Clidinium - C
Chlordiazepoxide/clidinium is a benzodiazepine and anticholinergic combination. Each Chlordiazepoxide Hydrochloride/Clidinium Bromide capsule contains active ingredients 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide. It works by relieving anxiety and reducing digestive secretions.
Mechanism of effect
Clidinium : Synthetic anticholinergic that has an antispasmodic and antisecretory effect on the GI tract
Chlordiazepoxide : Benzodiazepine with anxiolytic and sedative properties. Binds to benzodiazepine receptors on the postsynaptic gamma-aminobutyric acid (GABA) neuron at several sites within the CNS, including the limbic system. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors.
Pharmacodynamic
Chlordiazepoxide hydrochloride has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which is involved in emotional responses. Chlordiazepoxide hydrochloride revealed a "taming-action with the elimination of fear and aggression".
The oral LD50 of single doses of chlordiazepoxide hydrochloride, is 720 ± 51 mg/kg as determined in mice observed over a period of 5 days following dosage.
Clidinium bromide is an effective anticholinergic agent with activity approximating that of atropine sulfate against acetylcholine-induced spasms in isolated intestinal strips. Oral doses of 2.5 mg/kg to dogs produced signs of nasal dryness and slight pupillary dilation.
The oral LD50 of single doses of clidinium bromide is 860 ± 57 mg/kg as determined in mice observed over a period of 5 days following dosage.
Pharmacokinetics
Chlordiazepoxide : Chlordiazepoxide distributes throughout the body and is about 96% protein-bound. It crosses the CSF, placenta and is distributed into breast milk. Chlordiazepoxide undergoes oxidative metabolism in the liver, producing several active metabolites. Chlordiazepoxide and its metabolites have a half-life ranging anywhere from 5—100 hours. The main active metabolite, desmethyldiazepam, has a half-life of several days. Repeated dosing may lead to drug accumulation, particularly in liver disease. Elimination occurs primarily as active metabolites in the urine.
Clidinium : Clidinium does not cross the blood-brain barrier, placenta or eye due to poor lipid solubility. It is not known if clidinium crosses into breast milk, but its use may decrease production of milk due to anticholinergic effects. Clidinium is metabolized in the liver to its 3-hydroxy alcohol. The elimination half-life is biphasic with an initial half-life of 2.4 hours and a terminal half-life of 20 hours. Roughly one-third of the dose is excreted renally within the first 24 hours after dosing. Twenty to 40% of the dose is excreted in the feces.
Dosage
Because of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of Chlordiazepoxide Hydrochloride/Clidinium Bromide varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects. The usual maintenance dose is 1 or 2 capsules, 3 or 4 times a day administered before meals and at bedtime.
Geriatric Dosing
Dosage should be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion. The initial dose should not exceed 2 Chlordiazepoxide Hydrochloride/Clidinium Bromide capsules per day, to be increased gradually as needed and tolerated.
Side effects
dry mouth , constipation , dizziness , Blurred vision , urticaria , fever , itching , difficulty urinating , skin rush , swelling , yellowing of the skin , yellowing of the eyes , swelling of the face , swelling of the tongue , tightness in the chestAlerts
1-Taking Chlordiazepoxide Hydrochloride/Clidinium Bromide with opioid medicines, alcohol, or other central nervous system depressants can cause severe drowsiness, breathing problems (respiratory depression), coma and death.
2- Chlordiazepoxide Hydrochloride/Clidinium Bromide can cause abuse and dependence.
3-In debilitated and geriatric patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion.
4- The concomitant administration of Chlordiazepoxide Hydrochloride/Clidinium Bromide and other psychotropic agents such as the MAO inhibitors and phenothiazines is not recommended.
5-Paradoxical reactions to chlordiazepoxide hydrochloride, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients. The usual precautions are indicated when chlordiazepoxide hydrochloride is used in the treatment of anxiety states where there is any evidence of impending depression; it should be borne in mind that suicidal tendencies may be present and protective measures may be necessary.
6- Although clinical studies have not established a cause and effect relationship, physicians should be aware that variable effects on blood coagulation have been reported very rarely in patients receiving oral anticoagulants and chlordiazepoxide hydrochloride .
7-The usual precautions in treating patients with impaired renal or hepatic function should be observed.
8-Safety and effectiveness in pediatric patients have not been established.
Points of recommendation
1- Do not stop taking Chlordiazepoxide Hydrochloride/Clidinium Bromide without first talking to your healthcare provider. Stopping Chlordiazepoxide Hydrochloride/Clidinium Bromide suddenly can cause serious side effects such as seizures, shaking, stomach and muscle cramps, vomiting and sweating. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed .
2- Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuance of chlordiazepoxide. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time.
3- Do not drive, operate heavy machinery, or do other dangerous activities until you know how Chlordiazepoxide Hydrochloride/Clidinium Bromide affects you.
4- Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction.
5- Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians.
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