Usage
Chlordiazepoxide + Clidinium + Drotaverine is prescribed for the relief of symptoms associated with irritable bowel syndrome (IBS) and other gastrointestinal disorders characterized by smooth muscle spasms, pain, cramping, bloating, and discomfort. It is also used in managing visceral pain and as an adjunct therapy in functional bowel disorders. It can also be used as an adjunctive treatment of peptic ulcers and enterocolitis. It combines medications from three pharmacological classifications:
- Chlordiazepoxide: Benzodiazepine (Anxiolytic and Sedative)
- Clidinium: Anticholinergic (Antispasmodic)
- Drotaverine: Antispasmodic (Musculotropic)
This combination targets gastrointestinal spasms, excessive secretions, and anxiety related to IBS and similar conditions.
Alternate Names
This combination medication does not have a universally recognized international nonproprietary name (INN). It is commonly recognized by its constituent drugs. Some popular brand names include DVN IBS and Tispas CD.
How It Works
Pharmacodynamics: This triple combination exerts its therapeutic effects through the combined action of its components:
- Chlordiazepoxide enhances the effect of GABA, an inhibitory neurotransmitter, in the central nervous system, reducing anxiety and promoting muscle relaxation.
- Clidinium, an anticholinergic, inhibits the action of acetylcholine at muscarinic receptors. This reduces gastric acid secretion and intestinal motility, thereby relieving spasms and associated pain.
- Drotaverine, a direct smooth muscle relaxant, inhibits phosphodiesterase IV, leading to increased intracellular cAMP levels and subsequent smooth muscle relaxation in the gastrointestinal tract.
Pharmacokinetics:
- Chlordiazepoxide: It’s metabolized in the liver and excreted primarily in the urine.
- Clidinium: This drug is also metabolized in the liver, however, the exact excretion pathway isn’t well-documented.
- Drotaverine: After hepatic metabolism, drotaverine is primarily eliminated renally.
Receptor Binding/Enzyme Inhibition:
- Chlordiazepoxide binds to the benzodiazepine site on the GABAA receptor.
- Clidinium acts as a muscarinic receptor antagonist.
- Drotaverine inhibits phosphodiesterase IV.
Dosage
Standard Dosage
Adults:
The usual recommended dose is 1-2 capsules 3-4 times daily, administered before meals and at bedtime.
Children:
This combination is not recommended for children. Alternative treatment options should be considered and determined by a pediatrician.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 2 capsules/day) and titrate upward as needed and tolerated to minimize the risk of adverse effects such as ataxia, oversedation, and confusion.
- Patients with Renal Impairment: Dose adjustment may be necessary. Monitor renal function closely.
- Patients with Hepatic Dysfunction: Careful evaluation and dose adjustment are essential due to potential effects on drug metabolism.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, respiratory disorders, or other relevant conditions. Dose adjustments and close monitoring may be required.
Clinical Use Cases
The use of Chlordiazepoxide + Clidinium + Drotaverine in specific medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations isn’t standard practice. Other treatment strategies are generally preferred in these contexts.
Dosage Adjustments
Dose adjustments are necessary based on individual response and the presence of renal or hepatic impairment, comorbid conditions, and concomitant medications. Consult available drug interaction resources for detailed information.
Side Effects
Common Side Effects
Dry mouth, blurred vision, constipation, nausea, urinary retention, drowsiness, dizziness.
Rare but Serious Side Effects
Severe drowsiness, confusion, paradoxical reactions (agitation, hallucinations), allergic reactions, difficulty breathing, liver dysfunction, paradoxical excitement, memory impairment.
Long-Term Effects
Potential long-term effects include dependence on chlordiazepoxide, worsening of pre-existing glaucoma, cognitive impairment, and chronic constipation.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe allergic reactions, paradoxical CNS stimulation, respiratory depression, urinary retention requiring catheterization, angle-closure glaucoma.
Contraindications
Absolute contraindications include hypersensitivity to any component, glaucoma, prostatic hypertrophy, bladder neck obstruction, severe respiratory depression, paralytic ileus, and myasthenia gravis.
