ethylenediamine

[eth´ĭ-lēn-di″ah-mēn] a clear liquid with an ammonia like odor and a strong alkaline reaction; complexed with theophylline, it forms aminophylline.

aminophylline (theophylline, ethylenediamine)

Amnivent (UK), Phyllocontin (UK)

Pharmacologic class: Xanthine

Therapeutic class: Bronchodilator

Pregnancy risk category C

Action

Unclear. Thought to directly relax smooth muscle of bronchial airways and increase pulmonary blood flow by inhibiting phosphodiesterase.

Availability

Injection: 250 mg/10 ml

Oral liquid: 105 mg/5 ml

Tablets: 100 mg, 200 mg

Indications and dosages

➣ Symptomatic relief of bronchospasm in patients with acute symptoms who require rapid theophyllinization

Adults (nonsmokers): 0.7 mg/kg/hour I.V. for first 12 hours. Maintenance dosage is 0.5 mg/kg/hour I.V.

Children ages 9 to 16: 1 mg/kg/hour I.V. for first 12 hours. Maintenance dosage is 0.8 mg/kg/hour I.V.

Children ages 6 months to 9 years: 1.2 mg/kg/hour I.V. for first 12 hours. Maintenance dosage is 1 mg/kg/hour I.V.

➣ Chronic bronchial asthma

Adults and children: Dosage is highly individualized. Common initial dosage is 16 mg/kg/24 hours I.V. or 400 mg/24 hours I.V. in divided doses at 6- or 8hour intervals. If needed, dosage may be increased 25% at 3-day intervals.

Dosage adjustment

• Heart failure

• Hepatic disease

• Elderly patients

• Smokers

Off-label uses

• Dyspnea in patients with chronic obstructive pulmonary disease (COPD)

Contraindications

• Hypersensitivity to xanthine compounds or ethylenediamine

• Seizure disorders

Precautions

Use cautiously in:

• COPD, diabetes mellitus, glaucoma, renal or hepatic disease, heart failure or other cardiac or circulatory impairment, hypertension, hyperthyroidism, peptic ulcer, severe hypoxemia

• active peptic ulcer disease

• elderly patients

• neonates, infants, and young children.

Administration

• For I.V. use, dilute according to label directions and infuse at a rate no faster than 25 mg/minute.

• Don't give in I.V. solutions containing invert sugar, fructose, or fat emulsions.

• Give oral form at meals with 8 oz of water.

Adverse reactions

CNS: irritability, dizziness, nervousness, restlessness, headache, insomnia, stammering speech, abnormal behavior, mutism, unresponsiveness alternating with hyperactivity, seizures

CV: palpitations, sinus tachycardia, extrasystoles, marked hypotension, arrhythmias, circulatory failure

GI: nausea, vomiting, diarrhea, epigastric pain, hematemesis, gastroesophageal reflux, anorexia

GU: urine retention (in men with enlarged prostate), diuresis, increased excretion of renal tubular cells and red blood cells, proteinuria

Metabolic: hyperglycemia

Musculoskeletal: muscle twitching

Respiratory: tachypnea, respiratory arrest

Skin: flushing

Other: fever, hypersensitivity reactions (including exfoliative dermatitis and urticaria)

Interactions

Drug-drug. Adenosine: decreased antiarrhythmic effect of adenosine

Barbiturates, nicotine, phenytoin, rifampin: decreased aminophylline blood level

Beta-adrenergic blockers: antagonism of aminophylline effects

Calcium channel blockers, cimetidine, ciprofloxacin, disulfiram, erythromycin, hormonal contraceptives, influenza vaccine, interferon, methotrexate: elevated aminophylline blood level

Carbamazepine, isoniazid, loop diuretics (such as furosemide): increased or decreased aminophylline blood level

Ephedrine, other sympathomimetics: toxicity, arrhythmias

Lithium: increased lithium excretion

Drug-diagnostic tests. Aspartate aminotransferase, glucose: increased levels

Drug-herbs. Cayenne: increased risk of aminophylline toxicity

Drug-behaviors. Smoking: increased aminophylline elimination

Patient monitoring

See Monitor aminophylline blood level. Adjust dosage if patient has signs or symptoms of toxicity (tachycardia, headache, anorexia, nausea, vomiting, diarrhea, restlessness, and irritability).

• Assess for arrhythmias, especially after giving loading dose.

• Check vital signs and fluid intake and output.

• Monitor patient's response to drug, and assess pulmonary function test results.

Patient teaching

• Advise patient to take oral doses at meals with 8 oz of water.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Advise patient to establish effective bedtime routine to minimize insomnia.

• Caution patient not to change aminophylline brands.

• If patient smokes, tell him to notify prescriber if he stops smoking; dosage may need to be adjusted.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.