Duodopa intestinal gel

Uses

Levodopa and carbidopa is used for the treatment of Parkinson's disease, post-encephalitic Parkinsonism, and symptomatic Parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Duodopa intestinal gel 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 Duodopa intestinal gel 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.

Dosage

Duodopa intestinal gel dosage

Usual Initial Dosage: The optimum daily dosage must be determined by careful titration in each patient. If Levodopa 100 mg and Carbidopa 10 mg is used, dosage may be initiated with one tablet three or four times a day. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (2 tablets q.i.d.) is reached.

Maintenance dose: Therapy should be individualized & adjusted according to the desired therapeutic response. When more levodopa is required, Levodopa 250 mg and Carbidopa 25 mg should be substituted for Levodopa 100 mg and Carbidopa 10 mg. If necessary, the dosage of Levodopa 250 mg and Carbidopa 25 mgmay be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.

Side Effects

The most common adverse reactions reported with Levodopa and Carbidopa have included dyskinesias, such as choreiform, dystonic, and other involuntary movements, and nausea.

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.

Precaution

Levodopa alone, as well as combination, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction. It should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.

Interaction

Pyridoxine reverses effects of levodopa. Type B MAOIs have synergistic effect. Effect reduced by phenothiazines, haloperidol, reserpine, pyridoxine, diazepam, oxazepam, chlordiazepoxide, phenobarbitone. Effects of levodopa enhanced by carbidopa, amantadine, anticholinergics, amphetamine. Effects of sympathomimetic agents enhanced.

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

Pregnancy & Breastfeeding use

Pregnancy Category C. Levodopa has been detected in human milk. Caution should be exercised when administered to a nursing woman.

Contraindication

Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with Levodopa and carbidopa. These inhibitors must be discontinued at least two weeks prior to initiating therapy with Levodopa and carbidopa. Levodopa and carbidopa is contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.

Special Warning

Use in children: Safety and effectiveness of Carbidopa-Levodopa in infants and children have not been established, and its use in patients below the age of 18 years is not recommended.

Storage Condition

Protect from light and moisture, store below 30°C. Keep the medicine out of the reach of children.

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