Drug Interactions
Clinically significant drug interactions occur with other CNS depressants (alcohol, opioids, antihistamines), anticholinergic drugs (tricyclic antidepressants, some antipsychotics), monoamine oxidase inhibitors (MAOIs), and antacids (may decrease absorption). Concurrent use with these agents may potentiate side effects or alter drug metabolism. Always consult drug interaction resources for a comprehensive list of potential interactions before co-prescribing.
Pregnancy and Breastfeeding
This combination should generally be avoided during pregnancy, especially in the first trimester, due to potential risks to the fetus. If used during pregnancy, closely monitor the neonate for potential withdrawal symptoms. Chlordiazepoxide is excreted in breast milk and may cause undesirable effects on the infant. Clidinium’s excretion in breast milk is not well-established. Due to potential risks, this combination is generally not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: A combination drug targeting GI spasms, secretions, and anxiety related to gastrointestinal disorders.
- Side Effects: Common: Dry mouth, blurred vision, constipation, drowsiness, dizziness, urinary retention. Serious: Allergic reactions, paradoxical CNS stimulation, respiratory depression.
- Contraindications: Glaucoma, prostatic hypertrophy, bladder neck obstruction, severe respiratory depression, paralytic ileus, myasthenia gravis.
- Drug Interactions: CNS depressants, anticholinergics, MAOIs, antacids.
- Pregnancy & Breastfeeding: Avoid if possible during pregnancy and not recommended during breastfeeding.
- Dosage: 1-2 capsules 3-4 times/day (adults); elderly initially 2 capsules/day. Adjust for renal/hepatic impairment.
- Monitoring Parameters: Vital signs, bowel function, mental status, urinary function.
Popular Combinations
This drug is itself a combination and is not typically combined with other drugs for the same indications. It might be used alongside other medications for managing comorbidities, but such decisions should be made carefully, considering potential drug interactions.
Precautions
- General Precautions: Pre-screening for allergies, glaucoma, prostatic hypertrophy, myasthenia gravis, bladder neck obstruction, and other contraindications is essential.
- Specific Populations: Avoid or use with extreme caution in pregnant/breastfeeding women, children, and the elderly.
- Lifestyle Considerations: Avoid alcohol and activities requiring alertness (driving, operating machinery) due to potential drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Chlordiazepoxide + Clidinium + Drotaverine?
A: For adults, the usual dose is 1-2 capsules 3-4 times daily, taken before meals and at bedtime. Elderly patients should start with a lower dose (e.g., 2 capsules/day) and titrate upwards as needed. Pediatric use should be determined by a physician, although generally avoided.
Q2: What are the primary side effects?
A: Common side effects include dry mouth, blurred vision, constipation, nausea, urinary retention, drowsiness, and dizziness. More severe but less common effects include confusion, paradoxical reactions, allergic reactions, and respiratory depression.
Q3: Can this medication be used during pregnancy?
A: It’s generally recommended to avoid this medication during pregnancy, especially in the first trimester, due to potential fetal harm. If use is absolutely necessary, the patient must be informed of the risks.
Q4: Is it safe to take this medication while breastfeeding?
A: It is not recommended to use this medication during breastfeeding, as chlordiazepoxide is excreted in breast milk and may have adverse effects on the nursing infant.
Q5: How does this combination work in IBS?
A: It addresses the multiple factors contributing to IBS symptoms: chlordiazepoxide reduces anxiety, clidinium controls intestinal spasms and secretions, and drotaverine relaxes the smooth muscles of the GI tract.
Q6: Are there any specific dietary restrictions while on this medication?
A: Patients should maintain adequate hydration and fiber intake to prevent constipation. Avoiding alcohol is recommended. Specific dietary modifications based on individual IBS triggers can be beneficial.
Q7: Can this medication interact with other medications I’m taking?
A: Yes, it can interact with various drugs, including CNS depressants, anticholinergics, MAOIs, and antacids. Always inform your doctor about all other medications, including OTC drugs and supplements, to avoid potential interactions.
Q8: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember, unless it’s almost time for the next dose. Do not double the dose to catch up.
Q9: Are there any long-term risks associated with taking this medication?
A: Potential long-term risks include dependence on chlordiazepoxide, worsening of pre-existing glaucoma, cognitive impairment, and chronic constipation. Regular monitoring is crucial for patients on long-term therapy.
