Isobamate

Uses

Isobamateis a GABA-A receptor indirect agonist with CNS chloride channel conductance effect. GABA receptor agonists typically produce sedative effect and may also cause other effects such as anxiolytic, anticonvulsant and muscle relaxant. Metabolite of Carisoprodol, Meprobamate, has anxiolytic and sedative properties.Isobamatedecreases the impulses from brain and spinal cord to the muscle. This causes the muscle to relax and hence decrease the spasm. It has no direct action on muscle itself.

Isobamate is also used to associated treatment for these conditions: Pain, Acute, Acute Discomfort

How Isobamate works

The mechanism of action of carisoprodol in relieving discomfort associated with acute painful musculoskeletal conditions has not been confirmed. In studies using animal models, the muscle relaxation that is induced by carisoprodol is associated with a change in the interneuronal activity of the spinal cord and of the descending reticular formation, located in the brain .

The abuse potential of this drug is attributed to its ability to alter GABAA function . This drug has been shown to modulate a variety of GABAA receptor subunits . GABAA receptor modulation can lead to anxiolysis due to inhibitory effects on neurotransmission .

Dosage

Isobamate dosage

Adults (18 years and older): The recommended dose of Carilax is 250 mg three times daily and at bedtime (4 times daily). The recommended maximum duration of Carilax use is up to two or three weeks. Caution should be taken in patients with renal and hepatic impairment and also with reduced CYP2C19 activity.

Side Effects

Common side effects are drowsiness, dizziness and headache.

Toxicity

LD50 values

The LD50 values of carisoprodol for rats are 450 mg/kg for intravenous (IV) and intraperitoneal injection, and 1,320 mg/kg for gavage dosing. In mice, the LD50 values are 165 mg/kg for intravenous injection, 980 mg/kg for intraperitoneal injection, and 2,340 mg/kg for gavage dosing. The LD50 value for rabbits given carisoprodol by intravenous injection is 124 mg/kg .

Overdose

An overdose of carisoprodol leads to CNS depression, and in severe cases, induction of a coma. Shock, depression of respiratory function, seizures and death have also been reported in rare cases. Several symptoms may be associated with carisoprodol overdose, such as horizontal and vertical nystagmus, blurred vision, mydriasis, mild tachycardia and hypotension, respiratory depression, euphoria, CNS stimulation, muscular incoordination, and/or rigidity, confusion, headache, hallucinations, and dystonic reactions. Alcohol or other CNS depressants or psychotropic agents can exert additive effects on carisoprodol even when one of the agents has been ingested at the normal, therapeutic dose. Fatal accidental and non-accidental overdoses have both been reported with carisoprodol ingestion alone or ingestion of carisoprodol in combination with alcohol or psychotropic drugs .

A note on dependence and withdrawal

In the postmarketing reports after carisoprodol use, cases of dependence, withdrawal, and abuse have been reported with long-term use. The majority of dependence and withdrawal cases, as well as abuse, have occurred in patients with a history of addiction or who have used this drug in combination with other drugs having abuse potential. However, multiple post-marketing adverse event reports have been made of carisodopril-associated abuse when used without other drugs possessing abuse potential. Withdrawal symptoms have been observed and reported following sudden abrupt cessation after long-term carisodoprol use. To reduce the chance of carisodopril dependence, withdrawal, or abuse, carisodopril should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol. This drug should not be taken for longer than 2 to 3 weeks for symptomatic relief of acute musculoskeletal discomfort .

Use in pregnancy

This drug has been classified as Pregnancy Category C. There are no clinical trial data on the use of carisoprodol during human pregnancy. Animal studies show that carisoprodol crosses the placenta and leads to adverse effects on fetal growth and postnatal survival. In postmarketing reports, the main metabolite, meprobamate, has not demonstrated a consistent association between maternal use and an increased risk for specific congenital malformations .

Use in nursing

Limited data in humans demonstrate that this is found excreted in breast milk and may reach concentrations in breast milk of 2-4 times the maternal plasma concentrations . It is therefore advisable to exercise caution when this drug is used during breastfeeding .

Interaction

Caution should be exercised with patients who take other CNS depressants (eg.- alcohol, benzodiazepines, opioids, tricyclic antidepressants) with Carisoprodol.Co-administration of CYP2C19 inhibitors (Omeprazole, Fluvoxamine) with Isobamatecould result in increased exposure of Carisoprodol. Co-administration of CYP2C19 inducers (Rifampin) with Isobamatecould result in decreased exposure of arisoprodol.

Food Interaction

• Avoid alcohol.
• Take with or without food. The absorption is unaffected by food.

Volume of Distribution

0.93 to 1.3 L/kg, according to 4 different clinical studies .

Elimination Route

The absolute bioavailability of carisoprodol has not yet been established. The mean time to peak plasma concentrations (Tmax) of this drug was about 1.5-2 hours in clinical studies . Co-administration of a fatty meal with carisoprodol (350 mg tablet) had no impact on carisoprodol pharmacokinetics .

Half Life

The terminal half-life is approximately 2 hours .

Clearance

Following an oral dose of carisoprodol, the oral clearance (Cl/F) was 39.52 ± 16.83 L/hour .

Elimination Route

Isobamateis eliminated by the kidneys as well as other routes. The half-life of meprobamate is approximately 10 hours .

Pregnancy & Breastfeeding use

Pregnancy category: C.Maternal use of Isobamatemay lead to reduced or less effective infant feeding (due to sedation) and/or decresed milk production. Caution should be exercised when Isobamateis administered to a nursing woman.

Acute Overdose

Overdosage of Isobamatecommonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures have been reported with Isobamateoverdosage.Basic life support measures should be instituted in Isobamateoverdose. Induced emesis is not recommended due to the risk of CNS and respiratory depression. Gastric lavage should be considered soon after ingestion (within one hour). Circulatory support should be administered with volume infusion and vasopressor agents if needed. Seizures should be treated with intravenous benzodiazepines and the reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS depression, airway protective reflexes may be compromised and tracheal intubation should be considered for airway protection and respiratory support.

Storage Condition

Store in cool and dry place at room temperature 20° - 25°C, away from direct light. Keep out reach of children.

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