Theophylline + Vitamin B6

Usage

• Theophylline is prescribed to treat symptoms of asthma, chronic bronchitis, and emphysema. It is also used to treat apnea of prematurity in infants.
• Pharmacological Classification: Theophylline is a bronchodilator and belongs to the methylxanthine class. Vitamin B6 is a water-soluble vitamin.
• Mechanism of Action: Theophylline inhibits phosphodiesterase enzymes, leading to increased intracellular cyclic AMP (cAMP) levels, which relaxes bronchial smooth muscle, promoting bronchodilation. Theophylline also exhibits some anti-inflammatory actions in the lungs. Vitamin B6 is added to mitigate potential vitamin B6 deficiency, as theophylline may lower the body’s B6 levels.

Alternate Names

• Theophylline is also known as 1,3-dimethylxanthine.
• Vitamin B6 is also known as pyridoxine.
• Brand Names: Some popular brand names for theophylline include Elixophyllin, Theo-24, Theochron, Theo-Dur, Slo-Bid, and Uniphyl. Combined formulations of theophylline and vitamin B6 under a single brand name are less common, with most preparations given as separated prescriptions.

How It Works

• Pharmacodynamics (Theophylline): Theophylline relaxes bronchial smooth muscle, improving airflow in the lungs. It also has mild anti-inflammatory and immunomodulatory effects.

• Pharmacokinetics (Theophylline):

  • Absorption: Well-absorbed orally. Extended-release formulations provide sustained blood levels.
  • Metabolism: Primarily metabolized by the liver via CYP450 enzymes (CYP1A2, CYP2E1, CYP3A4).
  • Elimination: Primarily excreted renally. Clearance is affected by age, smoking status, liver function, and concomitant medications.

• Mode of Action (Theophylline): Theophylline mainly inhibits phosphodiesterase enzymes, leading to increased intracellular cAMP. It also antagonizes adenosine receptors and may affect intracellular calcium handling.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation (Theophylline): Inhibition of phosphodiesterases, adenosine receptor antagonism.

• Elimination Pathways (Theophylline): Primarily renal excretion of metabolites.

• Pharmacodynamics (Vitamin B6): Vitamin B6 is a cofactor for numerous enzymes involved in amino acid, glucose, and lipid metabolism. It is important for neurotransmitter synthesis and immune function.

• Pharmacokinetics (Vitamin B6):

  • Absorption: Readily absorbed in the small intestine.
  • Metabolism: Converted to active forms, pyridoxal phosphate, and pyridoxamine phosphate, in the liver.
  • Elimination: Primarily renal excretion.

• Mode of Action (Vitamin B6): Acts as a coenzyme in various metabolic reactions.

• Elimination Pathways (Vitamin B6): Renal excretion.

Dosage

Standard Dosage

Adults (Theophylline):

• Oral: Initial: 300 mg/day in divided doses every 6-8 hours. Adjust based on serum levels, targeting 10-20 mcg/mL. Maximum: 400-600 mg/day for maintenance; up to 1600 mg/day in severe cases with monitoring.
• IV: Loading dose: 5-7 mg/kg (ideal body weight) IV over 20 minutes. Maintenance: 0.4-0.6 mg/kg/hour IV, adjusted to maintain serum levels.

Adults (Vitamin B6): 10-25 mg/day orally.

Children (Theophylline):

• Dosage is based on age and weight, requires careful calculation and monitoring, and should be under the strict supervision of a physician. Use ideal body weight for calculations.
• Divided doses are usually given every 4-6 hours for immediate-release or every 8-12 hours for extended-release formulations.

Children (Vitamin B6): Based on age, typically 0.1-1.3 mg/day

Special Cases:

• Elderly Patients: Reduced clearance, lower initial doses and careful titration are needed.
• Patients with Renal Impairment: Reduced clearance, dose reduction based on creatinine clearance.
• Patients with Hepatic Dysfunction: Reduced metabolism, dose reduction.
• Patients with Comorbid Conditions: CHF, cor pulmonale, sepsis: lower dose. Concomitant medications affecting CYP450 enzymes require dose adjustments.

Clinical Use Cases

Dosage adjustments in specific scenarios are complex and depend heavily on serum monitoring and individual patient response. Consultation with a pulmonologist or critical care specialist is highly recommended in these cases. Guidelines exist for theophylline use in acute bronchospasm, status asthmaticus, and apnea of prematurity, but the drug is generally not a first-line agent in these situations.

