Teva Carbi-Levo
Teva Carbi-Levo Uses, Dosage, Side Effects, Food Interaction and all others data.
Carbidopa presents a chemical denomination of N-amino-alpha-methyl-3-hydroxy-L-tyrosine monohydrate. It potently inhibits aromatic amino acid decarboxylase (DDC) and due to its chemical properties, it does not cross the blood-brain barrier. Due to its activity, carbidopa is always administered concomitantly with levodopa. An individual formulation containing solely carbidopa was generated to treat nausea in patients where the combination therapy levodopa/carbidopa is not efficient reducing nausea.
The first approved product by the FDA containing only carbidopa was developed by Amerigens Pharmaceuticals Ltd and approved on 2014. On the other hand, the combination treatment of carbidopa/levodopa was originally developed by Watson Labs but the historical information by the FDA brings back to the approval of this combination therapy developed by Mayne Pharma in 1992.
When mixed with levodopa, carbidopa inhibits the peripheral conversion of levodopa to dopamine and the decarboxylation of oxitriptan to serotonin by aromatic L-amino acid decarboxylase. This results in an increased amount of levodopa and oxitriptan available for transport to the central nervous system. Carbidopa also inhibits the metabolism of levodopa in the GI tract, thus, increasing the bioavailability of levodopa.
Levodopa is a prodrug of dopamine that is administered to patients with Parkinson's due to its ability to cross the blood-brain barrier. Levodopa can be metabolised to dopamine on either side of the blood-brain barrier and so it is generally administered with a dopa decarboxylase inhibitor like carbidopa to prevent metabolism until after it has crossed the blood-brain barrier. Once past the blood-brain barrier, levodopa is metabolized to dopamine and supplements the low endogenous levels of dopamine to treat symptoms of Parkinson's. The first developed drug product that was approved by the FDA was a levodopa and carbidopa combined product called Sinemet that was approved on May 2, 1975.
Levodopa is able to cross the blood-brain barrier while dopamine is not. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrier. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylase.
| Trade Name | Teva Carbi-Levo |
| Generic | Carbidopa + levodopa |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | South Africa |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Carbidopa is a dopa decarboxylase inhibitor used in combination with levodopa for the symptomatic treatment of idiopathic Parkinson disease and other conditions associated with parkinsonian symptoms.
Carbidopa is indicated with levodopa for the treatment of symptoms of idiopathic Parkinson disease, postencephalitic parkinsonism and symptomatic parkinsonism followed by carbon monoxide or manganese intoxication.
The combination therapy is administered for the reduction of levodopa-driven nausea and vomiting.
The product of carbidopa should be used in patients where the combination therapy of carbidopa/levodopa provide less than the adequate daily dosage.
As well carbidopa can be used in patients where the dosages of carbidopa and levodopa require individual titration.
Levodopa is a dopamine precursor used in the management of Parkinson's disease, often in combination with carbidopa, as well as other conditions associated with parkinsonism.
Levodopa on its own is formulated as an oral inhalation powder indicated for intermittent treatment of off episodes in Parkinson's patients who are already being treated with carbidopa and levodopa. Levodopa is most commonly formulated as an oral tablet with a peripheral dopa decarboxylase inhibitor indicated for treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism following carbon monoxide intoxication or manganese intoxication.
Teva Carbi-Levo is also used to associated treatment for these conditions: Parkinson's Disease (PD), Postencephalitic parkinsonism, Symptomatic Parkinson Disease, Levodopa-driven nausea and vomitingParalysis agitans, Parkinson's Disease (PD), Parkinsonism, Postencephalitic parkinsonism, Restless Legs Syndrome (RLS), Advanced Motor fluctuations
How Teva Carbi-Levo works
Carbidopa is an inhibitor of the DDC which in order, inhibits the peripheral metabolism of levodopa. DDC is very important in the biosynthesis of L-tryptophan to serotonin and the modification of L-DOPA to dopamine.
DDC can be found in the body periphery and in the blood-brain barrier. The action of carbidopa is focused on peripheral DDC as this drug cannot cross the blood-brain barrier. Hence, it will prevent the metabolism of levodopa in the periphery but it will not have any activity on the generation of dopamine in the brain.
Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptors.
Toxicity
The LD50 of carbidopa is reported to be in the rat of 4810 mg/kg. In animal studies, carbidopa showed no incidences on neoplasia and showed no effect on the fertility status and development.
No reports of overdosage have been registered with the carbidopa-only product. In the event of overdosage, immediate gastric lavage is recommended as well as intravenous fluid administration. Continuous electrocardiographic monitoring is required.
There is no readily available data for the use of levodopa in pregnancy. Rabbits treated with levodopa and carbidopa produced smaller litters and their offspring developed visceral and skeletal deformities. Levodopa may lower prolactin and interfere with lactation but there is limited human data to demonstrate this effect. Levodopa is present in human breast milk and so the potential effects of nursing while taking levodopa should be considered before prescribing levodopa to nursing mothers. There is currently a lack of data on the safety and effectiveness of using levodopa in pediatric patients. Patients over 65 years of age are more likely to experience adverse effects associated with taking levodopa, however this generally is not sufficient to exclude this patient group from treatment.
Volume of Distribution
The volume of distribution reported for the combination therapy of carbidopa/levodopa is of 3.6 L/kg. However, carbidopa is widely distributed in the tissues, except in the brain. After one hour, carbidopa is found mainly in the kidney, lungs, small intestine and liver.
168L for orally inhaled levodopa.
Elimination Route
When levodopa/carbidopa is administered orally, 40-70% of the administered dose is absorbed. Once absorbed, carbidopa shows bioavailability of 58%. A maximum concentration of 0.085 mcg/ml was achieved after 143 min with an AUC of 19.28 mcg.min/ml.
Orally inhaled levodopa reaches a peak concentration in 0.5 hours with a bioavailability than is 70% that of the immediate release levodopa tablets with a peripheral dopa decarboxylase inhibitor like carbidopa or benserazide.
Half Life
The reported half-life of carbidopa is of approximately 107 minutes.
2.3 hours for orally inhaled levodopa. Oral levodopa has a half life of 50 minutes but when combined with a peripheral dopa decarboxylase inhibitor, the half life is increased to 1.5 hours.
Clearance
The reported clearance rate for the combination therapy of levodopa/carbidopa is 51.7 L/h.
Intravenously administered levodopa is cleared at a rate of 14.2mL/min/kg in elderly patients and 23.4mL/min/kg in younger patients. When given carbidopa, the clearance of levodopa was 5.8mL/min/kg in elderyly patients and 9.3mL/min/kg in younger patients.
Elimination Route
In animal studies, 66% of the administered dose of carbidopa was eliminated via the urine while 11% was found in feces. These studies were performed in humans and it was observed a urine excretion covering 50% of the administered dose.
After 48 hours, 0.17% of an orally administered dose is recovered in stool, 0.28% is exhaled, and 78.4% is recovered in urine
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