Theophylline
THEO-24
Pronunciation: thee-OF-i-lin
“Elixir Tree offline”
What it isNon-selective phosphodiesterase inhibitor and adenosine antagonist; asthma and COPD.
Why this oneOral bronchodilation with a mild anti-inflammatory effect, and it is very cheap where inhalers are not available.
What limits itA narrow therapeutic index needing levels, and CYP1A2 makes it interaction-prone — ciprofloxacin and smoking cessation both push it into toxicity.
Pearls
- Target peak level 6–12 mcg/mL.
- Toxicity: vomiting, hypokalemia, arrhythmias, seizures.
- Does not reduce COPD exacerbations.
- Lowers lithium levels by raising renal clearance.
Theophylline prescription history
Animated chart of estimated U.S. prescriptions per year, Asthma/COPD meds (1924–2026). Theophylline enters in 1940 (estimated).
FDA-approved for
- asthma/COPD (~1940)
Principal riskNarrow index; CYP1A2 interactions push it into toxicity
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityNarrow therapeutic index; overdose can cause refractory seizures and life-threatening tachyarrhythmias.
FDA label
Read the full label on DailyMed ↗
NO BOXED WARNINGS
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Chronic asthma and other chronic lung diseases (emphysema, chronic bronchitis) — maintenance | Adults 16–60 y and children >45 kg, no risk factors for impaired clearance | 300–400 mg/day Q24H | After 3 days, if tolerated: 400–600 mg/day Q24H | >600 mg/day only titrated by serum level (Table VI) |
| Chronic asthma / chronic lung disease — maintenance | Elderly >60 y, risk factors for impaired clearance, or levels not feasible (≥16 y and adults) | Low dose, titrate slowly (Table V) | Guided by serum level | 400 mg/day (elderly: exceed only if symptomatic and peak <10 mcg/mL) |
| Chronic asthma / chronic lung disease — maintenance | Children 12–15 y, <45 kg, no risk factors | 12–14 mg/kg/day (max 300 mg/day) Q24H | After 3 days: 16 mg/kg/day (max 400 mg/day); after 3 more days if needed: 20 mg/kg/day (max 600 mg/day), Q24H | 20 mg/kg/day up to 600 mg/day |
| Chronic asthma / chronic lung disease — maintenance | Children 12–15 y with risk factors for reduced clearance or levels not feasible | 12–14 mg/kg/day (max 300 mg/day) Q24H | Guided by serum level | 16 mg/kg/day up to 400 mg/day |
Titration Increase only if previous dose tolerated, at intervals of no less than 3 days
Renal No adjustment needed in adults and children >3 months; neonates with reduced renal function: reduce dose, monitor levels
Hepatic Clearance decreased ≥50% in hepatic insufficiency (cirrhosis, hepatitis, cholestasis): reduce dose and monitor serum levels closely
Serum-level adjustment (Table VI): <9.9 mcg/mL increase ~25%; 15–19.9 consider 10% decrease; 20–24.9 decrease 25%; 25–30 skip next dose and decrease ≥25%; >30 treat overdose
Instructions
- Take each morning at about the same time; do not exceed prescribed dose
- Once-a-day use not recommended at night; if BID, give second dose 10 to 12 hours after morning dose and before evening meal
- Doses ≥900 mg or 13 mg/kg (whichever is less): do not take less than 1 hour before a high-fat meal (marked rise in peak level)
- Normal/slow metabolizers suit QD; rapid metabolizers with end-of-interval symptoms may need higher QD dose or preferably BID
- Not for acute bronchospasm
- Individualize by peak serum level (target 10–20 mcg/mL; draw 12 hours post-dose at steady state); mg/kg on ideal body weight
- Stop any dose causing adverse effects, withhold until resolved, resume at lower tolerated dose
Available strengths
- ER cap 100, 200, 300, 400 mg
- ER tab 100, 200, 300, 400, 450, 600 mg
- sol 80 mg/15 mL
Cautions
- Concurrent illness: active peptic ulcer, seizure disorders, cardiac arrhythmias
- Conditions reducing clearance (age >60, neonates/infants, CHF, cor pulmonale, fever, hypothyroidism, liver disease, sepsis, shock, smoking cessation, interacting drugs) — reduce dose or fatal toxicity
- Signs of toxicity (nausea/vomiting): withhold and measure level immediately
- Do not increase dose for acute exacerbations; limit increases to about 25%
- Narrow therapeutic index — monitor serum concentrations
Adverse reactions
- Nausea
- Vomiting
- Headache
- Insomnia
- Diarrhea
- Irritability
- Restlessness
- Fine skeletal muscle tremor
- Transient diuresis
- Persistent vomiting, arrhythmias, seizures at levels >20 mcg/mL
Pregnancy Teratogenic in animals; no adequate human studies — use only if potential benefit justifies potential fetal risk.
Lactation Excreted into breast milk at about maternal serum concentration; may cause irritability or mild toxicity in nursing infants.
Cost
| Strength | #/mo | generic $/mo | CostPlus | |
|---|---|---|---|---|
| 100 mg | ER cap | 60 BID | $228.97 | not offered |
| 200 mg | ER cap | 60 BID | $340.07 | not offered |
| 300 mg | ER cap | 60 BID | $417.17 | not offered |
| 400 mg | ER cap | 60 BID | $587.59 | not offered |
Generic entry1982
Open Theophylline in the interactive console ↗
Memory aids: interaction avatars
Open Theophylline in the interactive console ↗
Self-check
- Which CYP pathway makes theophylline interaction-prone?
CYP1A2. - What smoking change can push theophylline into toxicity?
Smoking cessation.