Usage
- This combination medication is primarily prescribed for the treatment of nausea and vomiting during pregnancy (NVP), particularly in cases where conservative management has been ineffective. It is not recommended for other indications without consulting a doctor.
- Pharmacological Classification: Antiemetic, Vitamin Supplement. Doxylamine is an antihistamine (ethanolamine derivative) with antiemetic properties. Pyridoxal-5-phosphate (vitamin B6) and L-methyl folate (active form of folic acid) are vitamin/nutrient supplements that are essential for metabolic processes and cell synthesis, and are theorized to play a role in reducing NVP.
- Mechanism of Action: Doxylamine exerts its antiemetic action by antagonizing H1 histamine receptors, thus blocking histaminergic signaling to the vomiting center in the medulla. Pyridoxal-5-phosphate and L-methyl folate, while their exact mechanism in alleviating NVP is not fully elucidated, contribute to overall maternal health and fetal development during pregnancy.
Alternate Names
While the combination itself does not have a distinct international nonproprietary name (INN), the components do: Doxylamine succinate, Pyridoxal 5-phosphate, and L-Methylfolate calcium.
- Brand Names: Diclegis®, Bonjesta®, and other regional brand names. Some brands may also include other ingredients.
How It Works
- Pharmacodynamics: Doxylamine primarily acts as an H1 receptor antagonist. This action reduces the stimulation of the vomiting center in the brain. Pyridoxal-5-phosphate and L-methyl folate act as cofactors and substrates in crucial metabolic pathways.
- Pharmacokinetics: The precise pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of the combined formulation have not been completely characterized in the provided sources. Doxylamine is known to undergo hepatic metabolism and primarily renal excretion. Pyridoxal 5-phosphate also undergoes hepatic metabolism, while L-methylfolate is known to be involved in enterohepatic circulation.
- Mode of Action/Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Doxylamine competitively binds to H1 histamine receptors. No specific enzyme inhibition or neurotransmitter modulation has been described in the provided source, other than its interaction with the histaminergic system.
- Elimination Pathways: Doxylamine is largely excreted in the urine. Both Pyridoxal 5-phosphate and L-methylfolate are eliminated through various routes, including renal and hepatic pathways.
Dosage
Standard Dosage
Adults:
- Initial Dose: Two tablets at bedtime on Day 1.
- Subsequent Dosing: If symptoms persist on Day 2, take two tablets at bedtime and then commence three tablets on Day 3 (one tablet in the morning and two tablets at bedtime). If symptoms persist on Day 4, increase to four tablets daily (one tablet in the morning, one mid-afternoon, and two at bedtime).
Children: The safety and efficacy in children have not been established. This combination is not recommended for pediatric use.
Special Cases:
- Elderly Patients: While no specific dosage adjustments for the elderly are mentioned in provided sources, due to potential age-related decline in renal and hepatic function, caution should be exercised, and monitoring is recommended.
- Patients with Renal Impairment: Dosage adjustments may be needed based on the degree of impairment. Consult nephrology specialists and available resources to guide dose adjustment.
- Patients with Hepatic Dysfunction: Dosage adjustments may be necessary. Consult hepatology specialists and available resources to guide dose adjustment.
- Patients with Comorbid Conditions: Exercise caution in patients with asthma/COPD, cardiovascular disease, glaucoma, peptic ulcer disease, bladder neck obstruction, or depression.
Clinical Use Cases
This medication is primarily used for NVP. The provided sources do not recommend use for Intubation, Surgical Procedures, Mechanical Ventilation, ICU use, or Emergency situations.
Dosage Adjustments
Dosage should be individualized based on patient response and the presence of comorbidities or organ dysfunction. Always reassess the need for continued therapy.
