Deriphyllin injection
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Deriphyllin Injection
Deriphyllin is a combination product containing Etophylline (theophylline-7-acetic acid ethyl ester) + Theophylline (77 mg etophylline + 23 mg theophylline per mL in the standard injection). It is a bronchodilator belonging to the methylxanthine class, widely used in South Asia.
The injectable form is closely related to aminophylline (theophylline + ethylenediamine), the IV methylxanthine used globally. The pharmacology below applies to both.
Composition
| Component | Amount per mL |
|---|---|
| Etophylline | 77 mg |
| Theophylline | 23 mg |
Aminophylline injection (the global equivalent) contains 25 mg/mL (79% theophylline).
Mechanism of Action
Deriphyllin/theophylline acts through several molecular mechanisms:
- PDE inhibition — Non-selective phosphodiesterase (PDE3 primarily) inhibition → ↑ intracellular cAMP → smooth muscle relaxation → bronchodilation
- Adenosine receptor antagonism — Antagonizes adenosine receptors at therapeutic concentrations; adenosine causes bronchoconstriction in asthmatic airways via histamine and leukotriene release
- Anti-inflammatory effects — Activates histone deacetylase-2 (HDAC2), enhancing corticosteroid responsiveness and suppressing inflammatory gene expression; reduces eosinophil and neutrophil airway infiltration
- IL-10 release — Increases IL-10 (broad anti-inflammatory cytokine), reduced in asthma/COPD
- Apoptosis promotion — Promotes apoptosis in eosinophils and neutrophils, reducing chronic airway inflammation
Indications
- Acute severe asthma / status asthmaticus (when β₂ agonists are unavailable or insufficient)
- Acute exacerbations of COPD
- Neonatal apnea (aminophylline specifically)
- Adjunct bronchodilator in chronic asthma (now less preferred)
Dosing (IV)
| Indication | Dose |
|---|---|
| Loading dose (acute asthma) | 6 mg/kg IV over 20–30 min |
| Maintenance (continuous infusion) | 0.5 mg/kg/hr |
| Neonatal apnea | Loading: 5–6 mg/kg IV; Maintenance: 1–2 mg/kg/dose Q6–8 hr |
Each 1.2 mg/kg IV dose raises serum theophylline concentration by ~2 mg/L.
If patient is already on oral theophylline: halve the loading dose and monitor levels more frequently.
Paediatric Continuous Infusion Rates
| Age | Rate |
|---|---|
| Neonate | 0.2 mg/kg/hr |
| 6 weeks – 6 months | 0.5 mg/kg/hr |
| 6 months – 1 year | 0.6–0.7 mg/kg/hr |
| 1–9 years | 1–1.2 mg/kg/hr |
| 9–12 yr / young adult smoker | 0.9 mg/kg/hr |
| >12 yr healthy non-smoker | 0.7 mg/kg/hr |
Therapeutic Drug Monitoring
Serum theophylline levels must be monitored — narrow therapeutic index.
| Purpose | Target Level |
|---|---|
| Asthma | 10–20 mg/L |
| Anti-inflammatory effect (low-dose) | 5–10 mg/L |
| Neonatal apnea | 6–13 mg/L |
When to draw levels:
- IV bolus: 30 min after infusion
- IV continuous infusion: 12–24 hr after initiation
Adverse Effects
Related to plasma concentration; usually occur at >15 mg/L:
| System | Effect |
|---|---|
| GI | Nausea, vomiting, abdominal discomfort, ↑ acid secretion (PDE4 inhibition) |
| CNS | Headache, restlessness, behavioral disturbances; seizures at toxic levels (central A1 receptor antagonism) |
| CVS | Tachycardia, palpitations, cardiac arrhythmias (cardiac PDE3 inhibition + A1 antagonism) |
| Renal | Diuresis (adenosine A1 antagonism) |
| Metabolic | Hypokalemia (at high doses) |
Seizures may occur without prior warning symptoms at toxic levels.
Pharmacokinetics
- Absorption: Rapidly and completely absorbed
- Metabolism: Hepatic — primarily CYP1A2
- Wide interindividual variation in clearance → dose individualisation required
Factors Affecting Theophylline Clearance
| ↑ Clearance (lower levels) | ↓ Clearance (higher levels, toxicity risk) |
|---|---|
| Smoking (tobacco/marijuana) | Congestive heart failure |
| Enzyme inducers (rifampicin, barbiturates, ethanol) | Liver disease |
| High-protein, low-carb diet | Old age |
| Childhood | Pneumonia, viral infection |
| Barbecued meat | CYP inhibitors: cimetidine, erythromycin, ciprofloxacin, allopurinol, fluoxamine, zileuton |
Drug Interactions
- Fluoroquinolones (especially ciprofloxacin): inhibit theophylline metabolism → toxicity risk
- Erythromycin, cimetidine: ↑ theophylline levels
- Rifampicin, phenytoin, carbamazepine: ↓ theophylline levels (enzyme induction)
- β-blockers: antagonise bronchodilation
Contraindications / Cautions
- Active peptic ulcer disease
- Cardiac arrhythmias
- Epilepsy (seizure threshold lowered)
- Pregnancy: use with caution; breastfeeding — avoid for 2 hr after IV dose (causes infant irritability)
- Renal/hepatic impairment — reduce dose
Clinical Position (Current Practice)
IV aminophylline/deriphyllin is now seldom used as first-line for acute asthma — nebulised β₂ agonists are preferred. It is reserved for:
- Patients who fail to respond to or are intolerant of β₂ agonists
- Should not be added routinely to nebulised β₂ agonists (no added bronchodilation; increased side effects)
- In COPD, inhaled anticholinergics and β₂ agonists are preferred; theophylline is an add-on in severe disease
Sources:
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, Ch. 44
- Fishman's Pulmonary Diseases and Disorders — Phosphodiesterase Inhibitors
- The Harriet Lane Handbook, 23rd Ed. — Aminophylline monograph
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