with Huntington's disease, the median clearance values (CL/F) of the α-HTBZ, and the β-HTBZ metabolites of deutetrabenazine are approximately 47 L/hour and 70 L/hour, respectively .
Elimination Route
Ajuben Tablet 6 mg is mainly excreted in the urine as metabolites. In healthy subjects, about 75% to 86% of the deutetrabenazine dose was excreted in the urine, and fecal recovery accounted for 8% to 11% of the dose . Sulfate and glucuronide conjugates of the α-HTBZ and β-HTBZ, as well as products of oxidative metabolism, accounted for the majority of metabolites in the urine . α-HTBZ and β-HTBZ metabolites accounted for less than 10% of the administered dose in the urine .
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