Dosage Adjustments

Adjustments based on renal/hepatic function, drug interactions, age, and serum theophylline concentration are crucial.

Side Effects

Common Side Effects:

• Nausea, vomiting
• Headache
• Insomnia, anxiety
• Tremors
• Tachycardia, palpitations

Rare but Serious Side Effects:

• Seizures
• Cardiac arrhythmias

Long-Term Effects: Chronic toxicity may manifest as persistent gastrointestinal issues or cardiac problems with prolonged high doses.

Adverse Drug Reactions (ADR): Severe allergic reactions (rare), life-threatening arrhythmias.

Contraindications

• Hypersensitivity to theophylline
• Active peptic ulcer disease
• Uncontrolled seizure disorders

Drug Interactions

• CYP450 Interactions:
  • Inhibitors (cimetidine, erythromycin, fluconazole): increase theophylline levels.
  • Inducers (rifampin, phenobarbital): decrease theophylline levels.
• Other Interactions:
  • Adenosine: reduced efficacy of adenosine.
  • Beta-blockers: may attenuate bronchodilation.
  • Lithium: reduced lithium levels.
• Lifestyle factors like smoking may increase theophylline clearance.

Pregnancy and Breastfeeding

• Pregnancy: Theophylline crosses the placenta. Use with caution, weigh risks and benefits.
• Breastfeeding: Theophylline is excreted in breast milk. Monitor infant for irritability and feeding difficulties.

Drug Profile Summary

See above sections for summaries of mechanism of action, side effects, contraindications, drug interactions, pregnancy & breastfeeding, and dosage.

• Monitoring Parameters: Serum theophylline levels, heart rate, blood pressure, respiratory rate, signs of toxicity (nausea, vomiting, tremors, seizures).

Popular Combinations

Theophylline may be combined with other bronchodilators (e.g., beta-agonists) or corticosteroids in asthma management.

Precautions

• Careful monitoring of serum theophylline levels is essential, especially during initiation and dosage adjustments.
• Monitor patients with renal or hepatic impairment, cardiac conditions, and elderly patients closely for toxicity.
• Pre-existing seizures or peptic ulcers warrant caution.
• Avoid abrupt discontinuation, as this can precipitate bronchospasm.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Theophylline + Vitamin B6?

A: Theophylline dosage is highly individualized and based on serum levels, typically targeting 10-20 mcg/mL. Standard adult starting doses for oral theophylline are around 300 mg/day, but this should be adjusted. Vitamin B6 supplementation alongside theophylline is usually given at 10-25 mg/day.

Q2: What are the common side effects of Theophylline?

A: Common side effects include nausea, vomiting, headache, insomnia, anxiety, tremors, and palpitations.

Q3: How does Theophylline affect Vitamin B6 levels?

A: Theophylline can interfere with vitamin B6 metabolism, potentially leading to deficiency.

Q4: Are there specific contraindications for Theophylline + Vitamin B6 use?

A: Contraindications include hypersensitivity to theophylline, active peptic ulcer, and uncontrolled seizures.

Q5: What are the key drug interactions with Theophylline?

A: Theophylline interacts with numerous medications, including CYP450 inhibitors (e.g., cimetidine, erythromycin) and inducers (e.g., rifampin, phenobarbital).

Q6: How is Theophylline dosing adjusted in patients with renal impairment?

A: Theophylline dose should be reduced in patients with renal impairment based on creatinine clearance.

Q7: What is the role of therapeutic drug monitoring with Theophylline?

A: Therapeutic drug monitoring is essential to ensure serum theophylline levels remain within the therapeutic range (10-20 mcg/mL) and to minimize the risk of toxicity.

Q8: Can Theophylline be used during pregnancy and breastfeeding?

A: Theophylline can be used cautiously during pregnancy and breastfeeding, but the risks and benefits must be carefully weighed. Monitor infant for potential side effects during breastfeeding.

Q9: What are the signs of Theophylline toxicity?

A: Signs of toxicity include nausea, vomiting, seizures, cardiac arrhythmias, and severe agitation.

Q10: How is Theophylline administered in acute bronchospasm?

A: For acute bronchospasm, IV aminophylline can be used. The loading dose is typically 6-7 mg/kg IV (ideal body weight) over 20-30 minutes. The choice of maintenance dosing depends on multiple factors and serum level monitoring is needed.