Side Effects
Common Side Effects:
- Drowsiness
- Dizziness
- Blurred Vision
- Constipation
- Dry mouth
- Headache
- Restlessness
- Muscle pain/weakness
- Stomach pain
- Diarrhea
- Rash
Rare but Serious Side Effects:
- Vision problems
- Dilated pupils
- Difficulty/painful urination
- Fast/irregular heartbeat
- Shortness of breath
- Confusion
- Seizures
- Allergic reactions
Long-Term Effects:
Limited data is available on long-term effects.
Adverse Drug Reactions (ADR):
Severe ADRs such as seizures, confusion, shortness of breath, or allergic reactions require immediate medical attention.
Contraindications
- Hypersensitivity to any component of the medication
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs)
Drug Interactions
- Alcohol (increased drowsiness/dizziness)
- Other antihistamines (additive sedative effects)
- Anti-anxiety medications (additive sedative effects)
- MAOIs (potentially serious interactions)
- Sedative-hypnotics (additive sedative effects)
- Drugs that affect liver enzymes (consult resources for detailed list to evaluate potential changes in metabolism of components).
Pregnancy and Breastfeeding
- Pregnancy: Generally considered safe for use during pregnancy for the management of NVP. However, always discuss potential risks and benefits with the patient.
- Breastfeeding: Not recommended during breastfeeding as doxylamine is excreted in breast milk and may cause drowsiness or irritability in infants. If prescribed, advise patients to discontinue breastfeeding.
Drug Profile Summary
- Mechanism of Action: Doxylamine: H1 receptor antagonist. Pyridoxal-5-phosphate & L-methyl folate: Vitamins/Nutrients.
- Side Effects: Drowsiness, dizziness, blurred vision, constipation, dry mouth, etc.
- Contraindications: Hypersensitivity, concurrent MAOI use.
- Drug Interactions: Alcohol, other sedatives, MAOIs, medications metabolized via the liver.
- Pregnancy & Breastfeeding: Generally safe during pregnancy, avoid during breastfeeding.
- Dosage: See dosage section above.
- Monitoring Parameters: Monitor for efficacy in controlling NVP and observe for any adverse effects.
Popular Combinations
This combination is typically prescribed as a fixed-dose combination. Combining with additional antiemetics or sedatives is generally not recommended due to potential for additive adverse effects.
Precautions
- General Precautions: Evaluate patients for allergies, metabolic disorders, and organ dysfunction before initiating treatment.
- Pregnant Women: Assess risk/benefit ratio before prescribing.
- Breastfeeding Mothers: Advise against breastfeeding.
- Children & Elderly: Not recommended for pediatric use. Exercise caution in the elderly due to age-related changes in organ function.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxylamine + L-Methyl Folate Calcium + Pyridoxal-5-phosphate?
A: Initial dose: Two tablets at bedtime. Adjustments can be made based on symptom control as outlined in the dosage section.
Q2: What is the primary use of this medication?
A: Nausea and Vomiting during pregnancy (NVP).
Q3: Can this medication be used in breastfeeding mothers?
A: No, it is not recommended as it is excreted in breast milk and can affect the infant.
Q4: Are there any serious side effects I should be aware of?
A: Yes, rare but serious side effects include seizures, confusion, shortness of breath, and allergic reactions. Seek immediate medical attention if these occur.
Q5: What are the common side effects?
A: Drowsiness, dizziness, blurred vision, and constipation are common side effects.
Q6: Can this medication interact with other drugs?
A: Yes, it can interact with alcohol, other sedatives, MAOIs, certain antifungals like voriconazole, and other medications that are primarily metabolized by the liver.
Q7: What should I advise my patients regarding lifestyle while on this medication?
A: Advise patients to avoid alcohol, operate machinery with caution due to potential drowsiness, and to maintain a healthy diet.
Q8: Are there any contraindications to this medication?
A: Yes, hypersensitivity to the components and concomitant use of MAOIs are contraindications.
Q9: How does doxylamine work to control NVP?
A: Doxylamine is an antihistamine that blocks H1 receptors, which reduces the stimulation of the vomiting center in the brain.
