Pinaverium bromide

Usage

Pinaverium bromide is prescribed for the symptomatic treatment of:

• Irritable bowel syndrome (IBS), relieving pain, transit disorders (constipation and/or diarrhea), and intestinal discomfort (bloating).
• Functional disturbances of the biliary tract, alleviating associated pain.
• Preparation for a barium enema.

Pharmacological classification: Pinaverium bromide is classified as an antispasmodic agent, specifically a calcium antagonist.

Mechanism of Action: Pinaverium bromide acts by relaxing the smooth muscles in the gastrointestinal tract. It inhibits the influx of calcium ions into these muscle cells, reducing their contractility and thus alleviating spasms and pain.

Alternate Names

• International Nonproprietary Name (INN): Pinaverium bromide.

• Brand names: Dicetel, Eldicet, Pivertel.

How It Works

Pharmacodynamics: Pinaverium bromide selectively targets the smooth muscle of the gastrointestinal tract, primarily in the colon. By blocking calcium channels, it inhibits muscle contractions, reducing spasms and associated pain and discomfort. It has no significant anticholinergic or cardiovascular effects.

Pharmacokinetics:

• Absorption: Rapidly absorbed after oral administration, with peak plasma concentrations reached within an hour.
• Metabolism: Extensively metabolized in the liver.
• Elimination: Primarily eliminated in feces, with a small amount excreted in urine. The elimination half-life is approximately 1.5 hours.
• Bioavailability: Low oral bioavailability (<1%).
• Plasma Protein Binding: High (95-97%).

Mode of Action: Pinaverium bromide acts as a calcium antagonist, specifically blocking voltage-dependent calcium channels in the smooth muscle cells of the gastrointestinal tract. This inhibition of calcium influx reduces muscle contractility, leading to relaxation of the intestinal and biliary smooth muscles. It affects the colonic motor response to food and pharmacological stimuli, suggesting a role in managing IBS.

Dosage

Standard Dosage

Adults:

• Standard dose: 50 mg three times daily, taken with a glass of water during meals.
• Maximum dose: 100 mg three times daily (300mg total daily dose). The dosage can be adjusted as needed to 2 tablets twice a day.
• For barium enema preparation: 100 mg twice daily for three days prior to the procedure.

Children:

Pinaverium bromide is not recommended for use in children under 18 years, as its safety and efficacy have not been established. Limited data suggests a daily dose of 100-150mg for children between 5 and 15 years old, but due to the risk of esophageal lesions, further research needs to be done to establish effectiveness. This medication can damage the throat and should therefore not be administered to children without close monitoring and care.

Special Cases:

• Elderly Patients: Dosage adjustment is not typically required. However, initiating treatment with the lower end of the dose range (50mg three times per day) is recommended.
• Patients with Renal Impairment: No specific dosage adjustment guidelines are available. Close monitoring and dose adjustment based on clinical response are advised.
• Patients with Hepatic Dysfunction: No specific dosage adjustment guidelines are available. Close monitoring and dose adjustment based on clinical response are advised.
• Patients with Comorbid Conditions: No specific recommendations for other comorbidities. Careful consideration is necessary, particularly if interacting medications are used.

Clinical Use Cases

• Pinaverium bromide is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest.

Dosage Adjustments

Dose adjustments may be necessary in patients with renal or hepatic impairment based on individual patient response and clinical assessment.

Side Effects

Common Side Effects:

• Gastrointestinal: Nausea, constipation, diarrhea, abdominal pain/fullness, heartburn, distension.
• Other: Headache, dry mouth, drowsiness, dizziness, skin allergy (rash, pruritus, urticaria, erythema).

Rare but Serious Side Effects:

• Esophageal lesions (ulcers, strictures) if the medication is not swallowed properly.
• Hypersensitivity reactions: Angioedema, anaphylactic shock.

Long-Term Effects:

No specific long-term adverse effects have been reported.

Adverse Drug Reactions (ADR):

• Esophageal lesions require immediate attention if suspected, potentially leading to dysphagia and pain.
• Hypersensitivity reactions mandate immediate medical intervention.

Contraindications

• Hypersensitivity to pinaverium bromide or any of its excipients.
• Intestinal obstruction or severe motility disorders.
• Pre-existing esophageal lesions or hiatus hernia (use with caution).
• Galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (due to the presence of lactose in the formulation).

Drug Interactions

While clinical trials haven’t revealed significant interactions with cardiac glycosides, oral antidiabetics, insulin, oral anticoagulants (e.g., acenocoumarol), or heparin, caution is advised. Concomitant use with anticholinergics may enhance the spasmolytic effect. Interactions with specific drugs require attention:

• CYP450 interactions: Although not explicitly documented, metabolism by CYP enzymes is possible, and interactions with inducers or inhibitors may occur. This warrants careful consideration when prescribing with drugs metabolized by CYP enzymes.
• Numerous potential drug interactions have been suggested but not fully established. Consider interactions with other medications that prolong the QT interval or affect potassium levels, as these could be aggravated.

Pregnancy and Breastfeeding

• Pregnancy: Pinaverium bromide should be used during pregnancy only if clearly necessary, due to limited data on human safety. It has shown decreased gravidity performance in animal studies at high doses. Its use at the end of pregnancy may theoretically affect the newborn neurologically (hypotony, sedation).
• Breastfeeding: Not recommended as it’s unknown whether the drug is excreted in breast milk, and a risk to the nursing infant cannot be excluded.

Drug Profile Summary

• Mechanism of Action: Calcium antagonist, relaxing gastrointestinal smooth muscle.
• Side Effects: Nausea, constipation, diarrhea, abdominal pain, headache, drowsiness, esophageal lesions (rare).
• Contraindications: Hypersensitivity, intestinal obstruction, pre-existing esophageal lesions, galactose intolerance.
• Drug Interactions: Potentially with QT prolonging drugs and CYP450 substrates. Closely monitor. Limited data regarding its effects on other drugs may suggest that it is safe to use with medications that would otherwise interfere with other medications.
• Pregnancy & Breastfeeding: Use with caution in pregnancy if essential; avoid during breastfeeding.
• Dosage: Adults: 50 mg three times daily, up to 100 mg three times daily. Not recommended for children.
• Monitoring Parameters: Monitor for gastrointestinal side effects and esophageal symptoms. Assess for drug interactions based on concomitant medications.

Popular Combinations

Pinaverium bromide is sometimes combined with other medications for IBS and biliary disorders, including anticholinergics. Limited data are available, and the safety and efficacy should be assessed.

Precautions

• General Precautions: Screen patients for hypersensitivity, pre-existing esophageal lesions, and metabolic disorders affecting lactose absorption.
• Specific Populations:
  • Pregnant women: Carefully assess risks and benefits, consider alternatives.
  • Breastfeeding mothers: Avoid use.
  • Children: Not recommended.
• Lifestyle Considerations: Limit alcohol consumption. Advise patients about potential drowsiness and its impact on driving.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Pinaverium bromide?

A: For adults, the standard dose is 50 mg three times daily, taken with meals. This can be increased up to 100 mg three times daily if needed. Pinaverium bromide is generally not recommended for children under 18.

Q2: How does Pinaverium bromide work?

A: Pinaverium bromide is a calcium channel blocker that relaxes the smooth muscles of the gastrointestinal tract, reducing spasms and associated pain.

Q3: What are the common side effects of Pinaverium bromide?

A: Common side effects include nausea, constipation, diarrhea, abdominal pain or fullness, heartburn, headache, dry mouth, drowsiness, and dizziness. Esophageal lesions can occur if the medication isn’t swallowed correctly, with water and during meals.

Q4: Is Pinaverium bromide safe during pregnancy and breastfeeding?

A: Pinaverium bromide should be used during pregnancy only if clearly necessary, after discussing the risks and benefits with a physician. Its use is generally avoided during breastfeeding due to potential risks to the infant.

Q5: Are there any drug interactions I should be aware of with Pinaverium bromide?

A: Concomitant use with other QT prolonging drugs or those affecting potassium levels may warrant closer observation. Although specific CYP450 interactions aren’t well documented, theoretical interactions with CYP substrates are possible and should be considered.

Q6: What are the contraindications for using Pinaverium bromide?

A: The main contraindications include hypersensitivity to the drug, intestinal obstruction, pre-existing esophageal lesions, and galactose intolerance (due to lactose in the formulation).

Q7: How should Pinaverium bromide be taken?

A: The tablets should be swallowed whole with a glass of water during a meal. Do not crush, chew, or suck the tablets. This helps prevent esophageal irritation. Do not take while lying down or just before bedtime.

Q8: Can Pinaverium bromide be used long-term?

A: While there’s no documented evidence of specific long-term adverse effects, the duration of treatment should be determined based on the patient’s condition and response to therapy.

Q9. What should I do if I miss a dose?

A: If you miss a dose, take it as soon as you remember, unless it is close to the time of your next dose. Do not double up on doses.

Q10. What should I do in case of overdose?

A: No cases of overdose have been reported, and no specific antidote is known. If overdose is suspected, symptomatic treatment is recommended. Contact your local poison control center or emergency room immediately.